Brain : a journal of neurology
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Case Reports
Inherited prion disease with an alanine to valine mutation at codon 117 in the prion protein gene.
A large English family with autosomal dominant segregation of presenile dementia, ataxia and other neuropsychiatric features is described. Diagnoses of demyelinating disease, Alzheimer's disease, Creutzfeldt-Jakob disease (CJD) and Gerstmann-Sträussler-Scheinker syndrome have been attributed to particular individuals at different times. An Irish family, likely to be part of the same kindred, is also described, in which diagnoses of multiple sclerosis, dementia, corticobasal degeneration and new variant CJD have been considered in affected individuals. ⋯ Here we describe the phenotypic spectrum of inherited prion disease (PrPA117V). The diversity of phenotypic expression seen in this kindred emphasizes the logic of molecular classification of the inherited prion diseases rather than classification by specific clinicopathological syndrome. Indeed, inherited prion disease should be excluded by PRNP analysis in any individual presenting with atypical presenile dementia or neuropsychiatric features and ataxia, including suspected cases of new variant CJD.
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Randomized Controlled Trial Multicenter Study Clinical Trial
Possible mechanisms of action of nitric oxide synthase inhibitors in chronic tension-type headache.
It has been demonstrated recently that nitric oxide synthase (NOS) inhibition has an analgesic effect in patients with chronic tension-type headache. The aim of the present study was to investigate the influence of the NOS inhibitor, L-N(G) methyl arginine hydrochloride (L-NMMA), on two of the most prominent features of chronic tension-type headache, i.e. increased muscle hardness and increased myofascial tenderness. In a double blind, crossover designed trial, 16 patients with chronic tension-type headache were randomized to receive intravenous infusion of 6 mg/kg L-NMMA or placebo on 2 days separated by at least 1 week. ⋯ Compared with baseline, muscle hardness, 107 +/- 17 kPa/cm and tenderness, 18 +/- 11 were significantly reduced at 60 and 120 min to: hardness, 101 +/- 17 kPa/cm and 101 +/- 17 kPa/cm, respectively; tenderness, 15 +/- 11 and 14 +/- 11, respectively, after treatment with L-NMMA (P < 0.05 and P < 0.01, respectively), while there was no significant reduction at any time after treatment with the placebo. Compared with the placebo, the summary score of muscle hardness was significantly reduced (P = 0.04), while tenderness showed a non-significant reduction (P = 0.11) following treatment with L-NMMA. Since increased muscle hardness in patients with chronic tension-type headache may reflect sensitization of second order neurons due to prolonged nociceptive input from myofascial tissues, we suggest that the decrease in muscle hardness following treatment with L-NMMA may be caused by reduction of central sensitization.
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Turning attention towards or away from a painful heat stimulus is known to modify both the subjective intensity of pain and the cortical evoked potentials to noxious stimuli. Using PET, we investigated in 12 volunteers whether pain-related regional cerebral blood flow (rCBF) changes were also modulated by attention. High (mean 46.6 degrees C) or low (mean 39 degrees C) intensity thermal stimuli were applied to the hand under three attentional conditions: (i) attention directed towards the stimuli, (ii) attention diverted from the stimuli, and (iii) no task. ⋯ The attentional network disclosed in this study could be further subdivided into a non-specific arousal component, involving thalamic and upper brainstem regions, and a selective attention and orientating component including prefrontal, posterior parietal and cingulate cortices. A further effect observed in response to high intensity stimuli was a rCBF decrease within the somatosensory cortex ipsilateral to stimulation, which was considered to reflect contrast enhancing and/or anticipation processes. Attentional processes could possibly explain part of the variability observed in previous PET reports and should therefore be considered in further studies on pain in both normal subjects and patients with chronic pain.
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Visual information is conducted by two parallel pathways (luminance- and contour-processing pathways) which are thought to be differentially affected in migraine and can be investigated by means of pattern-reversal visual evoked potentials (VEPs). Components and habituation of VEPs at four spatial frequencies were compared between 26 migraineurs (13 without aura, MO; 13 with aura, MA) and 28 healthy volunteers. Migraineurs were recorded in the headache-free interval (at least 72 h before and after an attack). ⋯ Habituation behaviour was not significantly different between groups under the stimulating conditions employed. Prolonged N2 latency might be explained by the lack or attenuation of a contour-specific component N130 in migraineurs, indicating an imbalance of the two visual pathways with relative predominance of the luminance-processing Y system. These results reflect an interictally persisting dysfunction of precortical visual processing which might be relevant in the pathophysiology of migraine.
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Diabetes mellitus can affect both the peripheral and the central nervous system. However, central deficits are documented less well than peripheral deficits. We therefore compared the course of development of neurophysiological changes in the central and peripheral nervous systems in streptozotocin-diabetic rats. ⋯ The present study demonstrates that in streptozotocin-diabetic rats the course of development of peripheral and central neurophysiological changes differs. Peripheral impairments develop within weeks after diabetes induction, whereas central impairments take months to develop. Insulin can reverse both peripheral and central neurophysiological alterations.