1/63. adult-type metachromatic leukodystrophy with a compound heterozygote mutation showing character change and dementia.A 26-year-old Japanese woman slowly developed a change of character such as hypospontaneity and blunted affect, followed by obvious mental deterioration. She was diagnosed as having a disorganized type of schizophrenia at the first examination. Brain magnetic resonance imaging demonstrated diffuse high intensity in the cerebral white matter, particularly in the frontal lobes. The single photon emission computed tomography images using 123I-IMP disclosed diffuse cerebral hypofusion, especially in the frontal lobes. Electroencephalogram showed a moderate amount of 5-6Hz theta waves on the background of alpha activity. Nerve conduction velocities in the extremities were delayed. The level of leucocyte arylsulphatase was low. In the arylsulphatase A gene analysis, a compound heterozygote having the 99Gly-->Asp and 409Thr-->Ile mutations was confirmed. The patient was diagnosed as having metachromatic leukodystrophy. She gradually showed obvious dementing symptoms such as memory disturbance and disorientation. The characteristics of the psychiatric symptoms in the leukodystrophy are discussed.- - - - - - - - - - ranking = 1keywords = organ (Clic here for more details about this article) |
2/63. 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 = 57.734878765112keywords = nerve (Clic here for more details about this article) |
3/63. adult-onset MLD: a gene mutation with isolated polyneuropathy.A 22-year-old man presented with recurrent ulnar mononeuropathies and diffusely slow nerve conduction velocities. Arylsulfatase A (ASA) activity from leukocytes and fibroblasts was reduced, and urinary sulfatides were increased. sural nerve biopsy revealed a reduction in myelinated fibers and Schwann cell inclusions. Results of studies of CNS integrity, including cranial MRI, evoked potentials, and neuropsychologic tests, were normal. Molecular genetic analyses revealed a novel homozygous missense mutation (Thr286Pro) in the ASA gene.- - - - - - - - - - ranking = 115.46975753022keywords = nerve (Clic here for more details about this article) |
4/63. 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 = 57.734878765112keywords = nerve (Clic here for more details about this article) |
5/63. adult metachromatic leukodystrophy: three cases with normal nerve conduction velocities in a family.Here, we report three cases of late onset metachromatic leukodystrophy (MLD) within a family. The patients presented with psychiatric disturbances and dementia. The arylsulphatase A (ASA) level in leucocytes was zero in all the patients. The cranial magnetic resonance imaging (MRI) revealed bilateral symmetrical demyelination but the nerve conduction velocities were normal in all three cases. The clinical, biochemical, imaging and electrophysiological data of the family has been discussed.- - - - - - - - - - ranking = 288.67439382556keywords = nerve (Clic here for more details about this article) |
6/63. 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 = 115.46975753022keywords = nerve (Clic here for more details about this article) |
7/63. 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 = 58.734878765112keywords = nerve, organ (Clic here for more details about this article) |
8/63. Metachromatic leukodystrophy: on an atypical case.We describe an atypical case of juvenile metachromatic leukodystrophy. Motor conduction velocity was still within the normal range 3 years after clinical onset, in contrast to what is commonly found in this disease. Another unusual feature is the normal level of CSF protein. These data are discussed in the light of the sural nerve biopsy findings, which revealed only slight impairment.- - - - - - - - - - ranking = 57.734878765112keywords = nerve (Clic here for more details about this article) |
9/63. Late onset MLD with normal nerve conduction associated with two novel missense mutations in the ASA gene.Metachromatic leukodystrophy (MLD) rarely has its clinical onset in young adults, with a combination of cognitive and behavioural symptoms and peripheral neuropathy. Here we present an exceptional case with very late onset at 42 years of age and no clinical or neurophysiological sign of peripheral neuropathy. Molecular analysis revealed compound heterozygosity for two novel missense mutations affecting conserved residues in the arylsulphatase A (ASA) sulphatase and carboxyterminal domains, resulting in an 89% loss of enzymatic activity. This case indicates that MLD needs to be considered in the differential diagnosis of very late onset white matter diseases, even if not accompanied by peripheral nerve involvement.- - - - - - - - - - ranking = 288.67439382556keywords = nerve (Clic here for more details about this article) |
10/63. Multifocal slowing of nerve conduction in metachromatic leukodystrophy.Polyneuropathy is invariably associated with the late-infantile form of metachromatic leukodystrophy (MLD), and occurs frequently in the early juvenile, juvenile, and adult variants. Uniform slowing of nerve conduction velocity is the neurophysiologic hallmark of metachromatic leukodystrophy and other inherited demyelinating polyneuropathies. To evaluate the consistency of this principle, we reviewed nerve conduction studies in 9 children with late-infantile or early-juvenile metachromatic leukodystrophy. Each child had significant slowing of motor nerve conduction velocity (NCV). The compound muscle action potentials showed abnormal temporal dispersion in 3 of the 9 children, which is usually regarded as the hallmark of acquired demyelinating polyneuropathies. There are reports of multifocal slowing in other hereditary processes including X-linked charcot-marie-tooth disease, hereditary neuropathy with liability to pressure palsies, and adrenomyeloneuropathy. Although multifocal NCV slowing in a child with polyneuropathy is seen most commonly in acquired conditions, a hereditary process, including MLD, cannot always be excluded in this setting.- - - - - - - - - - ranking = 404.14415135578keywords = nerve (Clic here for more details about this article) |
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