Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038220 (status epilepticus)
 7,272 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report the clinical findings in 19 Finnish patients, including six pairs of siblings, with a new, early onset spinocerebellar ataxia. The slowly progressive clinical symptoms manifested between one and two years of age in previously healthy infants. The first manifestation of children at that age was clumsiness and loss of ability to walk. Ataxia, athetosis and muscle hypotonia with loss of deep tendon reflexes were discovered on clinical examination. By school age ophthalmoplegia and hearing loss were diagnosed, while sensory neuropathy developed by adolescence. In addition, an acute crisis with status epilepticus was a late manifestation. We found a marked decrease in sensory nerve condition velocities, a progressive loss of myelinated fibers in sural nerve specimen, and abnormal background activity in EEG with advancing age. The main finding in neuroradiological investigations was cerebellar atrophy. The occurrence of the disease in siblings and lack of manifestations in parents indicate recessive inheritance.
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PMID:Infantile onset spinocerebellar ataxia with sensory neuropathy: a new inherited disease. 813 12

We present six adult patients from three separate families, with a remarkably uniform heredo-ataxic syndrome, developing in three stages and ending in early death. The initial stage is determined by severe sensory neuropathy. The second stage is characterized further by progressive external ophthalmoplegia (PEO), probably caused by ocular myopathy, and progressive ataxia. During a short last stage there is epilepsia, and particularly myoclonic status epilepticus, of which four patients died unexpectedly. Sural nerve biopsies showed severe loss of myelinated fibres in a rather early stage of disease. Skeletal muscle biopsies (and a specimen of ocular muscle) revealed ragged-red fibres. Autopsy examination in two patients revealed multisystemic involvement of the nervous system, with, in particular, degeneration of spinal dorsal columns and spinocerebellar tracts. Pedigree data were compatible with an autosomal recessive disorder. Additional findings, particularly elevation of CSF lactate, suggested mitochondrial cytopathy as an essential feature of the multisystem degeneration in these patients.
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PMID:Mitochondrial cytopathy presenting as hereditary sensory neuropathy with progressive external ophthalmoplegia, ataxia and fatal myoclonic epileptic status. 867 7

We report on the age and the causes of death in 16 patients with mitochondrial diseases. Nine patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) died at a mean age of 34 years and three patients with chronic progressive external ophthalmoplegia at a mean age of 56 years. The causes of death were cardiopulmonary failure (n = 5), status epilepticus (n = 4), aspiration pneumonia (n = 2), pulmonary embolism (n = 2), renal failure (n = 1), metabolic disturbance (n = 1), and unknown causes (n = 1). Thus, many patients in this series died of medical complications, some of which may be prevented.
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PMID:Age and cause of death in mitochondrial diseases. 1048 54

We report on 3 siblings (2 females and 1 male) with chronic progressive external ophthalmoplegia (CPEO), compatible with inherited mitochondrial cytopathy. The younger of the two sisters died at the age of 37 due to progressive respiratory failure. The older one presented with a status epilepticus at the age of 39 and was treated with valproate. Five months after the start of treatment, she developed fulminant liver failure and died. The brother has suffered from CPEO since early childhood but has had so far no other symptoms of a mitochondrial disease. A muscle biopsy from the younger sister revealed ragged-red fibers and decreased activities of complex I and IV of the respiratory chain but no pathogenic mutations in the mitochondrial tRNA genes or in several locations in the coding region of the mitochondrial genome. In the older sister's liver (obtained post-mortem), mitochondrial DNA was fragmented and could not be investigated. The clinical presentation and the biochemical findings suggest that all 3 siblings suffered from a mitochondrial cytopathy. Since mitochondrial cytopathies and valproate-induced fulminant liver failure are both rare events, an association between them is likely. Mitochondrial diseases should therefore be considered as a risk factor for valproate-induced liver failure and be excluded before treatment with valproate.
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PMID:Mitochondrial diseases represent a risk factor for valproate-induced fulminant liver failure. 1095 15

