Rapid Increase in Neural Conduction Time in the Adult Human Auditory Brainstem Following Sudden Unilateral Deafness

Individuals with sudden unilateral deafness offer a unique opportunity to study plasticity of the binaural auditory system in adult humans. Stimulation of the intact ear results in increased activity in the auditory cortex. However, there are no reports of changes at sub-cortical levels in humans. Therefore, the aim of the present study was to investigate changes in sub-cortical activity immediately before and after the onset of surgically induced unilateral deafness in adult humans. Click-evoked auditory brainstem responses (ABRs) to stimulation of the healthy ear were recorded from ten adults during the course of translabyrinthine surgery for the removal of a unilateral acoustic neuroma. This surgical technique always results in abrupt deafferentation of the affected ear. The results revealed a rapid (within minutes) reduction in latency of wave V (mean pre = 6.55 ms; mean post = 6.15 ms; p < 0.001). A latency reduction was also observed for wave III (mean pre = 4.40 ms; mean post = 4.13 ms; p < 0.001). These reductions in response latency are consistent with functional changes including disinhibition or/and more rapid intra-cellular signalling affecting binaurally sensitive neurons in the central auditory system. The results are highly relevant for improved understanding of putative physiological mechanisms underlying perceptual disorders such as tinnitus and hyperacusis.     

Vestibular Function Measurement Devices

Vestibular function laboratories utilize a multitude of diagnostic instruments to evaluate a dizzy patient. Caloric irrigators, oculomotor stimuli, and rotational chairs produce a stimulus whose accuracy is required for the patient response to be accurate. Careful attention to everything from cleanliness of equipment to threshold adjustments determine on a daily basis if patient data are going to be correct and useful. Instrumentation specifications that change with time such as speed and temperature must periodically be checked using calibrated instruments.     

Reduction in oral corticosteroid use with mometasone furoate dry powder inhaler improves health-related quality of life in patients with severe persistent asthma.

Severe persistent asthma can have a substantial impact on a patient's health-related quality of life (HRQL), both as a result of symptoms and from side effects of treatment. The HRQL impact of two doses (400 and 800 microg twice daily) of mometasone furoate dry powder inhaler (MF DPI) was compared with placebo in patients with severe persistent asthma previously maintained on oral steroids as a component of a previously published randomized, 12-week, double-blind, placebo-controlled, multicenter trial. A 9-month open-label extension (OLE), with all patients treated with MF DPI, followed. Patients 12 years of age or older completed a generic HRQL measure, the Medical Outcomes Trust Short Form-36 (SF-36), and an asthma-specific measure, the Marks Asthma Quality of Life Questionnaire (AQLQ-M), at baseline, at endpoint (last evaluable visit) of the double-blind phase (EODBP), and after the first 3 months of the OLE. Of 132 patients enrolled in the study, 128 provided HRQL data at baseline and at EODBP. Mean SF-36 scores at baseline showed significant HRQL impairment compared with U.S. general population norms. With treatment, the reduction in oral corticosteroid (OCS) requirements of the MF-DPI-treated groups was accompanied by significant (p < 0.05) improvement over placebo in the physical domain of HRQL (SF-36 physical component summary score and the physical function subscale) at EODBP. MF-DPI-treated patients also showed significant improvements at EODBP in each of the four subscales of the AQLQ-M (p<0.05). From EODBP to the OLE 3-month endpoint, patients treated with MF DPI twice daily maintained, or improved, SF-36 scores in most domains. Symptomatic improvement and reduction in OCS use with MF DPI were accompanied by significant improvement in HRQL in patients with severe persistent asthma. These improvements were maintained during the 3-month period of the OLE in which HRQL was evaluated.     

Cerebral autoregulation is preserved in multiple system atrophy: A transcranial Doppler study.

Patients with multiple system atrophy (MSA) present large changes in blood pressure (BP) due to autonomic disturbances. We analyzed how this change may influence dynamic cerebral autoregulation (DCA). Simultaneous recordings of arterial BP (Finapres) and middle cerebral artery (MCA) blood flow velocity (BFV) (transcranial Doppler) were performed in 10 patients with MSA (61 +/- 12 yr of age) and 12 healthy volunteers (61 +/- 11 yr of age): cerebral BFV response to oscillations in mean BP was studied in the supine position by cross-spectral analysis of mean BP and mean MCA BFV. The DCA was also studied during the decrease in BP the first seconds when standing up from a sitting position by the assessment of the cerebrovascular resistance index (CR; mean BP/mean MCA BFV ratio). The MCA BFV/BP cross-spectral analysis showed a phase for the mid-frequency band (0.07-0.2 Hz) significantly larger in MSA, suggesting more active autoregulation in response to larger changes in BP. Changes in CR reflecting the rate of autoregulation, when standing did not differ between the two groups. These data suggest that dynamic cerebral autoregulation is preserved in MSA.     

A presenilin 1 mutation (L420R) in a family with early onset Alzheimer disease,seizures and cotton wool plaques,but not spastic paraparesis

Over 100 mutations in the presenilin‐1 gene (PSEN1) have been shown to result in familial early onset Alzheimer disease (EOAD), but only a relatively few give rise to plaques with an appearance like cotton wool (CWP) and/or spastic paraparesis (SP). A family with EOAD, seizures and CWP was investigated by neuropathological study and DNA sequencing of the PSEN1 gene. Aβ was identified in leptomeningeal vessels and in cerebral plaques. A single point mutation, p.L420R (g.1508T > G) that gives rise to a missense mutation in the eighth transmembrane (TM8) domain of PS1 was identified in two affected members of the family. p.L420R (g.1508T > G) is the mutation responsible for EOAD, seizures and CWP without SP in this family.