Ruth H Walker

..These studies may provide a better understanding of the function of the associated proteins and provide insight into the pathogenesis of these disorders...

..STN interventions may achieve at least part of their therapeutic effect in PD by normalizing the location of corticostriatal glutamatergic terminals and by altering striatal glutamatergic neurotransmission...

..Other symptoms including psychiatric manifestations should be managed in a symptom-oriented manner. NA syndromes have a relentlessly progressive course usually over two to three decades...

..It resembles classic Huntington's disease in clinical phenotype, inheritance pattern, and neuropathological features. We highlight the clinical features of this disorder, including chorea, dystonia, parkinsonism, and cognitive deficits...

..The effects of lesions differed depending upon the presence of dopamine. These results suggest that short-term electrical stimulation does not result in a direct inhibitory effect upon the subthalamic nucleus...

..This further decrease in dopamine turnover with STN stimulation would serve to maintain dopamine levels in the dopamine-depleted striatum, and may account for the therapeutic benefit of DBS in Parkinson's disease...

..Here the clinical details of two additional cases are presented, of which the genetic details have previously been published...

..In this article, recent developments in the field are presented...

..As in other neurodegenerative conditions, animal models are a promising strategy for the development of such therapies...

..One of six previously identified patients with HDL2 had acanthocytosis on peripheral blood smear, suggesting that HDL2 should be considered in the differential of chorea-acanthocytosis...

..A functional interference with neuronal signal processing induced by mutation of torsinA is consistent with current hypotheses regarding impairment of the center-surround mechanism in the striatum...

..This phenotypic variation, despite shared mutations, suggests the action of disease-modifying factors that may explain some of the difficulties with genotype-phenotype correlation in McLeod syndrome...

..These data indicate that lesions of the ZI can affect striatal neurochemistry and motor behavioral asymmetry and suggest potential mechanisms by which ZI lesions may improve symptoms in PD...

..Although most therapies at present are supportive, correct diagnosis is essential for appropriate genetic counseling, and ultimately, for future molecular therapies...

..The non-synonymous to synonymous nucleotide substitution rate ratio (omega=dN/dS) in these genes was examined. CYBB and RPGR show evidence of positive selection, whereas DMD, XK and OTC are subject to selective constraint...

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..Together, these data implicate compromised DA release regulation, possibly from cholinergic dysfunction, in the motor symptoms of this dystonia model...

..The eponym Levine-Critchley syndrome, subsequently termed neuroacanthocytosis, has been applied to symptomatically similar, but genetically distinct, disorders, resulting in clinical and diagnostic confusion...

..The characteristic acanthocytic appearance of red blood cells is attributed to abnormalities of a membrane protein, band 3, although the relationship between this and the neurodegenerative process has yet to be determined...

..Patient 2 had a single base substitution in the 3' splice sequence of intron 2 (IVS2-2a>g). In both cases mutations resulted in the absence of XK protein...

..Overexpression of mutant torsinA failed to protect cells against trophic withdrawal. These results suggest that torsinA may play a protective role in neurons against a variety of cellular insults...

..An understanding of the role of torsinA in cellular function and the impact of the mutation (deletion of a glutamic acid at residue 303) is likely to provide insights into the etiopathogenesis of primary dystonia...

..Autosomal dominant alcohol-responsive M-D is associated with mutations in the epsilon-sarcoglycan gene (SGCE) (six families) and with a missense change in the D2 dopamine receptor (DRD2)gene (one family)...

..This transgenic mouse model demonstrates behavioral and pathologic features similar to patients with early-onset dystonia and may help to better understand the pathophysiology of this disorder and to develop more effective therapies...

..The connection between the erythrocyte membrane abnormality, which results in the characteristic "thorny" protrusions, the vulnerability of the basal ganglia, and the respective genetic mutations, is obscure...

..The distribution of torsinA in rat brain as demonstrated by immunohistochemistry contrasts with the results of in situ hybridization studies of torsinA mRNA in human postmortem brain in which a more limited distribution was found...

..In the patients who received acupuncture, nonsignificant trends toward improvement were noted in the Activities of Daily Living score of the PDQ-39, the PDQ-39 Summary Index(c) 2005 Movement Disorder Society...

..We conclude that astrocyte-neuron lactate transport is required for long-term memory formation...

..The haplotype background may influence the disease phenotype since in many previous Caucasian families with the P301L mutation, the haplotype background has been H2...

..This study provides further evidence to support the notion that although levodopa can be toxic to dopamine neurons in vitro, it is not likely to be toxic to dopamine neurons in vivo and specifically in conditions such as PD...

..These findings contrast with results of recent cell culture studies of torsinA...

..The substantia nigra pars compacta contained a normal number of neurons but decreased tyrosine hydroxylase immunoreactivity. There were no histopathological markers of other metabolic or degenerative diseases...

..0098). The results further support the evidence that the repeat expansion at the chromosome 16q24.3 locus is the direct cause of HDL2 and provide preliminary guidelines for the genetic testing of patients with an HD-like phenotype...

..In both of the latter families, we also found a mutation of SGCE. The molecular mechanisms through which the detected mutations may contribute to myoclonus-dystonia remain to be determined...

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..This review summarizes the current state of knowledge regarding this group of diseases in order to facilitate clinical recognition, accurate diagnosis and appropriate management...

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