Effects of acute valproic acid administration on carnitine plasma concentrations in epileptic patients

Serial plasma samples collected after an acute administration of valproic acid, (VPA, 15 mg/kg as oral solution) in epileptic patients were selected for this study. The plasma samples were selected from three different groups of patients; patients on phenobarbital and phenytoin with clinical VPA intolerance (group A); patients on phenobarbital and phenytoin without clinical VPA toxicity (group B); and patients without phenobarbital and phenytoin and without clinical VPA toxicity (group C). Plasma samples from 6 patients per group were analyzed for carnitines and ammonia. Ammonia levels during acute study increased significantly (P less than 0.05) in patients who experienced VPA intolerance, while no changes were found in the other patients. After acute VPA administration, total carnitine was unchanged but free carnitine was decreased (P less than 0.05) and carnitine esters were increased (P less than 0.05) in all groups of patients studied. No difference in carnitine profiles was seen between patients with or without evidence of VPA administration has an important effect on carnitine metabolism. However, unlike the acute effect on ammonia metabolism, this acute effect does not seem to be correlated with any associated antiepileptic therapy, nor does it predict clinical VPA intolerance.     

Congenital hemiparesis: different functional reorganization of somatosensory and motor pathways.

OBJECTIVES: To investigate the reorganization of somatosensory and motor cortex in congenital brain injury. METHODS: We recorded motor evoked potentials (MEPs) following transcranial magnetic stimulation (TMS) and somatosensory evoked potentials (SEPs) in a 41 year old man with severe congenital right hemiparesis but only mild proprioceptive impairment. Brain magnetic resonance imaging showed a large porencephalic cavitation in the left hemisphere mainly involving the frontal and parietal lobes. RESULTS: TMS showed fast-conducting projections from the undamaged primary motor cortex to both hands, whereas MEPs were not elicited from the damaged hemisphere. Left median nerve stimulation evoked normal short-latency SEPs in the contralateral undamaged somatosensory cortex. Right median nerve stimulation did not evoke any SEP in the contralateral damaged hemisphere, but a middle-latency SEP (positive-negative-positive, 39-44-48 ms) in the ipsilateral undamaged hemisphere, with a fronto-central scalp distribution. CONCLUSIONS: Our data show that somatosensory function of the affected arm is preserved, most likely through slow-conducting non-lemniscal connections between the affected arm and ipsilateral non-primary somatosensory cortex. In contrast, motor function was poor despite fast-conducting ipsilateral cortico-motoneuronal output from the primary motor cortex of the undamaged hemisphere to the affected arm. This suggests that different forms of reorganization operate in congenital brain injury and that fast-conducting connections between primary cortex areas and ipsilateral spinal cord are not sufficient for preservation or recovery of function.     

Suprathreshold 0.3 Hz repetitive TMS prolongs the cortical silent period: potential implications for therapeutic trials in epilepsy.

OBJECTIVE: To investigate the after-effects of 0.3 Hz repetitive transcranial magnetic stimulation (rTMS) on excitatory and inhibitory mechanisms at the primary motor cortex level, as tested by single-pulse TMS variables. METHODS: In 9 healthy subjects, we studied a wide set of neurophysiological and behavioral variables from the first dorsal interosseous before (Baseline), immediately after (Post 1), and 90 min after (Post 2) the end of a 30 min long train of 0.3 Hz rTMS delivered at an intensity of 115% resting motor threshold (RMT). Variables under investigation were: maximal M wave, F wave, and peripheral silent period after ulnar nerve stimulation; RMT, amplitude and stimulus-response curve of the motor evoked potential (MEP), and cortical silent period (CSP) following TMS; finger-tapping speed. RESULTS: The CSP was consistently lengthened at both Post 1 and Post 2 compared with Baseline. The other variables did not change significantly. CONCLUSIONS: These findings suggest that suprathreshold 0.3 Hz rTMS produces a relatively long-lasting enhancement of the inhibitory mechanisms responsible for the CSP. These effects differ from those, previously reported, of 0.9-1 Hz rTMS, which reduces the excitability of the circuits underlying the MEP and does not affect the CSP. This provides rationale for sham-controlled trials aiming to assess the therapeutic potential of 0.3 Hz rTMS in epilepsy.     

Motor cortex excitability correlates with novelty seeking in social anxiety: a transcranial magnetic stimulation investigation

Social anxiety disorder (SAD) is characterised by fear of scrutiny by other people, avoidance of social situations and vegetative/motor symptomatology. The correlation between reduced striatal dopaminergic (DA) function, SAD motor symptoms and the high occurrence of SAD in patients with Parkinson’s disease (PD), suggests a link between SAD and movement diseases caused by dopamine dysfunction. However, little is known about the electrophysiological aspects of SAD. We applied single- and paired-pulse transcranial magnetic stimulation (TMS) to investigate excitatory and inhibitory mechanisms of the primary motor cortex (M1) in 15 SAD patients and the relationship between these neurophysiological measures and clinical symptoms or temperamental traits. Data were compared with those obtained in 15 age- and sex-matched healthy volunteers. SAD patients showed significantly higher harm avoidance scores and lower novelty seeking scores when compared to controls. TMS measures did not significantly differ between groups. However, in SAD patients the cortical silent period (CSP) duration and the amount of long-interstimulus interval intracortical inhibition were significantly correlated with the NS score. Accordingly with NS reduction and CSP shortening reported in PD, the relationship between NS levels and the excitability of inhibitory circuits of the M1 may support the hypothesis that DA dysfunction could underlie NS deficits in SAD. Furthermore, these data suggest that "trait variables" (i.e., NS) are more closely related to neurophysiological measures than SAD symptoms, which represent “state variables” linked to social performance.