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 myoclonus and epilepsy 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 Neurology, 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 nervous system. 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 seizure 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 anticonvulsant 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 headache. 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, dysarthria, slight dysmetria 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 tremor 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. Cerebrospinal fluid 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 seizures were not well sensation was decreased in both feet. Visual fields controlled with multiple anticonvulsants. 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 asterixis (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, cerebellum, 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. LFB-PA S-H stain. http://jnnp.bmj.com/ .2.X0't-A24~~~ ~ ~ ~ ~ ~ ~ ~~' f,v-,P 9 on September 28, 2021 by 44 A j J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.41.2.140 on 1 February 1978. Downloaded from Progressive