Jean-Pierre Malin

Changes of cortical motor area size during immobilization

Changes of motor cortex organization after lesions in the nervous system can be demonstrated by mapping the motor cortex with transcranial magnetic stimulation. We studied cortical plasticity in 22 patients who had a unilateral immobilization of the ankle joint without peripheral nerve lesion. The motor cortex area of the inactivated tibial anterior muscle diminished compared to the unaffected leg without changes in spinal excitability or motor threshold. The area reduction was correlated to the duration of immobilization. It could be quickly reversed by voluntary muscle contraction. This indicates a functional (and not morphological) origin of the phenomenon.

The glutamate antagonist Riluzole suppresses intracortical facilitation

SummaryThe effect of the glutamate antagonist riluzole on excitatory and inhibitory phenomena in the human motor system was studied by transcranial magnetic stimulation (TMS) and peripheral electrical nerve stimulation. The motor threshold, the intracortical inhibition and intracortical facilitation as assessed by paired TMS, the cortical and peripheral silent periods, F wave amplitudes and F wave latencies were measured.Riluzole suppressed the intracortical facilitation whereas other parameters remained unchanged, indicating that the neurotransmitter glutamate is mainly involved in facilitatory mechanisms in the motor system.

Quantitative sensory testing, neurophysiological and psychological examination in patients with complex regional pain syndrome and hemisensory deficits

&NA; Based on bed‐side neurological testing, it has recently been shown that 33% of chronic complex regional pain syndrome (CRPS) type I patients exhibit sensory impairments, which extend past the painful area of the affected limb in a hemisensory distribution (Pain, 80 (1999) 95). In the present study, the clinically observed changes in touch and temperature sensations on the side of the body ipsilateral to the affected limb were investigated quantitatively. Neurophysiological and psychological examinations were conducted to detect changes in the peripheral and central nervous system as well as psychopathological abnormalities. In 40 patients with CRPS, a bed‐side neurological examination was performed. Quantitative sensory testing was conducted at five locations on each side of the body. The evaluation of touch thresholds was performed using von Frey filaments (n=40). To measure cool, warm and heat pain thresholds quantitatively, a thermal stimulator using a Peltier‐element was used (n=28). With respect to clinical findings, the initiating trauma and severity of abnormalities on nerve conduction testing, three patients were diagnosed as having a reliable CRPS II (causalgia) and five patients a possible CRPS II. Thirty‐two patients were diagnosed as having a CRPS I. On clinical examination, 15 patients revealed generalized sensory deficits on the side of the body ipsilateral to the affected limb (hemisensory deficit, n=12; sensory impairment in the upper quadrant of the body, n=3). Patients with these generalized sensory deficits had a significantly longer illness duration (P<0.05) and a significantly higher percentage of mechanical allodynia/hyperalgesia than patients with spatially restricted sensory deficits (n=25) (P<0.05). In patients with generalized sensory impairment, thresholds for touch, warm and cold sensations, and for heat pain were significantly increased at all five locations tested ipsilaterally compared with the contralateral body side, except for the cool threshold on the chest and the heat pain threshold distally on the affected limb. In patients with sensory deficits limited to the affected limb, the touch threshold was significantly higher only in the distal part of the affected limb when compared with the contralateral limb. In these patients, thermal testing revealed almost no differences in cool, warm and heat pain thresholds when comparing both sides. Repeated thermal testing conducted in five patients with generalized sensory impairment reproduced the significant differences between both sides for cool, warm and heat pain thresholds. However, the correlation between the results obtained in the first and second examinations was poor. Neurophysiological recordings revealed pathological results in 46% for nerve conduction studies, 24% for somatosensory evoked potentials and 39% for sympathetic skin response. For all methods applied, there was no statistically significant difference in the incidence of pathological results between patients with generalized and patients with spatially restricted sensory abnormalities. Psychological examination using the structured clinical interview on DSM‐IV (SKID) demonstrated a high frequency of affective and anxiety disorders, however, without significant differences between both groups. We conclude that hemisensory impairment in patients with CRPS Type I is probably related to functional disturbances in processing of noxious events in the thalamus and may be a clinical correlate of subcortical brain plasticity in chronic pain.

