Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to find an effective treatment option for status epilepticus in progressive myoclonus epilepsy (PME), we reviewed the clinical course of 9 patients with PME. Initially, epilepsy was successfully treated with antiepileptics. However, it gradually became refractory to medication, and status epilepticus emerged 3-19 years after the onset of epilepsy. In these patients, status epilepticus in PME was classified into (1) myoclonic status epilepticus (MSE), (2) myoclonic-generalized status epilepticus (MGSE), and (3) generalized status epilepticus (GSE). MSE was common in patients with neuronal ceroid lipofuscinosis, and GSE was common in those with dentatorubral-pallidoluysian atrophy. MGSE was characterized by the mixture of escalating myoclonus and generalized seizures, and was observed in patients with Gaucher disease or unspecified PME. All patients were often refractory to infusion of benzodiazepines and barbiturates but phenytoin was able to terminate status epilepticus in 7 patients. Oral phenytoin administration as preventive therapy was effective in 6 patients. Aggravation of myoclonus was not provoked by these treatments. We propose that phenytoin should be considered as a treatment choice for PME patients at late stages to prevent the detrimental effects of prolonged or repeated status epilepticus on the brain tissues.
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PMID:Reassessment of phenytoin for treatment of late stage progressive myoclonus epilepsy complicated with status epilepticus. 1926 38

Juvenile neuronal ceroid lipofuscinosis (JNCL) is one type of the neuronal ceroid lipofuscinosis (NCLs), which is a group of pediatric neurodegenerative disorders. The symptoms of JNCL are retinal degeneration (rd), seizures, cognitive, and motor decline. The pathogenesis, summarized in this review, include apoptosis, autophagy, dysfunction in the structure associated with plasmalemma, oxidative stress and disruption of nitric oxide signaling, dysfunction of the mitochondrial and lysosome, unbalanced intracellular pH, and other relative mechanisms. Among them, only apoptosis and autophagy are well known. In apoptosis, the defects in CLN3 result in ceramide accumulation and upstream of mitochondrial membrane per-meabilization, which eventually induce caspase-dependent and caspase-independent cell death. Autophagy exists but is disrupted because the immaturity of autophagic vacuoles leads to the failure of autophagy circulation. Understanding of the pathogenesis, especially the pathways of cell death in JNCL, is helpful to explore the mechanism of neurodegenerative dis-orders, such as JNCL.
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PMID:[Mechanisms of juvenile neuronal ceroid lipofuscinosis (JNCL)]. 1968 37

Although inborn errors of metabolism (IEM) are a relatively rare cause of epilepsy in children, their diagnosis is important with respect to treatment, prognosis and genetic counselling. In addition to seizures and epilepsy, IEM may produce a complex clinical picture in which epilepsy is only one of the various neurologic manifestations including developmental delay/regression, mental retardation, movement disorders, micro-/macrocephaly, as well as cerebral grey and white matter changes. Dysmorphic features and cerebral dysgenesis may also be part of a metabolic epilepsy syndrome (e.g. disorders of peroxisomal biogenesis, glutaric aciduria type 2, pyruvate dehydrogenease complex deficiency). Metabolic epilepsies may dominate the clinical presentation (e.g. pyridoxine dependent epilepsy) or may precede further neurologic deterioration (e.g. neuronal ceroid lipofuscinosis) and additional organ involvement (e.g. liver failure in Alpers (POLG1) disease). Metabolic epilepsies often present with myoclonic seizures (e.g. Gaucher Disease type 3, mitochondrial syndromes) and, as a rule, patients presenting with predominantly myoclonic seizures should be carefully investigated for these types of metabolic epilepsies. Patients with very early onset of epilepsy are considered at high risk for an underlying IEM as well. In this review we present an overview of metabolic epilepsies based on various criteria such as treatability, age of onset, seizure type, and pathogenetic background. Exemplary disorders will be described in more detail including cerebral glucose transporter (GLUT1) deficiency, pyridoxine dependent epilepsy, neuronal ceroid lipofuscinosis, cathepsin D deficiency, Alpers syndrome (POLG deficiency), and guanidinoacetate methyltransferase (GAMT) deficiency.
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PMID:Metabolic epilepsies: approaches to a diagnostic challenge. 1976 Sep 6

