Early-onset progressive encephalophathy with migrant,continuous myoclonus

Three unusual cases of focal continuous myoclonus with onset during the first months of life, lasting from dozens of minutes to hours, are reported. During disease evolution, prolonged bilateral myoclonic seizures and generalized tonic-clonic seizures occur. Subsequently, a progressive encephalopathy with hypotonia and ataxia appears. A net worsening of the neurological condition is observed after the age of 4–5 years. Cortical atrophy is shown by CCT and MRI. Neurometabolic screening is not contributory. Repeated polygraphic recordings show continuous and segmental myoclonic jerks, localized in different muscles, at frequencies ranging between 0.5–1 c/s and 6–8 c/s. Moreover action myoclonus is recorded. During the first period of disease the EEG does not show any paroxysmal activity. As to the classification, this syndrome corresponds to an early onset progressive encephalopathy of unknown origin, similar in some aspects to Alper's disease. Another problem is the interpretation of the myoclonic phenomena. Some important aspects suggest a cortical origin of the diverse myoclonic phenomena observed in these cases.     

Myoclonic encephalopathy and diabetes mellitus in a boy

We describe an 18-month-old boy with insulin-dependent diabetes mellitus who developed idiopathic myoclonic encephalopathy (dancing eye syndrome) at 26 months of age. The neurological symptomatology (multifocal myoclonus, opsoclonus, ataxia, behavioural disturbance) developed within 10 to 14 days after presentation. Biological, neuroradiological, and scintigraphic examination excluded CNS infectious diseases, intoxication, or tumours. At onset of diabetes mellitus, anti-glutamic-acid decarboxylase (GAD) antibodies were observed, and markedly increased in titre when myoclonic encephalopathy occurred. Corticosteroid treatment resulted in a decrease in anti-GAD autoantibody titres and the disappearance of neurological disturbances. As GAD is expressed both in pancreatic beta-cells and cerebellar Purkinje cells, it is possible that a common autoimmune disorder in this patient may account for both the diabetes and myoclonic encephalopathy.     

Progressive dialytic encephalopathy

A subacutely progressive dialytic encephalopathy lasting for three to 15 months in 11 patients who had been on haemodialysis for 14 to 36 months was characterized by dementia, language disorder, myoclonic jerks, behavioural disturbance, distinctive EEG abnormalities, and normal or nonspecific neuropathological findings.     

Dialysis encephalopathy: a possible seizure disorder.

Dialysis encephalopathy is a progressive, fatal condition that occurs in patients receiving hemodialysis. It is characterized by abnormalities in speech, myoclonic jerks, and striking changes on the electroencephalogram. We observed dramatic reversal of the clinical symptoms and electroencephalographic abnormalities in four patients with this syndrome who were treated with diazepam. In this paper we propose that in dialysis encephalopathy, some of the symptoms and the electroencephalographic changes represent a form of seizure disorder.     

Reversible myoclonic encephalopathy revealing the AIDS-dementia complex

A 40-year-old HIV-positive right handed homosexual man was admitted for progressive mental deterioration coexisting with permanent segmental middle-amplitude arrhythmic, asynchronous and asymmetrical myoclonic jerks. EEG showed fronto-central bursts of rhythmic triphasic 1.5–2 Hz sharp waves similar to the characteristics periodic pattern of Jakob-Creutzfeldt disease. Biological procedures were negative, thus eliminating a metabolic encephalopathy. Dramatic neurological improvement occurred shortly after initiation of i.v. and then oral zidovudine which produced perfect EEG normalisation. This unusual electroclinical presentation of the AIDS-dementia complex underlines the fact that this affection may present a diagnostic challenge, particularly in individuals in whom HIV infection is unknown.     

