J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.41.2.140 on 1 February 1978. Downloaded from

Journal ofNeurology, Neurosurgery, and Psychiatry, 1978, 41, 140-149

Progressive and with dentatorubral degeneration: a clinicopathological study of the Ramsay Hunt syndrome

T. D. BIRD AND C. M. SHAW From the Departments of Medicine and Pathology, Divisions of , Medical Genetics, and Neuropathology, University of Washington School of Medicine, and the Seattle Veterans Administration Hospital, Seattle, Washington, USA

SUMMARY Ramsay Hunt's progressive myoclonus and epilepsy associated with dentatorubral degeneration is a rare disorder. We report a 19 year old woman with this clinical syndrome wlho also has a more mildly affected brother. Neuropathological examination of the young woman showed spinocerebellar and cerebral cortical degeneration in addition to dentatorubral involve- ment. The evidence suggests that this is a distinctive hereditary disorder producing neuronal guest. Protected by copyright. degeneration at several levels in the central .

Progressive myoclonic cerebellar dyssynergia with Clinical summary epilepsy is an uncommon clinical syndrome with multiple causes. Harriman and Millar (1955) The patient had a normal birth and development, divide progressive familial myoclonic epilepsy into and was an average student. At age 15 years she three categories. The first is a relatively uniform developed an awkward gait, clumsy hand co- group associated with intracellular inclusions ordination, and deteriorating school work. She (Lafora bodies), and the second is associated with soon developed nocturnal activity, and an various cerebral lipidoses. The third category is a EEG revealed irregular runs of 4-5 Hz moderate heterogeneous group of nonspecific degenerative voltage activity over the occipital areas, with diseases which include dyssynergia cerebellaris bilateral spike discharges in these same regions. myoclonica of Ramsay Hunt. This syndrome has She was placed on drugs and six also been called dentatorubral degeneration based months later began to complain of dull frontal on the postmortem findings of the case reported . by Hunt (1921). Subsequent reports of Ramsay Neurological examination at this time showed

Hunt's dentatorubral degeneration with patho- marked horizontal nystagmus on lateral gaze to http://jnnp.bmj.com/ logical confirmation are scarce. We have evaluated either side, , slight on finger- a patient who seems to belong to this variety of to-nose and heel-to-shin testing, poor rapid progressive myoclonic epilepsy. The rarity and alternating movements with the left hand, ataxic unusual nature of the syndrome justify docu- gait, and a fine of the head and hands. mentation of the clinical and pathological details Deep tendon reflexes were normal and plantar of this patient. In addition, other members of her responses were downgoing. Unusually high arched family have possibly associated neurological feet were noted.

findings which will also be described. contained 11.2 g/l protein, on September 28, 2021 by 3.3 mmol/l (60 mg/dl) sugar, one mononuclear Supported in part by grants NS01561-01, GM13543-21 and cell per mm3, and negative VDRL. Skull radio- HD02274-11 from the National Institutes of 14ealth, US Public graphs, pneumoencephalogram, and brain scan 1-fealth Service. were normal. She was treated with a combination Address for correspondence and reprint requests: Thomas D. Bird, MD, Division of Neurology, University of Washington School of of mephobarbitone, diphenylhydantoin, and Medicine, Seattle, Washington 98195, USA. ethosuximide. Accepted 29 August 1977 Three months later deep tendon reflexes were 140 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.41.2.140 on 1 February 1978. Downloaded from

