Resting state functional thalamic connectivity abnormalities in patients with post-stroke sleep apnoea: a pilot case-control study.

OBJECTIVE: Sleep apnoea is common after stroke, and has adverse effects on the clinical outcome of affected cases. Its pathophysiological mechanisms are only partially known. Increases in brain connectivity after stroke might influence networks involved in arousal modulation and breathing control. The aim of this study was to investigate the resting state functional MRI thalamic hyper-connectivity of stroke patients affected by sleep apnoea (SA) with respect to cases not affected, and to healthy controls (HC). PATIENTS AND METHODS: A series of stabilized strokes were submitted to 3T resting state functional MRI imaging and full polysomnography. The ventral-posterior-lateral thalamic nucleus was used as seed. RESULTS: At the between groups comparison analysis, in SA cases versus HC, the regions significantly hyper-connected with the seed were those encoding noxious threats (frontal eye field, somatosensory association, secondary visual cortices). Comparisons between SA cases versus those without SA revealed in the former group significantly increased connectivity with regions modulating the response to stimuli independently to their potentiality of threat (prefrontal, primary and somatosensory association, superolateral and medial-inferior temporal, associative and secondary occipital ones). Further significantly functionally hyper-connections were documented with regions involved also in the modulation of breathing during sleep (pons, midbrain, cerebellum, posterior cingulate cortices), and in the modulation of breathing response to chemical variations (anterior, posterior and para-hippocampal cingulate cortices). CONCLUSIONS: Our preliminary data support the presence of functional hyper connectivity in thalamic circuits modulating sensorial stimuli, in patients with post-stroke sleep apnoea, possibly influencing both their arousal ability and breathing modulation during sleep.

Chronic treatment with rivastigmine in patients with Alzheimer's disease: a study on primary motor cortex excitability tested by 5 Hz-repetitive transcranial magnetic stimulation.

OBJECTIVE: To investigate changes in cortical excitability and short-term synaptic plasticity we delivered 5 Hz repetitive transcranial magnetic stimulation (rTMS) over the primary motor cortex in 11 patients with mild-to-moderate Alzheimer's disease (AD) before and after chronic therapy with rivastigmine. METHODS: Resting motor threshold (RMT), motor evoked potential (MEP), cortical silent period (CSP) after single stimulus and MEP facilitation during rTMS trains were tested three times during treatment. All patients underwent neuropsychological tests before and after receiving rivastigmine. rTMS data in patients were compared with those from age-matched healthy controls. RESULTS: At baseline, RMT was significantly lower in patients than in controls whereas CSP duration and single MEP amplitude were similar in both groups. In patients, rTMS failed to induce the normal MEP facilitation during the trains. Chronic rivastigmine intake significantly increased MEP amplitude after a single stimulus, whereas it left the other neurophysiological variables studied unchanged. No significant correlation was found between patients' neuropsychological test scores and TMS measures. CONCLUSIONS: Chronic treatment with rivastigmine has no influence on altered cortical excitability and short-term synaptic plasticity as tested by 5 Hz-rTMS. SIGNIFICANCE: The limited clinical benefits related to cholinesterase inhibitor therapy in patients with AD depend on factors other than improved plasticity within the cortical glutamatergic circuits.

beta2-microglobulin serum level is not a marker of disease activity in multiple sclerosis.

Beta2-microglobulin (beta2-MG) is a pharmacodynamic marker of interferon-beta activity in multiple sclerosis (MS). Its role in the natural course of the disease is not fully known. We analyzed the spontaneous fluctuation of beta2-MG in free-treatment MS patients during a short-time course to quantify beta2-MG as a marker of disease activity/progression. Thirty MS patients were clinically assessed and imaged monthly over a 3-month period. Sera were collected concomitantly for the evaluation of beta2-MG, by means of an enzyme-linked immunosorbent assay. Sera from 20 healthy individuals (HI) were drawn and used as controls. The Mann-Whitney test was used when appropriate and time effect on radiological and biological measures was assessed by means of the random effect models. Eight (26.7%) patients experienced a clinical relapse but three (10%) required steroid treatment. A reduction in the contrast-enhancing lesion load (P = 0.02) and a trend (P = 0.07) toward a decrease in brain parenchyma fraction were observed. Baseline levels of beta2-MG were similar in patients and HI. Patients' beta2-MG values increased over the 3-month time period (P = 0.05) but did not exceed those detected in HI at any time point. These results failed to demonstrate the validity of beta2-MG as a surrogate marker of disease in MS.

Cutaneous silent period in hand muscle is evoked by laser stimulation of the palm, but not the hand dorsum.

