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Purpose: To clarify the neurophysiologic mechanism of epileptic negative myoclonus (ENM), we analyzed the magnetoencephalography (MEG) of a patient with ENM., Methods: The 52-year-old right-handed male had frequent ENM in the right upper limb during awake and monthly seizures with sudden tonic stiffening of the right forearm during sleep. MRI demonstrated a focal cortical dysplasia in the cortex of the posterior portion of the left superior frontal sulcus. Whole-head type MEG, electroencephalography and electromyography were simultaneously recorded during ENM. Single equivalent currents dipoles (ECDs) were calculated for each spike component followed by silent period (SP) in the right deltoid muscle. These MEG spike components were averaged with respect to their peaks, and single ECD was also calculated for the averaged spike component. Furthermore, we analyzed the MEG with the silent-period-locked-averaging (SPLA) method. Twenty MEG signal data were averaged with respect to the onset of SP. Twenty epochs in each of five separate periods of recording were repeatedly averaged. ECDs were calculated for spike components observed in each averaged epoch., Results: ECDs of each spike followed by SP were clustered near the cortex of the left central sulcus. In MEG spike averaging and SPLA method, ECDs at the peak of spike components were located near the right shoulder division of the primary sensorimotor cortex reproducibly. ECDs on the ascending phase before the peak were located lateral to the above ECD location in MEG spike averaging method., Conclusions: ENM was produced by an inhibitory action on the primary sensorimotor cortex corresponding to the body segment in which ENM occurs., (Copyright © 2014 Elsevier B.V. All rights reserved.)

l-2 hydroxyglutaric aciduria is a rare, autosomal recessively inherited metabolic disorder of organic acid metabolism. A 5-year-old boy presented with eyelid myoclonia with absences that proved difficult to control with first-line anticonvulsants. An electroencephalogram produced profoundly abnormal results, with generalized spike-and-wave discharges. The patient became seizure-free with a combination therapy of clonazepam, levetiracetam, and lamotrigine. Magnetic resonance imaging demonstrated subcortical white matter and basal ganglia alterations. Urinary organic acid analysis demonstrated increased excretion of l-2 hydroxyglutaric acid. Although rare, seizures can occur as a presenting sign of slowly progressing organic acidurias, e.g., l-2 hydroxyglutaric aciduria. Both eyelid myoclonia with absences and l-2 hydroxyglutaric aciduria comprise rare disorders. To our knowledge, this case report is the first of l-2 hydroxyglutaric aciduria presenting with symptomatic eyelid myoclonia with absences., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Lewy body syndromes (mainly Parkinson's disease and dementia with Lewy bodies) share many clinical features and usually have a slowly progressive course. Some patients may show rapid symptoms progression., Objective: To evaluate clinical and neuropathological features of patients with a rapidly progressive diffuse Lewy Body disease., Methods: Review clinical records and pathological findings of 6 cases with diffuse Lewy Body disease and rapid disease progression (less than 18 months before death)., Results: Mean age at disease onset was 72.5 years, and mean disease duration was 9 months. Onset consisted of delirium in 3 patients and rapidly progressive dementia in the other three. All cases presented visual hallucinations and delusions; cognitive symptoms were fluctuating in two, parkinsonism occurred in four, and myoclonus in three. Brain MRI did not show cortical or basal ganglia hyperintensities. Periodic sharp waves were absent on EEG. 14.3.3 protein in CSF was negative. Myocardial (123) I-metaiodo-benzyl-guanidine SPECT showed marked reduction in tracer uptake in the 2 patients tested. Neuropathological studies did not identify any particular feature that could differentiate rapidly progressive diffuse Lewy body disease from classical diffuse Lewy body disease., Conclusions: Diffuse Lewy body disease is a possible cause of rapidly progressive dementia and should be included in the differential diagnosis of confusional states of undetermined cause. In patients with rapidly progressive dementia, the presence of fluctuating cognition, parkinsonism, hallucinations, delusions, or severe dysautonomia, should raise the suspicion of diffuse Lewy body disease. Neuroimaging studies such as (123) I-metaiodo-benzyl-guanidine myocardial scintigraphy may support the clinical diagnosis of diffuse Lewy body disease. © 2011 Movement Disorder Society., (Copyright © 2011 Movement Disorder Society.)

