General Child Neurology

This is an x-ray of a young child with idiopathic infantile scoliosis. Genetic testing and MRI scans of the brain and spinal cord were normal. He had a right thoracic curve with a Cobb angle measuring 53.7 degrees. Despite Risser casting, his scoliosis has progressed severely. (Contributed by Dr. Daniel Bonthius.)

AP spinal x-ray of a 2-year-old boy with infantile scoliosis, following placement of MAGEC (MAGnetic Expansion Control) rods, spanning from T4 to L3. Screws are inserted into the vertebral pedicles bilaterally. Following placement of the hardware, the patient's scoliotic curve was reduced and stabilized. (Contributed by Dr. Daniel Bonthius.)

This image depicts a dorsal view of a patient’s left foot, revealing the effects of a condition known as late yaws. Late yaws develops in only about 10% of people who are infected with yaws. It begins at least 5 years after the appearance of early yaws, and it has the potential to cause severe damage to the skin, bones, and joints, especially in the legs. (Source: Photography by Susan Lindsley, Centers for Disease Control and Prevention, 1978. Public Health Image Library ID# 3831, Centers for Disease Control and Prevention, Atlanta, Georgia. Public domain.)

This patient demonstrates the effects of crab yaws on the palm of her left hand. Crab yaws is characterized by hyperkeratosis, with fissuring and ulceration of the soles of the feet and, less commonly, as was the case here, involves the palms of the hands. (Source: Photography by Susan Lindsley, Centers for Disease Control and Prevention, 1978. Public Health Image Library ID# 3829, Centers for Disease Control and Prevention, Atlanta, Georgia. Public domain.)

Anterior view of a child’s face showing numerous perioral papillomas, which developed as a result of the treponemal disease known as yaws. The first sign of yaws is the appearance of a painless papule, which grows into a papilloma. These large, early granulomatous lesions are highly infectious and display a yellow, crusty surface. (Source: Photography by Dr. JG Caldwell, Centers for Disease Control and Prevention, 1970. Public Health Image Library ID# 3832, Centers for Disease Control and Prevention, Atlanta, Georgia. Public domain.)

This image depicts a close inferoanterior view of a patient’s chin, showing papillomatous lesions that had developed in this 30-year-old woman after she breastfed her 13-month-old infant. The infection was diagnosed as yaws. It began as a lesion on her left breast and subsequently spread to her back. The Venereal Disease Research Laboratory test (VDRL) test produced a positive result of 1:8 and was accompanied by the microhemagglutination assay (MHA-TP) test, which was also reactive, or positive. Treatment for this patient consisted of an intramuscular injection of 2.4 mega (million) units of benzathine benzylpenicillin (benzathine penicillin G). (Source: Photography by Dr. Peter Perine, Centers for Disease Control and Prevention, 1979. Public Health Image Library ID# 3824, Centers for Disease Control and Prevention, Atlanta, Georgia. Public domain.)

These early papillomata of 2 weeks duration developed on the back of this 30-year-old woman with yaws. She also had an ulcerative, papillomatous lesion on her left breast that proved to be the initial site of the yaws infection after she breastfed her 13-month-old infant. The Venereal Disease Research Laboratory (VDRL) test produced a positive result of 1:8 and was accompanied by the microhemagglutination assay (MHA-TP) test, which was also reactive, or positive. Treatment for this patient consisted of an intramuscular injection of 2.4 mega (million) units of benzathine benzylpenicillin. These early, highly infectious papillomatous lesions, characteristically appear as large, yellow, and crusty. (Source: Photography by Dr. Peter Perine, Centers for Disease Control and Prevention, 1979. Public Health Image Library ID# 3836, Centers for Disease Control and Prevention, Atlanta, Georgia. Public domain.)

This papillomatous lesion of 2 weeks duration, developed on the left breast of a 30-year-old woman after she breastfed her 13-month-old infant. The infection was diagnosed as yaws. The infection began spreading to her back and chin. The Venereal Disease Research Laboratory (VDRL) test produced a positive result of 1:8 and was accompanied by the microhemagglutination assay (MHA-TP) test, which was also reactive, or positive. Treatment for this patient consisted of an intramuscular injection of 2.4 mega (million) units of benzathine benzylpenicillin. (Source: Photography by Dr. Peter Perine, Centers for Disease Control and Prevention, 1979. Public Health Image Library ID# 3835, Centers for Disease Control and Prevention, Atlanta, Georgia. Public domain.)

This image depicts a close view of the chin and neck of a 30-year-old woman who breastfed her 13-month-old infant and subsequently developed a lesion on her left breast, which was diagnosed as yaws. The infection spread to her back and chin. The Venereal Disease Research Laboratory (VDRL) test produced a positive result of 1:8 and was accompanied by the microhemagglutination assay (MHA-TP) test, which was also reactive, or positive. Treatment for this patient consisted of an intramuscular injection of 2.4 mega (million) units of benzathine benzylpenicillin. Note the marked improvement after only 1 week of antibiotic treatment. (Source: Photography by Dr. Peter Perine, Centers for Disease Control and Prevention, 1979. Public Health Image Library ID# 3839, Centers for Disease Control and Prevention, Atlanta, Georgia. Public domain.)

The face of this woman showed the ravages of a disease known as yaws, a nonvenereal endemic syphilis, caused by the spirochete Treponema pallidum subspecies pertenue. The condition caused degenerative changes to the cartilage and bones that made portions of her face sink inward. (Source: Photography by Dr. JG Caldwell, Centers for Disease Control and Prevention, 1970. Public Health Image Library ID# 15980, Centers for Disease Control and Prevention, Atlanta, Georgia. Public domain.)

The face of this young child revealed evidence of a disease known as yaws, a nonvenereal endemic syphilis, caused by the spirochete Treponema pallidum subspecies pertenue. Note the angular stomatitis, which begins as papules at the corners of the mouth and eventually splits, resulting in a painful open wound. (Source: Photography by Dr. JG Caldwell, Centers for Disease Control and Prevention, 1970. Public Health Image Library ID# 16981, Centers for Disease Control and Prevention, Atlanta, Georgia. Public domain.)

This 10-year-old Ghanaian boy exhibited secondary mucocutaneous papillomata, which had been due to yaws infection (frambesia tropica) caused by the spirochete Treponema pallidum subspecies pertenue. The lesions were evident at the corners of his mouth and chin. The Venereal Disease Research Laboratory (VDRL) test produced a positive result of 1:128 and was accompanied by the fluorescent treponemal antibody absorption (FTA-ABS) and microhemagglutination assay (MHA-TP) tests, which were both reactive, or positive. (Source: Photography by Dr. Peter Perine, Centers for Disease Control and Prevention, 1979. Public Health Image Library ID# 16903, Centers for Disease Control and Prevention, Atlanta, Georgia. Public domain.)

This image depicts the sole of a 9-year-old boy who exhibited plantar papillomatous lesions, which had been due to a yaws infection, also known as frambesia tropica, caused by the spirochete Treponema pallidum subspecies pertenue. The lesions were evident at the corners of his mouth and chin. The Venereal Disease Research Laboratory (VDRL) test produced a positive result of 1:128 and was accompanied by the fluorescent treponemal antibody absorption (FTA-ABS) and microhemagglutination assay (MHA-TP) tests, which were both reactive, or positive. (Source: Photography by Dr. Peter Perine, Centers for Disease Control and Prevention, 1979. Public Health Image Library ID# 16903, Centers for Disease Control and Prevention, Atlanta, Georgia. Public domain.)

Photographed from the patient’s left side, this image depicts the lower extremities of an individual with papulosquamous lesions of the left ankle and deformities to the leg bones (saber tibia or saber shin) due to yaws infection (frambesia tropica) caused by the spirochete Treponema pallidum subspecies pertenue. (Source: Photography by Dr. JG Caldwell, Centers for Disease Control and Prevention, 1970. Public Health Image Library ID# 16904, Centers for Disease Control and Prevention, Atlanta, Georgia. Public domain.)

The face of this 78-year-old man shows the ravages of chronic yaws, a nonvenereal endemic syphilis, caused by the spirochete Treponema pallidum, subspecies pertenue. The photograph shows degenerative changes to the cartilage and bones of the mid-face region, making it appear to have sunken inward, a facial deformity known as rhinopharyngitis mutilans or gangosa. This case of yaws was of 50 years duration. (Source: Photography by Dr. Peter Perine, Centers for Disease Control and Prevention, 1979. Public Health Image Library ID# 16932, Centers for Disease Control and Prevention, Atlanta, Georgia. Public domain.)

(Source: World Health Organization--Global Health Observatory, 2024. OurWorldinData.org/eradication-of-diseases. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

This is a photomicrograph of a yaws lesion exudate stained using a specific anti-treponemal fluorescein-labeled antibody, which revealed the characteristic corkscrew morphology exhibited by Treponema pallidum subspecies pertenue bacterial spirochetes. The slide was examined under ultraviolet light using a red filter. (Source: Photography by Dr. Peter Perine, Centers for Disease Control and Prevention, 1979. Public Health Image Library ID# 17890, Centers for Disease Control and Prevention, Atlanta, Georgia. Public domain.)

This patient demonstrates the effects of a condition known as crab yaws on the palm of his right hand. Crab yaws is characterized by hyperkeratosis with fissuring and ulceration of the soles of the feet and, less commonly, as was the case here, by hyperkeratosis involving the palms of the hands. (Source: Photography by Susan Lindsley, Centers for Disease Control and Prevention, 1978. Public Health Image Library ID# 16933, Centers for Disease Control and Prevention, Atlanta, Georgia. Public domain.)

This photograph depicts a 45-year-old woman from the Ivory Coast who displayed a facial lesion and underlying bone deformity as a result of a late tertiary yaws infection. This patient’s Venereal Disease Research Laboratory test (VDRL) produced a positive result of 1:16 and was accompanied by the microhemagglutination assay (MHA-TP) test, which was also reactive, or positive. (Source: Photography by Dr. Peter Perine, Centers for Disease Control and Prevention, 1979. Public Health Image Library ID# 3834, Centers for Disease Control and Prevention, Atlanta, Georgia. Public domain.)

This photograph depicts a lateral view of a 7-months pregnant woman’s torso. Note the maculopapular eruptions on her abdomen, which were determined to be due to a secondary syphilis infection caused by the bacterial spirochete, Treponema pallidum. A pregnant mother infected with the T. pallidum bacterium can transfer the infection to her unborn child, causing congenital syphilis. (Source: Photography by Centers for Disease Control and Prevention. Public Health Image Library ID# 17830, Centers for Disease Control and Prevention, Atlanta, Georgia. Public domain.)

This image depicts a dorsal view of a patient’s hands, which exhibited signs found in late congenital syphilis due to syphilitic bone disease that included osteoperiostitis, ulnar deviation of the middle fingers, and du Bois sign, which involves a shortening of the little finger. Congenital syphilis occurs when a developing infant within the womb is infected by the spirochete microorganism, Treponema pallidum, as it receives blood by way of the placenta. (Source: Photography by Renelle Woodall, Centers for Disease Control and Prevention, 1969. Public Health Image Library ID# 16750, Centers for Disease Control and Prevention, Atlanta, Georgia. Public domain.)

This close view of a patient’s hard palate revealed a perforation in the midline due to congenital syphilis caused by the bacterial spirochete, Treponema pallidum. (Source: Photography by Susan Lindsley, Centers for Disease Control and Prevention, 1972. Public Health Image Library ID# 16748, Centers for Disease Control and Prevention, Atlanta, Georgia. Public domain.)

This male infant was born with a condition known as congenital syphilis because his mother had been infected with the spirochete microorganism, Treponema pallidum, while pregnant and transferred the infection to her child by way of the placenta. Note the papular rash on his back, hips, and buttocks, which is one of the possible symptoms of a congenital syphilitic infection. (Source: Photography by Susan Lindsley, Centers for Disease Control and Prevention, 1973. Public Health Image Library ID# 16747, Centers for Disease Control and Prevention, Atlanta, Georgia. Public domain.)

This patient presented with a cutaneous pigmentation abnormality, occupying a region of the right shin from the knee to mid-tibia, composed of what appeared to be scarified, hyper-, and hypopigmented skin, known as pigmented pretibial scars, which was determined to be a symptom of congenital syphilis caused by the bacterial spirochete, Treponema pallidum. (Source: Photography by Brian Hill, New Zealand/Centers for Disease Control and Prevention, 1976. Public Health Image Library ID# 16745, Centers for Disease Control and Prevention, Atlanta, Georgia. Public domain.)

This female infant was born with congenital syphilis because while pregnant, her mother had been infected with the spirochete microorganism, Treponema pallidum. Note the papular rash on her chin and lips and the darkly pigmented spots on the soles of her feet, which are some of the possible symptoms of a congenital syphilitic infection. (Source: Photography by Susan Lindsley, Centers for Disease Control and Prevention, 1973. Public Health Image Library ID# 16743, Centers for Disease Control and Prevention, Atlanta, Georgia. Public domain.)

This image depicts an adult holding the right hand of a young child with late congenital syphilis to focus attention on the child’s fifth digit from a medial perspective. From this view, you will note a deformation known as du Bois sign, which involves a shortening of the little finger. (Source: Photography by Susan Lindsley, Centers for Disease Control and Prevention, 1973. Public Health Image Library ID# 16741, Centers for Disease Control and Prevention, Atlanta, Georgia. Public domain.)

This image depicted the umbilicus of an infant, which displayed an inflamed lesion that under a dark field examination revealed the presence of Treponema pallidum spirochetes and, hence, a diagnosis of congenital syphilis was made. A syphilid is any of the cutaneous and mucous membrane lesions characteristic of secondary and tertiary syphilis. It appears about 10 weeks after infection. (Source: Photography by Centers for Disease Control and Prevention, 1970. Public Health Image Library ID# 15566, Centers for Disease Control and Prevention, Atlanta, Georgia. Public domain.)

This image depicts a close view of the right eye of a patient revealing the pathologic changes in her cornea known as interstitial corneal keratitis, which was due to a congenital syphilitic infection and is a chronic progressive keratitis of the corneal stroma, often resulting in blindness, and frequently associated with congenital syphilis. Syphilis is caused by the bacterium, Treponema pallidum. (Source: Photography by Robert Sumpter, Centers for Disease Control and Prevention, 1967. Public Health Image Library ID# 12600, Centers for Disease Control and Prevention, Atlanta, Georgia. Public domain.)

This image depicts the dentition of a congenital syphilis patient, who due to this disease went on to develop what are known as Hutchinson’s teeth, in which case the teeth are widely spaced, and the bite surfaces of the incisors are notched. Syphilis is caused by the bacterium, Treponema pallidum. (Source: Photography by Robert Sumpter, Centers for Disease Control and Prevention, 1967. Public Health Image Library ID# 12599, Centers for Disease Control and Prevention, Atlanta, Georgia. Public domain.)

This image depicts the perineal region and upper thighs of an infant born with what was diagnosed as congenital syphilis caused by the bacterium, Treponema pallidum. In this particular case, one will note the presence of early cutaneous syphilids. A syphilid is any of the cutaneous and mucous membrane lesions characteristic of secondary and tertiary syphilis. It appears about 10 weeks after infection. (Source: Photography by Robert Sumpter, Centers for Disease Control and Prevention, 1967. Public Health Image Library ID# 12597, Centers for Disease Control and Prevention, Atlanta, Georgia. Public domain.)

