Michele Abbruzzese

Proprioceptive modulation of somatosensory evoked potentials during active or passive finger movements in man.

The effects of active and passive finger movements on somatosensory potentials evoked by stimulation of the median nerve at the wrist or of finger I were investigated in 15 healthy volunteers. As compared to the resting condition, both active and passive movements of the stimulated hand fingers induced a marked reduction in the amplitude of the primary cerebral response (N20-P25 complex) as well as of the N17 SEP component, which is supposed to reflect the activity of the thalamo-cortical radiation. The following cerebral SEP components, within 100 ms after the stimulus, were also depressed during motor activity. Neither N11 nor N13 components of the cervical response, reflecting the activation of dorsal columns and dorsal column nuclei respectively, were modified. The SEP changes induced by active or passive movements were absent after ischaemic block of large group I afferent fibers from the hand, thus suggesting the relevance of the feedback generated by such peripheral afferents during movement. The results indicate that the activation of peripheral receptors (probably muscle spindle endings) during both active and passive finger movement would induce a gating effect at both cortical and subcortical (thalamic) level, which might modulate selectively the different sensory inputs to the cortex.

New subcortical components of the cerebral somatosensory evoked potential in man

Two new components of the human SEP upon stimulation of the contralateral median nerve at the wrist have been identified. Such components have been called N16 and N17, according to their polarity and latency. N16 and N17, as well as the N14‐P15 complex, are generated by separate subcortical dipoles. Particularly, they are supposed to be far‐field reflections of the activity of the dorsal columns nuclei or the medial lemniscus (N14‐P15), the thalamus (N16) and the thalamo‐cortical radiation (N17). Moreover, it has been established that N14 is the very first intracranial component of the human SEP, the main peak of S wave and the preceding ones being extracranial in origin.

Task-dependent effects evoked by foot muscle afferents on leg muscle activity in humans

The effect of low intensity electrical stimulation of the posterior tibial nerve (PTN) at the ankle on the active triceps surae (TS) muscles was studied in normal subjects, both in a prone position and while standing. PTN stimulation regularly evoked the H-reflex in the flexor digitorum brevis and, in the prone position, a short-latency facilitatory effect in the soleus muscle. During standing, the facilitatory effect was preceded by a clear-cut reduction in electromyograph (EMG) activity. The inhibition-facilitation sequence was evoked in the gastrocnemii under both conditions, on average, though individual differences were present. An EMG modulation similar to that observed under standing conditions was present also in the prone position when subjects pressed the sole of the foot against the wall. Stimulation of sural or digital nerves did not evoke similar effects. It is concluded that foot muscle afferents establish oligosynaptic connections transmitting mixed effects to the TS motoneuronal pool, and that contact with the sole of the foot plays an enabling role for the inhibitory pathway directed to the soleus muscle.

Experimental Charcot-Marie-Tooth type 1A: A cDNA microarrays analysis

To reveal the spectrum of genes that are modulated in Charcot-Marie-Tooth neuropathy type 1A (CMT1A), which is due to overexpression of the gene coding for the peripheral myelin protein 22 (pmp22), we performed a cDNA microarray experiment with cDNA from sciatic nerves of a rat model of the disease. In homozygous pmp22 overexpressing animals, we found a significant down-regulation of 86 genes, while only 23 known genes were up-regulated, suggesting that the increased dosage of pmp22 induces a general down-regulation of gene expression in peripheral nerve tissue. Classification of the modulated genes into functional categories leads to the identification of some pathways altered by overexpression of pmp22. In particular, a selective down-regulation of the ciliary neurotrophic factor transcript and of genes coding for proteins involved in cell cycle regulation, for cytoskeletal components and for proteins of the extracellular matrix, was observed. Cntf expression was further studied by real-time PCR and ELISA technique in pmp22 transgenic sciatic nerves, human CMT1A sural nerve biopsies, and primary cultures of transgenic Schwann cells. According to the results of cDNA microarray analysis, a down-regulation of cntf, both at the mRNA and protein level, was found in all the conditions tested. These results are relevant to reveal the molecular function of PMP22 and the pathogenic mechanism of CMT1A. In particular, finding a specific reduction of cntf expression in CMT1A Schwann cells suggests that overexpression of pmp22 significantly affects the ability of Schwann cells to offer a trophic support to the axon, which could be a factor, among other, responsible for the development of axonal atrophy in human and experimental CMT1A.

