Coma due to supratentorial and cerebellar lesions

Richard Jackson MD

General Neurology

Updated 08.06.2024
Released 05.16.2020
Expires For CME 08.06.2027

Coma due to supratentorial and cerebellar lesions

Author: Richard Jackson MD

See Contributor Disclosures

Editor: Peter J Koehler MD PhD

Coma due to supratentorial and cerebellar lesions

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Introduction

Overview

Coma is characterized by the absence of arousal (wakefulness, vigilance) and awareness of self and environment, lasting for more than 1 hour. Comatose patients have closed eyes, do not communicate, and do not arouse to verbal, tactile, or noxious stimuli (12). The terminology and etiologies of coma have not changed historically since the seminal work by Plum and Posner. Workup starts with imaging to delineate anatomic from physiologic causes, which drives the ensuing investigation and treatment.

Key points

	• First action is to discriminate between structural and physiologic with noncontrast CT head.
	• Information regarding etiology must be taken from alternative sources such as family, medication lists, or the environment, as the patient cannot give any history.
	• Vital signs and laboratory values offer some clinical clues.
	• Airway, breathing, and circulation are the first tenets of care.
	• Etiology strongly influences outcomes.

Historical note and terminology

Plum and Posner first discussed the idea of coma when they stated, “the ancient Greeks knew that normal consciousness depends on the intact brain and that impaired consciousness signifies brain failure.” The word “coma” means “deep sleep or trance.” The patient is described as lying with eyes closed, not being able to be aroused to respond appropriately to stimuli even with vigorous stimulation. They acknowledge that the patient may grimace to painful stimuli and may demonstrate stereotyped withdrawal responses but does not make localizing movements (12). In 2008 Koehler and Wijdicks published a history of the historical events that led to the landmark publication of Stupor and Coma in which teachable and recognizable clinical signs were first reported, marking a paradigm shift in the treatment of coma (08). In 1974, the Glasgow Coma Scale was introduced for evaluating consciousness in traumatic brain injury and is still the most widely used scale (17). In 2001, the Richmond Agitation-Sedation Scale attempted to quantify consciousness and agitation in the intensive care population with a 10-point scale where coma was defined as RASS-5: no response to voice or physical stimulation (15).

Clinical manifestations

Presentation and course

Due to the nature of the disease, no history can be gained from the patient. History can be obtained from alternative sources such as the family, cell phone, prescription bottles, environment in which the patient was found, and the physical exam. The clinical clues from the family members include the rate of onset. Vascular structural etiologies such as subarachnoid hemorrhage, intracerebral hemorrhage, and ischemic stroke have an abrupt onset. Toxicities and overdoses can have a slower onset over minutes. Classic physical exam findings can be found below (18):

Vital signs.
	• Bradycardia. Sympatholytic, clonidine, barbiturates, gamma-hydroxy-butyrate, increased intracerebral pressure
	• Tachycardia. Psychotropic ketamine, adrenergic hyperactivity with intracerebral hemorrhage, MDMA
	• Hypotension. Sepsis, tricyclic antidepressants, sedative hypnotic, clonidine
	• Hypertension. Hypertensive encephalopathy, ketamine, phencyclidine, methylenedioxymethamphetamine, increased intracerebral pressure
	• Tachypnea. Metabolic acidosis
	• Bradypnea. Opioid, sedative hypnotic, medullary involvement
	• Hyperthermia. Environmental, infection, neuroleptic malignant syndrome, serotonin syndrome, salicylate, subarachnoid hemorrhage, hypothalamic disorders
	• Hypothermia. Environmental, hypoglycemia, sedative hypnotic, infection, hypothyroid
Eyes.
	• Miosis. Opioid and clonidine toxicity, pontine hemorrhage
	• Mydriasis. Anticholinergics, tricyclic antidepressants, methylenedioxymethamphetamine
	• Horizontal nystagmus. Alcoholism and antiepileptic medications
	• Vertical nystagmus. Phencyclidine, ketamine, brainstem disorders
	• Gaze deviation. Hemispheric lesion, contralateral pontine, seizure focus
	• Roving eye movements. Intact brainstem
Ears. Hemotympanum in 50% of basilar skull fractures
Dry mucous membrane. Dehydration, anticholinergic chemicals/medications
Salivation. Ketamine toxicity
Skin.
	• Dry. Anticholinergic medications/chemicals
	• Diaphoresis. Hyperadrenergic state
	• Coma bullae. Infection, barbiturate toxicity
	• Track marks. Intravenous drug use
	• Bowel sounds. Decreased opioid and anticholinergic medication/chemicals

