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After a brief description of the complex symptoms of myoclonias reference is made to the different systems of classification, and mention is made of the particular areas in which myoclonias appear after hypoxemic cerebral damage and which can be observed more frequently as a result of modern intensive therapy techniques. The 12 cases observed here form the basis for a description of the clinical and electronencephalographic symptoms and a discussion of the differential diagnosis; additionally, 2 autopsy results are discussed. In the cases at hand the myclonias seem to arise from subcortical areas. Finally, reference is made to the therapeutic measures quoted in recent literature and to the experiences gained by the authors, primarily with benzodiazepine.

We previously reported (Europ, Neurol., 3, 347-364, 1970) on two clinical observations of progressive myoclonus epilepsy in the same family. Now, we complete the clinical study showing the neuropathological findings concerning one of the two patients who died at the age of twenty. Degenerative neuronal alterations were found involving the olivo-cerebello-rubral system and, in a minor degree, the brain stem and thalamic structures. No Lafora bodies were found. These pathological features make it possible to suggest a differentiation from a first group of progressive myoclonus epilepsy (Unverricht-Lundborg) and another group (with epileptic manifestations) of dyssynergia cerebellaris myoclonica (Ramsay Hunt). We agree with the suggestion of other authors that it is difficult to establish precise differentiations between these groups at neuropathological level. We think however that the distinction is still possible on the basis of the clinical picture. Our observations cupport the hypothesis that our patient is an "abiotrophic" case of Unverricth-Lundborg syndrome, as we previously had suggested on clinical and especially neurophysiological findings.

One year after a gunshot wound in the popliteal fossa, a 30-year-old man began to experience cramps and myokymia in the left gastrocnemius muscle. Myokymia was characterized by vermicular fibrillary movements localized to the gastrocnemius muscle and accompanied by plantarflexion and dorsiflexion of the toes. Neurologic examination, nerve conduction velocities, electromyograms, and muscle biopsy findings showed affection of left common peroneal and posterior tibial nerves. The myokymia disappeared during sleep, spinal anesthesia, and treatment with carbamazepine.

The authors report the case of a 71 year-old woman presenting right velopharyngo-laryngeal and skeletal rhythmic myoclonus, associated with visual and phasic disorders. They appeared four months after an infarct in the region of the left posterior cerebral artery. The ischemia was of temporo-occipital location, very probably extending to the region of the left red nucleus, thereby interrupting the dento-olivary pathway. Several drugs which are usually active in the treatment of myoclonus proved ineffective. But carbamazepine at a dose of 600 mg per day was effective from the third day and remained so after seven months. It would seem to act by inhibiting the occurrence of paroxystic discharges of an epileptic type in the olivary body disinhibited by the underlying lesion.

Biopsy and autopsy findings in a girl who died at 7 1/2 months after having suffered from progressive axial hypotonia, myoclonus, EEG changes and retarded psychomotor development. Inclusions consisting of lamellar profiles, situated in membrane-bound cytosomes were found mainly in astrocytes, but also in neurones and in axons of peripheral nerves. Lipofuscin bodies were also increased in number. The patient belongs in the same category as cases studied by Towfighi et al. (1975) and Martin et al. (1977). Etiology and pathogenesis of this syndrome remain unknown. It is suggested, however, that the pathological changes observed might have been caused by the administration soon after birth of anti-epileptic drugs (diphenylhydantoin, clonazepam and nitrazepam).

A young woman, with negative family history, committed suicide after 6 years of myoclonus and mental deterioration. The neurons contained atypical myoclonus bodies which differed from the classical type in distribution, histochemistry and light and electron microscopic appearance.

Clinical and morphological studies were carried out on the dynamic of the changes taking place in cases of spontaneous congenital tremor in pigs. It was established that tremor set in immediately after parturition. With the advancement of age the force and intensity of the muscle contractions dropped. The signs of tremor persisted as long as after the fifteenth month of age. The affected animals exhibited delayed growth and development. Morphologically, there was hypoplasia of the cerebellum and the lower portions of the central nervous system. The changes in these organs were found even after the fifteenth month of age.