Myoclonic epilepsy with non-progressive encephalopathy

We report 6 cases of particular type of myoclonic epilepsy with non-progressive encephalopathy. It consists of a syndrome characterized by an onset of seizures in the first year of life, frequent myoclonic status, generalized spikes and waves on EEG and an unfavourable outcome with encephalopathy. At the beginning, the diagnosis is difficult, the symptomatology later suggests a progressive encephalopathy. In the present study, a detailed analysis of the early electroencephalographic aspects and of the arguments in favour of a non-progressive encephalopathy is proposed. Hypothesis of perinatal vascular lesions mainly involving the central areas is forwarded.     

Progressive encephalopathy in children with acquired immune deficiency syndrome

We are reporting the cases of four children with a diagnosis of acquired immune deficiency syndrome (AIDS) who demonstrated a progressive encephalopathy manifested by loss of motor milestones or intellectual abilities, and weakness with pyramidal tract signs. Two patients were ataxic. One child was cortically blind and suffered myoclonic jerks before his death. Two of the patients had isolated seizures at some time during the disease course. Two patients developed secondary microcephaly and all four patients showed cortical atrophy on computed tomographic scanning. Three of the patients died. Postmortem neuropathological findings included gross cortical atrophy, microglial nodules, and intranuclear inclusions, as are described in the subacute encephalitis reported in adult AIDS patients. We propose that the possible pathogenetic mechanisms of this encephalopathy include opportunistic or persistent viral infection of the brain.     

Epileptic phenomena in bismuth toxic encephalopathy.

Seventy patients admitted to hospital with bismuth encephalopathy had repeated clinical and EEG examinations. All the patients exhibited myoclonic jerks, but no paroxysmal features ever appeared on EEG. Computed tomography showed cortical hyperdensities. Seizures were observed in 22 patients, but epileptic EEG patterns appeared only when the bismuth blood level was below 1500 microgram/1. It is suggested that a high cortical intracellular bismuth concentration induces a "cortical inhibition" which causes suppression of physiological electrical brain activity, the absence of EEG paroxysmal phenomena during myoclonic jerks, and explains the rarity of epileptic seizures.     

Toxic encephalopathy due to ingestion of bismuth salts: clinical and EEG studies of 45 patients

Forty-five patients taking bismuth subnitrate orally for therapeutic reasons were admitted to hospital with a myoclonic encephalopathy of acute onset. The clinical features were similar, mostly with mental confusion, disorder of walking and standing, dysarthria, and myoclonic jerks. In 31 cases the EEG showed a characteristic pattern, not previously recognised, which assisted differential diagnosis.     

Subacute sclerosing panencephalitis with partial remission

Subacute progressive panencephalitis is usually a progressive and fatal disease, being uncommon temporary or definitive remissions. A three years old boy, previously vaccinated against measles, developed trembling, progressive and severe mental deterioration, partial seizures and myoclonic jerks. The electroencephalogram showed periodic high amplitude waves concomitantly with myoclonic jerks and the cerebrospinal fluid revealed an increase of the gammaglobulin fraction (16,8), benjoin coloidal reaction shifted to the left and the antimeasles antibody titres were positive (complement fixation text 1:16; neutralization test 1:32). In spite of that, two months after the beginning of the illness the patient showed mental and motor improvement and similar modifications of the electroencephalographic aspects and now, eleven months later, is well, remaining only a slight motor and mental deficiency.     

The use of the ketogenic diet in a patient with subacute sclerosing panencephalitis.

OBJECTIVE: To report on the effects of the ketogenic diet on a 9-year-old boy with myoclonic jerks due to subacute sclerosing panencephalitis (SSPE). METHODS: A 9-year-old boy presented with progressively worsening myoclonus unresponsive to valproic acid and clonazepam. He was started on the ketogenic diet maintaining urine ketones at greater than 80 mg x dl(-1). RESULTS: Within 2 weeks of dietary initiation, myoclonic jerks stopped. Four weeks later he developed cognitive slowing. Results of electroencephalogram and cerebrospinal fluid analysis were consistent with SSPE. Three months after ketogenic diet initiation, myoclonic jerks reappeared and were refractory to treatment. CONCLUSION: The ketogenic diet may be useful in controlling, even temporarily, the myoclonic jerks of SSPE.     