We studied 26 patients belonging to 20 families with a disorder caused by mutations in the POLG gene. The patients were homozygous for 1399 G/A or 2243 G/C (giving the amino acid changes A467T and W748S, respectively) or compound heterozygotes for these two mutations. Irrespective of genotype, the patients exhibited a progressive neurological disorder usually starting in their teens and characterized by epilepsy, headache, ataxia, neuropathy, myoclonus and late onset ophthalmoplegia. However, major differences in survival were seen depending on genotype, with compound heterozygotes having a significantly shorter survival time than patients homozygous either for the A467T or W748S (P = 0.006). Epilepsy occurred in 22 of the 26 patients and in the majority of these there was an occipital EEG focus. Episodes of both generalized and focal motor status epilepticus were common and highly resistant to treatment, even with generalized anaesthesia. Status epilepticus was the recorded cause of death in 9 of 11 patients. Liver failure was the sole cause of death in two patients and evolved terminally in six others, all but one of whom were being treated with sodium valproate. Two patients underwent liver transplantation, but only one survived. Delayed psychomotor development and subsequent cognitive decline also occurs. This study demonstrates the clinical spectrum of a disorder that combines features of Alpers' syndrome and a later onset mitochondrial spinocerebellar ataxia with epilepsy and headache. Patients with this disorder are at high risk of death from status epilepticus and from liver failure, if exposed to sodium valproate. Each mutation appears capable of producing a disorder that is recessively inherited, although we also find evidence in one patient suggesting that heterozygotes may manifest. Compound heterozygotes have a significantly more severe phenotype raising the possibility of a dominant negative effect.
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PMID:The spectrum of clinical disease caused by the A467T and W748S POLG mutations: a study of 26 cases. 1743 11

The C10orf2 gene encodes the mitochondrial DNA helicase Twinkle, which is one of the proteins important for mitochondrial DNA maintenance. Dominant mutations cause multiple mitochondrial DNA deletions and progressive external ophthalmoplegia, but recent findings associate recessive mutations with mitochondrial DNA depletion and encephalopathy or hepatoencephalopathy. The latter clinical phenotypes resemble those associated with recessive POLG1 mutations. We have previously described patients with infantile onset spinocerebellar ataxia (MIM271245) caused either by homozygous (Y508C) or compound heterozygous (Y508C and A318T) Twinkle mutations. Our earlier reports focused on the spinocerebellar degeneration, but the 20-year follow-up of 23 patients has shown that refractory status epilepticus, migraine-like headaches and severe psychiatric symptoms are also pathognomonic for the disease. All adolescent patients have experienced phases of severe migraine, and seven patients had antipsychotic medication. Epilepsia partialis continua occurred in 15 patients leading to generalized epileptic statuses in 13 of them. Eight of these patients have died. Valproate treatment was initiated on two patients, but had to be discontinued because of a severe elevation of liver enzymes. The patients recovered, and we have not used valproate in infantile onset spinocerebellar ataxia since. The first status epilepticus manifested between 15 and 34 years of age in the homozygotes, and at 2 and 4 years in the compound heterozygotes. The epileptic statuses lasted from several days to weeks. Focal, stroke-like lesions were seen in magnetic resonance imaging, but in infantile onset spinocerebellar ataxia these lesions showed no predilection. They varied from resolving small cortical to large hemispheric oedematous lesions, which reached from cerebral cortex to basal ganglia and thalamus and caused permanent necrotic damage and brain atrophy. Brain atrophy with focal laminar cortical necrosis and hippocampal damage was confirmed on neuropathological examination. The objective of our study was to describe the development and progression of encephalopathy in infantile onset spinocerebellar ataxia syndrome, and compare the pathognomonic features with those in other mitochondrial encephalopathies.
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PMID:Recessive twinkle mutations cause severe epileptic encephalopathy. 1930 94