Purpose of Review: This review examines recent developments in the field of myoclonus., Recent Findings: The range of clinical features in myoclonic dystonia has been extended and its underlying pathophysiology better defined. The diverse causes leading to jerky tremor and orthostatic myoclonus have been clarified and the need to consider drugs as potential causes highlighted. In patients with combined myoclonus and epilepsy, the major advance has been in our understanding of the natural history of these conditions, which can be more benign than hitherto thought. Finally, the new condition of primary progressive myoclonus of ageing has been identified, although it remains to be seen whether this is a pathological entity or not., Summary: Most progress has been in the characterization of myoclonic syndromes with dystonia and epilepsy. Therapeutic options remain limited, and exploration of the role of functional neurosurgery may be worthwhile in the future, given the debilitating nature of many myoclonic syndromes.

We assessed the prevalence of Wernicke encephalopathy (WE) in all 657 cases suspected of Creutzfeldt-Jakob (CJD) referred from 2001 to 2006 to the French Neuropathology Network of CJD. Clinical, biological and imaging data were reviewed when the diagnosis of WE was made at autopsy. No CJD was found in five cases suspected of sporadic CJD. In these five cases, myoclonus had been observed in four, CSF 14-3-3 protein in two. In 14 other cases, WE was combined with CJD, 13 of which were sporadic. These belonged mainly to the molecular variants of sporadic CJD associated with a long duration of disease. This stresses the necessity of remaining alert to the diagnosis of WE when CJD is suspected.

We present the clinical course and EEG evolution of an extreme low birth weight preterm neonate with an uncommon type of glycine encephalopathy. The patient presented with myoclonic jerks, apnea and encephalopathy three months after birth without satisfactory therapeutic response. During the first days of clinical symptoms the patient presented a paroxystic burst-attenuation EEG pattern which progressively evolved into an established typical burst-suppression pattern within a few days. West syndrome occurred four weeks later and the patient died at seven months of extra-uterine life due to a serious respiratory infection with cardio-respiratory arrest. Genetic analysis showed a non-previously described mutation affecting a consensus splice site (IVS2-1G > C 3) in the AMT gene encoding the T protein of the glycine cleavage system.

Purpose: To investigate the blood oxygenation level-dependent (BOLD) signal changes correlated with ictal and interictal epileptic discharges using electroencephalography-correlated functional magnetic resonance imaging (EEG-fMRI) in patients with eyelid myoclonia with absences (EMA) and then to explore the pathophysiological mechanisms of epileptic discharges and their effect on brain function., Methods: Four patients with EMA were investigated through the method of EEG-fMRI. The characteristics of BOLD signal changes linked to ictal and interictal epileptic discharges under different states of consciousness were explored., Results: Seven sessions of EEG-fMRI scanning in the four patients were obtained. The main regions of activation included thalamus, mesial frontal cortex, middle parietal lobe, temporal lobe, insula, midline structures, and cerebellum. Deactivations were mainly in the anterior frontal lobe, posterior parietal lobe, and posterior cingulate gyrus. Thalamic BOLD change was predominantly activation in most of our cases. The distribution of activation associated with ictal epileptic discharges was wider, and the distribution of deactivation was closer to pericortex compared with the BOLD change linked with interictal epileptic discharges., Conclusions: The activation in the thalamus may be associated with generalized spike wave in EMA; the combination of different patterns of activation with consistent pattern of deactivations ("default" pattern) in patients with EMA may prognosticate different states of consciousness in response to ictal and interictal epileptic discharges.

