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A case of progressive myoclonic ataxia in an AIDS patient is described, which evolved over a 13 month period. The ataxia persisted as the only clinical finding for several months before the appearance of a severe tetraparesis and cachexia. Throughout the clinical progression, magnetic resonance imaging (MRI) revealed the presence of bilateral, progressive, isolated, and symmetrical lesions involving the red nuclei, subthalami, thalami, lenticular nuclei, and primary motor cortices. Neuropathological examination, supplemented by in situ hybridisation for JC virus DNA, confirmed that the lesions were those of progressive multifocal leucoencephalopathy (PML). The exceptional clinical presentation of PML in this case is the first report of progressive myoclonic ataxia caused by PML. The selective nature of the lesions confirms the role of the dentato-rubral-thalamo-cortical tract in the pathogenesis of progressive myoclonic ataxia. The atypical MRI findings further emphasise the need for expanded diagnostic criteria for PML in AIDS patients and support the use of more aggressive diagnostic methods as new treatments become available.

We report a new family with palatal myoclonus, pyramidal tract signs, cerebellar signs, marked atrophy of the medulla oblongata and spinal cord, and autosomal dominant inheritance. These findings were almost identical with those in patients previously reported to have histopathologically confirmed adult-onset Alexander disease. Recently, heterozygous point mutations in the coding region of glial fibrillary acidic protein (GFAP) in patients with an infantile form of Alexander disease have been reported. We found a new heterozygous amino acid substitution, Val87Gly in exon 1 of GFAP, in the affected individuals in this family but not in 100 spinocerebellar ataxia (SCA) patients and 100 controls. Therefore, this family might have new clinical entities related to adult-onset Alexander disease and GFAP mutation.

Our aim was to localize the generator site of parasagittal epileptiform discharges in a patient with epilepsia partialis continua (EPC) in the right leg. We examined a 32-year-old woman with EPC whose conventional EEG did not show any epileptic discharge. We performed the jerk-locked back averaging (JLA) of EEG and magnetoencephalography (MEG) to localize the dipole source of sharp transients. The myoclonic discharges in the right soleus muscle were used as a trigger pulse. JLA revealed consistent EEG and MEG sharp transients that coincided consistently and constantly preceded the myoclonic jerks. JLA of EEG demonstrated sharp waves paradoxically distributed over the vertex and right hemisphere. However, the estimated dipoles of MEG were localized in a restricted area in the primary leg motor area in the left hemisphere, which was closely located in the abnormal lesion on the brain MRI. JLA of MEG is considered to be a useful non-invasive method for localizing the epileptogenic area in EPC even when paradoxical lateralization of electroencephalographic discharges was noted.

In an attempt to associate the clinical neurological syndromes with the neuropathological features of canine distemper (CD), 19 spontaneous cases with neurological involvement were examined, before and after euthanasia. Seventeen dogs were less than one year of age and all except two (89.4%) were unvaccinated against CD. Various extraneural signs associated with CD encephalomyelitis (CDE) were seen in 15 dogs. Generalized or localized myoclonus was the most common sign observed (13/19). Seventeen of the dogs presented with signs suggestive of one neuroanatomical location of lesions. Of these animals, seven had signs of cerebral, two of cerebellar, four of cervical, one of cervicothoracic, two of thoracolumbar and two of lumbosacral syndrome. The diagnosis of CD was confirmed immunohistochemically (detection of CD viral antigen), serologically (neutralizing serum antibody titre > or = 16) and histopathologically (CDV inclusion bodies, type of central nervous system lesions). An association of the neuroanatomical lesion location and the histopathological findings was noted in 14 out of 17 dogs (82.3%). Myoclonus could be attributed to lower motor neuron damage in eight out of 13 dogs (61.5%).

The animal model presented here resembles several of the key features of human myoclonus. Further study of the neuropathology and pharmacology of this animal model will hopefully increase our knowledge of the brain structures and systems affected in this disease and permit testing of therapeutic agents for the significant number of patients who do not respond to current treatments.

We report clinical, neuropathologic and molecular genetic data from an individual affected by a familial Alzheimer disease (AD) variant. The proband had an onset of dementia at age 29 followed by generalized seizures a year later. He died at age 40. Neuropathologically, he had severe brain atrophy and characteristic histopathologic lesions of AD. Three additional neuropathologic features need to be emphasized: 1) severe deposition of Abeta in the form of diffuse deposits in the cerebral and cerebellar cortices, 2) numerous Abeta deposits in the subcortical white matter and in the centrum semiovale, and 3) numerous ectopic neurons, often containing tau-immunopositive neurofibrillary tangles, in the white maner of the frontal and temporal lobes. A molecular genetic analysis of DNA extracted from brain tissue of the proband revealed a S169L mutation in the Presenilin 1 (PSEN1) gene. The importance of this case lies in the presence of ectopic neurons in the white matter, early-onset seizures, and a PSEN1 mutation. We hypothesize that the PSEN1 mutation may have a causal relationship with an abnormality in neuronal development.