Whipple disease (WD) is a rare multisystemic infection with a protean clinical presentation. The central nervous system (CNS) is involved in 3 situations: CNS involvement in classic WD, CNS relapse in previously treated WD, and isolated CNS infection. We retrospectively analyzed clinical features, diagnostic workup, brain imaging, cerebrospinal fluid (CSF) study, treatment, and follow-up data in 18 patients with WD and CNS infection. Ten men and 8 women were included with a median age at diagnosis of 47 years (range, 30-56 yr). The median follow-up duration was 6 years (range, 1-19 yr). As categorized in the 3 subgroups, 11 patients had classic WD with CNS involvement, 4 had an isolated CNS infection, and 3 had a neurologic relapse of previously treated WD. CNS involvement occurred during prolonged trimethoprim-sulfamethoxazole (TMP-SMX) treatment in 1 patient with classic WD. The neurologic symptoms were various and always intermingled, as follows: confusion or coma (17%) related to meningo-encephalitis or status epilepticus; delirium (17%); cognitive impairment (61%) including memory loss and attention defects or typical frontal lobe syndrome; hypersomnia (17%); abnormal movements (myoclonus, choreiform movements, oculomasticatory myorhythmia) (39%); cerebellar ataxia (11%); upper motor neuron (44%) or extrapyramidal symptoms (33%); and ophthalmoplegia (17%) in conjunction or not with progressive supranuclear palsy. No specific pattern was correlated with any subgroup. Brain magnetic resonance imaging (MRI) revealed a unique focal lesion (35%), mostly as a tumorlike brain lesion, or multifocal lesions (23%) involving the medial temporal lobe, midbrain, hypothalamus, and thalamus. Periventricular diffuse leukopathy (6%), diffuse cortical atrophy (18%), and pachymeningitis (12%) were observed. The spinal cord was involved in 2 cases. MRI showed ischemic sequelae at diagnosis or during follow-up in 4 patients. Brain MRI was normal despite neurologic symptoms in 3 cases. CSF cytology was normal in 62% of patients, whereas Tropheryma whipplei polymerase chain reaction (PCR) analysis was positive in 92% of cases with tested CSF. Periodic acid-Schiff (PAS)-positive cells were identified in cerebral biopsies of 4 patients. All patients were treated with antimicrobial therapy for a mean duration of 2 years (range, 1-7 yr) with either oral monotherapy (TMP-SMX, doxycycline, third-generation cephalosporins) or a combination of antibiotics that sometimes followed parenteral treatment with beta-lactams and aminoglycosides. Eight patients also received hydroxychloroquine. At the end of follow-up, the clinical outcome was favorable in 14 patients (78%), with mild to moderate sequelae in 9. Thirteen patients (72%) had stopped treatment for an average time of 4 years (range, 0.7-14 yr). Four patients had clinical worsening despite antimicrobial therapy; 2 of those died following diffuse encephalitis (n = 1) and lung infection (n = 1). In conclusion, the neurologic manifestations of WD are diverse and may mimic almost any neurologic condition. Brain involvement may occur during or after TMP-SMX treatment. CSF T. whipplei PCR analysis is a major tool for diagnosis and may be positive in the absence of meningitis. Immune reconstitution syndrome may occur in the early months of treatment. Late prognosis may be better than previously reported, as a consequence of earlier diagnosis and a better use of antimicrobial therapy, including hydroxychloroquine and doxycycline combination.
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PMID:Central nervous system involvement in Whipple disease: clinical study of 18 patients and long-term follow-up. 2414

Mutations in POLG are increasingly recognized as a cause of refractory occipital lobe epilepsy (OLE) and status epilepticus (SE). Our aim was to describe the epilepsy syndrome in seven patients with POLG mutations. We retrospectively reviewed the medical records of seven patients with POLG mutations and epilepsy. Mutation analysis was performed by direct sequencing of the coding exons of the POLG gene. Disease onset was at a median age of 18 years (range 12-26). Epilepsy was the presenting problem in six patients. All had focal seizures, with motor (n = 6) and visual (n = 6) phenomena. Six patients had secondarily generalized seizures and two patients had myoclonic seizures. Six patients had one or more episodes of refractory SE, including focal (n = 5), subtle (n = 4), myoclonic (n = 2) and convulsive (n = 3) SE. During or after SE, brain MRI showed lesions affecting the occipital lobe in all patients, probably due to continuous epileptic activity. Five of the six patients with SE died during treatment of SE, one due to valproate-induced hepatotoxicity. Associated clinical symptoms were ataxia (n = 6), polyneuropathy (n = 6), progressive external ophthalmoplegia (PEO) (n = 3) and migraine (n = 3). Epilepsy may be the first and dominant neurological problem caused by POLG mutations. The epilepsy may be severe and the condition of the patient may end in fatal SE. Refractory OLE and SE in a patient with polyneuropathy, ataxia, PEO or migraine warrant screening for POLG mutations. In this clinical setting, valproate should not be given in view of the risk of fatal hepatotoxicity.
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PMID:The spectrum of epilepsy caused by POLG mutations. 2610 64