Focal cortical atrophy in multiple sclerosis: relation to lesion load and disability

Multiple sclerosis (MS) is thought to predominantly affect white matter (WM). Recently, however, loss of cortical gray matter has also been described. Little is known about the cause of cortical atrophy in MS, whether it occurs early in the disease course, and whether it affects all cortical regions equally or if there is a preferential pattern of focal cortical atrophy. An automated method was used to compute the thickness at every vertex of the cortical surface of the brains of 425 early relapsing-remitting MS patients. We correlated cortical thickness with the WM lesion load and the Expanded Disability Status Scale score. Mean cortical thickness correlated with WM lesion load and disability. The correlations of cortical thickness with total lesion load and disability were most significant in cingulate gyrus, insula, and associative cortical regions. Conversely, primary sensory, visual, and motor areas showed a less significant relationship. The highest amount of atrophy per lesion volume or disability scale unit was in the anterior cingulate cortex. This study confirms the relation between cortical atrophy, WM lesion load, and disability in MS, and suggests that cortical atrophy occurs even in MS patients with only mild disability. Most interestingly, we show a specific regional pattern of focal atrophy in MS that is distinctively different from the one in normal aging. The predilection of the atrophic process for areas that are heavily inter-connected with other brain regions suggests that interruption of WM tracts by MS plaques contributes, at least in part, to the development of cortical atrophy.     

Kinematic and kinetic asymmetries in hemiplegic patients' gait initiation patterns.

OBJECTIVE: To assess the kinetic and kinematic characteristics of hemiplegic stroke patients' gait initiation patterns during the various gait initiation phases. DESIGN AND SUBJECTS: Gait initiation was studied in 3 hemiplegic subjects with a spastic equinus varus foot and 3 control subjects. METHODS: Temporal and kinetic analysis of gait initiation was performed with 2 AMTI force plates, and kinematic analysis of gait initiation with an ELITE optoelectronic system. A one-way ANOVA was performed directly on the phase durations, forces, centre of pressure displacements, stride length, and ankle motion range. RESULTS: Duration of the monopodal phase was shorter in hemiplegic patients when the affected leg rather than the sound one was used as the supporting leg. Propulsion forces were exerted by the hemiplegic patients' sound leg during the postural phase. Hemiplegic patients' body weight was supported more by the sound leg than by the affected leg. Knee was lifted higher on the affected side during the swing phase to compensate for the equinus. Initial contact was performed with a flat foot on the affected side. CONCLUSION: Quantitative data obtained on the gait initiation phase suggest that hemiplegic patients develop asymmetrical adaptive posturo-motor strategies to compensate for their impairments.     

MERTK mutation update in inherited retinal diseases

MER tyrosine kinase (MERTK) encodes a surface receptor localized at the apical membrane of the retinal pigment epithelium. It plays a critical role in photoreceptor outer segment internalization prior to phagocytosis. Mutations in MERTK have been associated with severe autosomal recessive retinal dystrophies in the RCS rat and in humans. We present here a comprehensive review of all reported MERTK disease causing variants with the associated phenotype. In addition, we provide further data and insights of a large cohort of 1,195 inherited retinal dystrophies (IRD) index cases applying state‐of‐the‐art genotyping techniques and summarize current knowledge. A total of 79 variants have now been identified underlying rod‐cone dystrophy and cone‐rod dystrophy including 11 novel variants reported here. The mutation spectrum in MERTK includes 33 missense, 12 nonsense, 12 splice defects, 12 small deletions, 2 small insertion–deletions, 3 small duplications, and 2 exonic and 3 gross deletions. Altogether, mutations in MERTK account for ～2% of IRD cases with a severe retinal phenotype. These data are important for current and future therapeutic trials including gene replacement therapy or cell‐based therapy.     

Cardiovascular changes induced by cold water immersion during hyperbaric hyperoxic exposure

The present study was designed to assess the cardiac changes induced by cold water immersion compared with dry conditions during a prolonged hyperbaric and hyperoxic exposure (ambient pressure between 1.6 and 3 ATA and PiO(2) between 1.2 and 2.8 ATA). Ten healthy volunteers were studied during a 6 h compression in a hyperbaric chamber with immersion up to the neck in cold water while wearing wet suits. Results were compared with measurements obtained in dry conditions. Echocardiography and Doppler examinations were performed after 15 min and 5 h. Stroke volume, left atrial and left ventricular (LV) diameters remained unchanged during immersion, whereas they significantly fell during the dry session. As an index of LV contractility, percentage fractional shortening remained unchanged, in contrast to a decrease during dry experiment. Heart rate (HR) significantly decreased after 5 h, although it had not changed during the dry session. The changes in the total arterial compliance were similar during the immersed and dry sessions, with a significant decrease after 5 h. In immersed and dry conditions, cardiac output was unchanged after 15 min but decreased by almost 20% after 5 h. This decrease was related to a decrease in HR during immersion and to a decrease in stroke volume in dry conditions. The hydrostatic pressure exerted by water immersion on the systemic vessels could explain these differences. Indeed, the redistribution of blood volume towards the compliant thoracic bed may conceal a part of hypovolaemia that developed in the course of the session.