This image depicts the buttocks and perineal region of an infant born with what was diagnosed as congenital syphilis caused by the bacterium, Treponema pallidum. In this particular case, one will note the presence of eroded, early syphilids. A syphilid is any of the cutaneous and mucous membrane lesions characteristic of secondary and tertiary syphilis. It appears about 10 weeks after infection. (Source: Photography by Robert Sumpter, Centers for Disease Control and Prevention, 1967. Public Health Image Library ID# 12596, Centers for Disease Control and Prevention, Atlanta, Georgia. Public domain.)

This image depicts a close view of a patient’s left eye, revealing the presence of cloudy corneal spots, which are known as interstitial corneal keratitis and were the result of a case of late congenital syphilis caused by the bacterium, Treponema pallidum. If not immediately treated, babies may become developmentally delayed, have seizures, or die. Symptoms may not become initially apparent but can develop within a few weeks. These signs and symptoms can be very serious. (Source: Photography by Susan Lindsley, Centers for Disease Control and Prevention, 1973. Public Health Image Library ID# 4149, Centers for Disease Control and Prevention, Atlanta, Georgia. Public domain.)

This photograph, from a 45-year-old woman from the Ivory Coast, depicts what is known as a tibial sabre deformity, which resulted from a late tertiary yaws infection. This patient’s Venereal Disease Research Laboratory test, or VDRL, produced a positive result of 1:16 and was accompanied by the microhemagglutination assay (MHA-TP) test, which was also reactive, or positive. A saber shin deformity is an abnormality of the tibia characterized by marked anterior bowing of the lower leg. This defect may be seen in some children with congenital syphilis and patients with yaws. (Source: Photography by Dr. Peter Perine, Centers for Disease Control and Prevention, 1979. Public Health Image Library ID# 3823, Centers for Disease Control and Prevention, Atlanta, Georgia. Public domain.)

This photograph depicts a perforated hard palate on a patient with congenital syphilis, due to gummatous erosion of the palatal bone and soft tissues. These destructive tumors can also attack the skin, long bones, eyes, mucous membranes, throat, liver, or stomach lining. (Source: Photography by Susan Lindsley, Centers for Disease Control and Prevention, 1971. Public Health Image Library ID# 2388, Centers for Disease Control and Prevention, Atlanta, Georgia. Public domain.)

This photograph depicts a patient exhibiting saber shin of the right lower leg, or osteoperiostitis of the tibia, due to congenital syphilis. (Source: Photography by Robert Sumpter, Centers for Disease Control and Prevention, 1967. Public Health Image Library ID# 2387, Centers for Disease Control and Prevention, Atlanta, Georgia. Public domain.)

This photograph depicts an intraoral view of a patient’s mouth exposing the abnormalities associated with the dentition, known as Hutchinson’s teeth, which resulted from a congenital syphilis infection by the bacterium, Treponema pallidum. Hutchinson’s teeth involves a narrowing and notching of the teeth, imparting a screwdriver-like shape to affected teeth, like these central incisors. (Source: Photography by Susan Lindsley, Centers for Disease Control and Prevention, 1971. Public Health Image Library ID# 2385, Centers for Disease Control and Prevention, Atlanta, Georgia. Public domain.)

This photograph depicts a close view of a patient’s right eye, which exhibited gross pathologic changes indicative of corneal interstitial keratitis due to a case of congenital syphilis caused by the bacterium, Treponema pallidum. Interstitial keratitis is an inflammation of the connective tissue structure of the cornea, and syphilis is the most common cause of this condition. (Source: Photography by Richard Deitrick, Centers for Disease Control and Prevention, 1966. Public Health Image Library ID# 2384, Centers for Disease Control and Prevention, Atlanta, Georgia. Public domain.)

Algorithms that can be applied to screening for syphilis with serologic tests. Abbreviations: CIA = chemiluminescence immunoassay; EIA = enzyme immunoassay; RPR = rapid plasma regain; TPPA = Treponoma pallidum particle agglutination; VDRL = Venereal Disease Research Laboratory. (Source: Papp JR, Park IU, Fakile Y, Pereira L, Pillay A, Bolan GA. CDC Laboratory Recommendations for Syphilis Testing, United States, 2024. MMWR Recomm Rep 2024;73(1):1-32. Public domain.)

(Source: Papp JR, Park IU, Fakile Y, Pereira L, Pillay A, Bolan GA. CDC Laboratory Recommendations for Syphilis Testing, United States, 2024. MMWR Recomm Rep 2024;73(1):1-32. Public domain.)

(Source: Papp JR, Park IU, Fakile Y, Pereira L, Pillay A, Bolan GA. CDC Laboratory Recommendations for Syphilis Testing, United States, 2024. MMWR Recomm Rep 2024;73(1):1-32. Adapted from: Peeling RW, Mabey D, Kamb ML, Chen XS, Radolf JD, Benzaken AS. Syphilis. Nat Rev Dis Primers 2017;3:17073. Public domain.)

(Source: Staneva M, Hobbs CV, Dobbs T. Spike in congenital syphilis, Mississippi, USA, 2016-2022. Emerg Infect Dis 2023;29(10):1965-72. Public domain.)

Error bars indicate 95% confidence intervals. (Source: Staneva M, Hobbs CV, Dobbs T. Spike in congenital syphilis, Mississippi, USA, 2016-2022. Emerg Infect Dis 2023;29(10):1965-72. Public domain.)

Numbers above bars are rates for each year. Rates were obtained by dividing the number of infants hospitalized with congenital syphilis by the total number of delivery hospitalizations per year. (Source: Staneva M, Hobbs CV, Dobbs T. Spike in congenital syphilis, Mississippi, USA, 2016-2022. Emerg Infect Dis 2023;29(10):1965-72. Public domain.)

(Source: Staneva M, Hobbs CV, Dobbs T. Spike in congenital syphilis, Mississippi, USA, 2016-2022. Emerg Infect Dis 2023;29(10):1965-72. Public domain.)

Maternal syphilis cases reported on the Brazilian National Notifiable Diseases Information System (SINAN) by 06/30/2022. Prescribed treatment was with at least one dose of benzathine penicillin, regardless of the clinical form. (Source: Health Surveillance Secretary of the Ministry of Health of Brazil [DVIAHV/HHS/MoH]. Miranda AE, Santos PC, Coelho RA, et al. Perspectives and challenges for mother-to-child transmission of HIV, hepatitis B, and syphilis in Brazil. Front Public Health 2023;11:1182386. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

HIV and syphilis cases reported on the Brazilian National Notifiable Diseases Information System (SINAN) by 06/30/2022. HBV cases reported on SINAN by 12/31/2021. (Source: Health Surveillance Secretary of the Ministry of Health of Brazil [DVIAHV/HHS/MoH]. Miranda AE, Santos PC, Coelho RA, et al. Perspectives and challenges for mother-to-child transmission of HIV, hepatitis B, and syphilis in Brazil. Front Public Health 2023;11:1182386. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

HIV and syphilis cases reported on the Brazilian National Notifiable Diseases Information System (SINAN) by 06/30/2022. HBV cases reported on SINAN by 12/31/2021. (Source: Health Surveillance Secretary of the Ministry of Health of Brazil [DVIAHV/HHS/MoH]. Miranda AE, Santos PC, Coelho RA, et al. Perspectives and challenges for mother-to-child transmission of HIV, hepatitis B, and syphilis in Brazil. Front Public Health 2023;11:1182386. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Timely testing is performed 30 or more days before delivery. Late identification of seroconversion is a new reactive syphilis test fewer than 30 days before delivery after a nonreactive test earlier in pregnancy. Adequate treatment is receipt of a penicillin-based regimen, dosed and spaced appropriately for the stage of syphilis, and commenced 30 or more days before delivery. (Source: McDonald R, O'Callaghan K, Torrone E, et al. Vital signs: missed opportunities for preventing congenital syphilis--United States, 2022. MMWR Morb Mortal Wkly Rep 2023;72(46):1269-74. Public domain.)

Reported number of cases of congenital syphilis among infants, by year of birth, and rates of reported cases of primary and secondary syphilis among females aged 15-44 years, by year--United States, 2012 to 2022. Cases per 100,000 population. Primary and secondary syphilis case data for all U.S. territories and freely associated states and outlying areas were not available for all years; therefore, rates presented include only the 50 states and the District of Columbia. (Source: McDonald R, O'Callaghan K, Torrone E, et al. Vital signs: missed opportunities for preventing congenital syphilis--United States, 2022. MMWR Morb Mortal Wkly Rep 2023;72(46):1269-74. Public domain.)

Each state and the District of Columbia. Note: Maternal syphilis rate is the number of live births to women with syphilis per 100,000 live births. (Source: National Center for Health Statistics, National Vital Statistics System, natality data file. Gregory EC, Ely DM. Trends and characteristics in maternal syphilis rates during pregnancy: United States, 2016-2022. NCHS Data Brief 2024;[496]:1-8. Public domain.)

(1) Significant increasing trend from 2016 to 2022 (p < 0.05). (2) Significant decreasing trend by timing of prenatal care for each year 2016 to 2022 (p < 0.05). Note: In 2022, 2.2% (77,228) of mothers did not receive prenatal care. (Source: National Center for Health Statistics, National Vital Statistics System, natality data file. Gregory EC, Ely DM. Trends and characteristics in maternal syphilis rates during pregnancy: United States, 2016-2022. NCHS Data Brief 2024;[496]:1-8. Public domain.)

(1) Significant increasing trend from 2016 to 2022 (p < 0.05). (2) Significant difference from other race and Hispanic-origin groups for 2022 (p < 0.05). (3) Significant difference from other race and Hispanic-origin groups except Black nonHispanic for 2022 (p < 0.05). (4) Significant difference from other race and Hispanic-origin groups except Native Hawaiian or Other Pacific Islander nonHispanic for 2022 (p < 0.05). (5) People of Hispanic origin may be of any race. (Source: National Center for Health Statistics, National Vital Statistics System, natality data file. Gregory EC, Ely DM. Trends and characteristics in maternal syphilis rates during pregnancy: United States, 2016-2022. NCHS Data Brief 2024;[496]:1-8. Public domain.)

(1) Significant increasing trend from 2016 to 2022 (p < 0.05). (2) Significant decreasing trend by increasing maternal age for 2022 (p < 0.05). (Source: National Center for Health Statistics, National Vital Statistics System, natality data file. Gregory EC, Ely DM. Trends and characteristics in maternal syphilis rates during pregnancy: United States, 2016-2022. NCHS Data Brief 2024;[496]:1-8. Public domain.)

Significant increasing trend from 2016 to 2022 (p < 0.05). (Source: National Center for Health Statistics, National Vital Statistics System, natality data file. Gregory EC, Ely DM. Trends and characteristics in maternal syphilis rates during pregnancy: United States, 2016-2022. NCHS Data Brief 2024;[496]:1-8. Public domain.)

(Source: Koplik H. The diseases of infancy and childhood. New York and Philadelphia: Lea & Febiger, 1910. Public domain.)

(Source: Tascini C, Iantomasi R, Sbrana F, et al. MAGLIO study: epideMiological Analysis on invasive meninGococcaL disease in Italy: fOcus on hospitalization from 2015 to 2019. Intern Emerg Med 2023;18[7]:1961-9. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

(Source: Tascini C, Iantomasi R, Sbrana F, et al. MAGLIO study: epideMiological Analysis on invasive meninGococcaL disease in Italy: fOcus on hospitalization from 2015 to 2019. Intern Emerg Med 2023;18[7]:1961-9. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

(Source: GBD 2019 Meningitis Antimicrobial Resistance Collaborators. Global, regional, and national burden of meningitis and its aetiologies, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet Neurol 2023;22[8]:685-711. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

(Source: GBD 2019 Meningitis Antimicrobial Resistance Collaborators. Global, regional, and national burden of meningitis and its aetiologies, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet Neurol 2023;22[8]:685-711. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

(Source: GBD 2019 Meningitis Antimicrobial Resistance Collaborators. Global, regional, and national burden of meningitis and its aetiologies, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet Neurol 2023;22[8]:685-711. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

(Source: GBD 2019 Meningitis Antimicrobial Resistance Collaborators. Global, regional, and national burden of meningitis and its aetiologies, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet Neurol 2023;22[8]:685-711. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Persons vaccinated by month and antigen during concurrent outbreaks of hepatitis A, invasive meningococcal disease, and mpox, Florida, USA, 2021 to 2022. The figure shows the number of adult persons (older than 18 years of age) vaccinated with their first dose, by month the first dose was administered. For hepatitis A, the number includes persons vaccinated with any Food and Drug Administration (FDA)-approved vaccine against hepatitis A virus. For meningococcal disease, the number includes persons vaccinated with any FDA-approved serogroup ACWY vaccine (Menveo [GlaxoSmithKline], Menactra [Sanofi Pasteur, Inc], MenQuadfi [Sanofi Pasteur, Inc]). For mpox, the number includes persons vaccinated with JYNNEOS (Bavarian Nordic). FDA, Food and Drug Administration. (Source: Doyle TJ, Gumke M, Stanek D, et al. Concurrent outbreaks of hepatitis a, invasive meningococcal disease, and mpox, Florida, USA, 2021-2022. Emerg Infect Dis 2024;30[4]:633-43. Public domain.)

Spatial distribution of outbreak-associated cases of hepatitis A and invasive meningococcal disease in an investigation of concurrent outbreaks in Florida, 2021 to 2022. (A) Locations of cases by postal (ZIP) code of patient residence; (B) detail of box from central Florida in panel A, in which more than one case of each disease were reported in the same postal code. Outside the area represented in that panel, no instances of both diseases were identified in the same postal code. Invasive meningococcal disease cases were georeferenced by postal code centroid. Small polygons are outlines of postal code areas. Light gray lines indicate county borders; dark gray lines indicate postal areas where cases were identified. (Source: Doyle TJ, Gumke M, Stanek D, et al. Concurrent outbreaks of hepatitis a, invasive meningococcal disease, and mpox, Florida, USA, 2021-2022. Emerg Infect Dis 2024;30[4]:633-43. Public domain.)

Epidemiologic curves of concurrent outbreaks of hepatitis A and invasive meningococcal disease by week of symptom onset, Florida, USA, November 1, 2021 to November 30, 2022. (A) Invasive meningococcal disease; (B) hepatitis A. The case definition for invasive meningococcal disease cases had two categories: confirmed and probable. The case definition for hepatitis A cases had three categories: confirmed, probable, and suspect. (Source: Doyle TJ, Gumke M, Stanek D, et al. Concurrent outbreaks of hepatitis a, invasive meningococcal disease, and mpox, Florida, USA, 2021-2022. Emerg Infect Dis 2024;30[4]:633-43. Public domain.)

Recommended meningococcal vaccines for persons at increased risk for meningococcal disease due to serogroups A, B, C, W, or Y and who are due for both meningococcal A, C, W, and Y vaccine and meningococcal B vaccine. Notes: (1) MenACWY products are interchangeable; the same vaccine product is recommended, but not required, for all doses. (2) Different manufacturers’ MenB vaccines are not interchangeable. (3) To determine whether MenACWY and MenB are indicated based on a person’s risk factors and timing of any previous meningococcal vaccines, clinicians should see previously published recommendations (Mbaeyi SA, Bozio CH, Duffy J, et al. Meningococcal vaccination: recommendations of the Advisory Committee on Immunization Practices, United States, 2020. MMWR Recomm Rep 2020;69[9]:1-41). (4) If MenB was received previously, but the vaccine manufacturer is not known, the series must be restarted with any licensed product to ensure completion of the series using products from a single manufacturer (Mbaeyi et al 2020). (5) If MenB-FHbp was received previously, MenACWY-TT/MenB-FHbp may be used provided the person has not received MenACWY-TT/MenB-FHbp previously or 6 or more months have passed since the previous dose of MenACWY-TT/MenB-FHbp.