Lithium-induced encephalopathy mimicking Creutzfeldt-Jakob disease

INTRODUCTION: Creutzfeldt-Jakob disease (CJD) has a poor prognosis. Certain clinical presentations can be suggestive yet mimic a curable disease. OBSERVATION: In the present study, we report the case of a 67-year-old man with a one-month history of progressive dementia, with myoclonic jerks and cerebellar syndrome suggesting a diagnosis of Creutzfeldt-Jakob encephalopathy. He had been treated for 9 years with lithium for a bipolar disorder. The results of the different investigations and the favorable course after discontinuation of lithium were in favor of the diagnosis of drug-induced Creutzfeldt-Jakob syndrome. CONCLUSION: This case illustrates the importance for researching a curable etiology in presence of clinical features suggesting a CJD.     

Whipple's disease with encephalopathy. A case report with review of the literature

A 58 year-old man developed a progressive encephalopathy four years after Whipple's disease onset with digestive, lymph node, and multiple joint lesions, treated over a period of two years. The diagnosis of neurological manifestations of Whipple's disease was based on clinical findings and the presence of PAS+ inclusion bodies in CSF cells. The outcome was fatal in spite of antibiotic therapy. Diagnostic features of this rare neurological affection are discussed. Preventive treatment and surveillance of patients with Whipple's disease are necessary even after well-conducted therapy.     

Vigabatrin caused rapidly progressive deterioration in two cases with early myoclonic encephalopathy associated with nonketotic hyperglycinemia

Vigabatrin, a structural analogue of gamma-aminobutyric acid (GABA), is used for the treatment of generalized and partial seizures in infants. The drug inhibits the GABA transaminase and elevates the GABA concentration in the brain. Here we present the vigabatrin experience in two patients with early myoclonic encephalopathy owing to nonketotic hyperglycinemia (glycine encephalopathy). Both patients had early infantile seizures characterized by fragmentary myoclonic jerks associated with burst-suppression pattern on electroencephalography. Nonketotic hyperglycinemia was diagnosed with elevated cerebrospinal fluid and plasma glycine levels. The seizures were initially thought to be infantile spasms, and vigabatrin (50 mg /kg/day) was started for the treatment of seizures. Rapidly progressive deterioration was noticed after a few days. Acute encephalopathy associated with sleepiness and respiratory failure developed. Vigabatrin produced acute encephalopathy, which regressed in a few days after vigabatrin was stopped in the first patient. However, in the second case, despite the discontinuation of vigabatrin, there was no recovery of general conditions. Our observations in two cases indicate the risk of using vigabatrin in patients with nonketotic hyperglycinemia. The elevated GABA concentration in the brain can enhance the encephalopathy, together with the elevated levels of glycine. (J Child Neurol 2006;21:82-84).     

Subacute sclerosing panencephalitis presenting with unilateral periodic myoclonic jerks

BACKGROUND: Subacute sclerosing panencephalitis (SSPE) is a rare complication of measles virus infection. The disease is characterized by behavioural abnormalities, intellectual deterioration, motor weakness, and generalized myoclonic jerks progressing to coma and death in one to two years in 80% of the cases. The myoclonic jerks are associated with characteristic generalized slow periodic complexes on electroencephalography (EEG). The symptoms and signs of SSPE are frequently quite variable. The clinical course is equally variable and difficult to predict. The characteristic periodic myoclonus can rarely occur unilaterally particularly in the early stages of the disease. As well, the periodic EEG complexes have been reported unilaterally in up to 3% of cases. CASE REPORT: A 12-year-old boy, who was seen at a later stage with atypical manifestation of myoclonic body jerks confined entirely unilaterally, combined with contralateral periodic EEG complexes. One could assume clinically that the more diseased hemisphere was responsible for generating the jerks. However, brain magnetic resonance imaging revealed asymmetric hemispheric changes suggesting that the less neurologically damaged hemisphere is responsible for generating the unilateral myoclonic jerks. This has led to the interpretation that the more severely damaged hemisphere has lost the neuronal connectivity required to generate these periodic myoclonic jerks. CONCLUSIONS: Subacute sclerosing panencephalitis may have asymmetric hemispheric involvement, not only early, but also in the advanced stages of the disease, which can result in unilateral periodic myoclonic jerks.     