Hemisensory impairment in patients with complex regional pain syndrome.

The purpose of the present study was to investigate the extent and quality of sensory impairment and their relation to pain characteristics and movement disorders in patients suffering from complex regional pain syndrome (CRPS) type I. Neurological testing was performed independently by two examiners in 24 patients with CRPS type I. In eight patients (33%), a hemisensory impairment with decreased temperature and pinprick sensation ipsilateral to the limb affected by CRPS could be observed. In four patients (17%), a sensory deficit in the upper quadrant of the body could be demonstrated and in eight patients (33%), sensory impairment was limited to the limb affected by CRPS. Mechanical allodynia and mechanical hyperalgesia could be observed in a higher percentage of patients with hemisensory deficit or sensory impairment in the upper quadrant (92%), than in those patients with sensory impairment limited to the affected limb (17%) (P < 0.005). In patients with left-sided CRPS, sensory abnormalities in the upper quadrant or hemisensory impairment were more frequently demonstrated (77%) than in patients with right-sided CRPS (18%) (P < 0.005). There was a high correlation (92%) for the sensory findings between the two examiners, and hemisensory abnormalities were stable over a period of 3-6 months in all six patients with repeated examinations. Motor impairment (contractures, weakness, tremor or difficulties in initiating movement) could be observed in a higher percentage in patients with sensory abnormalities in the upper quadrant or hemisensory impairment (83%) than in patients with sensory impairment limited to the affected limb (42%) (P < 0.05) and was significantly correlated with allodynia/hyperalgesia (P < 0.005). The results demonstrated that sensory deficits in patients with CRPS, frequently extend past the painful area of the affected limb. The increased frequency of mechanical allodynia and movement disorders in patients with hemisensory impairment or sensory deficits in the upper quadrant, might indicate that central mechanisms are involved in the pathogenesis of CRPS in these patients.

Functional Imaging of Perceptual Learning in Human Primary and Secondary Somatosensory Cortex

Cellular mechanisms underlying synaptic plasticity are in line with the Hebbian concept. In contrast, data linking Hebbian learning to altered perception are rare. Combining functional magnetic resonance imaging with psychophysical tests, we studied cortical reorganization in primary and secondary somatosensory cortex (SI and SII) and the resulting changes of tactile perception before and after tactile coactivation, a simple type of Hebbian learning. Coactivation on the right index finger (IF) for 3 hr lowered its spatial discrimination threshold. In parallel, blood-oxygen level-dependent (BOLD) signals from the right IF representation in SI and SII enlarged. The individual threshold reduction was linearly correlated with the enlargement in SI, implying a close relation between altered discrimination and cortical reorganization. Controls consisting of a single-site stimulation did not affect thresholds and cortical maps. Accordingly, changes within distributed cortical networks based on Hebbian mechanisms alter the individual percept.

Mutations in CAV3 cause mechanical hyperirritability of skeletal muscle in rippling muscle disease

Hereditary rippling muscle disease (RMD) is an autosomal dominant human disorder characterized by mechanically triggered contractions of skeletal muscle. Genome-wide linkage analysis has identified an RMD locus on chromosome 3p25. We found missense mutations in positional candidate CAV3 (encoding caveolin 3; ref. 5) in all five families analyzed. Mutations in CAV3 have also been described in limb-girdle muscular dystrophy type 1C (LGMD1C; refs. 6,7), demonstrating the allelism of dystrophic and non-dystrophic muscle diseases.

Influence of the N-methyl-d-aspartate antagonist memantine on human motor cortex excitability

The aim of our study was to investigate the effect of the N-methyl-D-aspartate (NMDA) antagonist memantine on motor excitability in humans. Seven healthy volunteers received memantine or placebo, respectively, over a period of 8 days. At day 8, transcranial magnetic stimulation (TMS) was performed using a paired pulses paradigm in order to assess intracortical inhibition and facilitation. Additionally, motor threshold and silent period duration after TMS were measured as well as M waves, F waves and peripheral silent period after electrical peripheral nerve stimulation. Intracortical inhibition was enhanced, and intracortical facilitation reduced after memantine ingestion in comparison to placebo, whereas no significant difference could be observed regarding the other neurophysiological parameters. We conclude that the NMDA receptor is involved in the regulation of excitability of intracortical interneuronal circuits.