Abbreviations: MenACWY = quadrivalent (serogroups A, C, W, and Y) meningococcal conjugate vaccine; MenACWY-TT/MenB-FHbp = Penbraya (Pfizer Inc) pentavalent (serogroups A, B, C, W, and Y) meningococcal vaccine; MenB-FHbp = Trumenba (Pfizer Inc) serogroup B meningococcal vaccine; MenB-4C = Bexsero (GSK) serogroup B meningococcal vaccine.

(Source: Collins JP, Crowe SJ, Ortega-Sanchez IR, et al. Use of the Pfizer pentavalent meningococcal vaccine among persons aged ≥10 years: recommendations of the Advisory Committee on Immunization Practices - United States, 2023. MMWR Morb Mortal Wkly Rep 2024;73[15]:345-50. Public domain.)

(Source: Advisory Committee on Immunization Practices, 1997. Public domain.)

(Source: Advisory Committee on Immunization Practices, 1997. Public domain.)

Colored etching by British caricaturist George Cruikshank (1792-1878) in 1819, after an illustration by Royal Navy officer and novelist Captain Frederick Marryat (1792-1848). (Source: Wellcome Collection, London, United Kingdom. Public domain.)

(A) Healing fractures of the 4th and 5th anterolateral ribs (arrows) in a 2-month-old boy. (B) Fracture of the distal right humerus with a displaced medial condyle (arrow) in a 7-month-old girl. (C) Spiral fracture of the left humerus (arrow) in a 7-month-old girl. (D) Midshaft fracture (arrow) of the right humerus in a 2-month-old boy. (Contributed by Dr. Daniel Bonthius.)

The innumerable hemorrhages extend to the periphery and are located within multiple layers of the retina. (Contributed by Dr. Daniel Bonthius.)

Progression of Axial T2 MRI findings in a 13-year-old male with a diffuse pediatric-type high-grade glioma, H3-wildtype and IDH-wildtype. (a, b) Obtained at time of diagnosis, MRI shows a diffuse, expansile T2 hyperintense signal that involved the corpus callosum and extended into the right cerebral hemisphere and cortical spinal tracts. (c, d) At the completion of radiation, MRI showed a slight increase in the T2/FLAIR hyperintensity in the subcortical white matter of the frontal lobes. (e, f) Two months after radiation, the tumor showed increased infiltration into the left cerebral hemisphere with midline shift to 11 mm. (g, h) After 8 months of this therapy, there was a significant decrease in enhancement along the corpus callosum, left peritrigonal white matter, and the centrum semiovale. (Contributed by Dr. Elizabeth Finch.)

Gibson was instrumental in recognizing the importance of lead-based paint in the development of childhood lead poisoning from 1897 to 1904. (Source: Gibson JL. A plea for painted railings and painted walls of rooms as the source of lead poisoning amongst Queensland children. 1904. Public Health Rep 2005;120[3]:301-4. Public domain.)

(Top) Distribution of housing age; percentage of houses built before 1973 for the cases’ local area. Values represent for each case, the percentage of housing built before 1973, for the small area (Lower Super Output Area) where the case resides. Data from the Valuation Office Agency (VOA) (2014). (Bottom) Distribution of housing age for Lead Exposure in Children Surveillance System (LEICSS) cases (2014–2020) in England using Ordnance Survey data. (Source: Crabbe H, Verlander NQ, Iqbal N, et al. As safe as houses; the risk of childhood lead exposure from housing in England and implications for public health. BMC Public Health 2022;22[1]:2052. Photography by Rebecca Ingham, Advanced Health Protection Practitioner, Yorkshire and Humber Health Protection Team (HPT), UK Health Security Agency (UKHSA), 2021. Open Government Licence v3.0, www.nationalarchives.gov.uk/doc/open-government-licence/version/3.)

Location of cases, counts per Upper Tier Local Authority (UTLA), UK Health Security Agency (UKHSA) Centre region areas, and percentage of housing built before 1973 per UTLA area (VOA data, 2014). (Source: Crabbe H, Verlander NQ, Iqbal N, et al. As safe as houses; the risk of childhood lead exposure from housing in England and implications for public health. BMC Public Health 2022;22[1]:2052. Photography by Rebecca Ingham, Advanced Health Protection Practitioner, Yorkshire and Humber Health Protection Team (HPT), UK Health Security Agency (UKHSA), 2021. Open Government Licence v3.0, www.nationalarchives.gov.uk/doc/open-government-licence/version/3.)

(Source: Crabbe H, Verlander NQ, Iqbal N, et al. As safe as houses; the risk of childhood lead exposure from housing in England and implications for public health. BMC Public Health 2022;22[1]:2052. Photography by Rebecca Ingham, Advanced Health Protection Practitioner, Yorkshire and Humber Health Protection Team (HPT), UK Health Security Agency (UKHSA), 2021. Open Government Licence v3.0, www.nationalarchives.gov.uk/doc/open-government-licence/version/3.)

This midsagittal view of the brain MRI of a patient with spinocerebellar ataxia type 1 reveals atrophy of the cerebellum and pons, referred to as olivopontocerebellar atrophy. (Contributed by Dr. Pichet Termsarasab.)

(Contributed by Dr. Federica Provini.)

(Source: Fang J, Partridge E, Bautista GM, Sankaran D. Congenital syphilis epidemiology, prevention, and management in the United States: a 2022 update. Cureus 2022;14[12]:e33009. Image by Geoanna M Bautista. Creative Commons Attribution [CC-BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Congenital syphilis is preventable if syphilitic mothers will take adequate treatment during the last five months of pregnancy. Poster for New York State Department of Health promoting proper treatment for syphilis in pregnant women, showing woman holding a baby. (Source: Poster by Hungarian-American artist Alexander Dux [1898-1971] as part of the Works Progress Administration Federal Art Project, between 1936 and 1939. US Library of Congress Prints and Photographs Division, Washington, DC. Public domain.)

(Source: Jackson GT. The ready reference handbook of diseases of the skin. New York and Philadelphia: Lea & Fibiger, 1908: 616. Public domain.)

(Source: Starr L, Westcott TS. An American text-book of the diseases of children. Philadelphia: WB Saunders, 1895. Plate V. Public domain.)

(Source: Starr L, Westcott TS. An American text-book of the diseases of children. Philadelphia: WB Saunders, 1895. Plate V. Public domain.)

(Source: Centers for Disease Control and Prevention, 2023. Public domain.)

Cases of primary and secondary syphilis among women aged 15 to 44 years. (Source: Centers for Disease Control and Prevention, 2023. Public domain.)

(Source: Centers for Disease Control and Prevention, 2023. Public domain.)

(Source: Centers for Disease Control and Prevention, 2023. Public domain.)

(Source: Centers for Disease Control and Prevention, 2023. Public domain.)

(Source: Centers for Disease Control and Prevention, 2023. Public domain.)

(Source: Centers for Disease Control and Prevention, 2023. Public domain.)

(Source: Centers for Disease Control and Prevention, 2023. Public domain.)

(Source: Centers for Disease Control and Prevention, 2023. Public domain.)

(Source: Centers for Disease Control and Prevention, 2023. Public domain.)

(Source: Centers for Disease Control and Prevention, 2023. Public domain.)

(Source: Centers for Disease Control and Prevention, 2023. Public domain.)

1890 Chromolithograph after a watercolor painting by British portrait artist and caricaturist Sir Leslie Ward (1851-1922). Ward's portraits were regularly published by Vanity Fair, under the pseudonyms "Spy" and "Drawl.” (Source: Wellcome Trust, London. Creative Commons Attribution 2.0 Generic [CC BY] license, creativecommons.org/licenses/by/2.0/deed.en.)

Oil painting by W. Swainson. (Source: Wellcome Trust, London. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0/deed.en.)

The Tuskegee Syphilis Study is a notorious example of human research carried out without informed consent and with actions that were intentionally deleterious to the subjects studied. (Source: US National Archives. Atlanta, Georgia. Public domain.)

(Source: Norsk Portræt-Galleri. Christiania, Norway. Norwegian publisher and author Nils Christian Tønsberg [1813-1897], 1877. Public domain.)

(Source: US Library of Congress Prints and Photographs Division, Washington DC. Public domain.)

Photo from 1911. (Source: Fritz Schaudinns, Verlag Leopold Voss, Hamburg, und Leipzig. Public domain.)

Line engraving. (Source: Wellcome Trust, London. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0/deed.en.)

Line engraving by French engraver Nicolas de Larmessin (1632-1694). (Source: Wellcome Trust, London. Public Domain Mark.)

Hieronymus Fracastorius (Girolamo Fracastoro) shows the shepherd Syphilus and the hunter Ilceus a statue of Venus to warn them against the danger of infection with syphilis. Engraving by Jan Sadeler I, 1588/1595, after Christoph Schwartz (approximately 1548-1592). (Source: Wellcome Trust, London. Public Domain Mark.)

The second son of Christopher Columbus (1451-1506) described its skin manifestations among the sailors returning from the first voyage to the New World in 1493, and it was termed mal de la Hispaniola. (Source: Biblioteca Capitular Colombina. Sevilla del Buen Recuerdo. Universidad de Sevilla Colección de bolsillo. Public domain.)

(Source: Hutchinson J. A clinical memoir on certain diseases of the eye and ear, consequent on inherited syphilis: with an appended chapter of commentaries on the transmission of syphilis from parent to offspring, and its more remote consequences. London: Churchill, 1863. Wellcome Trust, London. Public Domain Mark.)

Monochrome pencil and watercolor drawings of the teeth of two patients with congenital syphilis. (Source: Norman Moore, St. Bartholomew's Hospital Archives and Museum. Wellcome Trust, London. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0/deed.en.)

(Source: Fournier A. La syphilis héréditaire tardive. Paris: G. Masson, 1886. Illustration by Alfred Forgeron [1842-1910?]. Wellcome Trust, London. Public Domain Mark.)

(Source: Fournier A. La syphilis héréditaire tardive. Paris: G. Masson, 1886. Illustration by Alfred Forgeron [1842-1910?]. Wellcome Trust, London. Public Domain Mark.)

(Source: Fournier A. La syphilis héréditaire tardive. Paris: G. Masson, 1886. Illustration by Alfred Forgeron [1842-1910?]. Wellcome Trust, London. Public Domain Mark.)

Drawing in oil of a 16-year-old girl showing some of the effects of congenital syphilis. The teeth are “pegged” (Hutchinson teeth), and the bridge of the nose is flattened (saddle nose). Both eyes are affected with interstitial keratitis, and the right, which is also affected with kerato-globus (ie, generalized, noninflammatory cornea thinning and globular protrusion), was absolutely blind. Large patches of necrosis of the cranial bones are exposed by ulceration of the scalp. (Source: Wellcome Trust, London. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0/deed.en.)

Watercolor drawing of 6-week-old child. Both legs exhibit raised red areas of a ham-colored eruption, scaly in places. The feet are raw and red. Drawing presented to the Museum by Wilmot Parker Herringham, physician to St Bartholomew's Hospital. (Source: Wellcome Trust, London. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0/deed.en.)

Watercolor drawing of the face of a young girl, aged 11 years, showing ulceration in the nose as a result of congenital syphilis. Illustration by surgeon and Anatomist Thomas Godart (active 1852-1861), pathological artist at St. Bartholomew's Hospital, London. (Source: St Bartholomew's Hospital Archives & Museum, London. Wellcome Trust, London. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0/deed.en.)

Illustration by surgeon and Anatomist Thomas Godart (active 1852-1861), pathological artist at St. Bartholomew's Hospital, London. Watercolor drawing of a 2-year-old girl with congenital syphilis showing mucous patches on the dorsum of the tongue and at the corners of the mouth. (Source: St Bartholomew's Hospital Archives & Museum, London. Wellcome Trust, London. Public Domain Mark.)

Illustration by Surgeon Leonard Portal Mark (1855-1930), pathological artist at St. Bartholomew's Hospital, London. Watercolor drawing of the tongue of a 10-yaer-old boy, showing two large deeply excavated ulcers with raised and rugged edges, due to congenital syphilis. The child had previously been in the hospital with a similar condition of the tongue, which quite disappeared under treatment by iodide of potassium. Under this medicine, the symptoms quickly disappeared for the second time. (Source: St Bartholomew's Hospital Archives & Museum, London. Wellcome Trust, London. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0/deed.en.)

The 16-month-old girl’s mother had syphilitic sores on both nipples. Illustration by Surgeon Leonard Portal Mark (1855-1930), pathological artist at St. Bartholomew's Hospital, London. (Source: St. Bartholomew's Hospital Archives & Museum, London. Wellcome Trust, London. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0/deed.en.)

This man presented with complex symptomatology, subsequently diagnosed as complications of congenital syphilis. Note the stigmata indicative of this disease, including frontal bossing, mulberry molars, Hutchinson teeth, saddle nose, and a cataract in his right eye. (Source: CDC and Brian Hill, New Zealand. Public Health Image Library, image 16463. Public domain.)

The left palm of this newborn infant’s hand exhibited a copper-colored rash, characteristic of congenital syphilis. (Source: CDC, 1970. Public Health Image Library, image 16746. Public domain.)

(Source: CDC and Dr. Norman Cole, 1964. Public Health Image Library, image 2246. Public domain.)

Anterior view of a boy’s face, exhibiting rhagades that resulted from congenital syphilis. Rhagades are cracks or fissures in the skin around the mouth, considered a consequence of persistent infantile syphilitic rhinitis. (Source: CDC and Susan Lindsley, 1970. Public Health Image Library, image 2389. Public domain.)

Lateral view of a patient's right knee showing Clutton’s joints due to congenital syphilis. Clutton's joints, also referred to as symmetrical hydrarthrosis of the knee joints, is a painless condition that often occurs during the late stages of congenital syphilis. It involves synovitis, or swelling of the joint, accompanied by collections of fluid within the joint capsule. (Source: CDC and Tichard Deitrick, 1959. Public Health Image Library, image 12598. Public domain.)

Anterior view of knees of a patient knees diagnosed with Clutton’s joints due to congenital syphilis. Clutton's joints, or symmetrical hydrarthrosis of the knee joints, is a painless condition that often occurs during the late stages of congenital syphilis. It involves synovitis, or swelling of a joint, accompanied by collections of fluid within the joint capsule. (Source: CDC and J Pledger, 1976. Public Health Image Library, image 4102. Public domain.)

Using a dark field microscopy technique, this photomicrograph revealed the presence of Treponema pallidum spirochetes. A diagnosis of syphilis is confirmed with dark field microscopy demonstrating T. pallidum in material from suspected lesions or regional lymph nodes. A positive dark-field result is an almost certain diagnosis of primary, secondary, or early congenital syphilis. (Source: CDC and WF Schwartz, 1961. Public Health Image Library, image 10179. Public domain.)

