Introduction

Overview

In his Thèse de Paris in 1927, Raymond Garcin (1897-1971) described a step-by-step progressive unilateral involvement of all 12 cranial nerves, an exceedingly rare syndrome that is usually due to malignancy (sarcoma or carcinoma) at the base of the skull. Although the complete syndrome is exceedingly rare, this term is used for multiple cranial nerve palsies that do not fit any other named syndrome and involve half of the skull base and at least seven of the 12 cranial nerves. This article describes the various pathologies associated with Garcin syndrome. The prognosis of Garcin syndrome is dismal.

Key points

Historical note and terminology

In his gold-medal Thèse de Paris in 1927, French neurologist Raymond Garcin (1897-1971) described three personally examined cases and three historic cases of progressive, unilateral involvement of most of the 12 cranial nerves associated with osteoclastic lesions of the skull base but without either increased intracranial pressure or long-tract signs (25; 03; 05; 06; 30; 16; 35; 33; 36; 50; 20; 16). The syndrome had been briefly described in a single case the previous year by French neurologists Georges Guillain (1876-1961), Théophile Alajouanine (1890-1980), and Garcin—hence, one of the other eponyms for this disorder: Guillain-Alajouanine-Garcin syndrome (27). Garcin himself referred to the disorder as the “unilateral global cranial nerve paralytic syndrome.” Another term used for multiple cranial nerve palsies due to unilateral lesions of the skull base is “hemibase syndrome” or “hemibasal syndrome” (52).

Among Garcin's conclusions were the following:

Garcin's first case. Garcin's first case was reported in 1926 with Guillain and Alajnuanine (27). Henri Reder..., a 64-year-old man, presented at the Salpêtrière in November 1925 with left facial pain as the culminating symptom of a series of difficulties. In late 1919, he had presented with diplopia. In 1922, his sight had gradually declined on the left side, culminating in a few years with complete blindness in the left eye. In 1924, left deafness appeared. Finally, facial neuralgia developed in the territory of the left trigeminal nerve with very painful nocturnal exacerbation. In addition, he developed headaches, which began irregularly 2 to 3 years previously but became constant, located particularly in the frontal region.

On examination, he had left-sided cranial polyneuropathy manifest as anosmia, blindness (light perception only with marked optic atrophy), total paralysis of the third and sixth nerves (fourth not mentioned), anesthesia in the distribution of the trigeminal nerve (especially V1 and V2) but without evident involvement of trigeminal motor function, peripheral facial paralysis, deafness, anesthesia of the posterior part of the base of the left hemi-tongue (but without a curtain sign), and paresis of the hypoglossus with very accentuated fibrillary contractions on the hemitongue.

Radiographs of the skull base showed a disappearance of the sella turcica on the lateral image, abnormal transparency of the left petrous bone on the anteroposterior view, and clear alteration of the left petrous bone on a Stenvers view (ie, an oblique radiographic projection used to demonstrate the petrous temporal bone and internal acoustic meatus). The left petrous temporal bone had “disappeared in its anterior two thirds replaced by a few opaque nodules.”

The patient was initially treated for syphilis with mercurial suppositories, but this did not hinder the progression of his condition. He was hospitalized at the Salpêtrière, where radiotherapy treatment was immediately instituted. Nevertheless, his condition worsened: (1) trigeminal-distribution pain and headache gradually increased; (2) dysphagia developed with loss of the gag reflex; (3) tachycardia and pulse instability were evident; and (4) weakness of accessory nerve-innervated muscles (sternomastoid and trapezius) developed.

In January 1926, he presented with vomiting and cognitive impairment. Cerebrospinal fluid showed marked proteinuria and mild leukocytosis (20 cells per mm³, “including a few red blood cells”). Cerebrospinal fluid pressure was not elevated even though it was measured inappropriately in a seated position. The CSF Wassermann reaction was negative.

The patient's level of arousal progressively deteriorated from drowsiness to stupor to coma. He died on January 15, 1926.

At autopsy, a vast tumor with imprecise boundaries but lateralized to the left infiltrated the left skull base and filled the sella turcica. Subsequent extirpation of the cerebellum and brainstem was hampered by adhesions of the left cerebellopontine angle. At the level of these adhesions, a tumor the size of a hazelnut was in continuity with the petrous dura mater but had only rather loose connections with the brainstem.

Three apparently independent portions of the neoplasm were evident: (1) a pituitary locus, (2) a middle fossa bud adherent to the temporal lobe, and (3) a cerebellopontine extension; however, these extensions were, in reality, connected by thick subdural trabeculae. A sagittal and paramedian section of the skull base with a saw revealed a spongy state of the basisphenoid bone and the existence of neoplastic buds filling the sphenoid sinus. In the left hemisphere, serial horizontal sections showed neoplastic extension into the temporal lobe.