This is a report on the ultrastructural finding of the olivary hypertrophy in a case with palatal myoclonus. By light microscopy two types of neuronal changes were observed in the inferior olivary nucleus, i.e. the central chromatolysis and cytoplasmic vacuolation. Both types were also recognized by electron microscopy and the cytoplasmic vascuolation was identified as the vesiculated endoplasmic reticulum. In the reactive astrocytes, mitochondria were strikingly proliferated.

We postulate that palatal myoclonus after infarction of the brainstem or cerebellum, or both, is the manifestation of denervation supersensitivity secondary to lesions involving the dentatorubroolivary system. Two cases of our own and 31 from the English and French literature were analyzed in order to determine the delay between the occurrence of presumed anatomical lesions and the recognition of palatal myoclonus. The intervals varied from 2 to 49 months with the median between 10 and 11 months. The natural history of palatal myoclonus following brainstem infarction seemed consistent with the hypothesis.

A case is reported of an 18 year old man with progressive myoclonus epilepsy. Histopathological examination revealed the presence of numerous Lafora bodies in the cerebellar granular layer, without other significant changes in the central nervous system or in other organs.

A 28-year-old male of progressive myoclonus epilepsy was reported, who had showed a gradual progression in myoclonus, mental retardation and cerebellar symptoms, and had been treated with a large dosage of diphenylhydantoin. Neuropathologically, slight degenerative changes of the cerebrl cortex, especially in the IV layer, the external pallidum, and the dentate and olivary nuclei were observed. The most obvious change was diffuse reduction of Purkinje's and granular cells in the cerebellum. A congenital cyst was found with surrounding gliosis in the central tegmental tract of the pons. A significant relationship between myoclonus and the cyst was proposed, and furthermore, influences of diphenylhydantoin intoxication on the clinicopathological development of myoclonus epilepsy were emphasized.

In two cases of action myoclonus following hypoxic or shock encephalopathy, neuropathological examination disclosed mild or moderate scattered changes involving thalamus, griseum centrale mesencephali, and nucleus centralis superior. Other areas were affected only in one of these cases (striatum, nucleus subthalamicus or hippocampus, nuclei pontis, and cerebellar cortex). In another case (an alcoholic patient), the changes, which involved only corpus mamillare and thalamus, were those of Wernicke-Korsakoff encephalopathy. In one case of oscillatory myoclonus following septic shock, there were marked cerebellar changes involving deep nuclei and mild abnormalities in the thalamus and inferior olive. The last case of action myoclonus following acute methyl bromide intoxication was characterized by marked changes in the inferior colliculi and moderate or mild abnormalities of thalamus, griseum centrale mesencephali, nucleus centralis superior, nucleus reticularis tegmenti pontis, nuclei pontis, and dentatus. The findings are compared with the data of seven previously reported neuropathological examinations in action myoclonus following hypoxic encephalopathy.

We describe a kindred with 7 confirmed and 2 probable cases of subacute dementia accompanied by myoclonus. The inheritance pattern is consistent with autosomal dominance and shows anticipation. The pathological changes involve marked gliosis with neuronal loss of the dorsomedial and midline thalamic nuclei, with lesser involvement of the anterior, lateral, and posterior thalamic nuclei. Medullary olivary hypertrophy is prominent. Spongiform change is minimal or absent. Attempted disease transmission to primates from 3 affected family members has been unsuccessful; Western immunoblot tests have likewise failed to detect the presence of specifically reactive 27-30 kD Mr proteins in brain tissue from 2 of these patients. We conclude that this family has a rare inherited neurological systems degeneration with associated thalamic dementia, the clinical course of which is very similar to Creutzfeldt-Jakob disease.

Thirty-four newborn polled Hereford and polled Hereford cross calves affected with a condition previously described as neuraxial oedema and six normal calves were examined. None of the affected calves were seen to stand after birth and when first examined the calves were in lateral recumbency, with extension and crossing of the hindlimbs. All the affected calves were bright and alert, could lift their heads and apparently could see and hear. When the calves were encouraged to stand spontaneous and stimulus-responsive myoclonic extensor spasms, with whole body rigidity, were consistently observed. Thirty-two of the affected calves had macroscopic lesions in the coxae. No significant pathological or biochemical lesions were observed in the central nervous system of any of the calves. The water content of the cerebellum did not differ between normal and affected calves. As oedema of the central nervous system is not a feature of this condition it is more appropriate to describe it as inherited congenital myoclonus.