Plantar view of an infant’s feet, revealing the presence of syphilitic lesions, which resulted from congenital syphilis. (Source: CDC, 1970. Public Health Image Library, image 4148. Public domain.)

Dentition of a patient with congenital syphilis who developed mulberry molars, or Moon's molars, a condition where the bite surface of the permanent, first lower molar teeth, develop rounded surfaces to their cusps, resembling the surface of a mulberry. (Source: CDC and Robert Sumpter, 1967. Public Health Image Library, image 2386. Public domain.)

Anterior intraoral view of the mouth of a patient with congenital syphilis, revealing the presence of mulberry molars, or Moon's molars, involving the first molar, tooth number 19, located on the left lower jaw. (Source: CDC. Public Health Image Library, image 5341. Public domain.)

The photo exhibits an 8-year-old boy with obstetrical brachial plexus palsy sequelae and supination deformity of the forearm. (Source: Hamdi NB, Doubi M, Abalkhail TB, Mortada H. Clinical and psychosocial outcomes following correction of supination deformity in obstetrical brachial plexus palsy patients: A retrospective study. BMC Musculoskelet Disord 2022;23[1]:808. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

The photo exhibits a 25-year-old woman with obstetrical brachial plexus palsy sequelae and supination deformity of the forearm. (Source: Hamdi NB, Doubi M, Abalkhail TB, Mortada H. Clinical and psychosocial outcomes following correction of supination deformity in obstetrical brachial plexus palsy patients: A retrospective study. BMC Musculoskelet Disord 2022;23[1]:808. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

(A) Axial MRI shows intraocular T2-hypointense tumor in the right eye. (B) T1 gadolinium sagittal view of the same patient at diagnosis, shows a large pineal mass, with mixed cystic and solid components, contrast-enhancing. (C) Saggital T1 post-contrast spinal MRI demonstrates wide leptomeningeal dissemination with nodularity appearance. (Contributed by Dr. Adriana Fonseca.)

(TOP ROW) MRI shows typical features of ETMR in an 18-month-old girl. There is a well-delimited, large supratentorial intra-axial mass within the right thalami, measuring 4 x 3.8 x 3.8 cm and crossing midline and causing mild supratentorial hydrocephalus due to Silvian aqueduct compression. The lesion was hypointense in T1 (A) and hyperintense in T2 and FLAIR with multiple and small necrotic and cystic foci (B, C). There is no contrast enhancement (A). ADC map (D) demonstrated diffusion restriction, revealing high cellularity consistent with a malignant embryonal tumor.

(BOTTOM ROW) Pathology revealed an undifferentiated neoplasm with a diffuse pattern of proliferation in H-E stains consisting of pleomorphic cells with large areas of atypia and necrosis, abundant nucleoli, and cell-wrapping (E). There were some ependymoblastic rosettes (F). Immunoreactivity for Ki67 was 99% (G), INI-1 was retained in tumor cells (H), and LIN28 immunostain was avidly positive (I). Further molecular analysis revealed C19MC amplification by FISH (not shown). (Contributed by Dr. Adriana Fonseca.)

(Contributed by Dr. Bernard Maria.)

Large right frontal mass with cystic and solid components. The lesion shows evidence of hemorrhage and areas of calcification (panel C). (A) Axial T1 post-contrast imaging. (B) Axial T2 flair image. (C) Sagital T1 flair image. (Contributed by Dr. Adriana Fonseca.)

Shown are two different thresholds for "concerning" (based on data from the CDC). Illustration by Morgan Rehnberg on April 19, 2017. (Public domain.)

A composite representation of regions with significant volume loss for Cincinnati Lead Study Participants associated with mean childhood blood lead concentrations is shown in red and yellow overlaid upon a standard brain template for females (n = 74). The model is adjusted for age at time of scanning and birth weight. (Source: Cecil KM, Brubaker CJ, Adler CM, et al. Decreased brain volume in adults with childhood lead exposure. PLoS Med 2008;5[5]:e112. Creative Commons Attribution License, http://creativecommons.org/licenses/by/2.0.)

A composite representation of regions with significant volume loss for Cincinnati Lead Study Participants associated with mean childhood blood lead concentrations is shown in red and yellow overlaid on a standard brain template for males (n = 83). The model is adjusted for age at time of scanning and birth weight. (Source: Cecil KM, Brubaker CJ, Adler CM, et al. Decreased brain volume in adults with childhood lead exposure. PLoS Med 2008;5[5]:e112. Creative Commons Attribution License, http://creativecommons.org/licenses/by/2.0.)

A composite representation of regions with significant volume loss for Cincinnati Lead Study Participants associated with blood lead concentration at age 78 months (6.5 years) and adjusted for sex is shown in red and yellow overlaid on a standard brain template with the posterior coronal view highlighted below. (Source: Cecil KM, Brubaker CJ, Adler CM, et al. Decreased brain volume in adults with childhood lead exposure. PLoS Med 2008;5[5]:e112. Creative Commons Attribution License, http://creativecommons.org/licenses/by/2.0.)

The relationship of individual brain volume with mean childhood blood lead concentrations within a medial frontal cluster is illustrated by this plot. The model is adjusted for age at time of scanning and birth weight. (Source: Cecil KM, Brubaker CJ, Adler CM, et al. Decreased brain volume in adults with childhood lead exposure. PLoS Med 2008;5[5]:e112. Creative Commons Attribution License, http://creativecommons.org/licenses/by/2.0.)

A composite representation of regions with significant volume loss for male and female participants in the Cincinnati Lead Study (n = 157) associated with mean childhood blood lead level is shown with red and yellow clusters overlaid on a standard brain template. The first row presents views from the midline of the left and right hemispheres, respectively; the second row demonstrates views from the back and front of the cerebrum, respectively; the third row shows the lateral right and left hemispheres; and the fourth row shows views from below and above the cerebrum. (Source: Cecil KM, Brubaker CJ, Adler CM, et al. Decreased brain volume in adults with childhood lead exposure. PLoS Med 2008;5[5]:e112. Creative Commons Attribution License, http://creativecommons.org/licenses/by/2.0.)

Dense metaphyseal lines indicated by red arrow. (Source: Dr. Abhijit Datir via Wikimedia Commons. Creative Commons Attribution-Share Alike 3.0 Unported License, https://creativecommons.org/licenses/by-sa/3.0/deed.en.)

From 1994 to 1997, 262,287 children in New York State had blood lead levels drawn within 2 weeks of their first or second birthday. This illustration shows the seasonal and trend components. (Source: Haley VB, Talbot TO. Seasonality and trend in blood lead levels of New York State children. BMC Pediatr 2004;4:8.)

Burton's line is evident, and there has been additional lead complex deposited on the lateral margin of the tongue and the buccal mucosa. Illustration by Surgeon and Anatomist Thomas Godart (active 1852-1861). (Source: St. Bartholomew's Hospital Archives and Museum. Courtesy of the Wellcome Collection, London, England. Creative Commons Attribution 4.0 International [CC BY 4.0] License, http://creativecommons.org/licenses/by/4.0.)

(Source: Jouhadi Z, Bensabbahia D, Chafiq F, et al. Lead poisoning in children: a case report. Pan Afr Med J 2016;24:316. Creative Commons Attribution License, http://creativecommons.org/licenses/by/2.0.)

Assay of paint chips from the home built in 1960 revealed leaded paint. (Source: Jouhadi Z, Bensabbahia D, Chafiq F, et al. Lead poisoning in children: a case report. Pan Afr Med J 2016;24:316. Creative Commons Attribution License, http://creativecommons.org/licenses/by/2.0.)

(Source: Irawati Y, Kusnoputranto H, Achmadi UF, et al. Blood lead levels and lead toxicity in children aged 1-5 years of Cinangka Village, Bogor Regency. PLoS One 2022;17[2]:e0264209. Creative Commons Attribution License, https://creativecommons.org/licenses/by/4.0.)

Basophilic stippling indicated by black arrow (objective 1000x, Giemsa stain). (Source: Irawati Y, Kusnoputranto H, Achmadi UF, et al. Blood lead levels and lead toxicity in children aged 1-5 years of Cinangka Village, Bogor Regency. PLoS One 2022;17[2]:e0264209. Creative Commons Attribution License, https://creativecommons.org/licenses/by/4.0.)

Basophilic stippling of erythrocytes indicated by black arrows (objective 1000x, Giemsa stain). (Source: Irawati Y, Kusnoputranto H, Achmadi UF, et al. Blood lead levels and lead toxicity in children aged 1-5 years of Cinangka Village, Bogor Regency. PLoS One 2022;17[2]:e0264209. Creative Commons Attribution License, https://creativecommons.org/licenses/by/4.0.)

(Source: Yang Y, Li S, Wang H, et al. Chronic lead poisoning induced abdominal pain and anemia: a case report and review of the literature. BMC Gastroenterol 2020;20[1]:335. Creative Commons Attribution 4.0 International License, http://creativecommons.org/licenses/by/4.0. Figure edited by Dr. Douglas J Lanska.)

Basophilic stippling of erythrocytes indicated by red arrows. (Source: Yang Y, Li S, Wang H, et al. Chronic lead poisoning induced abdominal pain and anemia: a case report and review of the literature. BMC Gastroenterol 2020;20[1]:335. Creative Commons Attribution 4.0 International License, http://creativecommons.org/licenses/by/4.0.)

Basophilic stippling of erythrocytes indicated by red arrows. (Source: Yang Y, Li S, Wang H, et al. Chronic lead poisoning induced abdominal pain and anemia: a case report and review of the literature. BMC Gastroenterol 2020;20[1]:335. Creative Commons Attribution 4.0 International License, http://creativecommons.org/licenses/by/4.0.)

Illustration by Mikael Häggström on June 7, 2015. (Public domain.)

Basophilic stippling of erythrocytes indicated by black arrows. (Source: Dr. Herbert L Fred and Hendrik A van Dijk via Wikimedia Commons, https://cnx.org/contents/MZa_Ph4e@4/Images-of-Memorable-Cases-Case-81. Accessed October 11, 2022. Creative Commons Attribution [CC-BY 2.0] License, https://creativecommons.org/licenses/by/2.0/deed.en. Figure edited by Dr. Douglas J Lanska.)

Turner provided the first clinical description of childhood lead poisoning in 1892. (Source: Wikimedia Commons. Public domain. Photograph restored by Dr. Douglas J Lanska.)

Burton line indicated by black arrow. (Source: Yang Y, Li S, Wang H, et al. Chronic lead poisoning induced abdominal pain and anemia: a case report and review of the literature. BMC Gastroenterol 2020;20[1]:335. Creative Commons Attribution 4.0 International License, http://creativecommons.org/licenses/by/4.0.)

Burton line indicated by black arrow. (Source: Yang Y, Li S, Wang H, et al. Chronic lead poisoning induced abdominal pain and anemia: a case report and review of the literature. BMC Gastroenterol 2020;20[1]:335. Creative Commons Attribution 4.0 International License, http://creativecommons.org/licenses/by/4.0.)

Abdominal x-ray showing stool and gas shadows as well as points of increased density in an 8-year-old girl who had been treated with a red-colored folk medicine obtained from a traditional Chinese medicine practitioner (Shenzhen, Guangdong, China). Analysis showed the lead concentration of the "medicine" to be 22.3%. (Source: Ying XL, Markowitz M, Yan CH. Folk prescription for treating rhinitis as a rare cause of childhood lead poisoning: a case series. BMC Pediatr 2018;18[1]:219. Creative Commons Attribution 4.0 International License, http://creativecommons.org/licenses/by/4.0.)

A red-colored folk medicine obtained from a traditional Chinese medicine practitioner (Shenzhen, Guangdong, China) identified as the source of severe lead poisoning in a 7-year-old boy. Analysis showed the lead concentration of the "medicine" to be 14.8%. (Source: Ying XL, Markowitz M, Yan CH. Folk prescription for treating rhinitis as a rare cause of childhood lead poisoning: a case series. BMC Pediatr 2018;18[1]:219. Creative Commons Attribution 4.0 International License, http://creativecommons.org/licenses/by/4.0.)

Anteroposterior radiograph of the knees showing increased linear radiodensity at the distal femoral and proximal tibial and fibular metaphyses in a child treated by a traditional Chinese medicine practitioner (Shenzhen, Guangdong, China) with a lead-based folk medicine. (Source: Ying XL, Markowitz M, Yan CH. Folk prescription for treating rhinitis as a rare cause of childhood lead poisoning: a case series. BMC Pediatr 2018;18[1]:219. Creative Commons Attribution 4.0 International License, http://creativecommons.org/licenses/by/4.0. Figure edited by Dr. Douglas J Lanska to remove unnecessary areas outside of the x-ray image.)

Abnormally increased pigmentation of the gums (“lead line” or "Burton line") in a child treated by a traditional Chinese medicine practitioner (Shenzhen, Guangdong, China) with a lead-based folk medicine. (Source: Ying XL, Markowitz M, Yan CH. Folk prescription for treating rhinitis as a rare cause of childhood lead poisoning: a case series. BMC Pediatr 2018;18[1]:219. Creative Commons Attribution 4.0 International License, http://creativecommons.org/licenses/by/4.0.)

In May 2019, Missouri Department of Health and Senior Services identified a cake decorating material referred to as primrose petal dust as a lead hazard during an environmental investigation of an elevated blood lead level (12 μg/dL) in a Missouri resident child aged 1 year. Handheld x-ray fluorescence analyzer, which detected the presence of lead in a jar of bright yellow primrose petal dust that had been recently used in creating decorative flowers for the child’s home-baked birthday cake. The container for the primrose petal dust used for the cake was labeled as “nontoxic” and “made in USA,” and the brand was sold by a Florida cake decorating company, which marketed it as a nontoxic color for decorating baked goods, candies, chocolate, and sugar art. (Source: Viveiros B, Caron G, Barkley J, et al. Cake decorating luster dust associated with toxic metal poisonings--Rhode Island and Missouri, 2018-2019. CDC Weekly 2021;70[43]:1501-4. Public domain.)

Abbreviation: BLLs = blood lead levels. The number of reporting jurisdictions varied somewhat from year to year. Childhood Blood Lead Surveillance System, United States, 2009-2014. (Source: Raymond J, Brown MJ. Childhood blood lead levels in children aged <5 years--United States, 2009-2014. MMWR Surveill Summ 2017;66[3]:1-10. [CDC]. Public domain.)

The number of reporting jurisdictions varied somewhat from year to year. (Source: Raymond J, Brown MJ. Childhood blood lead levels in children aged <5 years--United States, 2009-2014. MMWR Surveill Summ 2017;66[3]:1-10. [CDC]. Public domain.)

(n = 61) Box plots illustrate the distributions of screening (initial) and diagnostic (confirmatory) blood lead levels. The tops of the boxes represent the 75th percentile and the bottoms the 25th percentile. The middle line of the box is the median. X represents the mean. Circles represent outliers. Whiskers indicate the standard deviations. (Source: Angelon-Gaetz KA, Klaus C, Chaudhry EA, Bean DK. Lead in spices, herbal remedies, and ceremonial powders sampled from home investigations for children with elevated blood lead levels--North Carolina, 2011-2018. MMWR Morb Mortal Wkly Rep 2018;67[46]:1290-4. [CDC]. Public domain.)

