Brain : a journal of neurology
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Five patients with small-fibre neuropathy characterized by temperature-dependent spontaneous pain, hyperalgesia/allodynia and signs of neurogenic inflammation were studied clinically and thermographically, and by microneurography. Thermography revealed hyperthermia confined to painful and hyperalgesic skin of distal extremities, in absence of sympathetic vasomotor denervation. Quantitative sensory testing documented either reduced thresholds or increased suprathreshold magnitude for heat pain. ⋯ Impulse doubling has previously been reported as occurring rarely in normal subjects and is attributable to unfiltering of multiple orthodromic impulses due to unidirectional conduction failure at branch points. A higher incidence of double firing in neuropathic pain patients is probably due to a reduced safety factor for conduction in the terminal arborizations of their C-nociceptors. These observations show that unidirectional conduction block provides a peripheral mechanism of temperature-dependent nociceptor hyperactivity in small-fibre neuropathy that may contribute to hyperalgesia.
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Common abnormalities within the schizophrenia spectrum may be essential for the pathogenesis of schizophrenia, but additional pathological changes may be required for the development of full-blown schizophrenia. Clarifying the neurobiological similarities and differences between established schizophrenia and a milder form of schizophrenia spectrum disorder would potentially discriminate the pathophysiological mechanisms underlying the core features of the schizophrenia spectrum from those associated with overt psychosis. High-resolution MRIs were acquired from 25 patients with schizotypal disorder, 53 patients with schizophrenia and 59 healthy volunteers matched for age, gender, handedness and parental education. ⋯ There were no significant between-group differences in volumes of the ventral medial prefrontal cortex or the orbitofrontal cortex. These findings suggest that volume reductions in the amygdala and hippocampus are the common morphological substrates for the schizophrenia spectrum, which presumably represent the vulnerability. Additional widespread involvement of the prefrontal cortex in schizophrenia may lead to the loss of inhibitory control in other brain regions and suggests (although it is not specifically be related to) its critical role in the manifestation of overt psychosis.
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Cerebral small-vessel disease is common in older people and may contribute to the development of dementia. The objective of the present study was to evaluate the relationship between measures of cerebral small-vessel disease on MRI and the rate of decline in specific cognitive domains in participants from the prospective, population-based Rotterdam Scan Study. Participants were 60-90 years of age and free from dementia at baseline in 1995-1996. ⋯ After exclusion of participants with an incident stroke, some of the associations of periventricular WML, brain infarcts and generalized brain atrophy with measures of information processing speed and executive function were no longer significant. This may indicate that stroke plays an intermediate role in the relationship between cerebral small-vessel disease and cognitive decline. Our results suggest that in older people cerebral small-vessel disease may contribute to cognitive decline by affecting information processing speed and executive function.
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To investigate postoperative changes in the cerebral glucose metabolism of patients with mesial temporal lobe epilepsy (MTLE), statistical parametric mapping (SPM) analysis was performed on pre- and postoperative (18)F-fluorodeoxyglucose PET (FDG-PET) images. We included 28 patients with MTLE who had undergone surgery and had been seizure-free postoperatively (16 had left MTLE and 12 right MTLE). All patients showed hippocampal sclerosis by pathology or brain MRI. ⋯ Subtraction between pre- and postoperative FDG-PET images in individual patients produced similar findings to the SPM results, and additionally showed that postoperative glucose metabolism increased in the anterior thalamus in 12/28 patients (42.8%). SISCOM (subtraction ictal-interictal SPECT co-registered to MRI) performed in 17 patients showed ictal hyperperfusion in the ipsilateral temporal lobe, including the temporal stem white matter, midbrain, insular cortex and cingulate gyrus, bilateral basal ganglia and thalami, and multiple small regions in the frontoparietal lobes during seizures. This study suggests that brain regions showing a postoperative increase in glucose metabolism appear to represent the propagation pathways of ictal and interictal epileptic discharges in MTLE, whereas the postoperative decrease in glucose metabolism may be related to a permanent loss of afferents from resected anterior-mesial temporal structures.
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Gain-of-function mutation in Nav1.7 in familial erythromelalgia induces bursting of sensory neurons.
Erythromelalgia is an autosomal dominant disorder characterized by burning pain in response to warm stimuli or moderate exercise. We describe a novel mutation in a family with erythromelalgia in SCN9A, the gene that encodes the Na(v)1.7 sodium channel. ⋯ We demonstrate that this mutation, which produces a hyperpolarizing shift in activation and a depolarizing shift in steady-state inactivation, lowers thresholds for single action potentials and high frequency firing in dorsal root ganglion neurons. Erythromelalgia is the first inherited pain disorder in which it is possible to link a mutation with an abnormality in ion channel function and with altered firing of pain signalling neurons.