We investigated a five-year-old girl suffering from genetically confirmed, action-induced myoclonus-dystonia (M-D) with functional magnetic resonance imaging (MRI). We compared the activation pattern by movements of her right hand as if drawing a picture, which elicited M-D, with simple snapping movements (without overt M-D). The drawing and snapping conditions resulted in activation of a motor network including the motor cortex, the putamen, and the cerebellar hemispheres. The direct comparison of the drawing condition with snapping as control revealed specific activations within the thalamus and the dentate nucleus. An age matched healthy control did not show significant activation within the thalamus or dentate nucleus.

We investigated a possible correlation between behavior during status epilepticus (SE) and underlying brain damage. Adult rats were electrically stimulated in the left amygdala to induce SE, which was stopped 2 hours later. We observed two different types of SE: (1) typical SE (TSE), with facial automatisms, neck and forelimb myoclonus, rearing and falling, and tonic-clonic seizures; (2) ambulatory SE (ASE), with facial automatisms, neck myoclonus, and concomitant ambulatory behavior. TSE was behaviorally more severe than ASE (P<0.05). Histology revealed neuronal loss in several brain areas. There was a positive correlation between SE type and amount of injured areas 24 hours and 14 days after SE (P<0.01). The areas more affected were piriform cortex and hippocampal formation. We suggest quality of seizures during SE may be considered in further SE studies, as our results indicate its influence on the severity of brain damage following this paradigm.

Posthypoxic myoclonus (PHM) is a syndrome of action and intention myoclonus that occurs in some patients who survive a cardiac arrest. Using PET and statistical parametric mapping, the authors observed a significant bilateral increase in glucose metabolism in the ventrolateral thalamus and pontine tegmentum in patients relative to controls. Interventions such as deep brain stimulation that interrupt networks that involve these structures may be useful in patients with severe PHM.

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.

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.

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.

We describe the MRI changes preceding the onset of myoclonus in two patients whose post-mortem examination confirmed the diagnosis of Creutzfeldt-Jakob disease (CJD). MRI showed changes in the striatum early in the course of CJD (2-6 months after the onset of apathy, interpreted as depression, and 1-2 months before the onset of further clinical symptoms). Only in one patient did electroencephalography record the typical triphasic sharp-waves, 1 month after MRI.

Acute and chronic effects of seizures induced by intraperitoneal (i.p.) injection of kainic acid (KA) were studied in developing rats (postnatal days (P) 5, 10, 20, 30, and adult 60). For 3 months following KA-induced status epilepticus, spontaneous recurrent seizure (SRS) occurrence was quantified using intermittent video monitoring. Latency to generalized seizures was then tested using flurothyl, and brains were histologically analyzed for CA3 lesions. In P5-10 rats, KA caused generalized tonic-clonic ('swimming') seizures. SRS did not develop, and there was no significant difference between control and KA-treated rats in latency to flurothyl-induced seizures. In contrast, rats P20 and older exhibited limbic automatisms followed by limbic motor seizures which secondarily generalized. Incidence and frequency of SRS increased with age. P20-30 rats with SRS had shorter latencies to flurothyl seizures than did KA-treated P20-30 rats without SRS or controls. KA-treated P60 rats (with or without SRS) had shorter latencies than controls to flurothyl seizure onset. SRS in P60 rats occurred sooner after KA than in P20-30 rats. CA3 lesions were seen in P20-60 rats with and without SRS, but not in P5-10 rats. These data suggest that there are developmental differences in both acute and chronic responses to KA, with immature animals relatively protected from the long-term deleterious effects of this convulsant.

Clinical, neurochemical and neuropathological findings on a case of late-infantile Gaucher disease with oculomotor apraxia, progressive myoclonus and prominent bulbar signs are reported. There was a marked increase in glucosylceramide in cerebral cortex and cerebellum; the increase was more in the range of that seen in the Norrbottnian type III than in type II Gaucher disease. Cerebral cortical changes were characterized by a band-like intraparenchymal accumulation of Gaucher cells in lamina IV with an accompanying astrogliosis. In the cerebellum, a focal severe loss of granule cells and a global loss of dentate nucleus neurons was recorded. Milder changes were seen in thalamus and brain stem where perivascular accumulation of Gaucher cells was present in all regions. The cerebral cortical changes resembled those seen in type II Gaucher disease and was much more marked than in the Norrbottnian type III, whereas the changes in the dentate nucleus were more severe than in both type II and type III. The phenotypic variability with different patterns of clinical symptoms and neuropathological changes in neuronopathic Gaucher disease is discussed.