We report a case of a child with opsoclonus-myoclonus syndrome. Neuroradiological studies indicated a lesion in the cerebellar vermis. A cerebellar biopsy revealed changes consisting of Purkinje and granular cell loss with gliosis. This case report documents the correlation of radiologic and pathological findings in a patient with opsoclonus-myoclonus syndrome.

A 59 years old diabetic man suffered from a rapid central neurological syndrome of unknown aetiology. He died after a nine weeks clinical course. Post-mortem examination showed widespread cortical micro infarcts with diabetic specific arteriolar lesions. This unusual manifestation in the clinical course of the diabetes is discussed in the light of data from the literature.

Two patients are reported with palatal myoclonus, progressive ataxia, and dysarthria, unresponsive to treatment with trihexyphenidyl or L-5-hydroxytryptophan. MRI showed enlargement of the inferior olives in one patient, consistent with the pathology usually associated with palatal myoclonus. The syndrome of progressive ataxia and palatal myoclonus should be distinguished from other ataxias and degenerations that affect the brainstem and cerebellum. Pathology and specificity of site of the lesions are distinctive.

The anatomical basis of palatal myoclonus and related rhythmic skeletal myoclonus is described. The most constant lesion is a special type of degeneration with hypertrophy of the olivary nucleus of the medulla oblongata, on the side opposite to the myoclonus when it is unilateral. This degeneration is usually secondary to a primary lesion located either in the ipsilateral (to the hypertrophied olive) central tegmental tract or in the contralateral dentate nucleus. To link these data, Trelles (1935, 1943) suggested a dentato-olivary pathway from the dentate nucleus to the contralateral inferior olive via the superior cerebellar peduncle and the central tegmental tract after crossing the midline. The existence of this pathway was demonstrated by Lapresle and Ben Hamida (1965-1971), first by showing a topistic relationship between dentate nucleus and contralateral inferior olive, then by delineating this pathway in the vicinity of the red nucleus at the crossing of the superior cerebellar peduncle and the central tegmental tract. The significance of these lesions with their ensuing symptoms is discussed. It is considered as a transsynaptic degeneration which probably reveals an archaic phenomenon, submerged but not lost through evolution.

Three new cases of methyl bromide poisoning (leakage from a fire extinguisher) are reported. Two of these were characterized, after an initial period of coma and myoclonic status, by an action myoclonus. Electrical data are presented. A follow up of 4 and 8 years allowed to study the effect of drugs, two of which (clonazepam and baclofene) being pecularly contributive. The third patient outlived for 5 years in a stuporous state with myoclonus. The anatomical findings consisted mainly of a necrosis of both inferior colliculi with gliosis in the upper brain stem reticular formation and moderate changes in the dentate and pontine nuclei. Their significance is discussed in view of physiological and experimental knowledge.

Three young women, 2 of them sisters, were found to have cherry-red spots at the macula when they were children. In 1 patient the spots faded before she was 20 years old. In all 3, incapacitating myoclonus and insidious visual loss developed in adolescence. Their intellect is normal and they have no gargoyle-like features. A variety of lysosomal inclusions were noted in cortical neurons in a biopsy specimen taken from 1 patient in childhood. Liver biopsy fifteen years later revealed mucopolysaccharide-like inclusions in Kupffer cells and hepatocytes. Lipofuscin bodies were abundant in neurons and hepatocytes. The patients excrete sialic acid-containing oligosaccharides not present in normal urine, suggesting a defect in degradation of glycoproteins. The specific enzymatic defect in these patients appears to be a deficiency of lysosomal neuraminidase.

A 68 year old woman is described with persisting muscular rigidity of the left lower leg together with transient myoclonic jerking in the left quadriceps muscle. Six weeks after onset a small cell carcinoma of the lung became manifest. With radiotherapy and chemotherapy complete remission was achieved. Segmental muscular spasm improved at the same time. Necropsy revealed loss and degeneration of alpha-motor neuron cells at one side of the anterior horn of the lumbar enlargement. This case may represent another manifestation of paraneoplastic subacute motor neuronopathy.

