SciCombinator

Discover the most talked about and latest scientific content & concepts.

Journal: Journal of the neurological sciences

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The scope of this study is the examination of NO(2)+NO(3), 3-nitrotyrosine (3-NT), S-nitrosothiols (RSNO), arginase activity and asymmetric (ADMA) and symmetric (SDMA) dimethyl-l-arginine concentrations in plasma of MS patients during interferon-β1b therapy.

Concepts: Amino acid, Multiple sclerosis, Nitrogen, Endothelium, Nitric oxide, Asymmetric dimethylarginine, Arginine, Nitric acid

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To develop an objective and precise neurophysiologic method from which to identify and characterize the presence and magnitude of relative afferent pupillary defects (RAPD) in patients with MS.

Concepts: Pupil

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Paroxysmal nonkinesigenic dyskinesia (PNKD) is a rare disorder in autosomal dominant inheritance. The clinical features and genetic findings of PNKD, rarely described in the Asians, were mostly delineated from European families. The present study characterized the clinical and genetic findings of a Taiwanese PNKD family. The clinical features of our five patients in successive three generations included onset age less than 10years, attack duration between 3min and 4h, and a variety of aura symptoms. The attacks were provoked not by sudden action but by emotional stress, caffeine, fatigue, heavy exercise and sleep deprivation. Sleep could abolish or diminish the attack and the attacks responded well to clonazepam. Sequencing the whole coding region of PNKD/MR-1 gene identified a heterozygous c.20C>T (p.Ala7Val) mutation which was clearly segregated in the five affected patients. Comparing our patients with previously reported 18 families with PNKD/MR-1 mutations, the majority of the patients exhibited quite similar manifestations in attack patterns and precipitating factors. The recurrent conservative mutations in different ethnicities indicate importance in the pathogenesis of PNKD.

Concepts: Family, Immune system, DNA, Genetics, Mutation, Sleep deprivation, Attack, Attack!

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PURPOSE: To investigate the incidence of retrocollis and to determine its clinical correlates in patients with idiopathic Parkinson’s disease (PD). METHODS: Seventy-four patients with PD at Hoehn and Yahr stage 5 were examined for abnormal neck postures and were classified according to neck posture. Differences in age, age at PD onset, disease duration, years from PD onset to Hoehn and Yahr stage 5, cognitive state, the levodopa equivalent dose (LED) for dopaminergic drugs, and rigidity of the neck and upper and lower extremities were examined to determine the clinical correlates of abnormal neck posture. We also evaluated retrocollis in 356 patients with PD at Hoehn and Yahr stage 1, 2, 3, and 4 and 65 age matched normal controls. RESULTS: Of the 74 patients with PD at Hoehn and Yahr stage 5 examined, 21 (28.4%) had retrocollis, 3 (4.1%) had antecollis, and 1 (1.4%) had antecollis and torticollis. Whereas, only one patient had retrocollis in PD patients at Hoehn and Yahr stage 4 and under. Patients with antecollis were significantly younger than those with normal neck posture and retrocollis. There were no differences in age at PD onset, disease duration, sex, years from PD motor symptom onset to Hoehn and Yahr stage 5, cognitive state, or LED between patients with and without abnormal neck postures. Neck rigidity scores were significantly higher in patients with retrocollis and antecollis than in those with normal neck posture. CONCLUSIONS: Retrocollis is not rare in patients with PD at Hoehn and Yahr stage 5, and the incidence appeared to increase as axial rigidity increased.

Concepts: Epidemiology, Death, Medical terms, Parkinson's disease, Dopamine, Hoehn and Yahr scale

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Since the era of Gaupp who introduced the concept of atheroscletic depressive disorder, the concept of late-life depression has been correlated with cerebrovascular comorbidities, microvascular lesions, frontal cortical and subcortical gray and white matter hyperintensities. The predominant neuropsychological deficits concern the domains of planning, organization and abstraction, with executive dysfunction being the predominant finding. MRI studies reveal a higher prevalence of white matter lesions in elderly patients with depression. Molecular mechanisms underlying the disease still remain unclear. Hyperhomocysteinemia has been associated with depression through its toxicity to neurons and blood vessels. Endothelial dysfunction is another possible mechanism referring to the loss of vasodilatation capacity. Inflammatory phenomena, such as increased peripheral leucocytes, elevated CRP and cytokine levels, could play a role in endothelial dysfunction. In this review we will briefly combine findings from neurobiological, epidemiological, structural and post-mortem data. A more complex model in late-life depression combining different modalities could be an elucidating approach to the disease’s etiopathogeny in the future.