The authors describe the case of a 22-year-old woman with involuntary contractions of the sternocleidomastoid and trapezius muscles that resulted in turning movements of the head. The jerks displayed the clinical and neurophysiological characteristics of segmental myoclonus (SM) restricted to muscles supplied bilaterally by the first four cervical segments. Magnetic resonance imaging disclosed a tumor in the midline above the cisterna magna that was later histologically proven to be a choroid plexus papilloma. The patient's involuntary movements did not extend to other muscle groups or, in particular, to the palate, as one might have expected in the case of brainstem lesions. Myoclonus was the sole clinical manifestation of the tumor in this patient; other signs and symptoms invariably reported in other cases of posterior fossa papilloma, such as increased intracranial pressure or cranial nerve palsies, were absent. Release from suprasegmental control is suggested as a possible pathophysiological mechanism in this case of SM.

A 39-y-o male with a history of human immunodeficiency virus infection and depression was admitted for diagnosis and treatment of tuberculosis and pneumocystis carinii pneumonia infections. Prior to admission, he was on 50 mg trazodone every evening for 2 mo for depression. He was admitted with a 2-w history of fever chills and fatigue and on admission had hand tremors which disappeared at rest. Four days post-admission the trazodone dose was increased to 100 mg and 20 mg fluoxetine was initiated. He became increasingly anxious and his hand tremor worsened 3 d after initiation of the regimen. To rule out drug induced tremor, both trazodone and fluoxetine were discontinued and symptoms resolved in 7 d. Clinicians should be aware of the potential for excessive seratonergic activities secondary to trazodone + fluoxetine interactions causing a worsening myoclonus adverse event.

A 15-year-old female adolescent with depression developed myoclonus after uninterrupted treatment with sertraline over 6 years. She was also receiving methylphenidate. Withdrawal of sertraline and continuation of methylphenidate did not result in any improvement. Treatment with valproic acid resulted in improvement of the movement disorder. This report suggests that myoclonus may be a side effect of sertraline in some adolescents. Further, we hypothesized that extended treatment over several years, young age, and a compromised central nervous system due to underlying disorders may be risk factors for the development of this side effect.

We describe a patient who has been complaining of brief jerk-like, rhythmic, involuntary movements involving the second digit of the left hand for the last three months. These involuntary jerks produced an adduction movement of the second digit and were unaffected by peripheral sensory stimuli. In addition, the patient experienced loss of dexterity in the left hand. On examination the patient showed hypotrophy of the first dorsal interosseous (FDI) muscle of the left hand and a dissociated sensory loss involving the C8-T1 dermatomes. Magnetic resonance imaging of the brain and spinal cord revealed a tonsilar hemiation characteristic of the Chiari I malformation associated with a syrinx extending from C4 to D5 that did not communicate with the fourth ventricle. The electrophysiological evaluation indicated the presence of a focal myoclonus of spinal origin that is likely to be caused by the syrinx.

We present a 66-year-old patient with segmental myoclonus evoked by a brainstem infarction. The myoclonus appeared soon after a cerebrovascular accident and it was evident in the soft palate, jaw, neck, shoulders and upper limbs. Brain MRI showed infarction in the left pons and left cerebellum. Small amounts of orally administered clonazepam were remarkably effective. Electroencephalogram (EEG) and auditory brainstem response (ABR) were normal. Somatosensory evoked potential (SSEP) revealed delays in P 14 and N19 recorded at C3 by right median nerve stimulation. These findings were normalized in 4 days. Seg-mental myoclonus is thought to be evoked by olivary hypertrophy following cerebrovascular accident in the brainstem and is said to be resistant to medication. The limited involvement of the brainstem in our patient may account for the transient segmental myoclonus. The prognosis for this type of segmental myoclonus is excellent.

