Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0040822 (tremor)
 18,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Calcineurin inhibition with tacrolimus has been used after renal transplantation (RTPL) as rescue therapy for insufficient immunological control or if cyclosporin A (CSA) toxicity occurred. Neurologic side-effects occur but are rare in children, usually presenting as tremor; however, serious complications, e.g. the posterior leukoencephalopathy syndrome are also documented. Twenty children (10 girls) were switched to tacrolimus: 11 (55%) for immunological reasons (n = 9: steroid-resistant rejection; n = 2: recurrent rejections) and nine for CSA side-effects. Tacrolimus was started at a median of 8 wk (range 10 d to 8.7 yr) after RTPL and was continued for a median of 2.5 yr (range 5 wk to 4.6 yr). Renal function significantly improved over a period of 12 months following conversion to tacrolimus (glomerular filtration rate 56 +/- 19 vs. 66 +/- 16 mL/min/1.73 m2; p < 0.03; n = 13). Fifteen of 20 (75%) patients tolerated tacrolimus well. The most frequent side-effects were neuropsychological and behavioral symptoms in three children, ranging from anorexia nervosa-like symptoms with weight loss, amenorrhea, depression and school problems to severe insomnia and to aggressive and anxious behavior in one child. Only the latter child was exposed to toxic tacrolimus blood levels. All side-effects were fully reversible after discontinuation of tacrolimus. In conclusion, tacrolimus had a beneficial effect on renal function and was well tolerated in the majority of pediatric patients. However, neuropsychologic and behavioral side-effects are important and maybe underrecognized in children.
 ...
PMID:Neuropsychologic side-effects of tacrolimus in pediatric renal transplantation. 1270 79

Two wirehaired dachshund puppies were presented with generalized tremor and gait abnormalities characterized by mild ataxia, tetraparesis and slightly abnormal proprioception. Neurological examination led to the suspicion of a diffuse generalized white matter lesion. Computerized tomography and pathological examination revealed a remarkable unilateral dilatation of the lateral ventricles in each dog. Histopathological examination showed a severe reduction of stainable myelin, widespread mild perineuronal oedema with vacuolations and multifocal reactive astrocytosis affecting the subcortical and deep periventricular white, and to a lesser degree, grey matter of the cerebral hemispheres, most prominently at the level of the optic chiasm. Axons showed a moderately reduced packing density; some axons were irregularly shaped and slightly thickened. There was no evidence of myelin breakdown products and neurones appeared to be well preserved. Brain stem, cerebellum and spinal cord were normal, as was the peripheral nervous system. This leukoencephalopathy in two dachshund puppies most closely resembles human periventricular leukomalacia caused by pre- or perinatal hypoxia-ischaemia.
 ...
PMID:Periventricular and subcortical leukoencephalopathy in two dachshund puppies. 1553 12

Vanishing white matter disease is a recently described leukoencephalopathy that is characterized by chronic and episodic neurological deterioration. These episodes often follow periods of fever or minor head trauma. It frequently presents in childhood with problems of ataxia and tremor. Five genes have been identified for the disease, EIF2B1-5, which encode the five subunits of translation initiation factor eIF2B. Mutations in each of the genes may independently cause the disease. The defect in eIF2B results in abnormalities in translation and its regulation, leading to abnormalities in protein synthesis and its regulation. Magnetic resonance imaging of the brain reveals extensive cerebral white matter abnormalities with evidence of white matter rarefaction and cystic degeneration, which has been confirmed pathologically. We report the first confirmed Australasian patient.
 ...
PMID:Vanishing white matter disease in a child presenting with ataxia. 1567 Feb 29

L-2-hydroxyglutaric aciduria (L2HGA) is a chronic slowly progressive neurodegenerative disease characterized mainly by psychomotor developmental delay and cerebellar dysfunction. We report the clinical, biochemical, and neuroimaging features of 29 patients from 22 families. The mean age at the time of diagnosis was 13.4 years (2.5-32 years). The mean follow-up period of patients was four years (1.5-16 years). The main clinical findings were mental retardation and cerebellar involvement with ataxic gait and intentional tremor. Additional findings were mental retardation, macrocephaly and seizures. Diagnosis was confirmed by increased urinary excretion of L-2-hydroxyglutaric acid in all patients and highly specific magnetic resonance imaging (MRI) pattern showing subcortical leukoencephalopathy with bilateral high signal intensity in dentate nuclei and putamens. During the follow-up period, all patients had a static encephalopathy course. The underlying metabolic defect and the possible role of L-2-hydroxyglutaric acid are studied in a subgroup of these families and under evaluation for publication.
 ...
PMID:L-2-hydroxyglutaric aciduria: a report of 29 patients. 1588 21