Progressive myoclonus and epilepsy with dentatorubral degeneration 141 absent in both lower extremities and vibratory than right. Her generalised were not well sensation was decreased in both feet. Visual fields controlled with multiple . and acuity were normal. An EEG demonstrated Four years after the onset of symptoms she epileptiform discharges, predominantly over the was completely bedridden and hardly able to left central and posterior regions. Repeat cere- carry on a meaningful conversation. She had a brospinal fluid findings were unchanged and CSF sudden respiratory arrest and was admitted to protein electrophoresis was normal. hospital in coma without response to painful One year after the onset of symp'oms the stimuli. She required intermittent assisted ventila- tremor and incoordination of her right hand had tion which maintained her arterial blood gases increased and she complained of visual blurring. and pH within the normal range. Frequent myo- Examination revealed that she was oriented and clonic jerks of face and all extremities continued. coherent, but her fund of general knowledge and She died six weeks after admission, aged 19 years. calculations were impaired. Pupillary light re- actions were normal. She now had vertical jerk Pathological findings nystagmus in addition to a worsening of her ataxic gait, dysmetria, and vibratory and position sensory General necropsy findings included severe chronic deficits. Plantar reflexes remained downgoing. She bronchitis, moderately severe interstitial pneumo- had "jerky twitches" of her head and upper nitis, severe acute and chronic cystitis, inspissated extremities that were described as both myoclonus secretion of the tracheobronchial tree, and and (sudden involuntary flexion, gingival hyperplasia. There was no evidence of a especially of the outstretched hands). Her EEG cardiomyopathy. had deteriorated with posterior slow waves and guest. Protected by copyright. diffuse epileptiform activity, worse on the left. Her verbal IQ was 85, performance IQ 71, and full scale IQ 77. The following tests were normal: serum sodium and potassium, complete blood count, blood sugar, blood urea nitrogen, total serum bilirubin, serum glutamic oxalacetic trans- aminase, serum ceruloplasmin, slit lamp exam.na- tion of the eyes, urine amino acid screen, ECG, rectal biopsy, and urine porphyrins. There were no metachromatic granules in the urine. Ulnar, median, and peroneal motor nerve conduction velocities were normal but that of the posterior tibial nerve was slightly slow (39 m/s). The patient's disease showed a slow but relent- less progression. Three years after the onset of symptoms she remained alert and oriented, but her mental capacity had deteriorated. She developed severe myoclonic jerking movements and dysmetria of all limbs. The myoclonic jerks http://jnnp.bmj.com/ included small twitches of individual muscles as well as sudden larger movements of a whole limb. They were often asymmetrical with the right side more involved. This jerking was worse with stimulation and movement, and decreased with rest and lethargy. There was no close correlation between the jerking of the limbs and the abnormal EEG activity. Plantar reflexes remained down- on September 28, 2021 by going. Her visual acuity was poor (20/160), and she could only identify moving hands. She had a right homonymous hemianopsia. Optic fundi and pupillary reflexes were normal. Optokinetic nystagmus was deficient in all directions but best with the stimulus moving toward her right. An Fig. 1 Coronal section of the right parieto-occipital EEG showed occipital delta activity, left more lobe showing cortical necrosis (arrows). J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.41.2.140 on 1 February 1978. Downloaded from

142 T. D. Bird and C. M. Shau

GROSS BRAIN FINDINGS cerebrum, , and brainstem were eM- The fresh brain weighed 1200 grams. The con- bedded in paraffin, stained with haematoxylin and volutional pattern of the cerebral hemispheres eosin, Nissl, Luxol-fast blue-periodic acid-Schiff- was normal but the sulci were slightly widened haematoxylin, and Holmes' axon and Holzer glial and the gyri were slightly narrow. The lateral fibre methods. Samples were also taken from ventricles were mildly enlarged. On a cut surface various areas, fixed in 4% glutaraldehyde in there were multifocal cortical lesions showing cacodylate buffer and processed for electron thinning of the cortex with dark brown dis- microscopic studies. colouration and granularity (Fig. 1). These lesions were most marked in the medial and inferior MICROSCOPIC EXAMINATION occipital cortices, parietal cortex, inferior frontal Cerebrum Multifocal lesions of the cerebral and superior temporal gyri, more marked on the cortex were found to be much more extensive left side. The substantia nigra was pale. The than those noted in the gross examination, and cerebellum was moderately atrophic and sclerotic. were of various degrees of severity. In a typical Multiple blocks from representative parts of the lesion, the whole thickness of the cortex was re- guest. Protected by copyright.

Fig. 2 Microscopic section of cerebral cortex with marked cortical necrosis (A). Higher magnification (B) shows cortical atrophy with neuronal loss, capillary and glial proliferation, and spongy degeneration of the subcortical white matter.