Objective: To study the electrophysiologic and pathologic findings in three patients with cortical myoclonus. In two patients the myoclonic ataxic syndrome was associated with proven celiac disease., Background: The pathologic findings in conditions associated with cortical myoclonus commonly involve the cerebellar system, but there has only been one report of cerebellar pathology in a patient in whom cortical myoclonus was physiologically characterized antemortem., Methods: Cortical somatosensory evoked potentials (SEPs) were recorded and EEG activity was averaged preceding myoclonic electromyographic activity. In one patient cortico-cortical inhibition was tested using two paired ipsilateral magnetic stimuli over the motor strip. Neuropathologic examination was carried out, including linear Purkinje cell densities/millimeter calculations for different regions of the cerebellum., Results: The electrophysiology showed evidence of dysfunction of the sensorimotor cortex with enlarged SEPs and a time-locked cortical potential preceding the action myoclonus. In addition, motor cortical inhibition was abnormal in one case. Pathology showed unremarkable primary sensory, motor, and premotor cerebral cortices, except for unilateral gliosis of the motor cortex in one case. The cerebellum showed patchy atrophy and ongoing degeneration. A striking feature was the greater severity of Purkinje cell loss and Bergmann gliosis in the outer aspects than in the depths of the folia., Conclusions: Pathologic abnormalities are paradoxically mainly located in the cerebellum in some patients with cortical myoclonus, despite clear electrophysiologic evidence of cortical dysfunction. This observation suggests that enhanced excitability of the sensorimotor cortex may arise as a distant effect of cerebellar pathology.

The sudden, brief, shock-like, involuntary movements caused by active muscular contractions or inhibitions characterize myoclonus. It is manifested in a wide variety of pathologic conditions affecting the brain, spinal cord, or peripheral nerves, and is thought to be related to neuronal hyperexcitability. The pathology, physiology, and pharmacology of myoclonus are not well understood as a result of the rarity of the disorder in people and the lack of a suitable animal model. Posthypoxic myoclonus is a major myoclonus syndrome which occurs as a result of severe cerebral ischemia/hypoxia. There has been tremendous interest in the development of a suitable animal model that reflects the etiology and clinical pathology of posthypoxic myoclonus. Recently, we have developed a new animal model of posthypoxic myoclonus in which rats were subjected to a mechanically induced cardiac arrest procedure. Herein, we describe the neurochemical, pharmacologic, and pathologic characteristics of this animal model of posthypoxic myoclonus.

Introduction: Cerebral anoxia is fundamental to morbidity and mortality after resuscitation from cardiac arrest. With no proven effective primary therapy for post-anoxic brain injury, the goal of neurologic care are supportive, to provide prognosis and prevention of further complications. With the multifaceted approach using electroencephalography (EEG), somatosensory evoked potentials (SEP), multiunit recordings, behavioral and histologic assessment, we investigated the hyperacute recovery period after resuscitation from cardiac arrest in a rat model to define the value of EEG and SEP in assessing neurologic injury., Methods: Two cohorts of rats were subjected to sham and graded asphyxic-cardiac arrest. EEG was collected during baseline, at injury, and 90 minutes into recovery in the first rat cohort. EEG bursting during the first 90 minutes of recovery was visually analyzed and correlated with the neurologic recovery at 24 hours after injury. The neurologic recovery was assessed using a neurodeficit score (NDS) with 80 as normal and 0 as brain dead. The next rat cohort subjected to asphyxic-cardiac arrest was studied using SEP and multiunit recording in the VPL; brain histologic studies were performed at 4 hours after the asphyxia., Results: The first rat cohort subjected to graded asphyxic-cardiac arrest emerged from EEG isoelectricity by burst-suppression pattern during the first 90 minutes after asphyxia. Six rats in the good outcome group (NDS >60) showed increased frequency of bursting, leading to return of EEG background activity. Six rats with a bad outcome (NDS <60) had low-intensity and persistent bursting without return of EEG background activity within 90 minutes of observation. Visual assessment showed increased EEG peak burst counts during the first 90 minutes of recovery for the rats with a good outcome compared with the rats with a bad outcome. In the second cohort, the rats were subjected to 3 minutes, 5 minutes, and 7 minutes of asphyxia. The N20 recovered to 60% of baseline in all three cases. The recovery profile of VPL is similar to that of cortical N2O for the animal with 3 minutes of asphyxia. However, VPL response is suppressed after 7 minutes of asphyxia leading to a divergence in the rate of recovery of the cortical N20 and VPL response. In both the animals (with mild and intermediate injury) in which the early response in VPL recovered to more than 50% of baseline, the recovery profile was similar to the N20 in cortical evoked potential (EP). The rats were killed 4 hours after asphyxia and the hematoxylin and eosin stain performed on the brains showed evidence of neuronal injury in the thalamic reticular nucleus (TRN) which seemed to correlate with the duration of asphyxia., Conclusion: We present a multimodality assessment of early neurologic recovery following resuscitation from cardiac arrest. The recovery of bursting and high-frequency oscillations may be regulated by interneurons in the TRN. The early selective vulnerability of these interneurons in the TRN may be crucial to the early neurologic recovery as assessed by EP, multiunit recording, EEG, and neurologic behavioral recovery.

