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International audience; Giant axonal neuropathy (GAN), a severe childhood disorder affecting both the peripheral nerves and the central nervous system, is due to mutations in the GAN gene encoding gigaxonin, a protein implicated in the cytoskeletal functions and dynamics. In the majority of the GAN series reported to date, patients had the classical clinical phenotype characterized by a severe axonal neuropathy with kinky hair and early onset CNS involvement including cerebellar and pyramidal signs. We present 12 patients (6 families) with GAN mutations and different clinical phenotypes. Four families were harbouring an identical homozygous nonsense mutation but with different severe clinical phenotypes, one patient had a novel missense homozygous mutation with a peculiar moderate phenotype and prominent skeletal deformations. The last family (4 patients) harbouring a homozygous missense mutation had the mildest form of the disease. In contrast with recent reported series of patients with typical GAN clinical features, the present series demonstrate obvious clinical heterogeneity.

International audience; OBJECTIVE: To study the pyramidal tract side effects (PTSEs) induced by the spread of current from the subthalamic nucleus (STN) to the pyramidal tract (PT), in patients with parkinsonism undergoing STN stimulation. METHODS: 14 patients bilaterally implanted with tetrapolar electrodes were assessed. For each side separately, the threshold of adverse effects induced by monopolar stimulation delivered by the chronically used contact was detected. The voltage was progressively increased until the patient experienced discomfort. All the PTSEs induced at 130 Hz (high-frequency stimulation (HFS)) and 2 or 3 Hz (low-frequency stimulation (LFS)) were videotaped. By superimposing the preoperative and postoperative MR images, the minimum distance (R) from the centre of the used contact to the medial border of the PT were measured. RESULTS: The progressive increase in voltage at HFS induced tonic motor contractions, mainly located in the face, in 27/28 electrodes. LFS induced synchronous rhythmic myoclonus in the same territory. PTSEs induced at threshold voltage by HFS were observed in the upper face at 13/28 electrodes (bilaterally in six cases) and in the contralateral lower face at five electrodes. A positive correlation was found between the stimulus intensity capable of eliciting motor contractions at HFS and R. CONCLUSIONS: HFS of the STN preferentially activates the corticobulbar tract over the corticospinal tract. Therefore, cranial motor contractions need to be looked for during electrical parameter setting. The positive correlation between the electrical intensity threshold for PTSEs and R reflects the need for millimetre accuracy in electrode positioning.

In humans a substantial part of corticospinal excitation to upper limb motoneurons is mediated through cervical premotoneurons located rostral to motoneurons, analogous to the feline system of C3-C4 propriospinal neurons. The indirect (disynaptic) component of the corticospinal command passing through the propriospinal relay may be updated by the extensive convergence at this level of afferent inputs (both excitatory and inhibitory) from the moving limb. Propriospinal neurons are potently inhibited by feedback inhibitory interneurons facilitated from the motor cortex, and this explains why artificial volleys delivered to the pyramidal system by itself have failed to demonstrate this indirect corticospinal projection. The strength of this indirect corticospinal projection may be estimated in routine practice by the amount of suppression elicited by a cutaneous volley on the ongoing electromyogram of extensor carpi radialis, and is increased in patients recovering from hemiplegia and in early Parkinson's disease.

Peripheral stimuli facilitate, at a pre-motoneuronal level, the responses elicited in human upper limb motoneurons (MNs) by transcranial magnetic stimulation over the motor cortex (TMS). Several features indicate that the relevant premotoneurones are distinct from segmental interneurones and located rostral to MNs. Thus, corticospinal volleys would have an indirect (propriospinal) pathway to upper limb MNs, in addition to the direct cortico-motoneuronal pathway. Slightly increasing the corticospinal input causes the facilitation to be reversed to inhibition. This is consistent with a well-developed system of inhibitory intemeurones activated by corticospinal and afferent inputs inhibiting propriospinal neurones (PNs). Corticospinal activation of these inhibitory interneurones would explain why propriospinally-mediated corticospinal EPSPs are weak in primate MNs after artificial (electrical or magnetic) activation of the corticospinal system by itself. However, indirect evidence for descending facilitation of PNs can be provided during normal voluntary contractions, while using the modulation of the ongoing EMG or of the H reflex.

We sought to determine why a given muscle appears represented in widespread loci in the motor cortex (MCx). To this end, we microstimulated every 500 microm along medio-lateral rows and recorded the evoked electromyographic (EMG) responses of up to a dozen forelimb muscles of the cat. A consistent finding in all animals studied was that along a given row, distal muscle responses could be elicited from medially situated cortical loci and conversely, proximal muscles responses from laterally situated cortical loci. In many such cases, the evoked EMG responses were such that the largest responses from a distal muscle were obtained by stimulation at a medially situated point and those of a proximal muscle from a laterally situated point. A Spearman correlation analysis showed that there was no correlation between cortical position and where the peak response of a given muscle occurred. These quantitative results strongly support the view that in the forelimb area of the cat MCx there exists widespread 'colonies' of corticospinal neurons with common spinal cord targets.

International audience; This paper will discuss experiments dedicated to the exploration of pathways linking the sensorimotor cortex (SMC) and the main bulbar nuclei involved in cardiovascular control: the nucleus tractus solitarius (NTS), the dorsal nucleus of the vagus (DMV) and the rostral ventrolateral medulla (RVLM). Results obtained through neurofunctional and neuroanatomical methods are presented in order to bring new answers to relevant points concerning somato-cardiovascular integration: firstly to show the ability of the SMC to influence neurons in bulbar cardiovascular nuclei, and secondly to identify pathways that transmit such influences. The neurofunctional approach, based on the identification of Fos-like immunoreactive neurons, indicated that the SMC has functional connections with cardiovascular bulbar nuclei. The neuroanatomical approach, which employed retrograde and anterograde axonal tracing methods, provided evidence of direct projections from the SMC to NTS/DMV and RVLM. Furthermore, experiments showed clearly that corticospinal neurons sent collaterals to bulbar cardiovascular nuclei, especially to the RVLM. Direct cortical projections to the NTS/DMV and the RVLM provide the anatomical basis for cortical influences on the baroreceptor reflex and sympathetic vasomotor mechanisms for blood pressure control, and support the hypothesis of cortical commands coupling somatic and cardiovascular outputs for action.