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Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neuronal ceroid lipofuscinoses are a group of rare neurodegenerative disorders that are characterised by an accumulation of autofluorescent lipopigments in neurons and extraneuronal tissues. We report on a 4-year-old boy who presented with an acute onset of seizures followed by rapid psychomotor deterioration, ataxia, and visual failure. Photic stimulation at 1 to 3 Hz elicited discrete spike and wave discharges in the electroencephalogram, which were diminished at a higher frequency of stimulation. The electroretinogram was extinct. Magnetic resonance imaging of the brain showed generalised cerebral and cerebellar atrophy. Electron microscopic examination of lymphocytes and samples of muscle and skin revealed characteristic curvilinear inclusion bodies. To our knowledge, this is the first case of late infantile neuronal ceroid lipofuscinosis to be reported in a Hong Kong Chinese patient.
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PMID:Classic late infantile neuronal ceroid lipofuscinosis in a Chinese patient. 1140 82

Neuronal ceroid lipofuscinosis, which is also known as Batten-Bielschowsky disease, is a group of neuro degenerative disorders, associated with various progressive symptoms including seizures, dementia, visual loss and cerebral atrophy. We experienced a case of late infantile neuronal ceroid lipofuscinosis in a 6-year-old boy who had progressive myoclonic seizures, ataxia, rapid psychomotor deterioration and visual loss. Photic stimulation at 2 to 5 Hz elicited a discrete spike and wave discharges in the occipital region on an electroencephalogram. Magnetic resonance imaging of the brain showed generalized cerebral and cerebellar atrophy. An electron microscopic examination of the skin revealed characteristic curvilinear inclusion bodies. An optic fundoscopy revealed a devastated retina and severe optic atrophy. We report this case with the brief review of related literature.
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PMID:A case of late infantile neuronal ceroid lipofuscinosis. 1272 77

Clinical picture of neuronal ceroid lipofuscinosis with late infantile onset (LINCL) is characterized by myoclonic seizures and psychomotor regression. We present a case of classic LINCL and reduced cerebrospinal fluid (CSF) pterins in a girl of normal psychomotor development and born to non-consanguineous parents. She first presented with febrile seizures at the age of four. At that time, brain computed tomography finding was normal, but electroencephalogram showed hypsarrhythmia. At the age of five, tremor, generalized ataxia, and motor and mental regression appeared. Brain magnetic resonance imaging showed cerebellar atrophy. Electron microscopy examination showed storage of intracytoplasmic curvilinear inclusions in neurons, fibroblasts, and secretory cells of the skin and rectal mucosa. Tripeptidyl peptidase I (TPP-I) activity in leukocytes was very low (5.4 nmol/h/mg protein; range in homozygote cases of LINCL, 0.4-26.0). Molecular genetic studies showed a homozygous mutation, R208X, in exon 6 of CLN2 gene. CSF analysis revealed very low neopterin (7.3 nmol/L; normal range, 9-30) and biopterin (4.1 nmol/L; normal range, 10-30), reduced homovanillic acid (266 nmol/L; normal range, 211-871), and low homovanillic acid/5-hydroxyindoleacetic acid ratio (1.21; normal ratio, 1.5-3.5). Treatment with L-Dopa/Carbidopa (4 mg/kg) and antiepileptics was introduced, but without significant effect. It seems that low CSF pterins and impaired dopamine turnover are secondary manifestations of classical LINCL caused by homozygous inheritance of the R208X mutation in CLN2 gene.
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PMID:R208X mutation in CLN2 gene associated with reduced cerebrospinal fluid pterins in a girl with classic late infantile neuronal ceroid lipofuscinosis. 1295 Jan 56

The palmitoyl protein thioesterase-2 (PPT2) gene encodes a lysosomal thioesterase homologous to PPT1, which is the enzyme defective in the human disorder called infantile neuronal ceroid lipofuscinosis. In this article, we report that PPT2 deficiency in mice causes an unusual form of neuronal ceroid lipofuscinosis with striking visceral manifestations. All PPT2-deficient mice displayed a neurodegenerative phenotype with spasticity and ataxia by 15 mo. The bone marrow was infiltrated by brightly autofluorescent macrophages and multinucleated giant cells, but interestingly, the macrophages did not have the typical appearance of foam cells commonly associated with other lysosomal storage diseases. Marked splenomegaly caused by extramedullary hematopoiesis was observed. The pancreas was grossly orange to brown as a result of massive storage of lipofuscin pigments in the exocrine (but not islet) cells. Electron microscopy showed that the storage material consisted of multilamellar membrane profiles ("zebra bodies"). In summary, PPT2 deficiency in mice manifests as a neurodegenerative disorder with visceral features. Although PPT2 deficiency has not been described in humans, manifestations would be predicted to include neurodegeneration with bone marrow histiocytosis, visceromegaly, brown pancreas, and linkage to chromosome 6p21.3 in affected families.
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PMID:Disruption of PPT2 in mice causes an unusual lysosomal storage disorder with neurovisceral features. 1452 5