(Source: Charkiewicz AE, Backstrand JR. Lead toxicity and pollution in Poland. Int J Environ Res Public Health 2020;17[12]:4385. Adapted from: Wani AL, Ara A, Usmani JA. Lead toxicity: a review. Interdiscip Toxicol 2015;8[2]:55-64. Creative Commons Attribution [CC-BY] License, http://creativecommons.org/licenses/by/4.0.)

Key: thin arrows=absorption pathways; bold arrows=excreting pathways; dashed arrows=movement inside the body. The main locations of Pb in the body (blood, bones, soft tissues).

(Source: Charkiewicz AE, Backstrand JR. Lead toxicity and pollution in Poland. Int J Environ Res Public Health 2020;17[12]:4385. Creative Commons Attribution [CC-BY] License, http://creativecommons.org/licenses/by/4.0.)

Additional references:
Giel-Pietraszuk M, Hybza K, Chełchowska M, Barciszewski J. Mechanisms of lead toxicity. Adv Cell Biol 2012;39:17-248.
Omeljaniuk WJ, Socha K, Soroczynska J, et al. Cadmium and lead in women who miscarried. Clin Lab 2018;64(1):59-67.
Lee JW, Choi H, Hwang UK, et al. Toxic effects of lead exposure on bioaccumulation, oxidative stress, neurotoxicity, and immune responses in fish: a review. Environ Toxicol Pharmacol 2019;68:101-8.

(Source: Charkiewicz AE, Backstrand JR. Lead toxicity and pollution in Poland. Int J Environ Res Public Health 2020;17[12]:4385. Adapted from: Wani AL, Ara A, Usmani JA. Lead toxicity: a review. Interdiscip Toxicol 2015;8[2]:55-64. Creative Commons Attribution [CC-BY] License, http://creativecommons.org/licenses/by/4.0.)

(n = 109) Blood was collected by fingerstick and analyzed with LeadCare II instrument. Upper limit of detection, 65 𝜇g/dL. (Source: Daniell WE, Van Tung L, Wallace RM, et al. Childhood lead exposure from battery recycling in Vietnam. Biomed Res Int 2015;2015:193715. Creative Commons Attribution [CC-BY] License, http://creativecommons.org/licenses/by/4.0.)

(Source: Havens D, Pham MH, Karr CJ, Daniell WE. Blood lead levels and risk factors for lead exposure in a pediatric population in Ho Chi Minh City, Vietnam. Int J Environ Res Public Health 2018;15[1]:93. Creative Commons Attribution [CC-BY] License, http://creativecommons.org/licenses/by/4.0.)

(Source: Zhang F, Liu Y, Zhang H, et al. Investigation and evaluation of children's blood lead levels around a lead battery factory and influencing factors. Int J Environ Res Public Health 2016;13[6]:541. Creative Commons Attribution [CC-BY] License, http://creativecommons.org/licenses/by/4.0.)

Number of cases of elevated blood lead levels 10 or more micrograms per deciliter among children aged younger than 5 years, by month in 2012 in the United States. (Source: Laidlaw MA, Filippelli GM, Sadler RC, Gonzales CR, Ball AS, Mielke HW. Children's blood lead seasonality in Flint, Michigan [USA], and soil-sourced lead hazard risks. Int J Environ Res Public Health 2016;13[4]:358. Graphed from public domain CDC data in: Raymond J, Brown MJ. Summary of notifiable noninfectious conditions and disease outbreaks: childhood blood lead levels--United States, 2007-2012. MMWR Morb Mortal Wkly Rep 2015;62[54]:76-80. Creative Commons Attribution [CC-BY] License, http://creativecommons.org/licenses/by/4.0.)

Abbreviation: DMT1, divalent metal transporter 1. (Source: *Slota M, Wasik M, Stoltny T, Machon-Grecka A, Kasperczyk S. Effects of environmental and occupational lead toxicity and its association with iron metabolism. Toxicol Appl Pharmacol 2022;434:115794. Creative Commons Attribution [CC BY] License, http://creativecommons.org/licenses/by/4.0. Figure modified by Dr. Douglas J Lanska.)

*Slota's work based on:
Kwong WT, Friello P, Semba RD. Interactions between iron deficiency and lead poisoning: epidemiology and pathogenesis. Sci Total Environ 2004;330[1-3]:21-37.
Strathmann FG, Blum LM. Toxic elements. In: Rafai N, Horwath AR, Wittwer CT, editors. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. 6th ed. Amsterdam: Elsevier. St. Louis, Missouri: 2018:907-10.
Camaschella C. Iron-deficiency anemia. N Engl J Med 2015;372(19):1832-43.

Six-year-old boy on the Children's Ward of the University Hospital, Philadelphia. (Source: Griffith CP. The diseases of infants and children. Vol. 1. Philadelphia, London: WB Saunders Company,1919. Image edited and restored by Dr. Douglas J Lanska.)

View of the left hip, showing necrotic areas in the centers of some spots. (Source: Boivard D Jr. Meningococcal septicaemia with sterile cerebrospinal fluid. In: Thatcher JS, Woolsey G, editors. Medical and surgical report of the Presbyterian Hospital in the City of New York. Vol. 8. New York City and Jamaica, New York: Polydore Barnes Company Printers, 1908;8:355-71.)

View of the left leg. (Source: Boivard D Jr. Meningococcal septicaemia with sterile cerebrospinal fluid. In: Thatcher JS, Woolsey G, editors. Medical and surgical report of the Presbyterian Hospital in the City of New York. Vol. 8. New York City and Jamaica, New York: Polydore Barnes Company Printers, 1908;8:355-71.)

(Source: Koplik H. The diseases of infancy and childhood designed for the use of students and practitioners of medicine. Fourth edition. Philadelphia and New York: Lea & Fibinger, 1918. Image edited and restored by Dr. Douglas J Lanska.)

(Source: Koplik H. The diseases of infancy and childhood designed for the use of students and practitioners of medicine. Fourth edition. Philadelphia and New York: Lea & Fibinger, 1918. Image edited and restored by Dr. Douglas J Lanska.)

(Source: Smith JL. Cerebro-spinal fever. In: Keating JM, editor. Cyclopaedia of the diseases of children: medical and surgical: the articles written especially for the work by American, British, and Canadian authors. Vol. 1. Philadelphia: JB Lippincott Company, 1889:514-54. Image edited and restored by Dr. Douglas J Lanska.)

(Source: Koplik H. The diseases of infancy and childhood designed for the use of students and practitioners of medicine. Fourth edition. Philadelphia and New York: Lea & Fibinger, 1918. Image edited and restored by Dr. Douglas J Lanska.)

Children's Hospital of Philadelphia. (Source: Griffith CP. The diseases of infants and children. Vol. 1. Philadelphia, London: WB Saunders Company, 1919. Image edited and restored by Dr. Douglas J Lanska.)

(Source: Griffith CP. The diseases of infants and children. Vol. 1. Philadelphia, London: WB Saunders Company, 1919. Image edited and restored by Dr. Douglas J Lanska.)

Children's Hospital of Philadelphia. (Source: Griffith CP. The diseases of infants and children. Vol. 1. Philadelphia, London: WB Saunders Company, 1919. Image edited and restored by Dr. Douglas J Lanska.)

Following acquisition, Neisseria meningitidis (Nme) must survive against host defenses and interactions with other members of the microbiome to inhabit the mucus of the nasopharynx. Eventual binding of the epithelial surface results in passage into the submucosa by transcytosis. (Source: Mikucki A, McCluskey NR, Kahler CM. The host-pathogen interactions and epicellular lifestyle of Neisseria meningitidis. Front Cell Infect Microbiol 2022;12:862935. Creative Commons Attribution 4.0 International License, http://creativecommons.org/licenses/by/4.0.)

Binding of N meningitidis to epithelial cells occurs by interaction of bacterial surface structures with their cognate receptors, resulting in inflammation, cellular restructuring, and transcytosis. (Source: Mikucki A, McCluskey NR, Kahler CM. The host-pathogen interactions and epicellular lifestyle of Neisseria meningitidis. Front Cell Infect Microbiol 2022;12:862935. Creative Commons Attribution 4.0 International License, http://creativecommons.org/licenses/by/4.0.)

In the bloodstream, Neisseria meningitidis (Nme) must resist antibody- and complement-mediated killing, acquire iron, and attach to the capillary endothelial surface to form microcolonies. Once attached, Neisseria meningitidis possesses several mechanisms to resist the actions of phagocytic cells, including neutrophils and macrophages. (Source: Mikucki A, McCluskey NR, Kahler CM. The host-pathogen interactions and epicellular lifestyle of Neisseria meningitidis. Front Cell Infect Microbiol 2022;12:862935. Creative Commons Attribution 4.0 International License, http://creativecommons.org/licenses/by/4.0.)

Binding of endothelial cells occurs by interaction of meningococcal surface structures with their cognate receptors, resulting in cortical plaque formation, transcytosis, and breakdown of tight junctions. (Source: Mikucki A, McCluskey NR, Kahler CM. The host-pathogen interactions and epicellular lifestyle of Neisseria meningitidis. Front Cell Infect Microbiol 2022;12:862935. Creative Commons Attribution 4.0 International License, http://creativecommons.org/licenses/by/4.0.)

Scanning electron micrograph of a single N meningitidis cell (colorized in blue) with its dense meshwork of pili (colorized in yellow). The scale bar is 1 μm. (Courtesy of Arthur Charles-Orszag, adapted by him from: Charles-Orszag A, Tsai FC, Bonazzi D, et al. Adhesion to nanofibers drives cell membrane remodeling through one-dimensional wetting. Nat Commun 2018;9[1]:4450. Creative Commons Attribution 4.0 International License, http://creativecommons.org/licenses/by/4.0.)

Arrowheads show plasma membrane protrusions. Scale bar, 500 nm. (Source: Charles-Orszag A, Tsai FC, Bonazzi D, et al. Adhesion to nanofibers drives cell membrane remodeling through one-dimensional wetting. Nat Commun 2018;9[1]:4450. Creative Commons Attribution 4.0 International License, http://creativecommons.org/licenses/by/4.0.)

Colorized crop shows plasma membrane protrusions (magenta, dotted lined) attached alongside bacterial type IV pili (yellow). Bacterial type IV pili have been stabilized with a monoclonal antibody. Abbreviation: T4P, bacterial type IV pili. Scale bars, 1 μm and 200 nm. (Source: Charles-Orszag A, Tsai FC, Bonazzi D, et al. Adhesion to nanofibers drives cell membrane remodeling through one-dimensional wetting. Nat Commun 2018;9[1]:4450. Creative Commons Attribution 4.0 International License, http://creativecommons.org/licenses/by/4.0.)

Bacterial type IV pili have been labeled with immunogold. Bacterial type IV pili have been stabilized with a monoclonal antibody and labeled with immunogold. Abbreviations: Protr, protrusions; T4P, bacterial type IV pili. Scale bars, 500 nm and 200 nm. (Source: Charles-Orszag A, Tsai FC, Bonazzi D, et al. Adhesion to nanofibers drives cell membrane remodeling through one-dimensional wetting. Nat Commun 2018;9[1]:4450. Creative Commons Attribution 4.0 International License, http://creativecommons.org/licenses/by/4.0.)

Transmission electron micrograph shows plasma membrane protrusions embedded in a meshwork of bacterial type IV pili. Abbreviation: T4P, bacterial type IV pili. Scale bars, 200 nm. (Source: Charles-Orszag A, Tsai FC, Bonazzi D, et al. Adhesion to nanofibers drives cell membrane remodeling through one-dimensional wetting. Nat Commun 2018;9[1]:4450. Creative Commons Attribution 4.0 International License, http://creativecommons.org/licenses/by/4.0.)

Transmission electron micrograph shows plasma membrane protrusions embedded in a meshwork of bacterial type IV pili labeled with immunogold. Abbreviation: T4P, bacterial type IV pili. Scale bars, 200 nm and 50 nm. (Source: Charles-Orszag A, Tsai FC, Bonazzi D, et al. Adhesion to nanofibers drives cell membrane remodeling through one-dimensional wetting. Nat Commun 2018;9[1]:4450. Creative Commons Attribution 4.0 International License, http://creativecommons.org/licenses/by/4.0.)

N meningitis infects trigeminal Schwann cells, resulting in the formation of multinuclear cells or cells with budding nuclei or horseshoe nuclei. (Source: Delbaz A, Chen M, Jen FE, et al. Neisseria meningitidis induces pathology-associated cellular and molecular changes in trigeminal Schwann cells. Infect Immun 2020;88[4]:e00955-19. Creative Commons Attribution 4.0 International License, http://creativecommons.org/licenses/by/4.0.)

Note how the sulci are obscured by the exudate. (Source: Koplik H. The diseases of infancy and childhood designed for the use of students and practitioners of medicine. Fourth edition. Philadelphia and New York: Lea & Fibinger, 1918. Image edited and restored by Dr. Douglas J Lanska.)

Note how the sulci are obscured by the exudate. (Source: Koplik H. The diseases of infancy and childhood designed for the use of students and practitioners of medicine. Fourth edition. Philadelphia and New York: Lea & Fibinger, 1918. Image edited and restored by Dr. Douglas J Lanska.)

Section of the spinal cord, showing the purulent exudate on the surface, more marked posteriorly and involving the anterior and posterior nerve roots. (Source: Koplik H. The diseases of infancy and childhood designed for the use of students and practitioners of medicine. Fourth edition. Philadelphia and New York: Lea & Fibinger, 1918. Image edited and restored by Dr. Douglas J Lanska.)

(Source: Huang L, Fievez S, Goguillot M, et al. A database study of clinical and economic burden of invasive meningococcal disease in France. PLoS One 2022;17[4]:e0267786. Creative Commons Attribution 4.0 International License, http://creativecommons.org/licenses/by/4.0.)

Rates are graphed for meningococcal infection (red), meningococcal meningitis (green), and meningococcemia (blue). (Source: Walter S, Gil-Prieto R, Gil-Conesa M, Rodriguez-Caravaca G, San Román J, Gil de Miguel A. Hospitalizations related to meningococcal infection in Spain from 1997 to 2018. BMC Infect Dis 2021;21[1]:1215.)

Rates are graphed for ages less than 1 (red), less than 2 (yellow), less than 5 (green), 5 to 9 (blue), and 10 to 14 (purple). Note that the first three age groups overlap. (Source: Walter S, Gil-Prieto R, Gil-Conesa M, Rodriguez-Caravaca G, San Román J, Gil de Miguel A. Hospitalizations related to meningococcal infection in Spain from 1997 to 2018. BMC Infect Dis 2021;21[1]:1215.)

Rates are graphed for ages less than 1 (red), less than 2 (yellow), less than 5 (green), 5 to 9 (blue), and 10 to 14 (purple). Note that the first three age groups overlap. (Source: Walter S, Gil-Prieto R, Gil-Conesa M, Rodriguez-Caravaca G, San Román J, Gil de Miguel A. Hospitalizations related to meningococcal infection in Spain from 1997 to 2018. BMC Infect Dis 2021;21[1]:1215.)

(Figure by Dr. Douglas J Lanska, based on tabular data in: Walter S, Gil-Prieto R, Gil-Conesa M, Rodriguez-Caravaca G, San Román J, Gil de Miguel A. Hospitalizations related to meningococcal infection in Spain from 1997 to 2018. BMC Infect Dis 2021;21[1]:1215.)