Neuropsychological investigations and event-related potentials in obstructive sleep apnea syndrome before and during CPAP-therapy

Patients with obstructive sleep apnea syndrome (OSAS) suffer from daytime sleepiness and a decline of cognitive functions. The study evaluated whether special cognitive disabilities predominate in OSAS. Besides the number connection test (ZVT), judging information processing and working velocity, computer-assisted (Wiener Testsystem and Zimmermann Testbatterie) neuropsychological testing was performed in 31 OSAS patients (50.1 +/- 9.4 years) before starting nasal continuous positive airway pressure (nCPAP) therapy. Identical test battery was performed in 10 male healthy volunteers (48 +/- 9.9 years). In addition visual evoked event-related potentials (ERPs) were recorded, the P3-component was evaluated. Impairment of alertness (P < 0.001), selective attention (P < 0.001) and continuous attention (P < 0.001) could be revealed, vigilance was not altered. Cognitive deficits were correlated with the degree of nocturnal hypoxemia. They were not linked to the apnea/hypopnea-index (AHI), arousal index or vigilance parameters. During 6 months of nCPAP-therapy (15 patients) alertness and continuous attention improved significantly (P < 0.01), intra-individual different pathological results persisted however. P3 latencies also remained prolonged. Chronic intermittent nocturnal hypoxemia in OSAS-patients obviously leads to cognitive deficits. ERP partially generated in subcortical cerebral structures represent a neurophysiological tool indicating brain dysfunction which cannot be evaluated by neuropsychological tests. Objective neuropsychological testing is needed in revealing therapeutic effects in OSAS-patients. Remaining deficits during sufficient nCPAP-therapy may reflect irreversible hypoxic cerebral damage.

Enhancement of inhibitory mechanisms in the motor cortex of patients with cerebellar degeneration: a study with transcranial magnetic brain stimulation

The excitatory state of the primary motor cortex can be studied by measuring either the postexcitatory inhibition after transcranial magnetic single stimulation (pI-S) or the refractory period with magnetic double stimulation (rP-D). The cerebellum may influence the excitability of the motor cortex by cerebellar inputs and outputs from side loops of transcortical projections. Therefore, we studied pI-S and rP-D in 24 patients with autosomal dominant cerebellar ataxia or idiopathic cerebellar ataxia, who were allocated to one group (Group A) with mild to moderate ataxia (n = 11) and to another group (Group B) with severe ataxia (n = 13). The results were compared with those obtained in 21 normal age-matched control subjects. The central motor conduction time (CMCT) was delayed in approximately half of the patients, demonstrating that the degenerative process, beyond the cerebellum, also affects the pyramidal tract. Mean CMCT was significantly delayed only in patients of Group B. pI-S was prolonged in 10 of our 24 patients; incidence of pathology in pI-S did not differ between the two patient groups. In 5 patients with normal CMCT, pathological pI-S results were found. Mean pI-S was prolonged in the whole patient group and in both subgroups as well. rP-D was prolonged in two patients of Group B only, but mean rP-D was significantly prolonged in the whole patient group. Prolonged postexcitatory inhibition and refractory period may be a consequence of a transient facilitation of cortical inhibitory interneurons, which results in a decreased excitability of primary motor cortex in patients with cerebellar degeneration.

Central fatigue assessed by transcranial magnetic stimulation

Central fatigue is a subjective phenomenon which can be examined using transcranial magnetic stimulation (TMS). To assess central fatigue, we compared TMS and peripheral electrical stimulations in patients with central nervous system (CNS) lesions and controls before and after an exhaustive task. The recovery times of motor evoked potential (MEP) amplitudes were significantly prolonged in the patient group whereas the recovery of F waves and compound muscle action potentials showed no significant changes. The results indicate that fatigue cannot be attributed either to intramuscular processes or to reduced spinal excitability, but reflects a supraspinal, probably cortical phenomenon. The measurement of MEP recovery times proved to be a simple and objective tool for the assessment of fatigue and for the differentiation between healthy controls and patients with CNS lesions.