Peripheral neuropathy is frequently reported in mixed cryoglobulinemia. As a close relationship has been established between mixed cryoglobulinemia and hepatitis C virus (HCV), the clinical, ...neurophysiological, and serologic findings of five patients affected by neuropathy, cryoglobulinemia and HCV infection were investigated. HCV infection was ascertained by the presence in the serum of anti-HCV antibodies detected by enzyme-linked immunosorbent assay(ELISA), and of HCV RNA assessed by polymerase chain reaction (PCR). Initial symptoms included paresthesias and painful dysesthesias in the legs. Later on, the patients developed a mainly asymmetric axonal polyneuropathy or a multifocal neuropathy associated with signs of systemic vasculitis. In this case series we report the short-term prognosis, as well as the response to interferon (IFN) alpha and conventional treatment. The presence of HCV RNA supports the hypothesis that a persistent HCV infection might be involved in the pathogenesis of mixed cryoglobulinemia and cryoglobulinemia-associated disorders.
Botulinum neurotoxins type A and E (BoNT/A and /E) are metalloproteases with a unique specificity for SNAP-25 (synaptosomal-associated protein of 25 kDa), an essential protein component of the ...neuroexocytotic machinery. It was proposed that this specificity is based on the recognition of a nine-residue sequence, termed SNARE motif, which is common to the other two SNARE proteins: VAMP (vesicle-associated membrane protein) and syntaxin, the only known substrates of the other six clostridial neurotoxins. Here we report on recent studies which provide evidence for the involvement of the SNARE motif present in SNAP-25 in its interaction with BoNT/A and /E by following the kinetics of proteolysis of SNAP-25 mutants deleted of SNARE motifs. We show that a single copy of the motif is sufficient for BoNT/A and /E to recognise SNAP-25. While the copy of the motif proximal to the cleavage site is clearly involved in recognition, in its absence, other more distant copies of the motif are able to support proteolysis. We also report on studies of poisoning human neuromuscular junctions with either BoNT/A or BoNT/E and describe the unexpected finding that the time of recovery of function after poisoning is much shorter in the case of type E with respect to type A intoxication. These data are discussed in terms of the different sites of action of the two toxins within SNAP-25.
Les neurotoxines botuliniques de type A et E (BoNT/A et BoNT/E) sont des métalloprotéases qui clivent de façon extrêmement spécifique la SNAP-25 (‘
synaptosomal associated protein of 25 kDa’), qui joue un rôle essentiel dans les processus de neuro-exocytose. II a été proposé que cette spécificité repose sur la reconnaissance d'un motif de neuf acides aminés, appelé motif SNARE, qui se retrouve dans les deux autres protéines ‘SNARE’, la VAMP (‘vesicle-associated membrane protein’) et la syntaxine, car ces protéines constituent les seuls substrats connus des six neurotaxines clostidiales. Nous avons étudié la protéolyse de mutants de SNAP-25 dans lesquels le motif SNARE est délété, et nous montrons que ce motif est impliqué dans l'interaction de la protéine avec BoNT/A et BoNT/E. Une seule copie de ce motif est suffisante pour que ces neurotoxines reconnaissent la SNAP-25 : le motif le plus proche du site de clivage joue un rôle évident dans cette reconnaissance, mais en son absence, d'autres copies plus éloignées de ce motif peuvent assurer la protéolyse. Nous décrivons aussi l'effet neurotoxique de BoNT/A et BoNT/E sur des jonctions neuromusculaires humaines : de façon inattendue, la récupération fonctionnelle est beaucoup plus rapide après l'action de la BoNT/E qu'après intoxication par la BoNT/A. Nous discutons ces résultats en fonction des sites de clivage de la SNAP-25 par ces deux toxines.
Previous studies have suggested that mental rotation can be accomplished by using different mental spatial transformations. When adopting the allocentric transformation individuals imagine the ...stimulus rotating in the picture plane, while when adopting the egocentric transformation they rely on sensorimotor mechanisms. How these mental transformations evolve during healthy aging has received little attention to date. Here we aimed at investigating how visual (i.e., allocentric) and sensorimotor (i.e., egocentric) imagery abilities change with normal aging. Fifteen elderly and 15 young participants were prompted to solve two different laterality tasks using either an allocentric or an egocentric frame of reference. Participants had to judge either the handedness of a visual hand (egocentric task) or the location of a marker to be either on the left or right side of the same visual hand (allocentric task). When performing the egocentric task, elderly participants were less accurate and slower for biomechanically awkward hand postures (i.e., lateral hand orientation). The findings revealed that healthy aging is associated with a specific degradation of the brain sensorimotor mechanisms necessary to accomplish egocentric mental transformations. Moreover, failure to find a difference in mentally rotating left or right hands suggests that aging does not necessarily evolve to impair non-dominant hand sensorimotor programs.
Unilateral neglect (UN) patients may fail to report sensory events occurring in the contralesional side of space or to explore through motor acts that portion of the space. In the present study we ...tested 20 patients with right-brain damage, 10 of whom with and 10 without UN. Patients performed two mental rotation tasks by either applying an effector-based (sensorimotor) transformation or an object-based (visuo-spatial) transformation. In the effector-based transformation, patients were asked to decide whether a rotated hand was left or right, while in the object-based transformation, they were asked to decide if a red dot was on the left or right side of a hand. Stimuli could be either left or right hands presented in a palm or back perspective, and could appear either on the left, on the right or on the center of a computer screen. The key result shows that patients with UN were impaired when they performed mental rotation using the effector-based transformation on left hands. The present finding suggests that UN is associated with a deficit in coupling visual information with proprioceptive signals arising from the left side of the body which, being affected, selectively reduces the patients' ability to apply sensorimotor transformations.
Since sleep bruxism (SB) is characterized by grinding and clenching of the teeth during sleep and could be an exaggerated manifestation of normal spontaneous rhythmic masticatory muscle activity, the ...aim of this study was to obtain a neurophysiological assessment of the excitability of the central jaw motor pathways in patients with signs and symptoms suggestive of SB.
A total of 30 subjects diagnosed with SB on the basis of self-report of tooth grinding were studied using the "recovery cycle" of the masseter inhibitory reflex (MIR) elicited by electric and magnetic stimulation of the mental nerves and by recording the motor potentials evoked in masseter muscles by transcranial magnetic stimulation. Tests were done during daytime, when the subjects were awake. The data obtained were compared with data from a population of normal subjects.
In the putative SB patients and in normal subjects, the MIRs evoked by single electric and magnetic stimuli were similar. With paired stimuli, the degree of suppression of the late silent period was significantly lower (P < .01) in the patients compared to normal subjects, particularly for magnetic stimuli, at various interstimulus intervals. No significant differences were found between the 2 groups of subjects in the masseter motor potentials evoked by transcranial magnetic stimulation.
Although the data were only obtained during wakefulness in patients self-reporting signs and symptoms suggestive of SB, the findings suggest that an abnormal excitability of the central jaw motor pathways may be present in SB subjects. This increased excitability could derive from an impaired modulation of brainstem inhibitory circuits and not from altered cortical mechanisms. These results support the view that bruxism is mainly centrally mediated and that it involves subcortical structures. The study also indicates that use of the MIR elicited by the double-shock technique could be valuable in the evaluation of bruxism.