Adult-onset dominant leukodystrophies are a heterogeneous group of rare disorders, whose etiology, pathogenesis and molecular background are still unknown. We report the neuropathological and biochemical investigations of the brains and their myelin proteins components in 2 members of an Italian family affected by an adult-onset autosomal dominant leukoencephalopathy. Clinical signs included spastic paraparesis, pseudobulbar syndrome, action tremor of head and hands, and moderate memory impairment. No mental deterioration or neuropathy was present. Onset was subacute (range 42-53 years) and progression spanned 4 to 7 years. The neuropathological phenotype overlapped that of orthochromatic leukodystrophies. The biochemical analysis revealed an abnormal myelin-associated glycoprotein (MAG); the defect was localized at the C-terminal domain of the L-MAG isoform, resulting in a protein approximately 5 kDa shorter than the normal counterpart. No mutation in the MAG gene-coding regions was uncovered, and linkage analysis formally excluded the entire MAG locus. We show that the identified MAG protein alteration is probably due to an abnormal post-translational event. Considering MAG function in the maintenance of myelin, the abnormal protein may have a role in the pathogenesis of this disease. This is the first report of a possible pathogenetic role of MAG in a hereditary disease affecting the central white matter.
 ...
PMID:Myelin-associated glycoprotein is altered in a familial late-onset orthochromatic leukodystrophy. 1591 83

Leukoencephalopathy with vanishing white matter (VWM), also called childhood ataxia with central nervous system hypomyelination (CACH), is an autosomal recessive disease caused by mutations in any of the five genes encoding subunits of the eukaryotic translation initiation factor eIF2B. Neuropathological findings comprise a severe, cavitating orthochromatic leukodystrophy with only small amounts of myelin breakdown products, and predominantly involving the cerebral hemispheric white matter. Within the white matter abnormal oligodendroglial cells are present with abundant "foamy" cytoplasm. In some regions oligodendroglial cells are increased in numbers. We present three sisters, 18, 11 and 8 years old, with the early to late childhood phenotype. The first signs of the disease were gait disturbances at 4, 2 and 6 years of age, respectively. Neurological examination showed mild tremor of hands and head, truncal ataxia, dysarthria, and hypotonia, after several years followed by spasticity. The course of the disease was slowly progressive. Intellectual abilities are relatively spared. The MRI showed diffusely abnormal white matter of the cerebral hemispheres. The FLAIR images revealed rarefaction of the affected white matter with some stripe-like structures, suggesting the presence of remaining tissue strands. The abnormalities were most pronounced with the middle sister, who had the earliest onset of the disease. A homozygous point mutation in the EIF2B2 gene was found, 638A>G. Both the parents were found to be carriers of this mutation. This is the first description of a Polish family with VWM.
 ...
PMID:Leukoencephalopathy with vanishing white matter due to homozygous EIF2B2 gene mutation. First Polish cases. 1682 98

Neurologic complications (NCs) are a significant cause of morbidity and mortality in patients who undergo liver transplantation (LT). The aim of this study was to evaluate the incidence and type of NCs and associated factors in pediatric LT patients. We retrospectively reviewed NCs in the medical records of 40 consecutive infants, children, and adolescents who underwent LT at our institution. The subjects consisted of 23 boys and 17 girls (median age, 8.5 +/- 0.85 yr; range, 11 months to 17 yr). The indications for LT were Wilson's disease in 10 patients, fulminant hepatic failure (FHF) in nine, and other types of chronic liver disease in 21. NCs were found in 14 patients (35%). Those 14 individuals experienced a total of 16 episodes of NCs (two separate episodes in two of the patients). The most common NCs were seizure (seven episodes in six patients) and posterior leukoencephalopathy syndrome (PLES; five episodes in four patients). Seizure was the presenting symptom in three episodes of PLES. Two episodes of diffuse encephalopathy were observed in two patients, and two episodes of psychiatric symptoms occurred in two patients. We also noted one episode of tremor in one patient, one episode of acute dystonic reaction in one patient, and one episode of headache in one patient. Patients with Wilson's disease had a higher incidence of NCs (60%) than did patients without Wilson's disease (26.7%); however, this difference was not significant. The incidence of NCs was 44% in patients with FHF and 35% in those without FHF. That difference also was not significant. Immunosuppressive agents were the primary cause of 13 of the 16 episodes of NC. Uremia with hypertension, hypoxia, and hypomagnesemia caused one neurologic episode each. NCs, which are frequent in the first 30 days after pediatric LT, did not affect survival in this group. NCs were reversed by the discontinuation or reduction of immunosuppressive agents in 12 episodes, correction of hypomagnesemia and the reduction of immunosuppressive agents in one episode, and the correction of uremia and hypertension in one episode. Refractory epilepsy developed in one patient, and death unrelated to NCs occurred in one. The mortality rate was 7.1% (n = 1) in patients with NCs and 15.4% (n = 4) in those without NCs (p = 0.64). NCs are an important complication after LT. It is essential that each transplantation team collaborate with pediatric neurologists to ensure the rapid and accurate diagnosis of NCs in infants, children, and adolescents after LT and to prevent the delay of appropriate treatment.
 ...
PMID:Neurological complications of liver transplantation in pediatric patients: a single center experience. 1730 Apr 94