Histologically, the basal tumor was considered a myxoid sarcoma with “monstrous stellate cells with anastomotic extensions ... immersed in an amorphous gelatinous substance,” but no photomicrographs of histologic sections were shown. A myxoid sarcoma cancer is a type of liposarcoma, a fatty tumor that develops in deep soft tissue; a cranial presentation would be very unusual. The histologic appearance of the temporal lobe graft was different, with the structure of a polymorphic sarcoma and a much more aggressive appearance than the basal tumor.

In summary, this patient presented a clinical syndrome characterized by global unilateral paralysis of the 12 cranial nerves on the left side. The absence of any sensory-motor symptom of the limbs on that side made it possible to localize the extra-cerebral seat of the process in question. This dissociation between the marked, progressive, extensive impairment of the cranial nerves and the absence of symptoms of deficit or irritation of the pyramidal and sensory pathways is characteristic of a progressive extracerebral disease involving the skull base.

Garcin's second case. Garcin's second case was on the service of French neurologist and neurosurgeon Clovis Vincent (1879-1947) and was initially reported by Garcin and J Dereux in 1926 (24).

Henriette Hen..., a 53-year-old woman, presented with headache and atrophy of the tongue. She developed a sudden headache in August 1925, which gradually increased in severity, with violent paroxysms associated with nausea and vomiting. The headache especially involved the left parieto-occipital area, and its severity greatly impaired her ability to sleep. After several months, she had difficulty articulating words. Examination then found dysphagia and a large polyp involving the left middle nasal meatus. The nasal polyp was deemed responsible for dysphagia (!) and was removed. When she was seen in February 1926, examination revealed damage to several cranial nerves on the left side: VI, VII (peripheral), VIII (auditory and vestibular branches), IX, X, XI, and XII. There were no motor or sensory disorders of the limbs. In March 1926, she began vomiting “with ingestion of the slightest food.” By March 1926, she was also found to have total anosmia on the left. The left corneal reflex was depressed, but facial sensation was normal, as was trigeminal motor function (Garcin interpreted the depressed corneal reflex as a sign of trigeminal nerve impairment, but a contribution from corneal exposure due to her peripheral facial palsy should have been considered). CSF analysis showed a lymphocytic pleocytosis (71 lymphocytes per mm³). The Wasserman reaction was negative in blood and CSF. By April, she tended to doze off but was fully arousable and had a left ptosis and facial hypesthesia (V1 and V2). She also had developed right hemifacial spasm, mild right-sided dysmetria, and a right Babinski sign--all on the side opposite to her progressive cranial polyneuropathy. She died on April 12, 1926.

On autopsy, a tumor the size of a walnut was discovered in the region of the cerebellopontine angle, attached by a narrow pedicle to the upper part of the left petrous bone and infiltrating the pons. Histologically, this was diagnosed as a fibrosarcoma of the left posterior fossa. This tumor, with clearly defined contours, pushed back the nerve fibers of the pons eccentrically and achieved considerable development. Not all of the reported cranial nerve abnormalities are explained by the reported autopsy results.

Garcin's third case. Garcin's third case was not reported before his thesis in 1927. The case was from the Nervous Diseases Clinic at the Salpêtrière of MM Georges Guillain and Pierre Mathieu.

In November 1921, a 45-year-old woman developed (?sudden) deafness (side or sides unspecified) during a “bad cold.” In March 1922, during a “new cold,” she developed “violent headaches ... predominantly in the neck area.” In November 1922, her hearing seemed to improve, and she became able to hear the ticking of a watch, but tingling and shooting sensations began in the right half of the tongue. In December 1922, she developed diplopia and severe pain in the neck, right hemiface, and right hemicranium. Examination identified mild hyperemia of the right optic disc and dysfunction of multiple cranial nerves on the right: V, VI, VII, VIII, IX, and XII (progressive hemiatrophy). A Wassermann reaction was positive in the blood but negative in CSF; she was nevertheless treated for syphilis with potassium iodide and then injections of mercury cyanide (mercuric cyanide), but she did not improve. Gradually, all of the cranial nerves were affected except the olfactory nerve. There were no motor or sensory abnormalities in her limbs. “What is immediately striking in this patient is the right ptosis accompanying total right facial paralysis.”