Because of inadequate response to or intolerable side effects of oral medication, nine patients with segmental, generalized, and focal myoclonus were treated with intramuscular botulinum toxin type A. All patients were evaluated with neuroimaging, routine and limb-monitored electroencephalography, electromyography, evoked potentials and appropriate biochemical studies. Patients were aged 2 to 22 years, with duration of myoclonus from 1 month to 10 years. Multiple medication trials included antiepileptic drugs, benzodiazepines, tryptophan, L-dopa/carbidopa, baclofen, and dantrolene. Patients were injected with botulinum toxin in their affected area with electromyographic guidance to affected muscles with different doses (8 to 20 units/kg), except two patients who were injected with 32 and 45 units/kg, respectively, at 4- to 8-month intervals. One patient did not complete botulinum toxin treatment because of subjective weakness, although there were virtually no side effects reported in patients completing therapy. Patients reported a dramatic reduction in painful myoclonus. In addition, patients exhibited improved functional skills, as demonstrated by markedly improved use of affected extremities and improvements in ambulation. One patient, who was nonambulatory prior to treatment, was able to walk afterward. Long-term benefits could be related to higher dosage used or negative feedback effect.

We describe a patient with an unusual clinical presentation of progressive multiple cranial nerve palsies, cerebellar ataxia, and palatal tremor (PT) resulting from an unknown etiology. Magnetic resonance imaging showed evidence of hypertrophy of the inferior olivary nuclei, brain stem atrophy, and marked cerebellar atrophy. This combination of progressive multiple cranial nerve palsies, cerebellar ataxia, and PT has never been reported in the literature. We have also reviewed the literature of PT secondary to neurodegenerative causes. In a total of 23 patients, the common causes are sporadic olivopontocerebellar atrophy (OPCA; 22%), Alexander's disease (22%), unknown etiology (43.4%), and occasionally progressive supranuclear palsy (4.3%) and spinocerebellar degeneration (4.3%). Most patients present with progressive cerebellar ataxia and approximately two thirds of them have rhythmic tremors elsewhere. Ear clicks are observed in 13% and evidence of hypertrophy of the inferior olivary nucleus in 25% of the patients. The common neurodegenerative causes of PT are OPCA/multiple system atrophy, Alexander's disease, and, in most of them, the result of an unknown cause.

A 40-year-old woman with myoclonic contractions bilaterally in the infrahyoid neck muscles, especially in the left cricothyroid muscle, was presented and successfully treated with botulinum toxin injections. The patient had a wide, aberrant vessel curving into the left dorsolateral reticular formation of the medulla oblongata. Based on our observations, we propose that symptomatic bulbar and palatal myoclonus is caused by pathology in the dorsolateral reticular formation, and not by inferior olivary dysfunction as is currently thought., (Copyright 1999 Lippincott Williams & Wilkins)

Although myoclonus commonly occurs in a later stage of Alzheimer's disease (AD), the pathological basis of this symptom is still unclear. In order to elucidate the neuropathological substrate of myoclonus in AD, we quantitatively assessed neuronal density and volume, with a discrimination between small and large neurons, at the rostral and caudal parts in the cerebellar dentate nucleus of 8 AD patients with myoclonus, 10 AD patients without myoclonus and 9 controls, using stereological probes. The neuronal numerical density of the large neurons at the rostral part and of total counts (rostral and caudal parts) in the myoclonic AD group were significantly greater than in the nonmyoclonic AD group. There were no significant differences in the density of small neurons between the two AD groups. The ratio of small neurons to large neurons (S/L ratio) of total counts was significantly lower in AD with myoclonus than in AD without myoclonus. The mean neuronal volume of the large neurons at the rostral part was significantly greater in myoclonic AD than in nonmyoclonic AD. Conversely, the volume of the small neurons at the rostral part was significantly lower in myoclonic AD than in nonmyoclonic AD. This study, for the first time, shows an increase in mean volume of large neurons and a decrease in mean volume of small neurons as well as a change in the S/L ratio in the dentate nucleus in AD with myoclonus. An imbalance in the S/L ratio as well as morphological changes of these neurons in the dentate nucleus may contribute to the pathological substrate of myoclonus in AD.

Homozygous tottering (tg/tg) and compound heterozygous tottering/leaner (tg/tg(la)) mutant mice exhibit juvenile onset of three abnormal neurological phenotypes: (i) petit mal-like epilepsy; (ii) ataxia; and (iii) an intermittent myoclonus-like movement disorder. Homozygous leaner mice (tg(la)/tg(la)) exhibit early onset of ataxia (postnatal days 10-12), and also exhibit the myoclonus-like movement disorder and evidence of absence seizure activity; the myoclonus-like disorder is most evident in the first month of life, then diminishes in severity and frequency. The ultrastructure of the cerebellar molecular layer was examined in adult (six to eight months) and juvenile (20-25 days) mice of all three mutant genotypes. In mice of all three genotypes and both ages, Purkinje cell dendritic spines were observed to make multiple contacts with individual parallel fiber varicosities in all sections analysed. These multiple synaptic units were observed in both anterior and posterior vermis and hemispheres of the cerebellum, and ranged from two to nine spines/parallel fiber varicosity. Occasionally, one of the postsynaptic spines belonged to an ectopic spine emerging from the proximal region of a Purkinje cell dendrite. This increase in the multiple synaptic index of some parallel fiber varicosities was observed in juvenile tottering mice before the onset of the symptoms of the neurological disorders. This is highly suggestive that the onset of the neurological phenotype is not a primary cause of multiple Purkinje cell dendritic spines synapsing with single parallel fiber varicosities in these mice, but on the contrary, that it could be the cause of the ataxic symptoms.