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Progressive myoclonus and epilepsy with dentatorubral degeneration 143

Fig. 3 Electron microscopic photographs of a rod-like body found in the hippocampus SIFdBP |PP| jWt0O'svastt (X 13000). Ij §KMai I| I|I 7Sify/t i(Lv}r * .tE|1Es K |w' , ty4 H4fOzy-N v gv zZostc?o6*iMDS i USB.S il | zz.)tvi _ .s) jrt., * * 4^ guest. Protected by copyright. *4s. t Si4 <.* 4% s s S '&-. sSS:.ffiS--y:e}vS tw; placed by proliferated capillaries and hypertrophic Basal ganglia The lenticular nuclei were normal. astrocytes (Fig. 2). The deeper.:...... layers were more >, U...... Focal spongy < f ., :degeneration, X neuronal loss and severely affected. Randomly scattered shrunken astrocytic proliferation similar to the cortical neurones were present in the deeper cortex but lesions were present in the dorsolateral thalamus. more neurones were usually preserved in layers II and III. Small vacuoles were scattered in the Cerebellum The loss of Purkinje cells and Berg- lesion or formed rows in layer II. Large areas of mann's gliosis were marked and widespread. The spongy degeneration were frequently present in granular cells were also lost but more focally. The the white matter immediately underneath the subcortical white matter was diffusely pale and cortical lesion (Fig. 2). In the more severely mildly spongy. The dentate nucleus was markedly affected cortex, hypertrophic astrocytes decreased atrophic with diffuse neuronal loss and glial and in number with the relative increase of capillaries capillary proliferation (Fig. 4). Only a few and the cortex became thin and loose with wavy shrunken neurones were scattered among astro- ill-defined spaces. Neurones were absent. In the cytes and capillaries. http://jnnp.bmj.com/ less severely involved cortex, focal accumulations of hypertrophic astrocytes were present with Brainstem There was moderate to marked degree relatively focal neuronal loss. In all lesions gitter of neuronal loss and corresponding gliosis in the cells were infrequently found. The hippocampus substantia nigra, red nucleus, locus coeruleus, and and adjacent temporal cortex were spared on both inferior olives. Extracellular melanin pigment sides but eosinophilic rod-like structures were and its phagocytosis were evident in both sub- found sporadically in the hippocampus. Electron stantia nigra and locus coeruleus. The brachium microscopic studies showed these rods to be conjunctivum was atrophic and pale in the on September 28, 2021 by densely fibrillar structures similar to those mesencephalon (Fig. 5A, B), and also in the described by Hirano et al. (1968) in Guamanian rostral pontine level (Fig. 5C, D). Marked de- amyotrophic lateral sclerosis and - generation with focal accumulation of gitter cells complex (Fig. 3). However, Alzheimer's was noted in the brachium conjunctivum at the neurofibrillary change, senile plaques, and mid pons level. granulovacuolar change were not found in the same regions. Marked degeneration of the dorsal J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.41.2.140 on 1 February 1978. Downloaded from

144 T. D. Bird and C. M. Shaw

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degeneration of the dorsal column was limited related. The father is living and well at age 48 http://jnnp.bmj.com/ to Goll's tract in the thoracic and cervical levels years, and has had no seizures or other neurologi- where the spinocerebellar tracts were also noted cal problems. We have been unable to examine to be degenerated (Fig. 6A, B). Neurones were him. The 46 year old mother is healthy, has had sparse in Clarke's nucleus. The corticospinal tracts no seizures, and has no neurological deficits on were spared. Dorsal roots in the cauda equina detailed examination. She has no pes cavus de- were diffusely fibrotic with marked loss of my- formity. Her EEG shows a small amount of theta elinated fibres. Only one spinal sensory ganglion activity in the left temporal region and is other-

from the lumbar region was available, showing cell wise unremarkable. Sensory and motor nerve con- on September 28, 2021 by loss and interstitial fibrosis. duction velocities in her upper and lower extremi- No Lafora bodies were seen in the central ties are normal. She has abnormally decreased nervous -system. amplitudes of evoked responses (2-3 mV) from both peroneal nerves. The patient's 23 year old Family history brother is living and well, and has a normal neurological examination. The patient's father is of German ancestry, the The patient's younger brother was normal until J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.41.2.140 on 1 February 1978. Downloaded from