A radiograph in the Stenvers position showed an indistinct upper edge of the right petrous temporal bone: the front third seemed eroded and merged with the shadow of a mass with poorly defined contours. A radiograph in Rose's position showed the difference in bone density that exists between the two petrous temporal bones; the anterior limits of the right petrous temporal bone were not apparent, with a portion completely erased by a shadow with blurred contours that extended forward to obscure the right sphenoid sinus.

The patient died shortly afterward. An autopsy could not be performed, but the radiographic examinations showed lesions that, combined with the clinical characteristics of the evolution of the disease, allowed Garcin to make the presumptive diagnosis of extensive basilar neoplasia, probably a fibrosarcoma.

Prior cases summarized by Garcin:

(1) Case of Turkish neurologist Sani Yaver (1922). Turkish neurologist Sani Yaver (1880-1971) presented a case of cranial polyneuropathy from a skull base sarcoma at the 10th International Congress of Otologie in Paris in 1922, which he attended as the Turkish delegate (64).

Ilias Djelal Eddine, a 65-year-old Ottoman subject working as a sheep merchant, presented for evaluation in March 1921, complaining of buzzing and deafness of his left ear associated with left inferior turbinate hypertrophy, a retracted left eardrum, and absence of the light triangle (Politzer's triangle), suggesting Eustachian tube dysfunction. With turbinate reduction surgery, his tinnitus resolved, and his hearing improved. In August, he presented with left otalgia, purulent discharge from his ear, and decreased auditory acuity. Examination disclosed left otitis media, which improved with myringotomy. However, he soon developed fever, dysphagia, and hoarseness caused by a peritonsillar abscess; this was incised, and he subsequently improved over the next 2 weeks.

On November 15, he presented again with sharp paroxysmal pain in the left auriculo-temporo-parietal region spreading towards the vertex associated with a purulent discharge from his left ear. In addition, he had diplopia in certain gaze positions, hypesthesia in the left temporoparietal region, tinnitus and pronounced reduction in auditory acuity on the left, and dizziness. The combination of suppurative otitis media, pain in the distribution of the trigeminal nerve (V3), and abducens nerve palsy was interpreted as consistent with Gradenigo syndrome (ie, the constellation of clinical symptoms classically caused by the spread of an otic infection into the apical part of the petrous temporal bone: “petrous apicitis”).

However, the following day, after profuse nasal hemorrhages, posterior rhinoscopy disclosed a sessile tumor “having the volume and multilobulated appearance of a raspberry.” When palpated, it had a soft consistency and bled easily and copiously. Histologic examination of a biopsy specimen identified the tumor as a fibrosarcoma.

The patient was readmitted on January 25, 1922, in worsened condition with left ptosis, complete anesthesia of the entire left face and cornea, internal and external ophthalmoplegia of the left eye, left peripheral facial palsy, left-sided deafness, and partial paralysis of the soft palate and tongue on the left.

Nearly 5 months later, on June 10, 1922, he was cachectic and weak. His visual acuity was decreased (5/10) on the left, and his cornea was “opalescent,” precluding fundoscopy (possibly from corneal damage resulting from corneal anesthesia and peripheral facial palsy). Olfactory function was “abolished.” His sense of taste (sugar, salt, vinegar) was abolished on the left half of the tongue, as was the mobility of the tongue on the same side. The nasal chamber was completely invaded by a budding, soft tumor, noticeably lowering the soft palate, which was paralyzed on the left. He had severe dysphagia.

Two weeks later he was noted to have a “quiet delirium,” and he experienced recurrent syncopal episodes. He developed a fever with stertorous respirations and pulmonary congestion and slipped into a coma. He died on June 29.

At autopsy, examination of the cranial cavity revealed thickened meninges that were difficult to peel off at the base. Raising the cerebral hemispheres and cutting the medulla oblongata showed an extensive tumor occupying the left middle fossa of the skull that extended forwards to the level of the greater wing of the sphenoid bone, backward to the vicinity of the foramen magnum, to the left to the middle of the petrous temporal bone, and to the right to the tip of the petrous temporal bone. This tumor was multilobulated and irregular in its contours. It encompassed in its substance all the cranial nerves coming from the pons and the left cerebral peduncle and, furthermore, invaded the tip of the left petrous temporal bone. On the right, in contrast, it repressed the nerves and did not penetrate the bone tissue. A sagittal cut showed that the tumor sank like a wedge into the sphenoid sinuses, whose walls disappeared, to “blossom into a cauliflower” in the nasal cavity and choanae (ie, openings between the nasal cavity and the nasopharynx), which it completely blocked.

The only other significant finding was that the lungs were severely congested, and there were “traces of ancient pleuropulmonary tuberculosis.”

