Brain : a journal of neurology
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Multicenter Study
Dissociation of phantom limb phenomena from stump tactile spatial acuity and sensory thresholds.
Most amputees experience phantom limb sensations and/or phantom limb pain as well as residual limb (stump) pain that are resistant to treatment. Phantom phenomena are not homogeneous; each patient presents with a unique combination of spontaneous or evoked sensations, pain, and/or awareness. In an effort to understand the underlying mechanisms, postamputation pain has been subclassified based on the perceived sensory qualities reported by the individual. ⋯ Thus, despite a common injury, the sensory abnormalities varied within this cohort of subjects. In addition, psychophysical threshold measures of sensory function did not reflect, in any simple way, subjective phantom phenomena. Therefore, classification of phantom phenomena based on peripheral sensory function may be a misleading step in the search for specific mechanisms underlying postamputation sensory phenomena.
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Multicenter Study
Grey and white matter flumazenil binding in neocortical epilepsy with normal MRI. A PET study of 44 patients.
In 20-30% of potential surgical candidates with refractory focal epilepsy, standard MRI does not identify the cause. gamma-Aminobutyric acid (GABA) is the principal inhibitory neurotransmitter in the brain. [(11)C]Flumazenil (FMZ) PET images most subtypes of GABA(A) receptors, present on most neurons. We investigated [(11)C]FMZ binding in grey and white matter in 16 normal controls and in 44 patients with refractory neocortical focal epilepsy and normal optimal MRI. Fourteen patients had unilateral frontal lobe epilepsy, five occipital lobe epilepsy (OLE), six parietal lobe epilepsy (PLE) and 19 neocortical epilepsy that was not clearly lobar. ⋯ In seven patients, the increases in FMZ binding were periventricular, in locations normally seen in periventricular nodular heterotopia on MRI. There were frontal and parietal increases in FMZ binding in grey and white matter in the PLE group and decreases in the cingulate gyrus in the OLE group. FMZ binding increases, particularly periventricular increases, were a prominent feature of MRI-negative focal epilepsies and may represent neuronal migration disturbances.
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Review Multicenter Study
Demyelinating and axonal features of Charcot-Marie-Tooth disease with mutations of myelin-related proteins (PMP22, MPZ and Cx32): a clinicopathological study of 205 Japanese patients.
Three genes commonly causing Charcot-Marie-Tooth disease (CMT) encode myelin-related proteins: peripheral myelin protein 22 (PMP22), myelin protein zero (MPZ) and connexin 32 (Cx32). Demyelinating versus axonal phenotypes are major issues in CMT associated with mutations of these genes. We electrophysiologically, pathologically and genetically evaluated demyelinating and axonal features of 205 Japanese patients with PMP22 duplication, MPZ mutations or Cx32 mutations. ⋯ Median nerve MCVs were well maintained independently of age, disease duration and the severity of clinical and pathological abnormalities, confirming that median nerve MCV is an excellent marker for the genetically determined neuropathic phenotypes. Amplitude of CMAPs was correlated significantly with distal muscle strength in PMP22 duplication, MPZ mutations and Cx32 mutations, while MCV slowing was not, indicating that clinical weakness results from reduced numbers of functional large axons, not from demyelination. Thus, the three major myelin-related protein mutations induced varied degrees of axonal and demyelinating phenotypic features according to the specific gene mutation as well as the stage of disease advancement, while clinically evident muscle wasting was attributable to loss of functioning large axons.
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Multicenter Study
Phenotypic variants of autoimmune peripheral nerve hyperexcitability.
Clinicians use many terms including undulating myokymia, neuromyotonia, Isaacs' syndrome and Cramp-Fasciculation Syndrome to describe the motor manifestations of generalized peripheral nerve hyperexcitability (PNH). Our previous findings in a selected group of patients with undulating myokymia or neuromyotonia, and EMG doublet or multiplet ('myokymic') motor unit discharges, indicated that an autoantibody-mediated potassium channelopathy was likely to be the cause of their disorder. This prompted us to search for a common pathogenesis in a wider spectrum of PNH syndromes. ⋯ We conclude that autoimmunity, and specifically VGKC antibodies in many cases, are strongly implicated in the pathogenesis of both groups, and that the EMG features reflect quantitative rather than qualitative differences between the diverse clinical syndromes. These findings also have relevance for disease management. A classification is proposed that distinguishes immune-mediated PNH (irrespective of whether VGKC antibodies are detectable by standard assays) from non-immune forms of PNH that include toxins, anterior horn cell degeneration in motor neurone disease and genetic disorders.
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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.