The clinico-pathologic features of two siblings with biopsy-proven adult onset neuronal ceroid lipofuscinosis (Kufs' disease) are described. A 38-year-old woman had intractable seizures, delusions and hallucinations followed by ataxia, declining cognitive function and death. At autopsy there was widespread cerebral neuronal accumulation of autofluorescent pigment, in which fingerprint profiles were demonstrated. Systemic involvement was not demonstrated. A 43-year-old brother developed slowly progressive cerebellar ataxia and was found to have similar neuronal autofluorescent pigment on brain biopsy. Nine years later there is gradual cognitive decline and profound ataxia. The salient features of Kufs' disease including cases published since 1988 are reviewed.
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PMID:Adult neuronal ceroid lipofuscinosis (Kufs' disease) in two siblings of an Irish family. 1460 83

Neuronal ceroid lipofuscinosis (NCL) is one of the most common progressive neurodegenerative diseases seen in childhood. NCL is inherited as autosomal recessive trait, and is characterized by the accumulation of 'ceroid lipofuscin' in neuronal and extraneuronal cells. Clinical features include seizures, ataxia, myoclonus, loss of vision, and mental and motor deterioration. Although the disease is widely seen across the world, there seems to be an information gap in Asian countries. To date, no comprehensive and detailed studies on NCL have been carried out in Turkey. However, one could predict that the disease is rather frequent in Turkey due to high rates of consanguineous marriages. Thirty-six Turkish patients were evaluated in this study. Sixteen (44.5%) patients were girls, and 20 (55.5%) were boys. Parents were consanguineous in 25 families (80%). In five families (14%), the disease was seen in two sibs. The diagnosis was based on clinical evaluation, and neurophysiological, neuroradiologic, enzymatic, and histopathological studies. Electron microscopic study was the main diagnostic laboratory test. Three patients were classified as infantile NCL, 11 were late infantile NCL, 5 were juvenile type NCL and 17 patients were Turkish variant NCL. In juvenile type, major initial symptom was visual impairment, whereas in all other types seizures were predominantly the first symptom at the onset of the disease. The initial symptoms of Turkish variant NCL were similar to those of late infantile type. Similar age at clinical symptoms and the presence of visual symptoms were common features of Turkish variant and juvenile NCL. Compared to late infantile NCL, Turkish variant, showed a more severe course regarding seizures. Electroencephalogram (EEG) showed abnormal features predominantly in Turkish variant, and were remarkable for occipital spikes. In patients with Turkish variant magnetic resonance imaging of the brain showed brainstem involvement, especially pons, in all patients except one; cerebral and cerebellar atrophy were seen with a slower course compared to late infantile NCL. Clinical picture of NCL in advanced stages of the disease was similar regardless of the subtype.
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PMID:Evaluation of 36 patients from Turkey with neuronal ceroid lipofuscinosis: clinical, neurophysiological, neuroradiological and histopathologic studies. 1507 67

We report the clinical, electrophysiological, radiological and morphological features in a series of 12 patients of histopathologically confirmed cases (infantile, juvenile and adult onset) of neuronal ceroid lipofuscinosis (NCL) observed from 1979 to 1998 at National Institute of Mental Health & Neurosciences (NIMHANS), Bangalore (South India). The commonest type of NCL was juvenile (n = 8, 67%) while infantile and adult forms were two each (n = 2, 16.8%). The age at presentation ranged from 2 to 45 years (mean--12.6, 14.3 years; median--7 years; M:F ratio of 2:1). Four patients (33%) had positive family history and five patients had history of consanguineous parentage (41.6%). The commonest presenting symptoms were regression of milestones (83.3%) and/or seizures, myoclonus (83.8%) followed by involuntary choreiform movements (50%), visual loss (41.6%), ataxia (33.3%) and abnormal behaviour (16.6%). Neuro-ophthalmological abnormalities like optic atrophy (50%), macular degeneration (33.3%) and retinitis pigmentosa (8.3%) were seen in two thirds. Nerve conduction studies (n = 4) revealed abnormalities in two, suggestive of sensorimotor neuropathy. Scalp EEG (n = 9) showed slowing of background activity (BGA) of varying degrees with paroxysmal bursts of seizure discharges in majority. Cranial CT scan (n = 4) revealed varying degrees of diffuse atrophy. Diagnostic brain biopsy was carried out in 11 and brain was examined at autopsy in 1 case. Histological examination revealed characteristic PAS and Luxol Fast Blue (LFB) positive, autofluorescent (AF) intracellular ceroid material, both in neurons and astrocytes in the grey matter. Electron microscopy (n = 5) revealed curvilinear (n = 4), lamellar (n = 2) and electron dense (n = 2) inclusions in neurons, astrocytes and vascular endothelial cells. To conclude, this neurodegenerative disease had varied but characteristic clinical presentations and required histopathological confirmation of diagnosis.
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PMID:Neuronal ceroid lipofuscinosis: a clinicopathological study. 1512 Nov 31