In summary, the patient had a large sarcoma, which originated in the vicinity of the tip of the petrous temporal bone, as evidenced by the ear problems that marked its beginning, and then progressed towards the base of the skull, causing Gradenigo syndrome before finally revealing itself on examination by a series of nasal hemorrhages when it entered the nasal cavity.

(2) Case of Polish neurologist Stanisław Kopczyński (1907). At the January 1907 meeting of the Neurological-Psychiatric Society in Warsaw, Polish neurologist Stanisław Kopczyński (1873-1933) presented a case with lesions of all 12 cranial nerves resulting from a brain tumor (15). In 1908, this case was abstracted in Neurologisches Centralblatt by Polish neurologist and psychiatrist Edward Flatau (1868-1932) (22). The following summary is based on Flatau's summary in German rather than Garcin's summary of Flatau's summary.

A 26-year-old woman complained of pain in the left half of her face and her left ear, difficulty swallowing, nausea, vomiting, and left-sided deafness for a year. The disease began with left facial paresthesias, followed by left-sided ptosis, difficulty swallowing, episodic headaches, nausea, and vomiting. Examination showed cachexia cervical lymphadenopathy predominating on the left where the lymph nodes were “enlarged and hard”; microscopic examination showed that it was an alveolar sarcoma. Neurologic examination disclosed a cranial polyneuropathy on the left side; loss of the sense of smell; ptosis and complete external and internal ophthalmoplegia with papilledema; anesthesia in all branches of the trigeminal with paralysis of trigeminal motor functions; facial paralysis; deafness; taste dysfunction (hypogeusia) and anesthesia in the corresponding half of the tongue, pharynx and larynx; difficulty swallowing; atrophy of the sternocleidomastoid and trapezius muscles; and lingual hemiatrophy. The dysfunction was not strictly unilateral, however. On the right side, there was smell abolition, “optic neuritis,” and abducens paralysis. No pathology was reported, but as Flatau noted, this pattern presumably resulted from an infiltration of the base of the brain, mainly on the left side, destroying the exiting cranial nerves.

(3) Case of Dinkler (1891). Dinkler was a student of German neurologist Wilhelm Heinrich Erb (1840-1921), cited by French neurologist Fulgence Raymond (1844-1910), the successor to Jean-Martin Charcot (1825-1893) (19; 48). The case is summarized from Raymond rather than Garcin, who made some errors in summarizing Raymond, or Dinkler, who had a lengthy case report.

A man in his fifties experienced “violent” headaches in the right half of the occiput in September 1888. In October, he experienced diplopia, and paralysis of the right medial and superior rectus muscles were noted (without mention of a dilated pupil, ptosis, or inability to infraduct?). The fundus was normal. In February 1889, anesthesia of the right conjunctiva, dizziness, and right-sided tinnitus were noted. In March, ophthalmoscopy revealed the existence of papillitis on the right with slight exophthalmos. A little later, he complained of an abnormal sensation in his mouth, as if the mucous membrane were inflamed everywhere. He heard less well in his right ear. In May, the patient complained of pain in the right half of the tongue and a swelling sensation in this area. The right pupil was dilated. Smell, taste, and hearing were severely blunted on the right, and sensation to pain and temperature were impaired on the face (trigeminal nerve distribution, side unspecified), and he had right trochlear, abducens, and facial palsies. In June, his headaches had worsened, causing him to cry out, and he experienced pain and anesthesia in the (right) face (trigeminal nerve distribution). By October, his masticatory muscles were almost completely paralyzed on the right, and he swallowed with difficulty. By November, the man had dysfunction of the following cranial nerves: I (R), II (R/L), III/IV/VI (R), V (R/L partial), VII (R), VIII (R), IX (R), X (R), XI (R), and XII (R). The patient died shortly after. Autopsy disclosed a basal tumor, which, in all likelihood, had its starting point in the right cavernous sinus; by developing in both directions, forwards and backward, it had caused the degeneration of the identified cranial nerves.

Later evolution of the Garcin syndrome. The Garcin syndrome definition has been modified to include cases with the involvement of seven cranial nerves ipsilaterally as well as a few contralaterally (49). In Europe, many cases of multiple cranial nerve palsies (even less than seven) that do not fit into any of the other named syndromes are reported under the umbrella of “Garcin syndrome.” Some reported cases have other symptoms, such as headaches and signs such as hypopituitarism (01). One case has been reported with papilledema (02).

For the purposes of this review, only cases involving at least seven cranial nerves on one side will be considered as “Garcin spectrum,” and the cases with all 12 cranial nerves on one side will be considered as “Garcin syndrome.”