(Source: Modification of work by the Centers for Disease Control and Prevention by CNX OpenStax on November 11, 2016. Copyright Holders: OpenStax Microbiology Publishers: OpenStax Microbiology Latest Version: 4.4 First Publication Date: Oct 17, 2016 Latest Revision: Nov 11, 2016. Creative Commons Attribution License [By 4.0], http://creativecommons.org/licenses/by/4.0.)

Bar graph of annual meningitis cases (blue bars) and deaths (blue bars) from meningitis reported from 1928 to 2018 in countries within the African meningitis belt. Note that meningitis case information is unavailable for the period 1948–1957 and that this temporal gap is omitted in the bar graph. The scales for cases and deaths are the left and right vertical axes, respectively. (Source: Mazamay S, Guégan JF, Diallo N, et al. An overview of bacterial meningitis epidemics in Africa from 1928 to 2018 with a focus on epidemics "outside-the-belt." BMC Infect Dis 2021;21[1]:1027. Creative Commons Attribution License [By 4.0], http://creativecommons.org/licenses/by/4.0.)

The areas in grey illustrate the different countries belonging to the meningitis belt. Note that meningitis case information is unavailable for the period 1948–1957. Typographical errors in the figure legend in the original have been corrected by Dr. Douglas J Lanska. (Source: Mazamay S, Guégan JF, Diallo N, et al. An overview of bacterial meningitis epidemics in Africa from 1928 to 2018 with a focus on epidemics "outside-the-belt." BMC Infect Dis 2021;21[1]:1027. Creative Commons Attribution License [By 4.0], http://creativecommons.org/licenses/by/4.0.)

Bar graph of case counts (blue bars) and death counts (blue bars) of meningitis reported from 1928 to 2018 in countries outside of the African meningitis belt. Countries are ranked from left to right according to the number of cases reported. Note that meningitis case information is unavailable for the period 1948–1957. The scales for cases and deaths are the left and right vertical axes, respectively. (Source: Mazamay S, Guégan JF, Diallo N, et al. An overview of bacterial meningitis epidemics in Africa from 1928 to 2018 with a focus on epidemics "outside-the-belt." BMC Infect Dis 2021;21[1]:1027. Creative Commons Attribution License [By 4.0], http://creativecommons.org/licenses/by/4.0.)

Bar graph of confirmed cases of meningitis and the responsible pathogens, Africa, 2000-2010 (before the MenAfrivac targeting N meningitidis serotype A). Abbreviation: Nm, Neisseria meningitidis. (Source: Mazamay S, Guégan JF, Diallo N, et al. An overview of bacterial meningitis epidemics in Africa from 1928 to 2018 with a focus on epidemics "outside-the-belt." BMC Infect Dis 2021;21[1]:1027. Creative Commons Attribution License [By 4.0], http://creativecommons.org/licenses/by/4.0.)

Bar graph of confirmed cases of meningitis and the responsible pathogens, Africa, 2011-2017 (after MenAfrivac targeting N meningitidis serotype A). Abbreviation: Nm, Neisseria meningitidis. (Source: Mazamay S, Guégan JF, Diallo N, et al. An overview of bacterial meningitis epidemics in Africa from 1928 to 2018 with a focus on epidemics "outside-the-belt." BMC Infect Dis 2021;21[1]:1027. Creative Commons Attribution License [By 4.0], http://creativecommons.org/licenses/by/4.0.)

Spatial distribution of meningitis cases by country in Africa, 2000-2010 (before MenAfrivac targeting N meningitidis
serotype A). The areas in grey illustrate the different countries belonging to the meningitis belt. Typographical errors in the figure legend in the original have been corrected by Dr. Douglas J Lanska. (Source: Mazamay S, Guégan JF, Diallo N, et al. An overview of bacterial meningitis epidemics in Africa from 1928 to 2018 with a focus on epidemics "outside-the-belt." BMC Infect Dis 2021;21[1]:1027. Creative Commons Attribution License [By 4.0], http://creativecommons.org/licenses/by/4.0.)

Spatial distribution of meningitis cases by country in Africa, 2011-2017 (after MenAfrivac targeting N meningitidis serotype A). The areas in grey illustrate the different countries belonging to the meningitis belt. Typographical errors in the figure legend in the original have been corrected by Dr. Douglas J Lanska. (Source: Mazamay S, Guégan JF, Diallo N, et al. An overview of bacterial meningitis epidemics in Africa from 1928 to 2018 with a focus on epidemics "outside-the-belt." BMC Infect Dis 2021;21[1]:1027. Creative Commons Attribution License [By 4.0], http://creativecommons.org/licenses/by/4.0.)

Bar graph of case counts (blue bars) and death counts (blue bars) of meningitis reported from 1928 to 2018 in countries within the African meningitis belt. Countries are ranked from left to right according to the number of cases reported. Note that meningitis case information is unavailable for the period 1948-1957. The scales for cases and deaths are the left and right vertical axes, respectively. (Source: Mazamay S, Guégan JF, Diallo N, et al. An overview of bacterial meningitis epidemics in Africa from 1928 to 2018 with a focus on epidemics "outside-the-belt." BMC Infect Dis 2021;21[1]:1027. Creative Commons Attribution License [By 4.0], http://creativecommons.org/licenses/by/4.0.)

The map was created by Nederlandse Leeuw on December 2, 2020. Creative Commons Attribution-Share Alike 4.0 International License, https://creativecommons.org/licenses/by-sa/4.0/deed.en. The composite image is by Dr. Douglas J Lanska.)

Photomicrograph of a Gram stain of spinal fluid at 1000x magnification. Neisseria meningitidis grew from this spinal fluid. Numerous polymorphonuclear leukocytes and the classic Gram-negative diplococci morphology are visible. (Photomicrograph by Microman12345 on February 13, 2019. Creative Commons Attribution 4.0 International License, http://creativecommons.org/licenses/by/4.0.)

This uterus was removed in the course of excising an ovarian mucinous cystadenoma. The photo shows the uterus and adnexa (less the initially excised left ovarian tumor) from the posterior aspect. The pale-yellow, right ovary is clearly seen on the upper right of the image. Both oviducts, visible at the top right and left, adjoin their respective separate cornua of this malformed uterus. (Photograph by Dr. Ed Uthman on May 26, 2000. Public domain.)

Original figure by Eternamente Aprendiz on July 19, 2011. Creative Commons Attribution-Share Alike 4.0 International License, https://creativecommons.org/licenses/by-sa/4.0/deed.en. Figure edited and modified by Dr. Douglas J Lanska.)

Transvaginal ultrasound showing a cross-section of a bicornuate uterus, with two cavities or "horns" visible at the left and right, respectively. In the "horn" to the right, a gestational sac is visible, with a diameter of 5.7 mm, corresponding to a gestational age of between 4 and 5 weeks. This projection did not transect the maximal diameter, thus, giving a bit smaller diameter in the image. The patient sought medical care because of a positive pregnancy test despite having an intrauterine device (IUD) with copper, presumably because the IUD was located in the other "horn." (Courtesy of Mikael Häggström on July 14, 2014. Public domain.)

Schematic representation of the position of the gross lesion evident at surgery. The irregular darked area at the top represents areas of damage to the perineural sheath. (Source: Clark LP, Taylor AS, Prout TP. A study in brachial birth palsy. Am J Med Sci 1905;130:670-707. Figure edited by Dr. Douglas J Lanska.)

Schematic representation of a rupture of the perineural sheath and hemorrrhage into its substance and into the meshes of the epineurium, resulting in the formation of a hematoma. Legend: (a) epineurium, (b) perineurium, (c) nerve bundles, (d) hemorrhage. (Source: Clark LP, Taylor AS, Prout TP. A study in brachial birth palsy. Am J Med Sci 1905;130:670-707.)

(Source: Clark LP, Taylor AS, Prout TP. A study in brachial birth palsy. Am J Med Sci 1905;130:670-707.)

(Source: Clark LP, Taylor AS, Prout TP. A study in brachial birth palsy. Am J Med Sci 1905;130:670-707.)

(Source: Clark LP, Taylor AS, Prout TP. A study in brachial birth palsy. Am J Med Sci 1905;130:670-707.)

Two years and 7 months after first operation and 6.5 months after the second operation, showing slight power of abduction. Deltoid activity. (Source: Taylor AS, Prout TP. Results from the surgical treatment of brachial birth palsy: with a note on the pathology. JAMA 1907;48[2]:96-104.)

Two years and 7 months after first operation and 6.5 months after the second operation, showing power to put the hand to the face, involving some external rotation of the humerus and some supination of the forearm. (Source: Taylor AS, Prout TP. Results from the surgical treatment of brachial birth palsy: with a note on the pathology. JAMA 1907;48[2]:96-104.)

(Sources: Clark LP, Taylor AS, Prout TP. A study in brachial birth palsy. Am J Med Sci 1905;130:670-707. Taylor AS, Prout TP. Results from the surgical treatment of brachial birth palsy: with a note on the pathology. JAMA 1907;48[2]:96-104.)

(Source: Clark LP, Taylor AS, Prout TP. A study in brachial birth palsy. Am J Med Sci 1905;130:670-707.)

(Source: Clark LP, Taylor AS, Prout TP. A study in brachial birth palsy. Am J Med Sci 1905;130:670-707.)

(Source: Clark LP, Taylor AS, Prout TP. A study in brachial birth palsy. Am J Med Sci 1905;130:670-707.)

(Source: Clark LP, Taylor AS, Prout TP. A study in brachial birth palsy. Am J Med Sci 1905;130:670-707.)

Ordinary position in which the patient held the right arm before operation. (Source: Clark LP, Taylor AS, Prout TP. A study in brachial birth palsy. Am J Med Sci 1905;130:670-707.)

(Source: Clark LP, Taylor AS, Prout TP. A study in brachial birth palsy. Am J Med Sci 1905;130:670-707.)

(Source: Clark LP, Taylor AS, Prout TP. A study in brachial birth palsy. Am J Med Sci 1905;130:670-707.)

(Source: Clark LP, Taylor AS, Prout TP. A study in brachial birth palsy. Am J Med Sci 1905;130:670-707.)

(Source: Clark LP, Taylor AS, Prout TP. A study in brachial birth palsy. Am J Med Sci 1905;130:670-707.)

(Source: Clark LP, Taylor AS, Prout TP. A study in brachial birth palsy. Am J Med Sci 1905;130:670-707.)

Ordinary position in which the patient held the right arm before operation. (Source: Clark LP, Taylor AS, Prout TP. A study in brachial birth palsy. Am J Med Sci 1905;130:670-707.)

(Source: Clark LP, Taylor AS, Prout TP. A study in brachial birth palsy. Am J Med Sci 1905;130:670-707.)

(Source: Duchenne [de Boulogne] GB. Paralysies obstétricales infantiles des membres supérieurs avec ou sans fractures, luxations ou autres complications. In: De l'électrisation localisée et de son application à la physiologie, à la pathologie et à la thérapeutique par courants induits et par courants galvaniques interrompus et continus. Paris: J B Baillière, 1872:353-67. Figure restored and edited by Dr. Douglas J Lanska.)

(Source: Duchenne [de Boulogne] GB. Paralysies obstétricales infantiles des membres supérieurs avec ou sans fractures, luxations ou autres complications. In: De l'électrisation localisée et de son application à la physiologie, à la pathologie et à la thérapeutique par courants induits et par courants galvaniques interrompus et continus. Paris: J B Baillière, 1872:353-67. Figure restored and edited by Dr. Douglas J Lanska.)

(Source: Duchenne [de Boulogne] GB. Paralysies obstétricales infantiles des membres supérieurs avec ou sans fractures, luxations ou autres complications. In: De l'électrisation localisée et de son application à la physiologie, à la pathologie et à la thérapeutique par courants induits et par courants galvaniques interrompus et continus. Paris: J B Baillière, 1872:353-67. Figure restored and edited by Dr. Douglas J Lanska.)

(Source: Duchenne [de Boulogne] GB. Paralysies obstétricales infantiles des membres supérieurs avec ou sans fractures, luxations ou autres complications. In: De l'électrisation localisée et de son application à la physiologie, à la pathologie et à la thérapeutique par courants induits et par courants galvaniques interrompus et continus. Paris: J B Baillière, 1872:353-67. Translation and figure restoration and editing by Dr. Douglas J Lanska.)

As described by Duchenne: Posterior and external dislocation of the shoulder (subacromial dislocation), dating from birth, in a 6-year-old boy, characterized: (1) by a relief located below the posterior angle of the acromion, formed by the head of the humerus which straddles the posterior edge of the glenoid cavity; (2) by an anterior subacromial depression; (3) by the distance outside and in front of the elbow, which cannot be brought closer to the trunk; (4) by the internal rotation of the arm, which cannot be externally rotated; (5) finally by the semi-flexion of the forearm, which cannot be extended. (Source: Duchenne [de Boulogne] GB. Paralysies obstétricales infantiles des membres supérieurs avec ou sans fractures, luxations ou autres complications. In: De l'électrisation localisée et de son application à la physiologie, à la pathologie et à la thérapeutique par courants induits et par courants galvaniques interrompus et continus. Paris: J B Baillière, 1872:353-67. Translation and figure restoration and editing by Dr. Douglas J Lanska.)

(Source: Smellie W. A treatise on the theory and practice of midwifery, to which is added, a set of anatomical plates, exhibiting the various cases that occur in practice, accurately engraved, with explanations. London: Alexander Cleugh and M Watson, 1790. Figure edited by Dr. Douglas J Lanska.)

Traction on the arm at this point can lead to severe traction on the brachial plexus and cervical nerve roots. (Source: Smellie W. A treatise on the theory and practice of midwifery, to which is added, a set of anatomical plates, exhibiting the various cases that occur in practice, accurately engraved, with explanations. London: Alexander Cleugh and M Watson, 1790. Figure edited by Dr. Douglas J Lanska.)

(Source: The MET, New York. Public domain.)

(Source: The National Gallery of Art, Washington, DC. Public domain.)

(Source: Museo Nacional del Prado, Madrid, España. Public domain.)

(Illustration by Lyonsam/Dmitry Dzhus August 23, 2007. Public domain.)

(Courtesy of the Wellcome Collection, London, England. Creative Commons Attribution 4.0 International License, https://creativecommons.org/licenses/by/4.0/deed.en.)

Cerebral angiogram showing an arteriovenous malformation being largely fed by the anterior cerebral artery, with predominant venous drainage to the superior sagittal sinus. (Contributed by Dr. Andrew Southerland.)

T1 brain MRI with contrast showing a 1.6 cm arteriovenous malformation in the right parasagittal region of the posterior cingulate gyrus, with large draining veins revealing predominant superficial venous drainage but with a lesser component of deep venous drainage as well. (A) Axial MRI, (B) sagittal MRI. (Contributed by Dr. Andrew Southerland.)

A 3-year-old girl with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) experiences cytotoxic edema over the left posterior head region after an episode of status epilepticus, mimicking a left posterior cerebral artery infarction. (Contributed by Dr. Brian Appavu.)

A 15-year-old male with influenza B experiences profound cytotoxic edema to the bilateral thalami consistent with acute necrotizing encephalopathy. (Contributed by Dr. Brian Appavu.)

A CT scan of the head (left) of a 7-year-old male with acute hepatic failure is normal. The patient experiences worsened encephalopathy and seizures, and a repeat CT scan approximately 24 hours later (right) demonstrates loss of gray-white differentiation and profound cerebral edema. (Contributed by Dr. Brian Appavu.)