Mutations in the CLN2 gene, which encodes a lysosomal serine protease, tripeptidyl-peptidase I (TPP I), result in an autosomal recessive neurodegenerative disease of children, classical late-infantile neuronal ceroid lipofuscinosis (cLINCL). cLINCL is inevitably fatal, and there currently exists no cure or effective treatment. In this report, we provide the characterization of the first CLN2-targeted mouse model for cLINCL. CLN2-targeted mice were fertile and apparently healthy at birth despite an absence of detectable TPP I activity. At approximately 7 weeks of age, neurological deficiencies became evident with the onset of a tremor that became progressively more severe and was eventually accompanied by ataxia. Lifespan of the affected mice was greatly reduced (median survival, 138 d), and extensive neuronal pathology was observed including a prominent accumulation of cytoplasmic storage material within the lysosomal-endosomal compartment, a loss of cerebellar Purkinje cells, and widespread axonal degeneration. The CLN2-targeted mouse therefore recapitulates much of the pathology and clinical features of cLINCL and represents an animal model that should provide clues to the normal cellular function of TPP I and the pathogenic processes that underlie neuronal death in its absence. In addition, the CLN2-targeted mouse also represents a valuable model for the evaluation of different therapeutic strategies.
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PMID:A mouse model of classical late-infantile neuronal ceroid lipofuscinosis based on targeted disruption of the CLN2 gene results in a loss of tripeptidyl-peptidase I activity and progressive neurodegeneration. 1548 30

The neuronal ceroid lipofuscinoses are a group of dominant neurodegenerative, progressive, and fatal disorders characterized clinically by myoclonic epilepsy, in variable association with dementia, ataxia, and visual loss. Neuronal ceroid lipofuscinoses were classified into several phenotypes according to their age of onset: infantile, late infantile, juvenile, and adult. A specific phenotype was named "northern epilepsy," and its onset of signs occurs between ages 5-10 years. Deficiencies in the lysosomal activity of two specific enzymes were found in several types of neuronal ceroid lipofuscinosis: palmitoyl-protein thioesterase 1, encoded by the CLN1 gene, and tripeptidyl-peptidase 1, encoded by the CLN2 gene. Several mutations in CLN2 were described previously. We describe a novel mutation in two siblings of Israeli-Arab origin, with a clinical picture compatible with late infantile neuronal ceroid lipofuscinosis. Both siblings were found to be homozygous for a deletion of a C nucleotide at position 775 in exon 7 of the CLN2 gene. These findings have implications for the worldwide epidemiology of neuronal ceroid lipofuscinosis.
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PMID:Late infantile neuronal ceroid lipofuscinosis: a new mutation in Arabs. 1974 52

Human ceroid-lipofuscinosis is marked by blindness, dementia, ataxia, and premature death. A canine model for this disease exists in English setters whose clinical, pathological and biochemical changes resemble the human disorder. In both syndromes, autofluorescent lipopigments, i.e.; lipofuscin and ceroid ("granular", "fingerprint" and/or "curvilinear bodies") are found in the nervous system, viscera, retina, and pigment epithelium (RPE). Retinal neurons of affected animals between 6 and 22 months of age, contain a variety of abnormal intracellular pigment inclusions. Pigment epithelial cells also contain distinctive cytosomes. Electroretinograms from affected animals showed a reduction in b-wave amplitude. Leukocyte, retinal, and RPE peroxidases, were decreased in affected animals, and also showed age-related changes. In the normal canine eye, peroxidase was associated with fractions containing plasma membranes and melanolysosomes. Improved fractionation techniques localized normal peroxidase to "heavy" fractions (1.24-1.28 g/ml), and peroxidase was decreased in these fractions in CCL animals. A new particle containing hexosaminidase, galactosidase, and acid lipase was observed in affected animals. When retinal homogenates from CCL dogs were injected into the vitreous of rabbit eyes they completely abolished the ERG recording. No such change was observed with homogenates from unaffected animals. The accumulation of large numbers of dense bodies in the retina and RPE in dogs with CCL, along with a decrease in peroxidase, suggests an impairment of degradative mechanisms. Furthermore, ceroid appears to be cytotoxic to the retina and RPE. The relationship of these cytotoxic properties to the accumulation of ceroid in the eye, is the subject of our future research.
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PMID:Morphological and biochemical abnormalities in a model of retinal degeneration: Canine ceroid-lipofuscinosis (CCL). 2048 51


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