Concepts: Inflammation, Blood vessel, Cognitive science, Endothelium, Attention-deficit hyperactivity disorder, Major depressive disorder, Dysthymia, Subcortical ischemic depression

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A mitochondrial dysfunction causes an abatement in ATP production, the induction of oxidative damage and the propagation of cell death pathways. It is additionally closely related to both glutamate excitotoxicity and neuroinflammation. All of these interconnected aspects of a cellular dysfunction are involved in the pathogenesis of numerous neurological disorders, including those with an acute (e.g. ischemic stroke) or a chronic (e.g. Huntington’s disease) onset. Both acute and chronic neurodegenerative disorders have been demonstrated to involve multiple imbalances of the kynurenine pathway metabolism in the pathogenesis of the disease. As regards neuroactive compounds featuring in the pathway, quinolinic acid is a specific agonist of N-methyl-d-aspartate receptors, and a potent neurotoxin with additional and marked free radical-producing and lipid peroxidation-inducing properties. The toxic effects of 3-hydroxy-L-kynurenine are mediated by free radicals. Besides the possibility of increasing brain kynurenic acid concentrations, L-kynurenine may have vasoactive properties, too. Kynurenic acid has proven to be neuroprotective in several experimental settings, but in consequence of its pharmacokinetic properties it is not applicable as systemic administration in human cases. The aim of this short review is to emphasize the common features of cerebral ischemia and Huntington’s disease and to highlight therapeutic strategies targeting the kynurenine pathway.

Concepts: Adenosine triphosphate, Stroke, Traumatic brain injury, Oxidative phosphorylation, Neurology, Excitotoxicity, Kynurenic acid, Kynurenine

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OBJECTIVES: Sleep disorders, especially restless legs syndrome (RLS) and rapid eye movement sleep behavior disorder (RBD), are common in spinocerebellar ataxia type 3 or Machado-Joseph disease (MJD), and a possible underlying dopaminergic dysfunction is implicated. This study assessed the relationship between sleep disorders in MJD and dopamine transporter (DAT) densities. PATIENTS AND METHODS: Twenty-two patients with MJD and twenty healthy subjects were enrolled in this study. MJD patients underwent clinical sleep evaluation and polysomnography. SPECT with [(99m)Tc]-TRODAT-1, was performed in all subjects. RESULTS: DAT densities were significantly reduced in MJD group when compared to controls. No significant correlation was found between DAT densities and RLS or RBD in MJD. CONCLUSION: Our study failed to demonstrate a clear correlation between sleep disorders and DAT densities in MJD patients, hence suggesting that extrastriatal and non-presynaptic dopamine pathways could be implicated in MJD-related sleep disorders.

Concepts: Sleep, Dopamine, Rapid eye movement sleep, Spinocerebellar ataxia, Pramipexole, Restless legs syndrome, Machado-Joseph disease, Periodic limb movement disorder

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Adult polyglucosan body disease (APBD) is a metabolic disorder usually caused by glycogen branching enzyme (GBE) deficiency. APBD associates progressive walking difficulties, bladder dysfunction and, in about 50% of the cases, cognitive decline. APBD is characterized by a recognizable leukodystrophy on brain MRI. We report here a novel presentation of this disease in a 35-year old woman who presented with an acute deterioration followed by an unexpected recovery. Enzymatic analysis displayed decreased GBE activity in leukocytes. Molecular analyses revealed that only one mutated allele was expressed, bearing a p.Arg515His mutation. This is the first observation reporting acute and reversible neurological symptoms in APBD. These findings emphasize the importance of searching GBE deficiency in patients presenting with a leukodystrophy and acute neurological symptoms mimicking a stroke, in the absence of cardiovascular risk factors.

Concepts: Brain, Metabolism, Enzyme, Glycogen storage disease, Enzymes, Glycogen storage disease type IV, Glycogen branching enzyme, Glycogen branching enzyme deficiency

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BACKGROUND: Vitamin B12 deficiency is a well recognized cause of posterolateral myelopathy. In Indian subcontinent, it may coexist with nutritional copper deficiency producing partial response of patients to B12 supplementation. Hence the study was planned to look for association of hypocupremia and B12 deficiency. METHODS: Twenty-three patients with posterolateral myelopathy (Romberg sign positive) were enrolled and investigated for levels of vitamin B12, copper and zinc and followed up for six months. RESULT: In three patients, copper deficiency alone was found to be the cause. In another three, both copper and vitamin B12 were deficient. In all these six patients, ceruloplasmin and 24h urinary copper were found to be low suggesting dietary copper deficiency. Hyperzincemia was found in four of these patients. Magnetic resonance imaging of spine was normal in lone Cu deficient patients but showed T2 hyperintensity of posterior column in lone B12 or combined B12 and copper deficiency. CONCLUSION: In cases of B12 deficiency myelopathy not responding to supplementation, copper deficiency must be sought at the earliest to avoid and treat persistent neurological disability.

Concepts: Nutrition, Magnetic resonance imaging, Zinc, Copper, Megaloblastic anemia, Vitamin B12, Vitamin B12 deficiency, Subacute combined degeneration of spinal cord

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A 69-year old man presents with a subacute history of worsening confusion, anxiety and abnormal gait. Brain MRI revealed an extensive non-enhancing signal abnormality of parieto-occipito-temporal white matter. CSF PCR was positive for JC virus, suggestive of progressive multifocal leukoencephalopathy (PML). Extensive workup for occult immunosuppression was negative. Although PML in an immunocompetent patient is exceedingly rare, biopsy confirmed the diagnosis. Mirtazapine and mefloquine therapies were initiated and JCV DNA titre decreased by 100-fold at six months. One year later, his clinical course had stabilized and neuroimaging was improved. Our case suggests that PML can rarely afflict immunocompetent individuals and that serotonin receptor targeting pharmacological therapy may improve the outcome.

Concepts: AIDS, Protein, Medicine, Serotonin, Progressive multifocal leukoencephalopathy, JC virus, Polyomavirus, 5-HT2C receptor