Due to the nature of the presentation as an endpoint of many diseases and a clinical syndrome, the clinical variants are varied as listed below (09):

Structural.
	• Trauma. History of trauma with immediate loss of consciousness. Eyes open to painful stimulus, localized to pain; brainstem reflexes are reactive.
	• Stroke. Sudden onset focal neurologic deficit followed by progressive obtundation. CT shows midline shift or bilateral thalamic infarction.
	• Subarachnoid hemorrhage. Sudden onset headache followed by nausea, then progressive obtundation.
	• Intracerebral hemorrhage. Sudden onset nausea or vomiting with focal neurologic deficit, then progressive somnolence.
	• Tumor. Increasing intensity of headaches, then vomiting and collapse. CT shows space-occupying lesion in the cortex or the cerebellum.
	• Demyelinating. Several days of fever and generalized weakness, low-grade fever, subacute progressive encephalopathy. CT nonspecific abnormalities.
	• Encephalitis. Subacute onset of headache, flu-like symptoms, fever. Normal cranial nerves, no papilledema with an abnormal lumbar puncture.
	• Hydrocephalus. Lethargy, headache, nausea, and vomiting. Abnormal CT with dilated ventricles.
	• Abscess. Subacute onset fever, altered mental status, nuchal rigidity, photophobia/phonophobia.
Nonstructural.
	• Thermoregulatory. < 35 or >40.5 (04); < 35: shivering, respiratory depression, cardiac dysrhythmias, mydriasis, hypotension > 40.5: sweating, flushing, tachycardia, weakness, hypotension, seizures
	• Medication. Decreased consciousness, myoclonus, seizure
	• Cefepime. Elderly, decreased GFR (11)
	• Valproic acid. Acute reduced consciousness, polypharmacy (02)
	• Tricyclic. Wide QRS, cholinergic syndrome (Shutter and Molyneaux 2018)
	• SSRI/antipsychotics. Rigidity, fever, myoclonus (Shutter and Molyneaux 2018)
	• Alcohols. Osmol gap, metabolic acidosis, renal failure (Shutter and Molyneaux 2018)
	• Poisoning Ciguatera: Pacific, Caribbean, Indian Ocean, convulsions and coma, consumption ciguatera (03) Carbon monoxide: history of exposure, elevated carboxyhemoglobin levels, headache, altered mental status (13)
	• Epilepsy. Onset of convulsions lasting longer than 5 minutes or two generalized tonic-clonic seizures without return to baseline in a 5-minute period with normal vital signs and pupillary responses
	• Endocrine. Acute blindness, hemodynamic instability, coma (06)
	• Circulatory shock. Hypotension
	• Cardiac arrest. Sudden collapse without pulse
	• Respiratory failure. Hypercarbia
	• Glucose. Hypoglycemic medications
	• Acid base and ionic. Restlessness, headache, AMS, coma usually during or after first treatment (19)
	• Hepatic and uremic encephalopathy. Progression to intermittent agitation, confusion, lethargy with no response to painful stimuli

Prognosis and complications

Coma etiology strongly influences outcomes, with reported mortality ranging from 25% to 87% (05). Five percent to 25% of patients remained moderately-severely disabled or in a permanent vegetative state. The mortality was highest for stroke (60% to 95%) and postanoxic coma (54% to 89%) and lowest for poisoning (0% to 39%) and epilepsy (0% to 10%).