Impairment of central motor conduction in diabetic patients

In 70 patients with diabetes mellitus (DM) we recorded the motor evoked potentials (MEPs) following magnetic stimulation of the motor cortex and spinal roots. Central motor conduction time (CMCT) was determined as the difference between MEP latencies after cortical and spinal stimulation. The mean CMCTs for the biceps, thenar and tibialis anterior muscles were prolonged in the DM group, as compared to normal controls, and 21 patients exceeded the CMCT upper confidence limit for at least one muscle. CMCT changes and peripheral conduction velocity abnormalities occurred independently and were related to different clinical parameters. We conclude that a subclinical impairment of central motor conduction is present in 30% of DM patients, independently from the occurrence of a diabetic peripheral neuropathy and possibly reflecting different pathophysiological mechanisms.

Assessment of motor neuron excitability in parkinsonian rigidity by the F wave

SummaryF-wave responses from abductor pollicis brevis muscle occurred more frequently, with a larger amplitude and longer duration in rigid parkinsonian patients than in age-matched normal controls. F-wave potentiation during voluntary contraction was impaired in parkinsonian patients. These findings suggest that spinal motor neuron excitability is enhanced in rigidity. F-wave amplitude was significantly correlated to the clinical evaluation of motor disability, so that the F wave may be regarded as a useful approach to quantitative evaluation of rigidity.

The effect of hand muscle vibration on the somatosensory evoked potential in man: an interaction between lemniscal and spinocerebellar inputs?

The effect of hand muscle mechanical vibration on the somatosensory potential (SEP) evoked by median nerve stimulation, was investigated in 10 healthy subjects. A marked decrease in the amplitude of the N17, N20 and P25 components of the cerebral SEP was observed, while the S11 and S13 components of the cervical response did not change. The amplitude reduction of the SEP components was larger when low frequency vibration was used. Recordings performed after cooling the hand further suggest that the reduction of the amplitude of the SEP components induced by vibration is likely to depend on activation of muscle receptors. These findings could reflect an interaction between limniscal and spino-cerebellar inputs, possibly occurring at the thalamo-cortical levels, a concept compatible with the hypothesis that muscle spindle afferents do contribute to kinaesthesia or position-sense.

Short-latency somatosensory evoked potentials in degenerative and vascular dementia.

Short-latency somatosensory evoked potentials (SEPs) were recorded from 54 patients with dementia as compared to 32 age-matched controls. SEPs were generally normal in patients with senile dementia of Alzheimer type, while patients with multi-infarct dementia showed a prolonged central conduction time, an increased latency of both N13 and N20 and a reduction of the primary cortical response amplitude. These findings suggest that recording SEPs may be useful in the differential diagnosis between degenerative dementia and multi-infarct dementia.

Impairment of PMP22 transgenic Schwann cells differentiation in culture: implications for Charcot-Marie-Tooth type 1A disease

Charcot-Marie-Tooth type 1A (CMT1A) is a hereditary demyelinating neuropathy due to an increased genetic dosage of the peripheral myelin protein 22 (PMP22). The mechanisms leading from PMP22 overexpression to impairment of myelination are still unclear. We evaluated expression and processing of PMP22, viability, proliferation, migration, motility and shaping properties, and ability of forming myelin of PMP22 transgenic (PMP22(tg)) Schwann cells in culture. In basal conditions, PMP22(tg) Schwann cells, although expressing higher PMP22 levels than control ones, show normal motility, migration and shaping properties. Addition of forskolin to the media induces an additional stimulation of PMP22 expression and results in an impairment of cells migration and motility, and a reduction of cell area and perimeter. Similarly, co-culturing transgenic Schwann cells with neurons causes an altered cells differentiation and an impairment of myelin formation. In conclusion, exposure of PMP22(tg) Schwann to the axon or to axonal-mimicking stimuli significantly affects the transition of transgenic Schwann cells to the myelinating phenotype.

Motor evoked potentials (MEPs) in lacunar syndromes

Motor evoked potentials (MEPs) evoked in the biceps, thenar and tibialis anterior muscles by electrical stimulation of the scalp and of the spinal regions were recorded in 32 patients with focal deficits due to minor cerebral ischemia of the lacunar type and in a control group. Somatosensory evoked potentials (SEPs) to median nerve stimulation were also recorded. The central motor conduction times (CMCTs) and the threshold intensities for eliciting MEPs in the relaxed muscles were significantly increased on the affected side. Central motor conduction, for at least one muscle, was altered in 18 patients. MEP abnormalities were related to pyramidal signs (though they could be observed also in a patient without any motor impairment) and occurred independently of a specific clinical picture or a radiologically confirmed lacunar lesion. SEPs were less frequently altered than MEPs.