To describe a family with a hereditary ferritinopathy (HF) due to a mutation in the ferritin light chain gene (FTL498-499InsTC mutation). Case reports of the clinical features, MRI, (18)FDG PET, and pathological findings observed in this family with two patients described in more details. Postural tremor (phenotype-1) or cerebellar signs (phenotype-2) were the first neurological symptoms detected. Parkinsonian, cerebellar and pyramidal syndromes, abnormal involuntary movements, dementia were observed in both phenotypes at more advanced stages. Beside characteristics T2* hypointense signals suggestive of iron accumulation in the striatum, mesencephalon, and cerebellum, we detected more diffuse changes including cerebellar, cortical and subcortical atrophy, cortical iron deposition, and severe leukoencephalopathy. (18)FDG PET showed frontal and cerebellum hypometabolism with more severe frontal defect in patients with cognitive decline. Pathological examination showed ferritin and iron deposition in the liver, kidney, muscle, skin, and in the central nervous system. Members of this family affected by HF due to the FTL498-499InsTC mutation have a specific clinical presentation with initial postural tremor or cerebellar ataxia, followed by pyramidal and extrapyramidal motor syndromes and late severe subcortical dementia.
 ...
PMID:Clinical phenotype and neuroimaging findings in a French family with hereditary ferritinopathy (FTL498-499InsTC). 1951 68

An array of movement disorders is associated with ethanol, illicit drugs, and tobacco. Heavy ethanol users experience withdrawal tremor and, less often, withdrawal parkinsonism, chorea, and myoclonus. Asterixis is a feature of hepatic failure. On the other hand, ethanol can ameliorate essential tremor and myoclonus-dystonia. Among opioid drugs, meperidine can precipitate myoclonus. Severe parkinsonism affected users of a synthetic meperidine analog contaminated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Spongiform leukoencephalopathy, sometimes with chorea and myoclonus, occurred in inhalers of heroin vapor (chasing the dragon). Psychostimulants including cocaine acutely cause stereotypies and dyskinesias. Phencyclidine toxicity causes myoclonus. Tobacco use, on the other hand, protects against Parkinson's disease. Clinicians need to consider substance abuse in patients with unexplained movement disorders.
 ...
PMID:Substance abuse and movement disorders. 2072 28

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a genetically transmitted small vessel disease clinically characterized by migraine, recurrent subcortical strokes, and cognitive and mood disorders. Pathogenic mutations are located on any of the exons of the NOTCH3 gene coding for epidermal-growth factor (EGF)-like repeats of the extracellular domain of the NOTCH3 receptor. Because the gene is large and the mutations cluster on some exons, many laboratories restrict the analysis to these exons. We report the first missense mutation involving exon 24 and causing CADASIL in a 64-year-old man. The patient was admitted to the hospital for a loss of consciousness accompanied by profuse sweating. On examination, some parkinsonian features were present. Over the last 4 years, he had developed postural instability and gait disturbances with repeated falls, behavioral disorders, and cognitive impairment. A diagnostic hypothesis of atypical parkinsonism had been advanced. The presence of multiple subcortical lacunar infarcts and leukoencephalopathy extended to the external capsule on cerebral MRI suggested the presence of CADASIL. The diagnosis was confirmed by finding a heterozygous mutation leading to a cysteine substitution on exon 24 of the NOTCH3 gene. One proband's brother, who had progressive gait disturbances, unilateral action tremor and bradykinesia, and an asymptomatic niece also resulted affected. This report underlines that when CADASIL is suspected the genetic analysis should be performed on all the NOTCH3 exons coding for EGF-like repeats including exon 24 and confirms that CADASIL may have heterogeneous phenotypes.
 ...
PMID:First report of a pathogenic mutation on exon 24 of the NOTCH3 gene in a CADASIL family. 2140 6


<< Previous 1 2 3 4 Next >>