1/45. Early thalamic and cortical hypometabolism in adult-onset dementia due to metachromatic leukodystrophy.A case of early-onset adult dementia with family history of dementia is reported, characterised by neuropsychological deficits, suggesting frontal involvement, with mild non specific white matter abnormalities on CT scan. Familial Alzheimer's disease was suspected but the neuropathological diagnosis on brain biopsy was metachromatic leukodystrophy. 18FDG-PET revealed a very peculiar pattern of metabolic impairment in thalamic areas, in medial and frontopolar regions, and in occipital lobes. Neuropsychological follow-up showed relatively stable difficulties of long-term memory and signs of frontal lobe dysfunction, similar to those observed in subcortical dementias. MRI subsequently showed periventricular leukoencephalopathy. The brain metabolic pattern observed in that case of metachromatic leukodystrophy was quite different from that reported in other types of dementia.- - - - - - - - - - ranking = 1keywords = brain (Clic here for more details about this article) |
2/45. neurophysiology and MRI in late-infantile metachromatic leukodystrophy.We present serial clinical, radiologic, and neurophysiologic findings of a patient with late-infantile metachromatic leukodystrophy who was first admitted at 30 months of age because of gait disturbance. The neurologic findings were consistent with mild spastic diplegia (occasionally with toe walking). magnetic resonance imaging disclosed diffuse high intensity in the cerebral white matter on T2-weighted images. Nerve conduction velocity studies and evoked-potential studies were markedly abnormal. Assay of arylsulfatase A activity in leukocyte culture disclosed a marked deficiency of the enzyme, confirming the diagnosis of late-infantile metachromatic leukodystrophy. Serial neurophysiologic studies demonstrated a marked decrease of nerve conduction velocities, both motor and sensory, as well as prolongation or disappearance of brainstem auditory-, visual-, and somatosensory-evoked potential latencies. magnetic resonance imaging studies revealed initially diffuse increased signal intensity of periventricular and subcortical white matter on T2-weighted images, progressing to cortical atrophy with involvement of the arcuate fibers and the cerebellar white matter, correlating with the clinical deterioration (severe spastic tetraplegia with optic atrophy and epilepsy).- - - - - - - - - - ranking = 0.5keywords = brain (Clic here for more details about this article) |
3/45. dementia with impaired temporal glucose metabolism in late-onset metachromatic leukodystrophy.An unusual case of very-late-onset metachromatic leukodystrophy (MLD) with dementia was studied. The patient was a 41-year-old male who presented with mild dementia and a single generalized tonic clonic seizure. Neuropsychological assessment demonstrated mild amnesia, visuospatial dysfunction and attention deficits with a slow psychomotor speed. MR brain imaging displayed confluent hyperintensities of periventricular and subcortical white matter. Low levels of arylsulfatase A confirmed the diagnosis. Impaired cortical glucose metabolism especially of the medial temporal and frontal cortices was observed using positron emission tomography and fluor-18-labeled fluorodesoxyglucose. The neuropsychological deficits are related to the location of deficits in glucose metabolism.- - - - - - - - - - ranking = 0.5keywords = brain (Clic here for more details about this article) |
4/45. Fetal metachromatic leukodystrophy: pathology, biochemistry and a study of in vitro enzyme replacement in CNS tissue.Brain tissue from a fetus with the diagnosis of metachromatic leukodystrophy (MLD) became available at autopsy. Pathologic studies of the CNS showed inclusion bodies within oligodendroglia. The morphology of myelin was normal. cells and myelin were isolated from the cerebrum; there was an increased level of sulfatide present in both fractions. in vitro studies of enzyme replacement in cultured MLD brain cells indicated that it may be possible to correct the abnormal sulfatide accumulation.- - - - - - - - - - ranking = 0.5keywords = brain (Clic here for more details about this article) |
5/45. An adult case of metachromatic leukodystrophy. light, polarization and electron microscopic study.The findings are described in an adult case of metachromatic leukodystrophy examined by light, polarization and electron microscopy. Symmetrical demyelination was found in the cerebral hemispheres, but was moderate in the cerebellum, brain stem and spinal cord. Early changes in myelin of peripheral nerves have been demonstrated by polarization microscopy. Various metachromatic structures have been described in glial cells and neurons by electron microscopy, indicating disturbances at different metabolic steps of lipid metabolism. There are minor but no essential ultrastructural differences in the disease of different ages.- - - - - - - - - - ranking = 0.5keywords = brain (Clic here for more details about this article) |
6/45. Isolated peripheral neuropathy in atypical metachromatic leukodystrophy: a recurrent mutation.BACKGROUND: Metachromatic leukodystrophy (MLD) is a genetic neurodegenerative disorder resulting from a deficiency of arylsulfatase A. Late onset forms are relatively rare. central nervous system (CNS) involvement is characteristic at all ages. methods: A patient in her late 40s with peripheral neuropathy was assessed by EEG, evoked potentials, CT and nerve conduction studies. Nerve and muscle biopsy samples were investigated by electron microscopy. Arylsulfatase A activity in leukocytes and excreted cerebroside sulfate were determined. The arylsulfatase A gene was investigated for mutations using polymerase chain reaction (PCR) and dna sequencing. The identified mutation was expressed transiently in African green monkey kidney (COS) cells to determine the effect of the mutation on arylsulfatase A activity. RESULTS: central nervous system functions were normal. Nerve conduction velocities were decreased. sural nerve biopsy showed inclusions typical of MLD. Arylsulfatase A was less than 5% of normal. A homozygous mutation thr286pro was identified in the arylsulfatase A gene and demonstrated to be deleterious through transient expression studies. CONCLUSIONS: Our patient has a progressive peripheral neuropathy but has apparently intact CNS function at her present age of 57 years. Biochemical, physiological and pathological findings are consistent with a diagnosis of MLD. A homozygous mutation, thr286pro, found in her arylsulfatase A gene, decreased enzyme activity to a level consistent with a late onset form of MLD.- - - - - - - - - - ranking = 1.5646583973484keywords = nervous system (Clic here for more details about this article) |