Two cases of Lance-Adams syndrome with anatomopathologic study are reported. There were evidences of diffuse neuronal degeneration in the brain. These changes were most seen in the neurones of the cortical layers, thalamus and subthalamic nuclei. The cells changes were similar to those seen in ischaemic disease. Some neurones showed intracytoplasmatic inclusions staining with the P.A.S. method. These inclusions were readily distinguished from the Lafora bodies.

Two postmortem case of multiple sclerosis treated by sterotactic operations for the intention shaking of limbs, trunk, and head, and for the action myoclonus are analyzed to determine the location of the substrate of myoclonic and ballistic movements, the location of the coagulations for relief of these movements, and whether fresh demyelinating foci are elicited by intracerebral interventions. In the first case of a clinically typical multiple sclerosis, the foci responsible for the severe action myoclonus and intention ataxia of the trunk are demyelinations in the right and left red nucleus resulting in nerve cell damage and loss and an almost complete destruction of myelinated fibers. The restricted foci in the white matter of the cerebellum which do not involve the cerebellar nuclei are not extensive enough or old enough to be the cause of the action myoclonus but may, perhaps, sustain the pathogenesis. - In the second case of cerebral palsy and combined multiple sclerosis (detected post mortem), the combination of the severe damage of putamen and caudate nucleus by status marmoratus and the extensive nerve cell and fiber damage due to demyelinating foci in the substantia nigra are probably the substrate of the jactitation and intention myoclonus of the left limbs. The stereotactic coagulation of the dentatothalamic and pallidothalamic fibers in the base of V. o.p. and V.o.a. at the point where they pass through the zona incerta (location confirmed post mortem) resulted in a nearly complete relief of hyperkinetic movements. In the first case, fresh demyelinating foci are present in both hemispheres with stereotactic interventions; these foci are located, amongother places, around the coagulation and the electrode track. In the second case, post mortem serial brain sections demonstrate that stereotactic operations even in subacute multiple sclerosis can be carried out without eliciting any exacerbation of demyelination foci. Therefore, the danger exists that stereotactic intervention in cases of multiple sclerosis may precipitate fresh demyelinating foci. As our clinical experience [Riechert and Richter, 1972a, b] indicates, however, this occurred in markedly less than 10% of the cases.

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).

Myoclonus is a characteristic neurological sign of subacute sclerosing panencephalitis (SSPE). Attempts were made to induce myoclonus in a large proportion of hamsters with a cell-associated strain of SSPE virus (the Biken strain) and thereby to establish an experimental model for study of the mechanism of development of this condition. When injected intracerebrally, Biken virus induced myoclonus within two to 14 days in 84% of the three- to nine-week-old hamsters tested. Electroencephalographic traces showed a periodic and synchronous discharge consisting of high-voltage slow waves and spikes that appeared coincidentally with myoclonus. Neurons in the cortex and thalamus of the affected animals had severely degenerated cytoplasm. Inflammatory changes, such as perivascular cuffing or infiltration of mononuclear cells, were not detected. Staining with immunoperoxidase revealed measles viral antigens in the cytoplasm and dendrites of the affected neurons. SSPE virus with the same properties as the parent virus was recovered from brain cells of sick animals by cocultivation with Vero cells.

Three siblings who suffered from progressive mental retardation, seizures, and rigidity showed degeneration of the cerebral cortex. This was manifested by severe to complete neuronal loss with astrogliosis and microgliosis. In one child a brain biopsy was performed at the age of 3 months. The only lesion found was large disorganized perinuclear mitochondria in the neurones. The possibility that the cerebral poliodystrophy is due to an inherited mitochondrial disorder is discussed.