Painful electrical stimulation of the fingers evokes an inhibitory response in hand muscles (cutaneous silent period, CSP). The aim of this study was to determine whether purely nociceptive thermal stimuli applied to the hand evoke a CSP. High-intensity laser pulses (205 +/- 44 mJ) were delivered to the dorsum and palm of the hand in five volunteers. Electromyographic signals were recorded from the ipsilateral first dorsal interosseous muscle. We then compared the laser-evoked CSP with the CSP induced by electrical stimulation. A clear laser CSP (latency 90 +/- 7 ms) was evoked in all subjects when laser pulses were applied to the palm of the hand, whereas no response was recorded after stimulation of the dorsum. Electrical stimulation of both the dorsum and the palm evoked a CSP (latency 65 +/- 5 ms), although the reflex threshold was significantly lower after stimulation of the palm. This study confirms that the CSP is a nociceptive response specific to limbs that grasp. In humans, palm nociceptors are probably more functionally effective than dorsal nociceptors in inducing the hand-muscle inhibition that interrupts hand prehension (so that a potentially noxious source is dropped) before proximal muscles withdraw the limb.

Excitability of the Adelta nociceptive pathways as assessed by the recovery cycle of laser evoked potentials in humans.

To investigate the excitability of Adelta nociceptive pathways and the nature of the vertex laser evoked potentials (LEPs), we studied the recovery cycle of the P2-LEP component and compared it with that of the P200 of the somatosensory evoked potential (SEP). Using two identical CO(2)-laser stimulators, we delivered paired stimuli to two adjacent skin spots on the hand at interstimulus intervals ranging from 250 ms to 2 s. The test P2-LEP was strongly inhibited at the 250-ms interstimulus interval ( P<0.01) and progressively recovered by the 2-s interval. The P200-SEP, after paired stimuli to the median nerve, showed a time course even slower than the P2-LEP ( P<0.01). Besides providing the LEP recovery curve in normal subjects, our findings indicate that the P2-LEP relays through a number of synapses similar to (or even lower than) that for the P200-SEP, thus lending further support to the view that the nociceptive P2-LEP is not an endogenous potential equivalent to the P300.

Thrombotic thrombocytopenic purpura: prospective neurologic, neuroimaging and neurophysiologic evaluation.

BACKGROUND AND OBJECTIVES: Neurologic symptoms are present in 60% of patients with thrombotic thrombocytopenic purpura (TTP) on initial examination and ultimately develop in about 90% of cases during the course of the disease. Despite central nervous system involvement being frequent, abnormalities in the brain of patients with TTP are infrequent on neuroimaging (CT/MRI) and neurophysiologic (EEG) evaluation, often reversible and mainly limited to symptomatic stages of the disease. The aim of our study was to establish the value of a complete neurologic screening as part of the work up of TTP. DESIGN AND METHODS: We prospectively evaluated 16 TTP patients, performing serial neurologic, neuroimaging and EEG examinations, independently of the presence of an objective central nervous system involvement. RESULTS: Our study shows that a complete neurologic evaluation is of modest help in improving the diagnosis of TTP, but may be useful for the neurologic management. INTERPRETATION AND CONCLUSIONS: Accurate neuroimaging and, especially, EEG evaluation and monitoring allowed us to identify patients who could benefit from anticonvulsive therapy, avoiding the unnecessary administration of the latter. The prognostic utility of complete neurologic screening in TTP remains to be conclusively demonstrated in larger prospective neurologic studies.

Naloxone-induced jumping activity in morphine-dependent mice: a pharmacological study on the role of DA2 receptors.

The morphine withdrawal syndrome is strictly related to modifications on neurotransmittorial systems at central and peripheral levels. Dopamine seems to play an important role. Particularly in the experimental withdrawal syndrome the jumping activity seems to be related to a hypersensitivity of DA receptors. While the role of DA1 receptors has been extensively studied, using agonist and antagonist drugs, the role of DA2 receptors is still little known. In our study we evaluated the changes of the jumping response that was induced by substances active on DA2 receptors (lisuride, tiapride) in mice made acutely dependent on morphine, in which we induced a withdrawal syndrome with naloxone. Haloperidol (DA1-DA2 blocker) did not provoke significant changes. Either tiapride or lisuride determined a sharp increase of jumping.

[Double-blind study of tiapride and placebo in patients with subcontinuous essential headache]. / Studio in doppio cieco coi tiapride versus placebo in pazienti con cefalea essenziale sub-continua.

25 patients with subcontinual primary headache were treated with Tiapride an Placebo in a controlled double-blind study. The duration of trial was 13 weeks. Blood samples were taken to value PRL in 10 patients and in 10 normal subjects. During the pharmacological trial no side-effects appeared. Authors refer results elaborated through statistical examinations. Tiapride is useful to reduce the frequency of the attacks (in 65% of the patients) with percentage of improvement statistically significant in comparison with placebo. Headache index appears influenced although in non statistically significant way.