Clinical vignette

A 53-year-old woman with hypertension and diabetes, noncompliant with medications, and no history of migraines presented to the emergency room with her husband for confusion and increasing intensity of headaches. In the emergency room, she acutely became comatose with a Glasgow Coma Scale of 3 and no brainstem reflexes and was intubated with a systolic blood pressure of 220. She was transported to the CT scanner, where a noncontrast head CT revealed a cerebellar hemorrhage with edema and mass effect compressing the fourth ventricle with blood tracking into the pons and up into the midbrain. She then became hypotensive without intervention to systolic blood pressure of 90/40, requiring phenylephrine for stabilization. Neurosurgery evaluated the patient and found no brainstem reflexes. She was taken emergently to the operating room for decompressive craniectomy, clot retrieval, and frontal ventricular drain. She never regained consciousness or brainstem reflexes but was found to have SPECT uptake in the cerebral hemispheres and polymorphic delta on her EEG with normal transcranial Doppler waveforms. MRI revealed edema in the brainstem without infarction. Her family decided to proceed with tracheostomy with PEG tube and transfer her to a nursing home.

Biological basis

Constantin Von Economo wrote about encephalitis lethargica from 1917 to 1931 based on his experiences during World War I. He proposed that waking influence stems from the upper brainstem passing through the deep gray matter and that the sleep-promoting area is in the rostral hypothalamus. The rostral hypothalamic localization for deep sleep was subsequently confirmed by lesional studies on animals by Nauta, Sweett, and Hobson and Sterman and Clemente from 1939 to the 1960s (12).

Victims of Von Economo encephalitis lethargica were found to have lesions involving the paramedian reticular activating formation of the midbrain at the junction with the diencephalon. This suggested that circuitry causes arousal of the forebrain and was located in the brainstem (12).

The development of EEG in 1929 by Hans Berger revealed that the waveform patterns recorded decreased in amplitude and frequency in correlation to patients’ level of consciousness. In 1935, Frederic Bremer found that cats with transected spinal cords between the medulla and spinal cord had a desynchronized wakeful pattern, but transection between the superior and inferior colliculi caused a high voltage slow wave pattern indicative of deep sleep with clinical behavioral unresponsiveness (01). Subsequent experiments by Moruzzi and Magoun confirmed that the midbrain reticular core relayed arousal signals to the cortex. Further experiments in cats with transections from the midpontine level or below promoting a continuous wakeful state further supported the lower brainstem as a synchronizing or sleep-promoting area (10).

In the 1980s, it was found that the thalamus has relay neurons with burst and transmission modes of firing. The transmission mode firing was found to be mainly operating during wakefulness. Individual neurons fire in patterns that reflect their incoming afferent inputs, which correlate with a desynchronized EEG. Burst mode was found to be secondary to calcium-activated potassium current when sodium channels become hyperpolarized, leading to rhythmic bursts that correspond to the slow waves on EEG reflecting large amounts of synchronized excitatory inputs to the cortex. The synchrony was originally thought to be located in the thalamic reticular nucleus but has since been found to arise from mesopontine afferents that span the entire thalamus, mainly in the pedunculopontine and laterodorsal tegmental nuclei as well as the midline and interlaminar nuclei (07).

The mesopontine level in the brainstem contains at least three different monoamine groups that project through the hypothalamus to the cortex; the locus coeruleus projects through the paramedian midbrain reticular formation, and the lateral hypothalamus innervates the cortex diffusely (07). Serotonergic neurons in the dorsal and median raphe nuclei project through a similar course (07). Dopaminergic cells in an extension of the ventral tegmental dopamine group along the midline of the midbrain into the area around the cerebral aqueduct and through the paramedian midbrain reticular formation are most active in wakefulness (07). Lesions of the prelocus coeruleus and medial parabrachial nuclei have been found to produce profound coma.