Epilepsia partialis continua in children with fulminant subacute sclerosing panencephalitis

Various inflammatory diseases of central nervous system, including subacute sclerosing panencephalitis, could cause epilepsia partialis continua. Two boys with epilepsia partialis continua with onset in terminal phase of atypical subacute sclerosing panencephalitis have been reported. Children were not vaccinated against measles, and the second case had history of measles at an early age. In both cases, the onset of subacute sclerosing panencephalitis was characterized by altered behavior and cognitive decline with very fast mental and neurological deterioration. One boy was suffering from complex partial seizures and myoclonic jerks synchronous with periodic electroencephalographic pattern. Diagnosis was proved by increased titers of antimeasles antibodies in both serum and cerebrospinal fluid. In terminal phase of the disease, epilepsia partialis continua of localized group of the muscles was diagnosed, with good response to intravenous infusion of midazolam. Surface electroencephalographic recordings during epilepsia partialis continua did not show the epileptic discharges. During the terminal phase of the disease, no other type of seizures and movement disorders were recognized, except epilepsia partialis continua. In spite of the treatment, period from the onset of disease to death lasted less than 3 months, suggesting very fulminant course of subacute sclerosing panencephalitis.     

Prolonged, progressive dementia with spongiform encephalopathy: a variant of Creutzfeldt-Jakob disease?

A 46-year-old female is described with prolonged, progressive dementia and a brain biopsy consistent with Creutzfeldt-Jakob disease (CJD). She had neither myoclonic jerks nor an electroencephalogram with periodic spikes and suppression. Five of her close relatives were also demented. The nosology of CJD was discussed in the light of this case in which histopathology was characteristic of spongiform encephalopathy but the clinical features were atypical. We concluded that it would be premature to expand the traditional diagnostic criteria to include such cases as having CJD but, at the same time, it would be prudent to handle tissue, linens and surgical instruments as if they were contaminated by the resistant agent of CJD.     

Cortical myoclonus in Janz syndrome.

OBJECTIVE: To evaluate the characteristics of EEG paroxysms and the relationship between EEG spikes and ictal myoclonic jerks in patients with juvenile myoclonic epilepsy (JME). METHODS: Six patients with a typical form of JME entered the study and underwent computerized polygraphic recordings. In each patient, the inter-peak spike interval was measured on repeated EEG bursts, and jerk-locked back averaging was performed on ictal epochs using a time window including the 100 ms before and the 100-200 ms after the point at which the jerk-related EMG potential diverged from baseline. RESULTS: In all cases, the myoclonic jerks were associated with polyspike waves (PSW) complexes. The frequency of repeated spikes within the PSW complex ranged from 16 to 27 Hz. Jerk-locked averaging revealed a positive-negative EEG transient with maximal amplitude on the frontal leads, which preceded the myoclonic jerk by 10.25+/-0.96 ms. A delay of 9.50+/-1.73 ms was measured between the jerk-locked positive peak detected on the frontal EEG leads of the two hemispheres; a comparable time lag was observed between the onset of myoclonic jerks in the two deltoid muscles. CONCLUSIONS: Our data suggest that the ultimate mechanism responsible for ictal myoclonic jerks in JME is largely similar to that sustaining cortical myoclonus in more severe pathological conditions such as progressive myoclonus epilepsies, despite the different pathogenic substrate and triggering mechanisms.