A 52-year-old, right-handed female presented with visuospatial dysfunction including left hemineglect, incomplete Balint's syndrome, and environmental agnosia, together with left-sided motor symptoms such as unskillful movement, dystonic postures, and myoclonus in the left hand, without significant dementia. Symptoms progressed to akinetic mutism prior to her death 10 years after onset of illness. Imaging studies such as MRI, SPECT, and PET studies showed severe, predominantly right-sided involvement of parietal and parieto-occipital areas. The motor signs might originate from the right parietal lesions such as area five or somatosensory area. Neuropathologic studies including immunocytochemistry showed tau-positive neurofibrillary tangles and abundant neuritic plaques with amyloid deposits, confirming the diagnosis of Alzheimer's disease. An analysis of serum apolipoprotein E revealed epsilon3/epsilon3 homozygosity. This case represents a variant of Alzheimer's disease conspicuous for progressive motor signs and visuospatial dysfunction with a striking laterality, reflecting asymmetric parietal involvement. Alzheimer's disease with asymmetric parietal atrophy is difficult to be clinically distinguished from corticobasal degeneration characterized by progressive unilateral motor signs and focal cortical signs.

Purpose: Results of a previous report showed that, if administered by intraventricular injection to access tissue normally protected by the blood-brain barrier, gadopentetate dimeglumine produced acute excitation, persistent ataxia, and widespread brain lesions in rats at 5-micromol/g brain but not at 3.8-micromol/g brain. The present study using gadodiamide was undertaken to see whether the effects were agent-specific., Methods: Rats, surgically prepared with a lateral ventricular cannula, were administered a slow injection at 2 microL/min of gadodiamide into the lateral ventricle, and behavioral and neuropathologic changes were noted., Results: Both gadodiamide and gadopentetate dimeglumine produced focal and generalized myoclonus over several hours. Gadodiamide did not produce the medium-term tremor or persistent ataxia seen after treatment with gadopentetate dimeglumine. Neuropathologic changes developed over 1 to 3 days and took three distinct forms: vacuolated thalamic lesions closely resembling those produced by gadopentetate dimeglumine; small but similar vacuolated symmetrical caudate lesions not produced by gadopentetate dimeglumine; and severe swelling and astrocytic hypertrophy and hyperplasia in the cerebellar vermis, again not produced by gadopentetate dimeglumine. Unlike gadopentetate dimeglumine, gadodiamide produced no spinal cord lesions. The cerebellar changes were seen at 1.25-micromol/g brain and above, behavioral changes at 2.5-micromol/g brain and above, and thalamic and caudate lesions at 10-micromol/g brain, the maximal dose used. Markedly reducing the rate of injecting the same volume over 28 hours prevented the acute excitation but did not reduce the severity of the morphologic effects., Conclusion: The acute excitatory effects of high intraventricular doses of gadopentetate dimeglumine and gadodiamide are similar and appear to be attributable to local action at the infusion site, but differences exist between the two agents in the character and topography of the distant morphologic changes. The cerebellum was the brain area most sensitive to gadodiamide in this experimental model. It is unlikely that gadodiamide would gain access to the brain at these tissue doses when used intravenously for conventional clinical imaging, but our experimental model suggested that it had some unexpectedly specific neuropathologic potential.

In almost all of the earlier reported cases of Kufs' disease, the adult form of ceroid lipofuscinosis, the diagnosis was ascertained by cerebral tissue examination, while peripheral biopsy examination revealed an apparent poor diffusion of specific lipofuscinic deposits, the finger print profiles (FPs). We report the ultrastructural data from skin, muscle and rectal biopsy specimens from two siblings, both still living, who present clinical features of Kufs' disease. We observed the presence of FPs in locations that differ from the previous classic reports. Our results emphasize the value of extracerebral biopsies for the diagnosis of Kufs' disease in vivo, and suggest some physiopathological assumptions based on vascular wall involvement.