There are also glutamatergic neurons thought to amplify the arousal signal in the mesopontine tegmentum that are incapable of maintaining a wakeful state in the absence of the other groups. As the ascending arousal systems pass through the hypothalamus, histaminergic neurons in the tuberomammillary nucleus and lateral hypothalamic area augment the ascending projections that project to the cortex and the thalamus (07). Some of the lateral hypothalamic neurons contain orexin or GABA and fire fastest during wakefulness (07). Cholinergic and noncholinergic neurons also augment the signal in the magnocellular basal forebrain nuclei receiving afferents from the hypothalamic and monoaminergic ascending systems (07).

Management

Diagnostic and therapeutic steps should occur simultaneously. An organized and sequential plan can form the basis for discovering common causes of unresponsiveness and for selecting studies for less common causes of coma (14).

Prehospital.
	• ABC
	• Glasgow Coma Scale
	• Pupils
	• Vital signs and access
	• Establish airway
	• Correct hypoglycemia
	• Administer naloxone
	• Treat for shock with fluids and pressors
	• Collect information on prodromal symptoms, timeline, past medical history, medications, toxic substance use, recent illness, signs of trauma/environmental exposure/signs of intoxication
Hospital. Per Emergency Neurological Life Support Guidelines, after stabilization of ABCs and the cervical spine then the physical exam can establish the diagnosis of coma:
	• Level of consciousness
	• Brainstem assessment
	• Evaluation of motor responses
	• Appraisal of breathing patterns
Then the patient is assessed for reversible conditions.
	• Dextrose for glucose < 70
	• Thiamine in chronic ethanol users, bariatric surgery patients, malabsorption syndromes
	• Apnea/bradycardia/small pupils give naloxone
	• Possible flumazenil in benzodiazepine or polysubstance abuse
	• Physostigmine for anticholinergic toxicity
	• Atropine for cholinergic toxicity
	• Hypertension can be a sign of increased intracranial pressure or stroke
	• Search for signs of trauma that might need emergent surgery such as epidural hematoma, subarachnoid hemorrhage, or intracerebral hemorrhage (07)

Focused history and past medical history by collateral information should be reviewed first, then stat labs, head CT, and CTA head and neck for structural causes. If there is persisting uncertainty, consider EEG and lumbar puncture.

References

01: Bremer F. Cerveau “isolé” et physiologie du sommeil. CR Soc Biol 1935;118:1235-41.
02: Camilleri L. Sodium valproate induced encephalopathy. Clin Med 2018;(5):430-2. PMID 30287443
03: Chan T. Characteristic features and contributory factors in fatal ciguatera fish poisoning-implications for prevention and public education. Am J Trop Med Hyg 2016;94(4):704-9. PMID 26787145
04: Cheshire Jr W. Thermoregulatory disorders and illness related to heat and cold stress. Auton Neurosci 2016;196:91-104. PMID 26794588
05: Horsting M, Franken M, Meulenbelt J, van Klei, de Lang DW. The etiology and outcome of non-traumatic coma in critical care: a systematic review. BMC Anesthesiol 2015;15:65. PMID 25924678
06: Ishii M. Endocrine emergencies with neurologic manifestations. Continuum (Minneap Minn) 2017;23(3 Neurology of Systemic Disease):778-801. PMID 28570329
07: Kandel ER, Schwartz JH, Jessel TM. Principles of neural science. 4th ed. McGraw-Hill, New York; 2000:871-909.
08: Koehler PJ, Wijdicks EF. Historical study of coma: looking back through medical and neurological texts. Brain 2008;131(Pt 3):877‐89. PMID 18208847
09: Lee K. The NeuroICU Book. 2nd Ed. McGraw-Hill Education, 2018.
10: Moruzzi G, Magoun HW. Brain stem reticular formation and activation of the EEG. Electroencephalogr Clin Neurophysiol 1949;1(4):455-73. PMID 18421835
11: Payne L, Gagnon D, Riker R, et al. Cefepime-induced neurotoxicity: a systemic review. Crit Care 2017;21(1):276. PMID 29137682
12: Plum F, Posner J. The diagnosis of stupor and coma. Philadelphia: Davis, 1966.
13: Rose J, Wang L, Xu Q, et al. Carbon monoxide poisoning: pathogenesis, management, and future directions of therapy. Am J Respir Crit Care Med 2017;195(5):596-606. PMID 27753502
14: Sarwal A, Stern-Nezer S, Tran D. Emergency Neurological Life Support: Approach to the Patient with Coma. 2019 Neurocritical Care Society. ENLS Guidelines.
15: Sessler C, Gosnell, M, Grap M, et al. The Richmond Agitation-Sedation Scale: validity and reliability in adult intensive care unit patients. Am J Respir Crit Care Med 2002;166(10):1338-44. PMID 12421743
16: Shutter L MD, Molyneaux B MD. Neurocritical care. Oxford University Press, 2018.
17: Teasdale G, Jennett B. Assessment of coma and impaired consciousness. A practical scale. Lancet 1974;2(7872):81-4. PMID 4136544
18: Traub S, Wijdicks E. Initial diagnosis and management of coma. Emerg Med Clin North Am 2016;34(4):777-93. PMID 27741988
19: Zepeda-Orozco D, Quigley R. Dialysis disequilibrium syndrome. Pediatr Nephrol 2012;27(12):2205-11. PMID 22710692

