Brain : a journal of neurology
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Comparative Study
The time course of epidermal nerve fibre regeneration: studies in normal controls and in people with diabetes, with and without neuropathy.
We sought to develop and validate a standardized cutaneous nerve regeneration model and to define the rate of epidermal nerve fibre (ENF) regeneration first in healthy control subjects and then in neuropathic and neuropathy-free subjects with diabetes. Next, we assessed the effect of different factors on the rate of nerve fibre regeneration and investigated whether such an approach might offer insight into novel trial designs and outcome measures. All subjects had a standardized topical capsaicin dressing applied to the distal lateral thigh. ⋯ First, topical capsaicin application can produce a uniform epidermal nerve fibre injury that is safe and well tolerated, and offers an efficient strategy to measure and study nerve regeneration in man. Secondly, using our techniques, reduced rates of nerve regeneration were found in people with diabetes without evidence of neuropathy and indicate that abnormalities in peripheral nerve function are present early in diabetes, before signs or symptoms develop. These results suggest that regenerative neuropathy trials could include non-neuropathic subjects and that trial duration can be dramatically shortened.
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Neuroimaging studies in healthy subjects have yielded controversial results about the neural substrates of autobiographical memory. Moreover, the neural networks responsible for autobiographical amnesia remain poorly understood. Since autobiographical memory is frequently altered in Alzheimer's disease (AD), we used this degenerative disorder as a model and applied a correlative approach between resting cerebral glucose utilization (CMRGlc) and temporally graded memory scores to identify the cerebral structures whose synaptic dysfunction subserves the impairment in autobiographical memory. ⋯ These findings show striking differences in metabolic correlations with the autobiographical time period, in agreement with prevalent theories of normal functioning of human memory. Thus, in accordance with theories of long-term memory consolidation, we find the expected implication of the hippocampal region in the recall of recent memories, and a disengagement of this structure when the retention interval is beyond 5 years. Moreover, according to the hemispheric encoding/retrieval asymmetry model based on activation studies in healthy subjects, the fact that recent memories preferentially involved the right prefrontal cortex whereas remote memories involved the left prefrontal cortex supports the notion of semanticization of memories with time interval, such that preserved remote memories in AD have a predominantly semantic character.
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Inflammation contributes to brain damage caused by ischaemic stroke. Macrophages, as the prevailing inflammatory cell population in stroke lesions, can be visualized using ultrasmall superparamagnetic iron oxide (USPIO) as a cell-specific contrast agent for MRI. In this single-centre open-labelled clinical phase II study we tested the potential of USPIO-enhanced MRI for macrophage imaging in human ischaemic stroke lesions. ⋯ Importantly, USPIO-induced signal alterations throughout differed from signatures of conventional gadolinium-enhanced MRI, thus being independent from breakdown of the blood-brain barrier. We suggest that increasing USPIO-enhancement on T1-weighted images indicates brain infiltration by USPIO-laden macrophages. Thus, USPIO-enhanced MRI may provide an in vivo surrogate marker of cellular inflammation in stroke and other CNS pathologies.
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Skin denervation in type 2 diabetes: correlations with diabetic duration and functional impairments.
Sensory neuropathy is a prominent component of diabetic neuropathy. It is not entirely clear how diabetes influences skin innervation, and whether these changes are correlated with clinical signs and laboratory findings. To investigate these issues, we performed skin biopsies on the distal leg of 38 consecutive type 2 diabetic patients with sensory symptoms in lower limbs (25 males and 13 females, aged 56.2 +/- 9.4 years) and analysed the correlations of intraepidermal nerve fibre (IENF) densities in skin with glycaemic status (duration of diabetes, HbA1C, and fasting and post-prandial glucose levels), and functional parameters of small fibres (warm and cold thresholds) and large fibres (vibratory threshold and parameters of nerve conduction studies). ⋯ On clinical examination, 15 patients showed no sign of small-fibre impairment, but seven of these patients had reduced IENF densities. In conclusion, small-fibre sensory neuropathy presenting with reduced IENF densities and correlated elevation of warm thresholds is a major manifestation of type 2 diabetes. In addition, the extent of skin denervation increases with diabetic duration.