Progressive myoclonus and epilepsy with dentatorubral degeneration 145

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-W Fig. 5 Sections of the midbrain (A,B) and rostral pons (C.D) show marked pallor and gliosis of the brachium conjunctivum and red nucleus. Medial lemniscus and spinothalanmic tracts are also involved (C.D). LFB-PAS-H stain (A.C) and Holzer stain (B,D). age 14 years when he developed a fine tremor of is almost identical to an early tracing from his his hands and was noted to drop dishes at home. sister. Urine amino acid screen was negative on Neurological examination at the age of 17 years this man, his mother, and his brother. revealed a fine tremulousness of outstretched hands, mild pes cavus deformity, absent deep ten- A maternal uncle of the patient has had life- don reflexes, horizontal nystagmus on lateral long jerking of his eyes, and was born with a strabismus that resolved gaze, and a loss of vibratory and position sensation spontaneously. Neuro- http://jnnp.bmj.com/ in both feet. Plantar reflexes were downgoing. He logical examination at age 62 years was remark- has had no intellectual change, , dysarthria, able only for a quick oscillating horizontal seizures, or myoclonus. Electromyography showed movement of his eyes on forward gaze which was giant motor unit potentials in the extensor digi- not made worse by eye movements. Retinae, optic torum brevis muscle. Ulnar and median motor discs, and maculae were normal. He had no nerve conduction velocities were in the borderline history of seizures or myoclonus. range but peroneal nerve conduction velocity (33 Another 48 year old maternal uncle had m/s) and distal latency (7.9 ms) were abnormal. moderate nonprogressive mental retardation of on September 28, 2021 by Sural and median sensory nerve conduction unknown cause without seizures. He had no velocities could not be obtained after considerable ataxia, tremor, sensory deficits or myoclonus. effort. His EEG was markedly abnormal with Deep tendon reflexes were normal with downgoing bilateral bursts of 3 Hz waves posteriorly and a plantar reflexes. Rapid alternating movements moderate amount of 3-7 Hz arrhythmic activity were clumsy. There were a few beats of rotary over all regions bilaterally. There were sharp nystagmus on right lateral gaze. His EEG was transients but no epileptiform activity. This EEG normal. J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.41.2.140 on 1 February 1978. Downloaded from

146 T. D. Bird and C. M. Shaw

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A Fig. 6 Sections of the cervical cord (A) and thoracic cord (B) show degeneration of Goll's tract and spinocerebellar tract. LFB-PAS-H stain.

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Discussion They had no clinical evidence of spinal cord in- volvement and no postmortem studies. The second In 1914 Ramsay Hunt reported three patients with group consisted of one set of twin brothers (both a slowly progressive and other affected) who, in addition to progressive cerebellar evidence of cerebellar disease under the title symptoms beginning in adolescence, also had myo- "dyssynergia cerebellaris progressiva". No ne- clonus, epilepsy, depressed deep tendon reflexes, cropsy study was available at the time, but it was sensory loss in the feet, and pes cavus deformity. thought that the primary lesion was in the effer- One of the brothers, who had signs of mental im- ent dentate system. One of these patients came to pairment, died at age 36 years. Neuropathological http://jnnp.bmj.com/ necropsy some years later and was diagnosed as study showed atrophy of the dentate nucleus, having Wilson's disease (Whittier, 1952). Critchley degeneration of the superior cerebellar peduncle, (1962) reported three additional cases of dys- degeneration of the posterior columns and synergia cerebellaris progressiva. The pathological Clarke's nucleus and the spinocerebellar tracts. findings in one of his cases included degeneration The long motor (pyramidal) tracts were not in- of dentatorubrothalamic pathways, subfrontal volved. The cerebral cortex, red nucleus, cranial white matter, spinocerebellar, spinothalamic, nerve nuclei, and inferior olives were normal. spinotectal and rubrospinal tracts. Ramsay Hunt described the twins as having "dys- on September 28, 2021 by In 1921 Ramsay Hunt reported six additional synergia cerebellaris myoclonica associated with patients under the title "dyssynergia cerebellaris Friedreich's ataxia". The syndrome was later myoclonica-primary atrophy of the dentate sys- named "the Ramsay Hunt syndrome" by Green- tem". This report actually described two groups field (1954) but also known as dentatorubral of patients. The first group consisted of four un- degeneration. related persons with progressive dysarthria, inten- Dentatorubral degeneration is a neuropatho- tion tremor, dysmetria, and myoclonus epilepsy. logical diagnosis since the clinical syndrome of J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.41.2.140 on 1 February 1978. Downloaded from

