Brain : a journal of neurology
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Patients presenting with subacute amnesia are frequently seen in acute neurological practice. Amongst the differential diagnoses, herpes simplex encephalitis, Korsakoff's syndrome and limbic encephalitis should be considered. Limbic encephalitis is typically a paraneoplastic syndrome with a poor prognosis; thus, identifying those patients with potentially reversible symptoms is important. ⋯ Over the same period, only one paraneoplastic case of limbic encephalitis was identified between the two main centres. Thus, VGKC-Ab-associated encephalopathy is a relatively common form of autoimmune, non-paraneoplastic, potentially treatable encephalitis that can be diagnosed by a serological test. Establishing the frequency of this new syndrome, the full range of clinical presentations and means of early recognition, and optimal immunotherapy, should now be the aim.
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In Parkinson's disease, functional imaging studies during limb motor tasks reveal cerebral activation abnormalities that can be reversed by subthalamic nucleus (STN) stimulation. The effect of STN stimulation on parkinsonian dysarthria has not, however, been investigated using PET. The aim of the present study was to evaluate the effect of STN stimulation on regional cerebral blood flow (rCBF) during speech production and silent articulation in patients with Parkinson's disease. ⋯ These abnormal activations are different from those reported during hand motor tasks. They could be a compensatory mechanism, but might also arise directly as part of the pathophysiology of Parkinson's disease. STN stimulation tends to reverse these abnormal activations, which is consistent with the observed improvement of Parkinson's disease dysarthria.
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Enhanced cerebrovascular permeability and cellular infiltration mark the onset of early multiple sclerosis lesions. So far, the precise sequence of these events and their role in lesion formation and disease progression remain unknown. Here we provide quantitative evidence that blood-brain barrier leakage is an early event and precedes massive cellular infiltration in the development of acute experimental allergic encephalomyelitis (EAE), the animal correlate of multiple sclerosis. ⋯ MRI showed that the USPIO load in the brain was significantly diminished in lovastatin-treated animals. Data indicate that cerebrovascular leakage and monocytic trafficking into the brain are two distinct processes in the development of inflammatory lesions during multiple sclerosis, which can be monitored on-line with MRI using USPIOs and Gd-DTPA as contrast agents. These studies also implicate that USPIOs are a valuable tool to visualize monocyte infiltration in vivo and quantitatively assess the efficacy of new therapeutics like lovastatin.
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Taxol is a highly effective anticancer agent that causes peripheral neuropathy as its major toxic side effect. The neuropathy is characterized by degeneration of sensory axons that may be severe enough to be dose limiting. Axonal degeneration involves the activation of the calcium-activated proteases calpains, and here we tested whether systemic inhibition of calpains with the peptide alpha-ketoamide calpain inhibitor AK295 can reduce the clinical and pathological effects of Taxol in a rodent model of Taxol neuropathy. ⋯ AK295 inhibited the activation of calpains but did not interfere with the antimitotic effects of Taxol on microtubules, nor did it inhibit caspase-mediated cell death. These data implicate calpains in the pathogenesis of Taxol neuropathy, and demonstrate that AK295 can prevent axonal degeneration and clinical neuropathy in mice. In addition, AK295 did not interfere with the primary antineoplastic effects of Taxol on microtubules and cell death, suggesting that systemic calpain inhibition may be a good strategy for preventing neuropathy in patients being treated with Taxol.
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The aim of this study was to determine whether trigeminal nerve discharge associated with painful stimulation of the temple would intensify symptoms of motion sickness in migraine sufferers. If so, this would support the notion that symptoms such as nausea and headache interact with each other during attacks of migraine. Symptoms of motion sickness were rated at 2 min intervals during 15 min of optokinetic stimulation in 27 migraine sufferers and 23 age- and sex-matched controls. ⋯ In the absence of painful stimulation, increases in pulse amplitude during optokinetic stimulation were greater in migraine sufferers than controls, possibly because the discomfort associated with motion sickness triggered extracranial vasodilatation in migraine sufferers as part of a fight-or-flight (defense) response. Extracranial vasodilatation did not differ between migraine sufferers and controls when ice was applied to the temple or hand during optokinetic stimulation, implying that the additional discomfort associated with painful stimulation of the head and hand evoked a defense response in controls. These findings suggest that a mechanism which boosts extracranial neurovascular reflexes to stress and which heightens symptoms of motion sickness, increases susceptibility to migraine.