Rett syndrome (RS) is one of the most frequent causes of mental retardation in females. As there are no known biochemical, genetic, or morphological markers, diagnosis is based on clinical phenotype including severe dementia, autism, truncal ataxia/apraxia, loss of purposeful hand movements, breathing abnormalities, stereotypies, seizures, and extrapyramidal signs. Myoclonus, although reported in some series, has never been characterized. We studied 10 RS patients, age 3 to 20 years, and observed myoclonus in 9. Severity of myoclonus did not correlate with that of the other symptoms or with age. Multifocal, arrhythmic, and asynchronous jerks mainly involved distal limbs. Electromyographic bursts lasted 48 +/- 12 msec. Burst-locked electroencephalographic averaging generated a contralateral centroparietal premyoclonus transient preceding the burst by 34 +/- 7.2 msec. Motor evoked potentials showed normal latencies, indicating integrity of the corticospinal pathway. Somatosensory evoked potentials were enlarged. The C-reflex was hyperexcitable and markedly prolonged (62 +/- 4.3 msec), mainly due to increase in cortical relay time (28.4 +/- 4.5 msec). We conclude that RS patients show a distinctive pattern of cortical reflex myoclonus with prolonged intracortical delay of the long-loop reflex.

We report the electrophysiologic findings of myoclonus in a patient with Huntington's disease (HD). This patient was studied postoperatively after a bilateral fetal cell transplant in his striatum. Incomplete transient improvement was seen in the myoclonus, followed by gradual deterioration. The myoclonus itself had a cortical correlate and was associated with an enlarged somatosensory evoked potential (SEP), consistent with the presence of cortical reflex myoclonus. An enlarged SEP has not been previously reported in myoclonus associated with HD. The postulated mechanisms for myoclonus, when it occurs in HD, have differed in the literature. The reason for the transient improvement of the myoclonus following transplantation is unclear, but this case raises the possibility that basal ganglia circuits may modulate cortical myoclonic activity.

We present a case of progressive supranuclear palsy (PSP) with palatal myoclonus occurred in a 64-year-old man. The nucleus olivaris of the medulla oblongata showed high signal intensity on T2-weighted MR images, indicating brainstem tegmental atrophy, which were confirmed as hypertrophy of the nucleus inferior olivaris at autopsy. The characteristic neuropathological findings were marked grumose degeneration of the dentate nucleus, degeneration and gliosis of the superior cerebellar peduncle, and hypertrophy of the bilateral olivary nuclei. As far as we know, although a few cases of PSP with olivary hypertrophy have been described, only one case has presented with palatal myoclonus.

Focal and segmental, but not generalized, myoclonus have been described with human immunodeficiency virus (HIV) infection. We describe three patients with generalized myoclonus and acquired immunodeficiency syndrome (AIDS) dementia complex. In each, myoclonus persisted until death, invariably after a course of a few months. In two patients, myoclonus was elicited by sudden auditory stimuli and resembled a startle response. This form of myoclonus may be subcortical in origin. We suggest that the AIDS dementia complex be included among the causes of myoclonic dementia.

The short-latency reflex myoclonus that appears to be characteristic of cortical-basal ganglionic degeneration (CBGD) was investigated in two patients. Stimulating the digital nerves of the middle finger caused exaggerated reflex activity in the first dorsal interosseus (FDI) muscle of that hand with a latency of 46-51 ms. Magnetic stimulation over the contralateral cortex, delivered 25 ms after the digital nerve stimulus, resulted in greater than expected facilitation of FDI, implying spatial summation. Poststimulus time histograms (PSTH) of individual FDI motor units indicated that this spatial summation was occurring "upstream" from the motoneurons. It is argued that this occurs at the motor cortex. Magnetic stimulation over the cortex in normal subjects results in short-latency facilitation of the contralateral motoneurons followed by inhibition. This inhibition was less in the patients with CBGD. It is argued that this results from the loss of an intrinsic cortical and corticothalamic inhibitory mechanism.

The diagnosis of degenerative diseases or syndromes in the nervous system in based on their morphological picture. The changes occur in selected CNS structures or systems being induced in the course of more or less known processes sometimes with known, more often unknown etiology. Degenerative syndromes may be classified according to the topography of changes. They appear often with aging, but also in even greater number in infants. We tried to analyze the problem and find out to what degree the structure and topography of CNS degenerative changes in infants depend on maturity of nervous tissue constituting the background of pathologic process. The cases with two syndromes representative for small infants: progressive poliodystrophy of Alpers type and a degenerative syndrome with cerebral calcifications and disseminated demyelination were examined from this point of view. Our observations revealed that the stage of CNS development stipulates the type and topography of degenerative changes.