Progressive myoclonus and epilepsy wvith dentatorubral degeneration 147 progressive myoclonus epilepsy is nonspecific and 2. The clinical presentation of the disease in this can be produced by numerous disorders, such as family includes early progressive intellectual de- Lafora body myoclonic epilepsy, cerebral lipi- terioration before the respiratory arrest in the doses, Creutzfeldt-Jacob disease, and even hypoxic patient, and a markedly abnormal EEG in her . Even so, such pathological con- affected brother who has not had seizures. The firmations are meagre and controversial. There left sided preponderance of the cortical lesion in has not been a reported case with only dentatoru- the patient also correlates with her EEG findings bral degeneration. The few cases described include and right visual field defect. other lesions in the brainstem (Hanel and Biel- schowski, and Louis-Bar and van Bogaert, both 3. Our case does not represent an isolated ob- cited by Greenfield, 1954; dc Barsy et al., 1968), servation of cerebral cortical degeneration associ- in the basal ganglia (Titica and van Bogaert, 1946; ated with familial progressive myoclonus epilepsy Andre-van Leeuwen and van Bogaert, 1949), and and dentatorubral degeneration. Similar findings in the spinal cord as in the original case of have been reported by Haltia et al. (1969) and Ramsay Hunt. Netsky (1968) considers these re- Skre and Loken (1970, case 3). The siblings re- ported cases to be variants of either Friedreich's ported by Morse (1949) may also represent this ataxia or olivopontocerebellar degeneration. In re- association. viewing the literature on the Ramsay Hunt syn- drome we also have found difficulties in defining 4. Other authors have noted that focal cerebral this entity precisely. cortical necrosis may result from persistent focal The dentatorubral degeneration and spinal cord seizure activity associated with hypoxaemia that lesions in our patient closely resemble the findings is not severe enough to produce similar damage guest. Protected by copyright. in the single patient studied morphologically by elsewhere (Knopman et al., 1977), demonstrating Ramsay Hunt in 1921. Our patient differs from that an underlying disorder of neurones may that of Ramsay Hunt in showing extensive cere- sometimes make an important contribution to the bral cortical degeneration and degeneration in the final neuropathological changes. thalamus, substantia nigra, locus coeruleus, Based on our patient and other similar cases in inferior olive, and subcortical white matter. We the literature, we propose that dentatorubral initially interpreted the cortical lesion as being degeneration represents the variable expression secondary to hypoxia because the patient had a of a multifocal progressive neuronal disorder such respiratory arrest followed by frequent seizure as occurs in poliodystrophy cerebralis progressiva. activity six weeks before her death. We recognise The spinal cord lesions represent Wallerian degen- that many observers would favour such an ex- eration from death of spinal sensory ganglia and planation. However, the evidence supporting the Clarke's neurones. Degeneration of cerebral cor- cerebral cortical lesion as a part of the primary tical neurones may or may not accompany degen- disease is intriguing and compelling, and we favour eration of the dentate nucleus which was so this interpretation for the following reasons: prominent in the original case of Ramsay Hunt. The extensive loss of cerebellar Purkinje cells 1. The lesion in the cerebral cortex in the present could be a result of hypoxia, chronic phenytoin case is different from the usual hypoxic cortical intoxication, part of the primary disease process, necrosis or pseudolaminar necrosis in several or a combination of these factors. http://jnnp.bmj.com/ aspects. There is practically no cystic necrosis and The Hirano bodies found in the hippo- there are no gitter cells present in spite of evi- campus by electron microscopy are nonspecific dence of a marked neuronal loss. The presence changes that have been described in various de- of randomly preserved neurones in the lesions is generative diseases, including Alzheimer's disease, also against ischaemic necrosis. The number of Parkinsonism-dementia complex, Down's syn- hypertrophic astrocytes present in the cortex is drome, and others (Hirano et al., 1968). However, disproportionately large. This histological lesion they have not been found in patients as young as resembles more the degenerative process noted in this, and are unusual to be found independent of on September 28, 2021 by other areas, such as the dentate nucleus and in- other senile changes. Degeneration of other brain ferior olive. Although the cerebral cortical lesion stem structures, such as the red nucleus, sub- is diffuse, it spares the inferior temporal cortex stantia nigra, and inferior olives (as seen in our and hippocampus. This pattern is more character- case), has been reported in other patients (Curcio istic of primary neuronal disorders, such as - and Pedace, 1955; Christophe and Gruner, 1956; dystrophy cerebralis progressiva (Alper's disease) Yokoi et al., 1965; de Barsy et al., 1968; Haltia than of . et al., 1969). J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.41.2.140 on 1 February 1978. Downloaded from