The Neuronal Ceroid Lipofuscinoses (NCLs) are lysosomal storage diseases (LSDs) affecting the central nervous system (CNS), with generally recessive inheritance. They are characterized by pathological lipofuscin-like material accumulating in cells. The clinical phenotypes at all onset ages show progressive loss of vision, decreasing cognitive and motor skills, epileptic seizures and premature death, with dementia without visual loss prominent in the rarer adult forms. Eight causal genes, CLN10/CTSD, CLN1/PPT1, CLN2/TPP1, CLN3, CLN5, CLN6, CLN7/MFSD8, CLN8, with more than 265 mutations and 38 polymorphisms (http://www.ucl.ac.uk/ncl) have been described. Other NCL genes are hypothesized, including CLN4 and CLN9; CLCN6, CLCN7 and possibly SGSH are under study. Some therapeutic strategies applied to other LSDs with significant systemic involvement would not be effective in NCLs due to the necessity of passing the blood brain barrier to prevent the neurodegeneration, repair or restore the CNS functionality. There are therapies for the NCLs currently at preclinical stages and under phase 1 trials to establish safety in affected children. These approaches involve enzyme replacement, gene therapy, neural stem cell replacement, immune therapy and other pharmacological approaches. In the next decade, progress in the understanding of the natural history and the biochemical and molecular cascade of events relevant to the pathogenesis of these diseases in humans and animal models will be required to achieve significant therapeutic advances.
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PMID:Therapeutic approaches to the challenge of neuronal ceroid lipofuscinoses. 2123 44

This study sought to genetically define the first family diagnosed with neuronal ceroid lipofuscinosis from Qatar. Onset was in late infancy (3 years), and sequencing in the affected children revealed a novel homozygous c.613C>T change in exon 3 of ceroid-lipofuscinosis, neuronal 5, corresponding to a missense mutation of a conserved amino acid, p.Pro205Ser. The clinical manifestations of the disease in this family largely resemble those of ceroid-lipofuscinosis, neuronal 5 disease, variant late infantile that was first described in Finland and include mental decline, visual deterioration, ataxia, and epileptic seizures. This description of ceroid-lipofuscinosis, neuronal 5 disease in an Arab family adds to the clinical and molecular diversity of the variant late-infantile neuronal ceroid lipofuscinoses, which were originally reported in Europe and are increasingly recognized in other populations.
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PMID:Neuronal ceroid lipofuscinosis in Qatar: report of a novel mutation in ceroid-lipofuscinosis, neuronal 5 in the Arab population. 2144 11

Loss-of-function mutations in CLN3 are responsible for juvenile-onset neuronal ceroid lipofuscinosis (JNCL), or Batten disease, which is an incurable lysosomal disease that manifests with vision loss, followed by seizures and progressive neurodegeneration, robbing children of motor skills, speech and cognition, and eventually leading to death in the second or third decade of life. Emerging clinical evidence points to JNCL pathology outside of the CNS, including the cardiovascular system. The CLN3 gene encodes an unusual transmembrane protein, CLN3 or battenin, whose elusive function has been the subject of intense study for more than 10 years. Owing to the detailed characterization of a large number of disease models, our knowledge of CLN3 protein function is finally coming into focus. This review will describe the most current understanding of CLN3 structure, function and dysfunction in JNCL.
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PMID:The juvenile Batten disease protein, CLN3, and its role in regulating anterograde and retrograde post-Golgi trafficking. 2254 70

A 3-year-old male, hybrid mallard duck (Anas platyrhynchos) was presented with a 2-year history of progressive, ascending paresis and paralysis. On presentation, the bird was in sternal recumbency and displayed intermittent focal seizures and intention tremors. Proprioceptive deficits and absent withdrawal reflexes were observed in both pelvic limbs, wing extension was limited, and reflexes were diminished bilaterally. Other findings included emaciation and dehydration. Results of a complete blood count and plasma biochemical analysis revealed anemia, hypoproteinemia, hypoglycemia, and hyperuricemia. Radiographs were unremarkable and results of an Aspergillus antibody were weakly positive. The duck went into cardiopulmonary arrest and died approximately 1 hour after initiating treatment with intravenous crystalloid fluids. A postmortem diagnosis of neuronal ceroid lipofuscinosis (NCL) was made based on the presence of neuronal granular cytoplasmic material that was autofluorescent and stained with periodic acid-Schiff and Luxol fast blue. To our knowledge, this is only the second case report of NCL in an avian species and the first in waterfowl.
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PMID:Neuronal ceroid lipofuscinosis in a mallard duck (Anas platyrhynchos). 2264 36