The Mongolian gerbil (Meriones unguiculatus) is known as a genetic model of epilepsy. Seizure behavior ranges from subtle events like arrest of motor activity and facial spasms to grand mal seizures followed by automatisms. Exploratory behavior in a stressful situation represents the most effective environment for provoking seizures in gerbils. Modifications of the inhibitory hippocampal circuits have been suggested as a cause of seizure susceptibility in the gerbil. This study presents a quantitative analysis of the hippocampal parvalbumin (PV)-immunoreactive and gamma-aminobutyric acid (GABA)-immunoreactive neurons in gerbils whose seizure sensitivity had been scored. PV is a cytosolic calcium-binding protein synthesized by a subpopulation of GABAergic neurons and thought to be responsible for the fast spiking capability of this subset of neurons. We show that the number of PV-immunoreactive neurons in the CA1 field of the gerbil hippocampus decreases in repeatedly seizing animals as compared to non-seizing controls. The lowest density of PV-immunoreactive neurons was observed 1 hour after the last generalized seizure. No changes in the density of GABA-immunoreactive neurons in field CA1 paralleled the obvious loss of perikaryal PV-immunoreactivity. The CA1 field represents the final output region to extrahippocampal brain areas, and its recruitment or not into seizure activity is crucial for the spreading of hippocampal discharges to the adjacent neocortex. A reduction of such a calcium-buffering system in the soma and dendrites may affect the spike characteristics of PV-containing GABAergic neurons and may alter their response to glutamatergic transmission. A reduced inhibitory control of pyramidal cells may ensue, facilitating neuronal excitability as a result.

In a case of acute disseminated encephalomyelitis displaying opsoclonus-myoclonus syndrome, magnetic resonance images (MRI) disclosed pontine lesions involving part of the pontine paramedian reticular formation and the raphe nucleus. Shrinkage of the lesions correlated with the patient's clinical state. This observation supports the hypothesis that a pontine lesion can cause opsoclonus-myoclonus syndrome.

An auditory test battery consisting of pure tone audiometry, the auditory brainstem response (ABR), the nonsense monosyllable perception test, the dichotic listening test and the Token test were administered to three patients with palatal myoclonus. All patients had ABR abnormalities correlated with the location of brainstem lesions, despite relatively normal pure-tone threshold. In two of the three patients, both the nonsense monosyllable test and the dichotic listening test revealed dominance on the side ipsilateral to the lesion, while ABR abnormalities were present on the contralateral side. In one patient who had bilateral ABR abnormalities, both the monosyllable perception and dichotic listening test scores were poor for bilateral ears. These results suggest that brainstem lesions producing palatal myoclonus could have an effect on auditory perception.

The opsoclonus-myoclonus syndrome (OMS) is a potentially devastating paraneoplastic or paraviral syndrome. Although it is a rare disorder, it has major implications for cancer, virology, immunology, developmental neurobiology, and molecular pharmacology. The mechanism of brain injury in OMS is unknown, but evidence suggests immune system dysregulation. This article surveys recent clinical and laboratory evidence for the autoimmune theory and discusses how some current therapies for OMS may exert their effects through immunomodulation. Specific testable hypotheses on the immunologic defect in OMS involving both B cells and T cells, the nature and mechanisms of brain injury, and their clinical correlations are proffered. The current therapeutic armamentarium provides a broad spectrum of nonselective immunotherapies, including noncytotoxic and cytotoxic drugs, intravenous immunoglobulins, and plasma exchange, some selected for induction and others for maintenance. The use of combination immunotherapies may allow steroid sparing, targeting of more than one immunologic effector pathway, and a mixture of early- and late-acting drugs. More selective immunotherapies, now available or in preclinical and clinical trials, have great potential for the treatment of OMS but require precise information on the underlying immunological problem. These data provide possible new directions for immunologic research and therapy in OMS.

Purpose: The one-and-a-half syndrome is an eye movement disorder characterized by a unilateral gaze palsy and an ipsilateral internuclear ophthalmoplegia. The authors describe a previously unrecognized association between the one-and-a-half syndrome and oculopalatal myoclonus (OPM)., Methods: Five clinical cases are presented, with pertinent physical findings and radiologic studies., Results: A previously unrecognized association of the one-and-a-half syndrome with subsequent development of OPM appears to exist. Involvement of the facial nerve in patients with the one-and-a-half syndrome may be a predictor of the subsequent development of OPM., Conclusion: Patients with the one-and-a-half syndrome and facial nerve palsy should be followed closely for possible future development of OPM.

We report four patients with a progressive myoclonic ataxic syndrome and associated coeliac disease. The onset of the neurological syndrome followed the gastrointestinal and other manifestations of coeliac disease while on a gluten-free diet, in the absence of overt features of malabsorption or nutritional deficiency. The condition progressed despite strict adherence to diet. The neurological syndrome was dominated by action and stimulus sensitive myoclonus of cortical origin with mild ataxia and infrequent seizures. Plasmapharesis and immunosuppressive treatment were tried in two patients but were not beneficial. Post-mortem examination of the brain in one case showed selective symmetrical atrophy of the cerebellar hemispheres with Purkinje cell loss and Bergmann astrocytosis, and with preservation of the cerebral hemispheres and brainstem. Coeliac disease should be considered in the differential diagnosis of all patients presenting with a progressive myoclonic ataxic syndrome.