148 T. D. Bird and C. M. Shaw The family history of this patient is of consider- deterioration, myoclonic jerks, ataxia, epilepsy, able interest. Her 17 year old brother undoubtedly abnormal electroencephalogram, hypoactive deep has the same disease, presently manifesting as tendon reflexes, and diminished position and vibra- absent deep tendon reflexes, pes cavus, tremulous- tory sensation. The neuropathological findings ness, mild nystagmus, decreased appreciation of include dentatorubral and spinocerebellar degen- vibration and position, and abnormal nerve con- eration associated with cortical neuronal degenera- duction studies. His EEG is markedly abnormal tion in advanced cases. The presence of progressive and similar to his sister's. In such families the intellectual deterioration and seizures, the con- EEG may be a useful early indicator of the pres- sistently elevated CSF protein, the lack of long ence of the disease. Whether this young man will motor tract involvement and the absence of car- have a deteriorating clinical course remains to be diomyopathy and scoliosis make our present seen. patient different from typical Friedreich's ataxia No other member of this family has had a (Geoffroy et al., 1976). disorder similar to that of the two siblings. We conclude that this is likely to be an autosomal re- The Muscular Dystrophy Association aided the cessive degenerative disease, probably reflecting study of this family and Dr Robert Wilkus re- an inborn error of metabolism. It should be noted viewed the electroencephalograms. Dr J. T. that both Lafora body myoclonic epilepsy and Robson examined one of the family members. classical Friedreich's ataxia are also autosomal recessive disorders. It is possible that the mild References nerve conduction abnormalities in the mother, the uncle's retardation, and the other uncle's Andre-van Leeuwen, M.. and van Bogaert, L. (1949). guest. Protected by copyright. nystagmus are mild manifestations of the Hereditary ataxia with optic atrophy of the retro- recessive gene in heterozygote carriers. On the bulbar neuritis type and latent pallido-Luysian other degeneration. Brain, 72, 340-363. hand, these findings could be coincidental Christophe, J., and Gruner, J. (1956). La dyssynergie and unrelated. A less likely possibility is that this cerebelleuse myoclonique de Ramsay Hunt. Revue disease is an autosomal dominant disorder with Neurologique. 95, 297-309. highly variable expressivity. Other reports of the Critchley, M. (1962). Dyssynergia cerebellaris pro- Ramsay Hunt syndrome have included family gressiva. Transactions of the A merican Neurological pedigrees consistent with both autosomal recessive Association, 87, 81-85. (Christophe and Gruner, 1956; Noad and Lance, Curcio, F. I., and Pedace, E. A. (1955). Disinergia 1960; Skre and Loken, 1970) and dominant inheri- cerebelosa mioclonica. A cta Neuropsiquiatrica tance (Franceschetti et al., 1954; Kreindler et al., Argentina. 1, 327-341. 1959; de Barsy et al., 1968; Ziegler et al., 1974), de Barsy, T., Myle, G., Troch, C., Matthys, R., and reflecting the heterogeneity of this syndrome. Martin. J. J. (1968). La dyssynergie cerebelleuse The identity of Ramsay Hunt's dyssynergia cere- myoclonique (R. Hunt): affection autonome ou variante du type degeneratif de l'epilepsie-myoclonie bellaris myoclonica remains controversial because progressive (Unverricht-Lundborg) approache of the scarcity of necropsied cases, the extensive anatomo-clinique. Journal of the Neurological Sci- overlapping of clinical manifestations with other ences, 8, 111-127. disorders, and the nonspecific nature of myoclonus Franceschetti, A., Klein, D., and Willener, H. and epilepsy (Watson and Denny-Brown, 1953; (1954). Dyssynergie cerebelleuse myoclonique pro- http://jnnp.bmj.com/ Swanson et al., 1962). gressive (Ramsay-Hunt) a transmission dominante The report by Ramsay Hunt (1921) of affected dans une famille bernoise. Schweitzer Archives fur twin boys implies that they had two diseases: Neurologie und Psychiatrie, 74, 419-423. Friedreich's ataxia and dentatorubral degeneration. Geoffroy, G., Barbeau, A., Breton, G., Lemieux, B., (It should be noted that neither the twins des- Aube, M., Leger, C., and Bouchard, J. P. (1976). cribed by Ramsay Hunt nor our present patient Clinical description and roentgenologic evaluation had the corticospinal tract lesions found in classi- of patients with Friedreich's ataxia. Le Journal We contend that those Canadien des Sciences Neurologiques, 3, 279-286. cal Friedreich's on September 28, 2021 by ataxia.) Greenfield, J. G. (1954). The Spino-cerebellar Degen- twin brothers and our present patient represent a erations. Charles C. Thomas: Springfield, Illinois. single hereditary disorder producing primary Haltia, M., Kristensson, K.. and Sourander, P. (1969). neuronal degeneration in several levels of the Neuropathological studies in three Scandinavian nervous system. We believe Ramsay Hunt's syn- cases of progressive myoclonus epilepsy. A cta drome is a specific clinicopathological disorder Neurologica Scandinavica, 45, 63-77. whose clinical features include childhood or Harriman, D. G. F., and Millar, J. H. D. (1955). adolescent onset, familial occurrence, progressive Progressive familial myoclonic epilepsy in three J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.41.2.140 on 1 February 1978. Downloaded from