Contributors

All contributors' financial relationships have been reviewed and mitigated to ensure that this and every other article is free from commercial bias.

Author

Richard Jackson MD

Dr. Richard Jackson of University of Vermont has no relevant financial relationships to disclose.
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Editor

Peter J Koehler MD PhD

Dr. Koehler of Maastricht University has no relevant financial relationships to disclose.
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Patient Profile

Age range of presentation: Any age
Sex preponderance: No sex preponderance
Heredity: None
Population groups selectively affected: None
Occupation groups selectively affected: None

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Coma due to supratentorial and cerebellar lesions

Differential Diagnosis

Encephalopathy
Locked-in syndrome
Hypoactive delirium
Catatonia
Psychogenic unresponsiveness

Also Relevant

Coma due to drug intoxication
Disorders of consciousness
Encephalitis lethargica
Hepatic encephalopathy
Illicit drug use: neurologic complications
- Ischemic stroke
- Metabolic encephalopathy and metabolic coma
- Nontraumatic intracerebral hemorrhage
- Severe closed head injury
- Subarachnoid hemorrhage
- Traumatic intracerebral hemorrhage

Clinical Categories

General Neurology

Coma due to supratentorial and cerebellar lesions

Coma due to supratentorial and cerebellar lesions

Introduction

Overview

Key points

Historical note and terminology

Clinical manifestations

Presentation and course

Prognosis and complications

Clinical vignette

Biological basis

Differential diagnosis

Diagnostic workup

Management

References

Contributors

Author

Editor

Patient Profile

ICD & OMIM codes

This is an article preview.
Start a Free Account
to access the full version.

Questions or Comment?

Also in This Category

Brain death/death by neurologic criteria

Hepatic encephalopathy

Bowel dysfunction in neurologic disorders

Coma due to primary brainstem and diencephalic lesions

Transient visual loss

Neuroimaging in acute stroke

Sports activities: neurologic complications

Neurotechnology: brain-computer and brain-machine interfaces

Coma due to supratentorial and cerebellar lesions

Introduction

Overview

Key points

Historical note and terminology

Clinical manifestations

Presentation and course

Prognosis and complications

Clinical vignette

Biological basis

Differential diagnosis

Diagnostic workup

Management

References

Contributors

Author

Editor

Patient Profile

ICD & OMIM codes

This is an article preview. Start a Free Account to access the full version.

Questions or Comment?

Also in This Category

Brain death/death by neurologic criteria

Hepatic encephalopathy

Bowel dysfunction in neurologic disorders

Coma due to primary brainstem and diencephalic lesions

Transient visual loss

Neuroimaging in acute stroke

Sports activities: neurologic complications

Neurotechnology: brain-computer and brain-machine interfaces

This is an article preview.
Start a Free Account
to access the full version.