We describe three patients with Huntington's disease, from two families, in whom myoclonus was the predominant clinical feature. The diagnosis was confirmed at autopsy in two cases and by DNA analysis in all three. These patients all presented before the age of 30 years and were the offspring of affected fathers. Neurophysiological studies documented generalised and multifocal action myoclonus of cortical origin that was strikingly stimulus sensitive, without enlargement of the cortical somatosensory evoked potential. The myoclonus improved with piracetam therapy in one patient and a combination of sodium valproate and clonazepam in the other two. Cortical reflex myoclonus is a rare but disabling component of the complex movement disorder of Huntington's disease, which may lead to substantial diagnostic difficulties.

Over the last 5 years the Pediatric Neurology service at King Faisal Specialist Hospital and Research Centre (KFSH&RC) has seen 131 infants and children with movement disorders. Forty-nine (37%) had identifiable biochemical defects, 25 of which were organic acidemias. Nineteen of 29 patients with dystonia had organic acidemias, primarily glutaric aciduria type 1 (7 patients), bilateral striatal necrosis (4 patients), and 3-methyl glutaconic aciduria (3 patients). All patients with parkinsonian rigidity (n = 11) had organic acidemias; again, the greatest number accounted for by glutaric aciduria type 1 (7 patients), who had both parkinsonian rigidity combined with dystonia. Myoclonus occurred in only 1 of 25 and chorea in 7 of 25 patients with organic acidemias. At the least all patients had bilateral lesions of putamen and head of caudate, seen best in MRI brain scans as increased T2 signal intensities with normal volume, and later with volume loss.

Neuropathological studies show that about 20% of all patients suffering from an acinetic-rigid syndrome can not be given the diagnosis of idiopathic Parkinson's disease. Among these non-idiopathic Parkinson-syndromes the corticobasal degeneration (CBD) can be regarded as a separate disease entity. The pathological findings of moderate predominantly frontal and parietal cerebral atrophy, cortical Pick-cells and specific corticobasal inclusion bodies are considered valuable features which support the diagnosis. The clinical Characteristics of CBD are demonstrated in 3 patients including an acinetic-rigid syndrome, limb apraxia and "alien limb"-syndrome, as well as reflex myoclonus. Eye movement disorders, dementia and other rare symptoms may also be present. Electrophysiological reflex-testing helps to corroborate diagnosis. These findings and a summary which includes the previously published cases of CBD show that CBD in most cases can be diagnosed intra vitam.

We have previously reported that rats exhibited audiogenic myoclonus at 3 days after cardiac arrest. This phenomenon peaked at 14 days, gradually tapered off at older ages, and disappeared in most rats by 60 days following cardiac arrest. Because treatment with the 5-HT2-selective agonist, (+/-)-1-2,5-dimethoxy-4-iodophenyl-2-aminopropane (DOI) significantly attenuated audiogenic myoclonus in these postcardiac-arrest rats, the involvement of 5-HT2 receptors in posthypoxic stimulus-sensitive myoclonus was suggested. In the current study, we, therefore, examined the binding properties of 5-HT2 receptors in the rat bain at various time points following cardiac arrest. The affinity constant of [3H]ketanserin binding to 5-HT2 receptors in cortical membranes of rats did not change. In contrast, Bmax values were found to be reduced at 3 and 14 days after cardiac arrest with some recovery after 60 days. Taken together with previous results, these results indicate that hypoactivity of central 5-HT2 neurotransmission may underlie the development of posthypoxic stimulus-sensitive myoclonus in rats.

This is a case of Alzheimer disease with myoclonus and periodic spikes on EEG. A 56-year-old man developed progressive dementia and, 3 years later, generalized convulsions. Eight years later, he showed myoclonus and periodic spikes on EEG. Cranial CT showed cortical atrophy and ventricular dilatation. He became apallic and died of pneumonia at the age of 65.9 years after the onset of the disease. The brain weighed 1,050 g. Neuropathologically, diffuse neuronal loss, abundant neurofibrillary tangles and senile plaques, particularly diffuse plaques, were found extensively in the cerebral cortex. The white matter was preserved. In the Ammon's horn, abundant neurofibrillary tangles and senile plaques were observed. Grumose degeneration of the cerebellar dentate nucleus, Kuru plaques or prions were not found. Numerous diffuse plaques of the cerebral cortex have rarely been reported in autopsy cases of Alzheimer disease with myoclonus and periodic spikes on EEG.