7/45. ganciclovir-resistant cytomegalovirus encephalitis in a bone marrow transplant recipient.A 20-year-old patient, who received a bone marrow transplant in order to treat metachromatic leukodystrophy (MLD), succumbed to cytomegalovirus (CMV) encephalitis. After CMV viremia developed, the patient received ganciclovir, but he was switched to foscarnet when ganciclovir resistance was suspected. foscarnet was discontinued because of concern about its potential central nervous system toxicity. autopsy samples of brain and cerebrospinal fluid contained CMV dna with a UL97 mutation (M460V) known to confer ganciclovir resistance. No foscarnet resistance mutations were found.- - - - - - - - - - ranking = 1.9412653460653keywords = nervous system, central nervous system, brain (Clic here for more details about this article) |
8/45. Late infantile form metachromatic leukodystrophy: report of one case.Metachromatic leukodystrophy (MLD) is a neurodegenerative disorder with autosomal recessive inheritance, in which cerebroside sulphate (sulphatide) accumulates in the central and peripheral nervous systems due to a deficiency of arylsulphatase A. This article presents a 2-year-old boy who had occasional shortness of breath, horizontal nystagmus and unstable gait for 3 months prior to the entry. He was admitted to our hospital due to shortness of breath, frequent apnea, generalized hypotonia and conscious disturbance. The lumbar puncture, brain CT scan, serum amino acid analysis, urine organic acid assay and nerve conduction velocity of lower extremities all showed negative findings. The electron microscopic finding of muscle elicited lipid deposition. The auditory brainstem response showed bilateral impairment. The routine EEG revealed diffuse slow waves. The brain MRI showed widespread low signals over the white matter of bilateral frontal and parietotemporal areas of the cerebral hemispheres, as well as the white matter of the bilateral cerebellar hemispheres, and the brain stem in the T1-weighted image corresponding the high signals in T2-weighted image. The blood leukocyte lysosomal enzyme activity test revealed arylsulphatase A deficiency. Rapid progressive neurological deterioration was noted since admission. Unfortunately, the patient expired due to respiratory failure in the final.- - - - - - - - - - ranking = 2.7823291986742keywords = nervous system, brain (Clic here for more details about this article) |
9/45. adult onset metachromatic leukodystrophy without electroclinical peripheral nervous system involvement: a new mutation in the ARSA gene.BACKGROUND: Metachromatic leukodystrophy (MLD) is a lysosomal storage disease caused by the deficiency of arylsulfatase A (ARSA). Clinically, the disease is heterogeneous with respect to the age of onset, affection of peripheral and central nervous systems, and progression. OBJECTIVES: To analyze mutations in the ARSA gene of a patient with adult-onset MLD with no signs of peripheral polyneuropathy and to emphasize the clinical, neuroradiologic, neuropathologic, and genetic features of the disease. DESIGN: Case study of a patient clinically presenting with rapidly progressive dementia and behavioral abnormalities. We report the findings of clinical evaluation and neurophysiologic and neuropathologic studies of peripheral nerves; we also performed dna sequence analysis, transfections, metabolic labeling, and immunoprecipitation of mutant ARSA polypeptides. SETTING: genetic research and clinical unit, university hospital. RESULTS: Genetic analysis revealed homozygosity for a novel mutation in exon 3 of ARSA (F219V). This substitution leads to a misfolded unstable enzyme with a specific activity less than 1% of normal. There were no clinical or neurophysiologic signs of peripheral nervous system dysfunction. Typical neuropathologic signs for MLD were absent from nerve biopsy specimens. CONCLUSIONS: This novel mutation is associated with progressive psychocognitive impairment without clinical or electrophysiologic signs and only minor morphologic signs of peripheral nerve affection. The F219V substitution causes reduction in enzyme activity to an extent unexpected for an adult patient with MLD.- - - - - - - - - - ranking = 5.3529113394362keywords = nervous system, central nervous system (Clic here for more details about this article) |
10/45. Atypical leukodystrophy with accumulations of sulfatide and mucopolysaccharide.1. follow-up studies of two siblings with mental retardation, progressive paraplegia and dementia were reported. 2. The brain and visceral organs of a patient (elder brother) who died recently were investigated histopathologically, electronmicroscopically and neurochemically. a. Moderate, diffuse demyelination occurred throughout the white matter of the central nervous system. b. Two abnormal materials were deposited in the white matter: one showed metachromasia containing sulfatide and another had staining characteristics of acid mucopolysaccharide histochemically. Electronmicroscopically, the former was a conglomerate of electron-dense materials of various degrees and the latter had a membrane-limited granular structure. The myocardium contained the same mucopolysaccharide material as that in the brain. c. Slight increase of sulfatide was found in the cerebral white matter. Arylsulfatase A activities were preserved in the brain as well as in the liver. Contents of hexosamine and uronic acid in the white matter were about three or five times as much as that of the controls. electrophoresis on cellulose acetate membrane showed that acid glucopeptide was the main component of the mucopolysaccharide extracted from the brain.- - - - - - - - - - ranking = 3.4412653460653keywords = nervous system, central nervous system, brain (Clic here for more details about this article) |
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