A case of progressive myoclonic epilepsy (P.M.E.) is described. The clinical picture consisted of epileptic seizures, myoclonus and slight mental deterioration associated with a severe progressive cerebellar syndrome. The disease had a course of almost 20 years. Histological studies of the C.N.S. showed severe loss of Purkinje cells, sligth regressive changes in both dentate and olivary nuclei, nerve cells atrophy of anterior horn motoneurons, degeneration of Goll's and Burdach's spino-olivary and anterior spino-cerebellar tracts. Features of cellular lipidosis and/or neuronal amiloid inclusions were not seen. The case was therefore classified in the group of degenerative P.M.E. Its peculiar pathologic aspects consisted of slight but diffuse brain stem regressive changes associated with systemic degeneration involving the spino-cerebellar pathways. The clinical features of our patient emphasize the problem of differential diagnosis between. P.M.E. and D.C.M. thought of by French authors to be an autonomous entity both clinically )severe cerebellar syndrome, intentional myoclonus, absence or late appearance of epilepsy, slight or absent mental deterioration) and anatomically (primary atrophy of the dentate system). However there are many cases, similar to the one reported, which have a clinical course suggesting a diagnosis of D.C.M., but which differ neuropathologically from Hunt's syndrome because of the absence of primary atrophy of the dentate system. These borderline cases give supporting evidence to the concept of continuity between classical P.M.E. and D.C.M., as well as to the authors' opinion that 1unt's syndrome must be classified as a varient of degenerative P.M.E.

Myoclonic contractions of muscles in the abdominal wall and lower extremities developed in a 47-year-old paraplegic woman. The spinal cord was compressed from T-3 to T-8 by an extradural renal cell carcinoma metastasis. To our knowledge, previous studies of patients with sinal myoclonus have not reported a pathologic correlation. In our patient, a focal morphologic change that consisted of vacuolar degeneration and chromatolysis of anterior horn cells was found at the levels of the spinal cord corresponding to the involved muscles. The myoclonus may be spinal in origin and due to an increased excitability of anterior horn cells during the period of sublethal injury.

Ocular bobbing and myoclonus were unusual findings in a patient with central pontine myelinolysis. Pathological findings confirmed the diagnosis of pontine and extrapontine myelinolysis.

Two cases of spinal myoclonus are described; in both patients myoclonus was responsive to stimuli and absent during sleep. The first patient was considered to have viral neuronitis and the condition resolved spontaneously. The second patient had spinal cord ischaemia; there was electro-physiological evidence of abnormal alpha motor neurone activity and histological study of the spinal cord revealed a severe reduction in small and intermediate neurones. This supports the theory that spinal myoclonus may result from abnormal activity of alpha motor neurones released from control by spinal internuncial neurones.

Multiple cerebral petechiae associated with intravascular globules of neutral fat and localized primarily within the white matter are distinctive lesions which secure the pathologic diagnosis of cerebral fat embolism. The abundance of these lesions in an unknown, but presumably small, percentage of cases of fat embolism, along with the even more widespread distribution of embolic fat droplets throughout both white and gray matter, suggest that these lesions and emboli must have a profound effect on neurologic function. Nevertheless, respiratory insufficiency is by far a more common clinical manifestation of the fat embolism syndrome and the neurologic involvement of such patients is often attributed to the secondary effects of generalized hypoxia. The following patient with overt respiratory and neurologic symptoms re-emphasizes the direct primary effect of fat emboli within the central nervous system as a cause of white matter hemorrhages and neurologic deterioration. Explantations for the selectivity of the lesions for the cerebral white matter are explored.

The neuropathological basis for myoclonic encephalopathy associated with neuroblastoma has never been demonstrated. In our 6-year-old patient, the brain changes were restricted to the cerebellum and consisted of demyelination, gliosis, and loss of Purkinje's cells.

There have been many reports in the literature of an association of the opsoclonus-myoclonus syndrome and occult neuroblastoma in children. This syndrome is of interest due to the fact that it appears to be a neurological manifestation of an occult carcinoma (without a metastasis to the CNS). This paper examines pathologic, diagnostic, and etiologic issues concerning this syndrome as well as discussing the functional implications of cerebellar lesions associated with it and how those lesions may produce the symptoms observed.