A 4-year-old female underwent multimodality neurologic monitoring with intraparenchymal intracranial pressure monitoring. The pressure reactivity index was used to evaluate cerebrovascular pressure reactivity efficiency. When plotting the pressure reactivity index over cerebral perfusion pressure in an epoch of 8 hours, there is a parabolic curve, suggesting that the optimal cerebral perfusion pressure for cerebrovascular pressure reactivity efficiency (CPPOpt) is approximately 64.8 mmHg, with an estimated lower limit of cerebrovascular pressure reactivity (LL) at approximately 48.9 mmHg and an upper limit of cerebrovascular pressure reactivity (UL) at approximately 80.8 mmHg. In the fourth row from the top, the green band represents the theoretical range of LL and UL, the red line represents real-time calculated CPPOpt, and the yellow line represents the patient’s actual cerebral perfusion pressure values. (Contributed by Dr. Brian Appavu.)

A 15-year-old male with refractory intracranial hypertension after severe traumatic brain injury. Intracranial pressure steadily rises and initially correlates with intracranial pressure pulse amplitude. RAP, which correlates intracranial pressure to amplitude, is over 1, suggesting impaired brain compliance. This is further reflected in the scatter plot (right) correlating intracranial pressure and amplitude. As intracranial pressure exceeds 65 mmHg, amplitude decreases with rising intracranial pressure, suggesting that the critical threshold of brain compliance has been exceeded. (Contributed by Dr. Brian Appavu.)

Uncal herniation and bilateral medial cytotoxic edema in a 6-year-old patient with cerebral edema in the setting of diabetic ketoacidosis. (Contributed by Dr. Brian Appavu.)

Hydrostatic edema resulting from obstructive hydrocephalus in a 3-year-old male with severe traumatic brain injury. (Contributed by Dr. Brian Appavu.)

Cytotoxic edema involving the bilateral basal ganglia and occipital lobes in a 1-year-old patient with hypoxic-ischemic brain injury secondary to cardiac arrest. (Contributed by Dr. Brian Appavu.)

Vasogenic edema in a 7-year-old patient with posterior reversible encephalopathy syndrome. (Contributed by Dr. Brian Appavu.)

This midsagittal view of the brain MRI of a patient with spinocerebellar ataxia type 6 demonstrates pure cerebellar atrophy without pontine atrophy. (Contributed by Dr. Pichet Termsarasab.)

EEG recorded during two brief typical myoclonic absence seizures during hyperventilation occurring concomitant with an abrupt onset and offset of generalized spike-wave discharges. (10a) The patient’s head bent forward and left with a vague look, then there was a synchronous upward-abducted jerk of the upper limbs (right more than left) and right leg concomitant with brief unsteadiness. (Top arrow) The start of upper limb movement. (Low arrow) Body unsteadiness. (10b) Two similar but more brief clinical events occurred in consequence. (Contributed by Dr. Athanasios Covanis.)

During hyperventilation concomitant with generalized 3 Hz spike-wave discharges of higher amplitude frontal regions and a duration of about 5.5 seconds, the following episodes were recorded: (a) eyes open, no response, and rhythmic nodding of his head; and (b) initial single myoclonic jerking of upper limbs concomitant with eye-opening, no response, and rhythmic up-down jerking of his head. (Contributed by Dr. Athanasios Covanis.)

During hyperventilation (first arrow), the patient stopped responding. There were mild horizontal head movements associated with similar leg movements, ending with a tonic spasm of the adductor muscles bringing the legs close together. The concomitant EEG abnormality was characterized by generalized spike-wave discharges of higher amplitude frontal regions. The episode lasted about 8 seconds (second arrow). Also during hyperventilation in another episode, a single eyelid jerk and a single upper limb myoclonic jerk were part of the described myoclonic absence seizure. Perinatal and past history were noncontributory. Neurologic examination, neuroimaging, and relevant investigations were normal. The electroclinical events responded to sodium valproate, and he had remained free of seizures and EEG discharges for 3 years when last seen. (Contributed by Dr. Athanasios Covanis.)

EEG from a boy with a variability of typical myoclonic absence seizure while standing. Synchronous with the generalized spike-wave discharge, the upper part of his body, upper limbs, and right leg rhythmically jerk with concomitant unsteadiness, but he doesn’t fall. During the event, the body slightly turned to the right and the head to the left. (Contributed by Dr. Athanasios Covanis.)

The polygraphic video-EEG spike-wave generalized discharge was recorded in a 5-year-old boy during hyperventilation while standing. The recorded generalized spike-wave discharge was initially associated with abrupt onset of rhythmic upward jerking of upper limbs; his head bent forward and jerked, his eyes were open and vague, and there was impairment of consciousness for 4.5 seconds (a), followed by a very brief partial recovery (b) (horizontal black bar) and a second similar but milder episode (c), with the difference that rhythmic upward jerking occurred in the right upper limb while the left upper limb remained close to his body with minor jerky movements and concomitant purposeless body movements. The second episode lasted about 11.5 seconds. (Contributed by Dr. Athanasios Covanis.)

An 11-year-old boy suffered from epilepsy with myoclonic absences of idiopathic (unknown) cause since the age of 12 months when he was noticed to have jerks of the upper part of his body (head, upper limbs) mostly induced by noise. These episodes, observed a few times per week, were described as earthquake-like. At the age of 6-years-old, he was reported to have about 10 episodes daily of vague looks concomitant with rhythmic jerking of the head and upper limbs. The episodes had not responded to high doses of sodium valproate, lamotrigine, clobazam, or levetiracetam. When ethosuximide was introduced to his treatment instead of lamotrigine, absence episodes responded, but he had for the first time three generalized tonic-clonic seizures during which his head and eyes turned left and mouth twisted; clonic-myoclonic movements of upper limbs occurred for a few minutes, and he did not respond for about 45 minutes. The typical myoclonic absence episodes were recorded during video-EEG at the age of 11-years-old following the relapse of three generalized tonic-clonic seizures. In 5a, the generalized spike-wave discharge onset is abrupt whereas in 5b the spike-wave discharge is preceded by high amplitude slow waves. In 5b, during hyperventilation, the head bent down, eyes were open, and there was no response to verbal command concomitant with rhythmic upward jerking of upper limbs during the generalized spike-wave discharge. Neurologic assessment revealed no lateralizing signs, and the MRI was negative. The episodes were controlled 80% combining sodium valproate and ethosuximide at optimal daily doses. The family and patient history were noncontributory. (Contributed by Dr. Athanasios Covanis.)

Basic sleep-awake video-EEG from girl at the age of 8 years old who started having episodes with eyelid blinking, no responsiveness, and de novo mouth movement. She was having 10 to 15 episodes daily. The video-EEG did not show abnormalities. During hyperventilation, the generalized spike-wave discharge evoked was associated with the following seizure: eyelid flutter, no response to verbal commands, and concomitant de novo mouth movements. Some high-amplitude, 3 Hz slow waves heralded or followed the generalized discharges. A few other episodes recorded lasted from 11 to 14 seconds with similar electroclinical expression. Her seizures were finally controlled on ethosuximide and lamotrigine. After 4 years of good electroclinical response, lamotrigine was phased-out. Eight months later, her EEG, during hyperventilation showed some irregular spike-wave discharges, and during intermittent photic stimulation at 10 flashes per second, a generalized spike-wave discharge was evoked, but there were no concomitant clinical events. About 6 months later, she started having similar absence seizures, and lamortigine was added to ethosuximide again. The patient history was noncontributory except for 10 febrile seizures when we was younger than 5 years old. Neurologic assessment was normal. Family history revealed her father had three febrile seizures in infancy. (Contributed by Dr. Athanasios Covanis.)

EEG in 5-year-old boy shows generalized spike-wave ictal discharge similar to childhood absence epilepsy preceded by high amplitude delta-theta waves in centroposterior regions. The discharge immediately starts with rhythmic horizontal head jerking. The boy’s eyes remained open with a vague look and no response. His head turned to the right side while jerking. He recovered after about 12 seconds. (Contributed by Dr. Athanasios Covanis.)

From video-EEG of a 22-month-old boy, the EEG shows three repeated generalized spike-wave discharges, each associated with a brief typical absence seizure with concomitant rhythmic eyebrow and head jerking. During video-EEG, frequent generalized spike-wave discharges were recorded--some associated with clinical events. He was given and responded to sodium valproate. Up to the age of 20 years old when he was last seen, a few attempts to withdraw treatment were associated with relapses, two with generalized tonic-clonic seizure during sleep. The cognitive development had been assessed as borderline low. His older sister also had idiopathic generalized epilepsy. (Contributed by Dr. Athanasios Covanis.)

Illustrated is a generalized spike-wave discharge of a 15-month-old boy with a 2-month history of frequent episodes of sudden loss of contact associated with perioral and eyebrow rhythmic jerks. The discharge was associated with impairment of consciousness and concomitant eyebrow and perioral rhythmic jerky movements. The electroclinical event lasted up to 19 seconds. The absence seizures are similar to those of childhood absence epilepsy. He responded on an appropriate daily dose of sodium valproate. (Contributed by Dr. Athanasios Covanis.)

Generalized fast activity during sleep is around 16 Hz. (Contributed by Dr. Athanasios Covanis.)

Subtle tonic seizure with neck flexion concomitant with a 9-second generalized EEG discharge during sleep. (Contributed by Dr. Athanasios Covanis.)

A full-blown tonic neck and upper body flexion during sleep, lasting 10 seconds. Widespread biphasic delta transient with superimposed low-amplitude fast activity and evolution with higher amplitude generalized fast paroxysmal activity. (Contributed by Dr. Athanasios Covanis.)

An atypical absence event during which the patient has interrupted activity and is motionless with staring, lasting about 14 seconds with concomitant generalized slow-spike and polyspike-wave activity while awake. (Contributed by Dr. Athanasios Covanis.)

MRI of a patient with H3K27M-mutant midline glioma. (2A) Brain MRI axial view, post gadolinium contrast with heterogenous enhancement in the left thalamus. (2B) Brain MRI T2 flair sequence with expansile hyperintensity in the left thalamus without surrounding edema. (2C) Brain MRI sagittal view post gadolinium contrast with heterogenous enhancement in the left thalamus. (Contributed by Dr. Jigisha Thakkar.)

MRI of a patient with H3K27M mutant midline glioma. (1A) Brain MRI axial view post gadolinium contrast with heterogenous enhancement in the pons. (1B) Brain MRI T2 flair sequence with expansile hyperintensity in the pons without surrounding edema. (1C) Brain MRI coronal view post gadolinium contrast with heterogenous enhancement in the pons. (Contributed by Dr. Jigisha Thakkar.)

Three-dimensional computer-generated image of Neisseria diplococcal bacteria. Extending from the organisms’ exterior are type IV pili, or hair-like appendages, which improve surface adherence. The artistic recreation was based on scanning electron microscopic imagery. Image by Alissa Eckert, Medical Illustrator, for the Antibiotic Resistance Coordination and Strategy Unit, Centers for Disease Control and Prevention, 2013. (Courtesy of the Public Health Image Library, Centers for Disease Control and Prevention.)

Neisseria meningitidis uses adhesive organelles called Type IV pili, which help them interact with each other to form colonies and adhere to the surface of epithelial cells in the human nasal tract. Pili can be several microns in length but are only 7 nm in diameter. In this image, the bacteria have been stained with salts of uranium to increase contrast in the electron microscope. Individual pili can be seen radiating from the bacterium, in addition to outer membrane vesicles that have been shed by the bacteria. Electron microscopic image by Eric Johnson. (Courtesy of the Wellcome Collection, London. Attribution 4.0 International [CC BY 4.0].)

Three-dimensional, computer-generated image, of diplococcal, gram-negative, Neisseria meningitidis bacteria, based on scanning electron microscopic (SEM) imagery. (Image by Sarah Bailey Cutchin, Centers for Disease Control and Prevention, 2016. Courtesy of the Public Health Image Library, Centers for Disease Control and Prevention.)

This 20-month-old infant underwent amputations including both feet and her left hand at the wrist, after having contracted meningococcal septicemia, or meningococcemia. The disease caused multiple arterial occlusions, which resulted in gangrene in the amputated extremities. (Contributed by Dr. Douglas Lanska.)

A 4-month-old female infant’s gangrenous left knee due to meningococcemia. This infection causes arterial occlusions, which in turn cause ischemic insults to develop with ensuing gangrene of the affected body regions. (Courtesy of the Public Health Image Library, Centers for Disease Control and Prevention.)

A 4-month-old female infant’s gangrenous feet, due to meningococcemia. This infection causes arterial occlusions, which in turn cause ischemic insults to develop with ensuing gangrene of the affected body regions. (Courtesy of the Public Health Image Library, Centers for Disease Control and Prevention.)

A 4-month-old female infant’s gangrenous right hand, due to meningococcemia. This infection causes arterial occlusions, which in turn, cause ischemic insults to develop with ensuing gangrene of the affected body regions. (Courtesy of the Public Health Image Library, Centers for Disease Control and Prevention.)

A man's chest, revealing a red lesion on the skin in the right lateral pectoral region. The lesion was determined to be due to meningococcemia. (Courtesy of the Public Health Image Library, Centers for Disease Control and Prevention.)

(Photograph by Elias Goldensky, Philadelphia. Source: The World's Work: A History of Our Time. New York: Doubleday, Page & Company, 1904;9[2]:5550.)

German caricature showing von Behring extracting horse serum with a tap. Even in caricature, the recognition went to Behring and not Ehrlich. (Courtesy of the Wellcome Collection, London. Public domain.)

(Courtesy of the Wellcome Collection, London. Attribution 4.0 International [CC BY 4.0].)

Ehrlich was instrumental in the work that developed serum therapy for diphtheria. Although Behring cheated him out of both financial reward and recognition, Ehrlich did win the 1908 Nobel Prize in Physiology or Medicine for his contributions to immunology. (Courtesy of the U.S. Library of Congress.)

Behring introduced serum therapy for diphtheria and was controversially awarded a solo Nobel Prize in Physiology or Medicine for this in 1901. Actually, the work had been done by both Behring and Paul Ehrlich (1854-1915), but Behring apparently cheated Ehrlich out of both recognition and financial reward. They had produced their diphtheria serum by repeatedly injecting the bacterial toxin into a horse. The serum was then used effectively during an epidemic in Germany. A chemical company offered a contract to both men, but Behring took the considerable financial rewards for himself. (Courtesy of the University of Marburg, Germany.)

Wiechselbaum identified the meningococcus (designated as Diplococcus intracellularis meningitidis) in cerebrospinal fluid and established the connection between the organism and epidemic meningitis. (Courtesy of the U.S. National Library of Medicine.)

With Ettore Marchiafava (1847-1935), Celi described intracellular micrococci in cerebrospinal fluid. (Courtesy of Wikimedia Commons. Public domain. Photograph restored by Dr. Douglas J Lanska.)

With Angelo Celli (1886-1914), Marchiafava described intracellular micrococci in cerebrospinal fluid. (Courtesy of the Wellcome Collection, London. Public domain. Photograph restored by Dr. Douglas J Lanska.)

Neisser discovered Neisseria gonorrhoeae in 1879. (Photograph courtesy of the U.S. National Library of Medicine. Photograph restored by Dr. Douglas J Lanska.)

