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AbstractParkinson’s disease (PD) is classically considered to be a motor system affliction; however, also non-motor alterations, including sleep disorders, are important features of the disease. The aim of this review is to provide data on sleep disturbances in PD in the following grouping: difficulty initiating sleep, frequent night-time awakening and sleep fragmentation, nocturia, restless legs syndrome/periodic limb movements, sleep breathing disorders, drug induced symptoms, parasomnias associated with rapid eye movements (REM) sleep, sleep attacks, reduced sleep efficiency and excessive daytime sleepiness. Research has characterized some of these disturbances as typical examples of dissociated states of wakefulness and sleep that are admixtures or incomplete declarations of wakefulness, REM sleep, and non-REM (NREM) sleep. Moreover, sleep disorders may precede the typical motor system impairment of PD and their ability to predict disease has important implications for development of neuroprotective treatment; in particular, REM sleep behavior disorder may herald any other clinical manifestation of PD by more than 10 years.

Alzheimer's disease (AD) is a neurodegenerative disorder with cognitive and memory decline, personality changes, and synapse loss. Increasing evidence indicates that factors such as oxidative and nitrosative stress, glutathione depletion, and impaired protein metabolism can interact in a vicious cycle, which is central to AD pathogenesis. In the present study, we demonstrate that brains of AD patients undergo oxidative changes classically associated with a strong induction of the so-called vitagenes, including the heat shock proteins (HSPs) heme oxygenase-1 (HO-1), HSP60, and HSP72, as well as thioredoxin reductase (TRXr). In inferior parietal brain of AD patients, a significant increase in the expression of HO-1 and TRXr was observed, whereas HO-2 expression was decreased, compared with controls. TRHr was not increased in AD cerebellum. Plasma GSH was decreased in AD patients, compared with the control group, and was associated with a significant increase in oxidative stress markers (i.e., GSSG, hydroxynonenal, protein carbonyl content, and nitrotyrosine). In AD lymphocytes, we observed an increased expression of inducible nitric oxide synthase, HO-1, Hsp72, HSP60, and TRXr. Our data support a role for nitrative stress in the pathogenesis of AD and indicate that the stressresponsive genes, such as HO-1 and TRXr, may represent important targets for novel cytoprotective strategies.

In order to determine the mono- or oligosynaptic character of connections between pyramidal axons and individual spinal motor neurons, we constructed peri-stimulus time histograms (PSTHs) of the firing probability of voluntarily activated single motor units (SMUs) of various upper and lower limb muscles upon slightly suprathreshold transcranial anodal electrical stimulations of the motor cortex in normal subjects. Weak anodal cortical stimuli are known to activate preferentially fast-conducting pyramidal axons directly, bypassing cell bodies and cortical interneurons. A narrow bin width (0.1 ms) was chosen to measure precisely the duration of the PSTH excitatory peak, which corresponds to the rise time of the underlying compound excitatory post-synaptic potentials (EPSP). A short duration PSTH peak indicates sharp-rising EPSPs, most commonly encountered in the case of monosynaptic connections. In flexor carpi radialis and soleus SMUs, the PSTHs of built-in responses to anodal cortical stimuli were compared with those produced by 1A afferent stimulation able to elicit a Hoffmann reflex, which is known to be largely monosynaptic. In all upper and lower limb muscles, excitable SMUs responded to anodal cortical stimuli with a highly synchronized peak of increased firing probability. In flexor carpi radialis and soleus SMUs, the mean duration of this peak was significantly narrower than that evoked by 1A afferent stimulation, indicating that monosynaptic corticomotor neuronal transmission dominates low-threshold motor units, even in proximal arm and leg muscles. In the various muscles studied, and particularly in forearm SMUs, we did not observe broad PSTH peaks against the activation of non-monosynaptic corticomotor neuronal pathways, even with near-threshold stimuli. In some triceps and forearm flexor SMUs, subthreshold anodal pulses caused significant inhibition of their voluntary firing, with a latency consistent with activation of 1A inhibitory interneurons by the descending volleys. Measurements of the maximal number of counts in the excitatory PSTH peak upon anodal cortical stimuli provide comparisons of the strength of monosynaptic inputs to various muscles which seems to be maximal for hand and finger extensor muscles, and also for deltoid.