Myoclonus and progressive intellectual deterioration developed in a 46-year-old woman with trisomy 21 (Down's syndrome) during the final stages of her illness. Her condition was clinically diagnosed as Creutzfeldt-Jakob disease, but necropsy demonstrated the changes characteristic of Alzheimer's disease and cerebrovascular amyloidosis.

Sections of dental pulp were removed from a tooth of a boy 3 years 10 months of age with myoclonic seizures. When stained with hematoxylin and eosin, these sections showed eosinophilic inclusions. Ultrastructurally, these inclusions were large cytosomes filled with whorls of electron-opaque substance. The opaque material consisted of bilaminate strands, approximately 15 nm in diameter, arranged in a curvilinear pattern compatible with that seen in the late infantile form of "ceroid-lipofuscinosis." Most histochemical staining reactions were compatible with ceroid or lipofuscin, with the exception of the diamine silver reaction. Late infantile ceroid-lipofuscinosis represents another disease in which asymptomatic accumulation of storage material occurs in the dental pulp.

The case is described of a woman of 26 suffering (like her mother, a brother and a sister) from a progressively degenerating cerebellar syndrome, at first considered to be hereditary cerebellar ataxia, but which, after action myoclonus appeared, was diagnosed as dyssynergia cerebellaris myoclonica (D.C.M.). Anatomical verification however revealed a syndrome of olivo-ponto-cerebellar atrophy comprising massive demyelinisation of the white matter of the cerebellum and of the cerebellopontine fibres; atrophy of the pontine nuclei; the cerebellar cortex itself was severely affected; moderate nigral lesions; marked spinal lesions of the cerebellospinal fasciculi and of the posterior columns; lesions of the anterior horns and of the bulbar nuclei; cortical chromatolysis. The fact that the dentate system remained unaffected, also noted in some cases of olivo-ponto-cerebellar atrophy with myoclonus, whilst in a number of other cases the lesion remains clinically silent, emphasises the difficulty in establishing an accurate correlation between myoclonus and dentate nucleus. Discussion of the nosological limits of D.C.M.: confirmed cases generally displayed lesions of the dentate system and hereditary degenerative spino-cerebellar lesions. The same clinical symptoms can be observed in cases which do not come under this classification--or even under that of degenerative conditions of the cerebellar system--and D.C.M. appears to be only a syndrome, the Ramsay-Hunt syndrome.

A kindred in which at least 11 individuals in 3 consecutive generations have continuous muscle movement, i.e., myokymia, and periodic ataxia, has been studied. Three patients, a 24-year-old woman, her 4-year-old son and her 27-year-old sister, have been studied in detail. The disorder is inherited as an autosomal-dominant trait and presents in early childhood with attacks of ataxia of 1-2 min in duration, with associated jerking movements of the head, arms and legs. Attacks are provoked by abrupt postural change, emotional stimulus, and caloric-vestibular stimulation. At the age of 12 years approximately, facial and extremity myokymia appears. Physical findings include large calves, normal muscle strength and widespread myokymia of face, hands, arms and legs with a hand posture resembling carpopedal spasm. EMG studies at rest showed continuous spontaneous activity of otherwise normal motor units. Nerve conduction velocities were normal. Gastrocnemius biopsy in 2 patients showed fiber type grouping and small angular fibers, and was consistent with denervation. Histographic analysis of the biopsies demonstrated enlargement of both fiber types, particularly of Type I fibers. These findings are consistent with chronic denervation and an abnormality of motor neuron population or firing. The myokymia described here is of interest not only because of its genetic association with a movement disorder, but also because the muscle findings support a peripheral basis for the muscle movements.

A case of spastic quadriplegia with myoclonic movement was studied by both light and electron microscope. Argentophilic inclusions were found in a unique distribution involving the cerebral cortex, brain stem, cerebellum, and the spinal cord, including the motor neuron system. The fine structure of the inclusions consisted of accumulation of previously undescribed straight or wavy tubules approximately 120A wide devoid of periodic constriction.