(A) A frontal view of the microcephaly. (B) Normal tone and alertness. (C) CT scan shows calcifications and ventriculomegaly. (D) MRI shows polymicrogyria. (E) Diffuse calcifications on MRI. (F) Small cerebellum and redundant occipital skin on MRI. (Contributed by Dr. Abelardo Araujo.)

Kaiser Wilhelm II of Germany in exile at the Dutch manor of Doorn in September 1933, in civilian clothes and with a cigarette. Wilhelm had been forced to abdicate in 1918 at the end of WWI. (Photograph by German photographer Oscar Tellgmann [1857–1936]. Source: Deutsches Bundesarchiv/German Federal Archive.)

Kaiser Wilhelm II in 1905. Wilhelm in dress military regalia, wearing an elaborate "eagle spike" Pickelhaube helmet. He is resting his diminutive and deformed left hand on a sword hilt and then covering it with his normal right hand. (Photograph enlarged and restored by Dr. Douglas J Lanska. Photography by Reichard & Lindner; published by Gustav Liersch & Co.)

Prince Wilhelm in 1877 as an 18-year-old student in Kassel. In 1859, Wilhelm suffered an Erb palsy during a difficult breech birth. The deformity affected him throughout his life. As was typical of him, he tried (albeit unsuccessfully) to hide his deformity whenever possible. Here he is hiding his damaged left hand behind his back. (Photograph restored by Dr. Douglas J Lanska. Photograph by Emil Rothe, Cassel [now Kassel], Germany [Kassel was spelled Cassel until 1926]. Creative Commons Attribution-Share Alike 4.0 International license.)

Prince Wilhelm c1875 as a 16-year-old boy in Berlin. Note how his left hand is hidden by crossing his arms and positioning the left hand so that it is behind a table. (Photograph by German painter and photographer Carl Wilhelm Brasch [1825-1886], Berlin. Source: George Grantham Bain Collection, U.S. Library of Congress.)

Prince Wilhelm c1871 as a 12-year-old boy in Berlin. Note the small size of his left hand, a result of his Erb palsy from obstetric trauma. The white glove is a prop, intended to suggest, by extension, a longer left arm. Despite his age, his wears a military uniform, and his military, tassel-topped, Pickelhaube helmet rests on a table behind his right elbow. (Photograph by German painter and photographer Carl Wilhelm Brasch [1825-1886], Berlin. Source: George Grantham Bain Collection, U.S. Library of Congress.)

Homocysteine is converted to methionine by receiving a methyl group from 5-methyltetrahydrofolate (active form of folate; betaine). Irreversible removal of homocysteine occurs via the transsulphuration pathway, which combines Hcy with serine to form cystathionine. B6: vitamin B6, B12: vitamin B12, BHMT: betaine homocysteine methyltransferase, CBS: cystathionine beta synthase, CTH: cystathionine gamma ligase, DH: dihydro, DMG: dimethylglycine, HCy: homocysteine, Met: methionine, MS: methionine synthase (MTR gene), MHTFR: methylenetetrahydrofolate reductase, TH: tetrahydro. Adapted from (Larsson et al 2019).

Note in EEG (a) fragmented generalized spike-and-wave and EEG (b) generalized 3 Hz mainly slow-wave discharges during sleep, with no concomitant clinical events recorded. Ictal-EEG (c) shows hyperventilation. During the evoked generalized spike-and-slow wave discharge, eyes opened with the head slightly turning back (first arrow) and after about half a second closed again (second arrow). (Contributed by Dr. Athanasios Covanis.)

Sleep-EEG of 12-year-old female with a history of jerks on awakening. During the brief, about 1 second, generalized spike-and-wave discharge, her eyes opened, eyelids slightly jerked, and eyeballs turn upwards left. Eyes closed again immediately after the discharge. While awake, concomitant with myoclonic jerks, a transient eye-stare was also observed. She was also photosensitive to photic stimulation. (Contributed by Dr. Athanasios Covanis.)

A generalized spike-and-wave discharge in a 13-year-old boy with a history of infrequent staring episodes that for 10 days before the EEG had increased up to eight episodes daily. During sleep, some generalized spike-and-wave discharges were recorded with no clinical symptoms. During hyperventilation, he stopped counting, his eyes remained closed, and he became restless with some chewing movements. He recovered immediately after the discharge. (Contributed by Dr. Athanasios Covanis.)

Hyperventilation. Note a provoked regular generalized spike-and-wave discharge associated with typical absence seizure of abrupt onset and termination. The background EEG activity is normal. (Contributed by Dr. Athanasios Covanis.)

(a) Sleep EEG. During sleep, three generalized spike-and-wave discharges of 7.5, 6, and 4 seconds’ duration were recorded. During the 7.5-second 3 Hz generalized spike-and-wave discharge, (a) she slowly opened her eyes wide and had a vague look with concomitant upward tonic spasm of eyebrows for 1.5 seconds; then her eyebrows relaxed to the usual position. Immediately after the discharge, she became conscious for 1.5 seconds and slept again. In a similar discharge of 6 seconds, her eyes slowly opened to a stare, and then her eyes closed immediately after the discharge. During the third discharge (4 seconds), the eyes remained closed. (b) Awake EEG. Hyperventilation while standing: Concomitant with the 3 Hz generalized spike-and-wave discharge, she stopped overbreathing, had a vague look, was not responding, and became slightly unsteady with the body and head bent foreword. Two seconds before the end of the discharge, she scratched her neck with her left hand. Other similar typical absence seizures were recorded during hyperventilation. (Contributed by Dr. Athanasios Covanis.)

After treatment with botulinum toxin injection, this boy's gait has improved, he is flat-footed, and he wears ankle-foot orthosis. (Contributed by Dr. Yasser Awaad.)

This boy with spastic-diplegic cerebral palsy walked on tiptoes and used a walker to ambulate until treatment with intrathecal baclofen. (Contributed by Dr. Yasser Awaad.)

This boy with spastic-diplegic cerebral palsy walked on tiptoes until treatment with botulinum toxin injections. (Contributed by Dr. Yasser Awaad.)

This 28-year-old woman presented at 11 years of age with toe walking. She has mild intellectual impairment, emotional difficulties, and anger control problems; severe hypokinetic dysarthria, hypophonia, and drooling; marked bradykinesia and rigidity in the neck and all extremities; postural tremor in both hands; facial, oromandibular, and truncal dystonia; and dystonic posturing of her hands, left worse than the right, with flexion of the metacarpophalangeal and distal interphalangeal joints. When she walks, her toes touch the ground before her heels due to dystonic muscle contractions. MRI of the brain shows hypointensity in the medial globus pallidus on T2-weighted images ("eye-of-the-tiger") and hyperintensity on T1 images consistent with pantothenate kinase-associated neurodegeneration (PKAN), formerly known as Hallervorden-Spatz syndrome. PKAN is caused by a mutation in the PANK2 gene (Schneider SA, Bhatia KP, Hardy J. Complicated recessive dystonia parkinsonism syndromes. Mov Disord 2009;24(4):490-9). This patient is a cousin of two other patients with PKAN, shown in other clips, the 32-year-old man with tongue protrusion and his teenage sister. (Contributed by Dr. Joseph Jankovic.)

Three members of a family with alcohol-responsive, myoclonus-dystonia (DYT11) with a mutation in the epsilon-sarcoglycan (SGCE) gene on chromosome 7q (Cazurro-Gutiérrez A, Marcé-Grau A, Correa-Vela M, et al. ε-Sarcoglycan: unraveling the myoclonus-dystonia gene. Mol Neurobiol 2021;58(8):3938-52). All 3 demonstrate the combination of myoclonus and dystonia, the latter chiefly manifested by dystonic writer’s cramp. (Contributed by Dr. Joseph Jankovic.)

These are two members of a family with Friedreich ataxia and dystonia. Note the ataxia, marked scoliosis (much improved with Harrington rods), high-arched feet, and dystonic writer's cramp. (Contributed by Dr. Joseph Jankovic.)

Aerobic gram-negative Neisseria meningitidis diplococcal bacteria (aerobic gram-negative, magnification 1150x). (Courtesy of Public Health Image Library, Centers for Disease Control and Prevention; contributed by Dr. Douglas Lanska.)

A photomicrograph of Neisseria meningitidis recovered from the urethra of an asymptomatic male; Magnified 1125X. (Courtesy of Public Health Image Library, Centers for Disease Control and Prevention; contributed by Dr. Douglas Lanska.)

Coronal T2-weighted MRI scan of an infant with abusive head trauma revealing an acute subdural hemorrhage along the convexity of the left hemisphere. (Contributed by Dr. Bhagwan Moorjani.)

Head CT scan of an infant with abusive head trauma revealing an acute subdural hemorrhage along the convexity of the left hemisphere and interhemispheric fissure. (Contributed by Dr. Bhagwan Moorjani.)

Head CT scan of an infant 3 months after suffering abusive head trauma shows diffuse cystic encephalomalacia of the bilateral cerebral hemispheres. (Contributed by Dr. Bhagwan Moorjani.)

Polish-American virologist Albert Sabin (1906-1993) developed the first effective trivalent live-attenuated (oral) poliovirus vaccine. (Contributed by Dr. Douglas Lanska. Source: Woodward T. The Armed Forces Epidemiological Board: its first fifty years. Falls Church, VA: Office of the Surgeon General, Department of the Army, 1990. Public domain photograph of a U.S. Army soldier taken in the course of the person’s official duties.)

With use of a femoral approach, a transvenous sheath is advanced across the foramen into the left atrium, where a folded disc is expanded and pulled back, opposing the primum and secundum septa closed. This step is followed by deployment of a right-sided disc, at which time the 2-disc device is released. Clopidogrel and aspirin are recommended for a period of 3 months to prevent thrombus formation on the device, with aspirin therapy continued for an additional 3 months, until endothelialization is complete. However, a study looking at markers of platelet activation and activation of the coagulation system in patients with cryptogenic stroke who underwent transcatheter closure of their patent foramen ovales found that there was enhanced thrombogenesis and not platelet activation and, thus, recommended the use of anticoagulation as opposed to antiplatelet agents for the short-term (Bedard et al 2007). Antibiotic prophylaxis for 6 months is recommended. Complete late closure of the foramen has been reported in 80% to 95% of patients. (Reproduced with permission from: Kizer JR, Devereux RB. Clinical practice. Patent foramen ovale in young adults with unexplained stroke. N Engl J Med 2005;353:2361-72. Copyright 2005 Massachusetts Medical Society. All rights reserved.)

A 4-month-old female infant with gangrene of the hands and lower extremities due to meningococcemia. (Courtesy of the Public Health Image Library, Centers for Disease Control and Prevention; contributed by Dr. Douglas Lanska.)

A 4-month-old female infant with gangrene of the hands due to meningococcemia. (Courtesy of the Public Health Image Library, Centers for Disease Control and Prevention; contributed by Dr. Douglas Lanska.)

This 2-year-old girl began seizing shortly after birth and at one point had infantile spasms. After treatment of the infantile spasms, she converted to partial and generalized seizures. The problem was to identify which tubers were the ones responsible for the intractable epilepsy. MRI (A) disclosed multiple tubers over both hemispheres. Scalp EEG showed bilateral interictal discharges. However, magnetoencephalography studies identified one tuber in the left inferior frontal gyrus that generated most of the interictal spike discharges, and an ictal event while in the magnetoencephalography machine was localized to be in the same region. After removal of that single tuber (focal resection), this child has remained seizure-free for over 8 years. Thus, patients with multiple bihemispheric cortical abnormalities may be surgical candidates if the areas generating seizures can be accurately identified. (Contributed by Dr. Gary W Mathern.)

This 5-year-old presented with status epilepticus to an outside hospital. Serial MRI scans were read by several experienced pediatric neuroradiologists as normal despite focal EEG abnormalities over the left central-temporal region. After failure of intravenous pentobarbital with coma and EEG burst suppression, the child was transferred for further management. Metabolic workup was negative. FDG-PET and MRI co-registration identified an abnormal area of hypometabolism over a deep gyrus at the posterior end of the left Sylvian fissure (white arrow, both panels) concordant with the scalp EEG localization. In the operating room, this area was mapped and resected, and the pathology was identified as cortical dysplasia. The status epilepticus stopped; there was no language deficit; and she has remained seizure-free for over 5 years. This case is an example of a child who was initially classified as having nonlesional focal epilepsy but, instead, had a difficult-to-identify structural lesion that was causing status epilepticus. (Contributed by Dr. Gary W Mathern.)

This 18-month-old first presented with seizures at 5 months of age; the seizures progressed to infantile spasms by 7 months of age. The infantile spasms were successfully treated with ACTH, but other partial and generalized seizures occurred, including sudden tonic events that affected the right body more than left and lasted 10 to 15 seconds with a frequency of more than 30 times per day. At 18 months, the child was not walking or talking. Neurologic examination showed a right hemiparesis. Scalp EEG showed bilateral but more left than right hemisphere interictal EEG spikes and polyspikes with greater background slowing over the left hemisphere. Ictal events appeared generalized over both hemispheres. Left hemispherectomy was offered because of evidence of progressive epilepsy-induced encephalopathy, and there was an unexpected increase in neurologic deficits because of surgery. This child has remained seizure-free for more than 10 years after surgery and is now able to walk, talk, and participate in school activities. This case exemplifies how young children often require large resections in order to obtain seizure control and improve cognitive development. (Contributed by Dr. Gary Mathern.)

Once venous is blood is removed via the venous cannula, the ECLS pump (either a roller head pump or a centrifugal pump may be used) circulates blood forward to a semi-permeable membrane lung. In the membrane lung, gradient-related diffusion of gases, namely oxygen and carbon dioxide, occurs. Oxygen diffuses from the sweep gas being applied to the membrane into the blood; carbon dioxide diffuses from the blood into the sweep gas. The now-oxygen rich blood is warmed during its flow through a heater and infused into the aorta via the carotid artery cannula placed to provide venoarterial ECLS. In the case of venovenous ECLS, this oxygen-rich blood is infused into the right atrium via the infusion lumen of the double lumen venous cannula. During venoarterial ECLS, the central venous oxygen saturation can be continuously monitored by a fiber-optic catheter placed in the venous side of the circuit. (Provided and reproduced courtesy of the Extracorporeal Life Support Organization; contributed by Dr. Heidi J Steflik.)

(Top) Video-EEG prior to diazepam. There was continuous spike and occasional polyspike-and-slow wave activity mainly at 3 Hz that lasted until the administration of diazepam. Note also slower or faster components and some topographic variability of the discharge. The patient was fully alert, attentive, and cooperative. Movements and speech were normal. There were no abnormal ictal symptoms other than severe global memory deficit and global diminution of content of consciousness. She was unable to remember her name, how many children she had, the current date, and her location. She could not perform simple calculations but could repeat up to five numbers given to her. She could read text correctly, and she wrote her address correctly, although she could not remember it on verbal questioning. She did not know where she was, but given the choice between various locations, she correctly recognized that she was in the hospital. (Bottom) Relative normalization of the EEG started within a minute from onset of diazepam administration, and the patient was able to say the correct date, her address, the name of the hospital, how many children she had, and her name. Note in the EEG the fragmentation of the discharge and the reappearance of alpha rhythm. She continued having problems with calculations, and there were still some memory disturbances even after the intravenous administration of another 5 mg of diazepam and 400 mg of sodium valproate. However, she was sufficiently well to be allowed to leave the hospital with her husband, and she recovered completely at home. (Contributed by Dr. C P Panayiotopoulos.)