Neuronal ceroid lipofuscinosis is a group of progressive neurodegenerative disorders characterized by accumulation of ceroid lipopigment in lysosomes in neurons and other cell types. This study is a retrospective review of charts of patients with a diagnosis of infantile and late-infantile neuronal ceroid lipofuscinosis seen between January 2009 and December 2011. Of the 16 patients, 5 had infantile type and 11 had late-infantile neuronal ceroid lipofuscinosis. Diagnosis was confirmed by appropriate enzyme assay. Clinical presentation was quite varied. Common presenting features included refractory seizures, developmental delay/regression, and abnormal movements. Visual failure was not common in the present case series, and novel neuroimaging finding in the form of isolated dentate nucleus hyperintensities were noted. During follow-up, all patients had a progressive downhill course and one patient died. Prenatal diagnosis could be offered to one family. This study suggests that infantile and late-infantile neuronal ceroid lipofuscinosis is not uncommon in this region of the country and the phenotype may be different.
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PMID:Clinico-investigative profile of infantile and late-infantile neuronal ceroid lipofuscinoses. 2282 94

We report an 11 year old girl with multi-focal spontaneous myoclonus, generalized seizures and behavioural changes. She was found to have sub-clinical hypothyroidism and elevated anti-thyroid peroxidase antibodies. A diagnosis of Hashimoto encephalopathy (or Steroid Responsive Encephalopathy with Autoimmune Thyroiditis) was made in view of consistent clinical and laboratory features. The patient showed and maintained significant improvement with valproate, clonazepam and long term prednisolone. Other findings included mild cerebral cortical grey matter atrophy on brain magnetic resonance imaging and intermittent slowing with generalized poly-spike-and-wave discharges on electroencephalography. Other causes of progressive myoclonus epilepsy (PME) syndrome including subacute sclerosing panencephalitis, Lafora body disease, Juvenile Neuronal Ceroid Lipofuscinosis, Late onset gangliosidosis, Sialidosis, mitochondrial disorders and coeliac disease were ruled out by appropriate investigations. No other auto-immune abnormality was detected. This case emphasizes that Hashimoto encephalopathy should be considered in the etiologies of PME syndrome in adolescents since it is a treatable entity.
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PMID:Hashimoto encephalopathy presenting as progressive myoclonus epilepsy syndrome. 2284 Feb 75

The most common progressive myoclonus epilepsies are the late infantile and late infantile-variant neuronal ceroid lipofuscinoses (onset before the age of 6 years), Unverricht-Lundborg disease (onset after the age of 6 years) and Lafora disease. Lafora disease is a distinct disorder with uniform course: onset in teenage years, followed by progressively worsening myoclonus, seizures, visual hallucinations and cognitive decline, leading to a vegetative state in status myoclonicus and death within 10 years. Biopsy reveals Lafora bodies, which are pathognomonic and not seen with any other progressive myoclonus epilepsies. Lafora bodies are aggregates of polyglucosans, poorly constructed glycogen molecules with inordinately long strands that render them insoluble. Lafora disease is caused by mutations in the EPM2A or EPM2B genes, encoding the laforin phosphatase and the malin ubiquitin ligase, respectively, two cytoplasmically active enzymes that regulate glycogen construction, ensuring symmetric expansion into a spherical shape, essential to its solubility. In this work, we report a new progressive myoclonus epilepsy associated with Lafora bodies, early-onset Lafora body disease, map its locus to chromosome 4q21.21, identify its gene and mutation and characterize the relationship of its gene product with laforin and malin. Early-onset Lafora body disease presents early, at 5 years, with dysarthria, myoclonus and ataxia. The combination of early-onset and early dysarthria strongly suggests late infantile-variant neuronal ceroid lipofuscinosis, not Lafora disease. Pathology reveals no ceroid lipofuscinosis, but Lafora bodies. The subsequent course is a typical progressive myoclonus epilepsy, though much more protracted than any infantile neuronal ceroid lipofuscinosis, or Lafora disease, patients living into the fourth decade. The mutation, c.781T>C (Phe261Leu), is in a gene of unknown function, PRDM8. We show that the PRDM8 protein interacts with laforin and malin and causes translocation of the two proteins to the nucleus. We find that Phe261Leu-PRDM8 results in excessive sequestration of laforin and malin in the nucleus and that it therefore likely represents a gain-of-function mutation that leads to an effective deficiency of cytoplasmic laforin and malin. We have identified a new progressive myoclonus epilepsy with Lafora bodies, early-onset Lafora body disease, 101 years after Lafora disease was first described. The results to date suggest that PRDM8, the early-onset Lafora body disease protein, regulates the cytoplasmic quantities of the Lafora disease enzymes.
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PMID:Early-onset Lafora body disease. 2296 47


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