Mechanisms of motor recovery after a stroke are still poorly understood. A contribution of the healthy hemisphere has been proposed based on clinical and neuroimaging data.We report our observations from a group of patients studied serially during the first two months after stroke and another group of patients studied in the chronic phase after stroke using transcranial magnetic stimulation and the MRC scale for estimation of hand motor deficit. Among the patients studied in the acute and subacute phase (n = 16), recordable motor evoked potentials (MEPs) in the affected hand after contralateral hemispheric stimulation were present in all cases who improved their hand motor score. There was a strong correlation between MEP amplitude/latency and hand motor scores at day 60. In the patients studied in the chronic phase (n = 16), MEPs after stimulation of the affected hemisphere were observed in all patients with or without recovery, although the MEP amplitude was reduced in the four patients with no hand motor improvement, and normal in all patients with motor score improvement. There was also a significant correlation between the MEP amplitude/latency and hand motor scores. An ipsilateral response after focal stimulation of the intact hemisphere was only observed in one case (who did not recover).Our data do not suggest a significant participation of the intact hemisphere or of corticoreticulospinal pathways in motor recovery after stroke. Conversely, the persistence of a functional pyramidal tract seems necessary for recovery to occur after a cortical stroke.

In 14 patients with spasticity, efficacy and tolerance of 10 mg diazepam and 50 mg tetrazepam have been compared in a double-blind double-dummy cross-over study. To assess efficacy, the changes in four electrophysiologic tests have been used: Hmax/Mmax ratio, Tmax/Mmax ratio, vibratory inhibition of H reflex, and conditioned amplitudes of Sol H reflex at 70 and 200 ms after stimulation of the tibial nerve at the ankle. Tolerance was evaluated by the induced somnolence (intensity x duration). Electrophysiologic test results were moderately modified in the same direction after both drugs. For the Hmax/Mmax, Tmax/Mmax ratio, and conditioned values, the differences between diazepam and tetrazepam were not significant. For vibratory inhibition, changes induced by tetrazepam were more intense and of longer duration than after diazepam (p = 0.07), indicating that tetrazepam is more potent for reinforcing presynaptic inhibition. Tolerance, as assessed by intensity and duration of somnolence, was significantly better for tetrazepam. The efficacy and tolerance of tetrazepam suggest that it is a more useful agent for the treatment of spasticity than diazepam.

Some evidence suggests that high-intensity motor training slows down the severity of spinocerebellar ataxia. However, whether all patients might benefit from these activities, and by which activity, and the underlying mechanisms remain unclear. We provide an update on the effect and limitations of different training programmes in patients with spinocerebellar ataxias. Overall, data converge of the finding that intensive training is still based either on conventional rehabilitation protocols or whole-body controlled videogames (“exergames”). Notwithstanding the limitations, short-term improvement is observed, which tends to be lost once the training is stopped. Exergames and virtual reality can ameliorate balance, coordination, and walking abilities, whereas the efficacy of adapted physical activity, gym, and postural exercises depends on the disease duration and severity. In conclusion, although a disease-modifying effect has not been demonstrated, constant, individually tailored, high-intensity motor training might be effective in patients with degenerative ataxia, even in those with severe disease. These approaches may enhance the remaining cerebellar circuitries or plastically induce compensatory networks. Further research is required to identify predictors of training success, such as the type and severity of ataxia and the level of residual functioning.

Previous studies found an early impairment of the short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) to transcranial magnetic stimulation (TMS) in Parkinson's disease. However, very little is known on the TMS correlates of rapid eye movement (REM) sleep behavior disorder (RBD), which can precede the onset of a a-synucleinopathy.

THE effect of thyrotropin-releasing hormone tartrate (TRH-T) on the decrease in H Max/M Max ratio, an index of the spinal motoneurone pool, induced by haloperidol, was studied in 15 healthy volunteers. In all subjects, the H response was examined by an electromyographic apparatus. The values were expressed as H Max/M Max ratio, that gives an index of excitability of the spinal motoneurone pool. It was found that the mean H Max/M Max ratio value significantly decreased after haloperidol administration, but this effect was completely reversed by the injection of TRH-T. This finding suggests that the peptide may modulate motoneurone functions.