Progressive myoclonus and epilepsy with dentatorubral degeneration 149 families: its clinical features and pathological basis. vous System, Volume I. pp. 1163-1185. Edited by Brain, 78, 325-349. J. Minckler. McGraw-Hill: New York. Hirano, A., Dembitzer, H. M.. Kurland, L. T.. and Noad, K. B., and Lance, J. W. (1960). Familial myo- Zimmerman, H. M. (1968). The fine structure of clonic epilepsy and its association with cerebellar some intraganglionic alterations. Neurofibrillary disturbance. Brain. 83, 618-630. tangles, granulovacuolar bodies and "rod-like" Skre. H., and Loken, A. C. (1970). Myoclonus epilepsy structures as seen in Guam amyotrophic lateral and subacute presenile (lementia in heredo-ataxia. sclerosis and parkinsonian-dementia complex. Jour- Acta Neurologica Scandinavica, 46, 18-42. nal of Neuropathology and Experimental Neur- Swanson, P. D., Luttrell, C. N., and Magladery. J. W. ology, 27, 167-182. (1962). Myoclonus-a report of 67 cases and re- Hunt, J. R. (1914). Dyssynergia cerebellaris pro- view of the literature. Medicine (Baltimore), 41, gressiva-a chronic progressive form of cerebellar 339-356. tremor. Brain, 37, 247-268. Titica, J.. and van Bogaert. L. (1946). Heredo- Hunt, J. R. (1921). Dyssynergia cerebellaris myo- degenerative . A contribution to the clonica primary atrophy of the dentate system: a question of primary atrophy of the corpus Luysii. contribution to the pathology and symptomatology Brain, 69, 251-263. of the cerebellum. Brain. 44, 490-538. Watson, C. W., and Denny-Brown, D. (1953). Myo- Knopman, D., Margolis, G.. and Reeves, A. G. (1977). clonus epilepsy as a symptom of diffuse neuronal Prolongecl focal epilepsy and hypoxemia as a cause disease. A rchives of Neurology and Psychiatry of focal brain damage: a case study. A nnals of (Chicago), 70, 151-168. Neurology. 1, 195-198. Whittier, J. R. (1952). The graphic study of ballism Kreindler, A., Crighel, E., and Poilici, I. (1959). and related hyperkinesia. Journal of Neuropathology Clinical and electroencephalographic investigations and Experimental Neurology, 11, 300-316. in myoclonic cerebellar dyssynergia. Journal of Yokoi, S., Kobori. H., and Yoshihara, H. (1965). Neurology, Neurosurgery. and Psychiatry, 22, 232- Clinical and neuropathological studies of myoclonic guest. Protected by copyright. 237. epilepsy. Acta Neuropathologica, 4, 370-379. Morse, W. I. (1949). Hereditary myoclonus epilepsy- Ziegler, D. K., Van Speybroech, N. W.. and Seitz, two cases with pathological findings. Bulletin of the E. F. (1974). Myoclonic epilepsia partialis continua Johns Hopkins Hospital. 84, 116-130. and Friedreich ataxia. A rchives of Neurology Netsky, M. G. (1968). Degenerations of the cere- (Chicago). 31, 308-31 1. bellum and its pathways. In Pathology of the Ner- http://jnnp.bmj.com/ on September 28, 2021 by