V. De Pasqua

Projections from basal ganglia to tegmentum: a subcortical route for explaining the pathophysiology of Parkinson's disease signs?

Abstract Functional changes in the organisation of neuronal circuitries are generally used to explain parkinsonian motor symptoms and levodopa-induced dyskinesias. Based on information from histology and neurophysiological microrecordings of specific basal ganglia nuclei, the most widely accepted scheme is based on a central loop which starts in the cerebral cortex, makes multiple relays in the basal ganglia, and returns to the cerebral cortex. Transcranial magnetic stimulation studies, however, reveal no significant differences in the excitability of the motor cortex between normal subjects and patients with Parkinson’s disease. Furthermore, electrophysiological and audiospinal facilitation studies indicate that the activity of reticular nuclei is altered in Parkinson’s disease. It therefore appears that a circuit with the cortex as the only recipient of basal ganglia output is an oversimplification. This paper explores the relationships between various basal ganglia nuclei and proposes a subcortical pathway via which modifications in the basal ganglia may influence motor function.

Reduced excitability of the motor cortex in untreated patients with de novo idiopathic “grand mal” seizures

OBJECTIVES Transcranial magnetic stimulation (TMS) was used to investigate motor cortex excitability, intracortical excitatory, and inhibitory pathways in 18 patients having experienced a first “grand mal” seizure within 48 hours of the electrophysiological test. All had normal brain MRI, and were free of any treatment, drug, or alcohol misuse. Results were compared with those of 35 age matched normal volunteers. METHODS The following parameters of responses to TMS were measured: motor thresholds at rest and with voluntary contraction, amplitudes of responses, cortical silent periods, and responses to paired pulse stimulation with interstimulus intervals of 1 to 20 ms. RESULTS In patients, there were significantly increased motor thresholds with normal amplitudes of motor evoked potentials (MEPs), suggesting decreased cortical excitability. Cortical silent periods were not significantly different from those of normal subjects. Paired TMS with short interstimulus intervals (1–5 ms) induced normal inhibition of test MEPs, suggesting preserved function of GABAergic intracortical inhibitory interneurons. On the contrary, the subsequent period of MEP facilitation found in normal subjects (ISIs of 6–20 ms) was markedly reduced in patients. This suggests the existence of abnormally prolonged intracortical inhibition or deficient intracortical excitation. In nine patients retested 2 to 4 weeks after the initial seizure, these abnormalities persisted, although to a lesser extent. CONCLUSION The present findings together with abnormally high motor thresholds could represent protective mechanisms against the spread or recurrence of seizures.

The vestibulo-collic reflex is abnormal in migraine

Interictal evoked central nervous system responses are characterized in migraineurs by a deficit of habituation, at both cortical and subcortical levels. The click-evoked vestibulo-collic reflex (VCR) allows the assessment of otolith function and an oligosynaptic pathway linking receptors in the saccular macula to motoneurons of neck muscles. Three blocks of 75 averaged responses to monaural 95-dB normal hearing level 3-Hz clicks were recorded over the contracted ipsilateral sternocleidomastoid muscle in 25 migraineurs between attacks and 20 healthy subjects, without vestibular symptoms. Amplitudes, raw and corrected for baseline electromyography, were significantly smaller in migraine patients. Whereas in healthy volunteers the VCR habituated during stimulus repetition (-4.96% ± 14.3), potentiation was found in migraineurs (4.34% ± 15.3; P = 0.04). The combination with a reduced mean amplitude does not favour vestibular hyperexcitability as an explanation for the habituation deficit in migraine, but rather an abnormal processing of repeated stimuli in the reflex circuit.

Abnormalities of the vestibulo-collic reflex are similar in migraineurs with and without vertigo.

The amplitude and habituation of the click-evoked vestibulo-collic reflex (VCR) was found reduced between attacks in migraineurs without complaints of ictal or interictal vertigo or dizziness, compared with healthy subjects. As a next step we recorded VCR in 17 migraine patients (eight with migraine without aura and nine with migraine with aura) who presented ictal migrainous vertigo according to the criteria defined by Neuhauser et al., using a method described previously. Migraineurs with migrainous vertigo have similar VCR abnormalities as patients without vertigo, i.e. a decreased global amplitude and absence of habituation. Potentiation seemed more pronounced in migraineurs with vertigo (7.46 ± 18.6), but the difference was not significant.

Inhibition of the nociceptive R2 blink reflex after supraorbital or index finger stimulation is normal in migraine without aura between attacks

In order to explore possible interictal brainstem dysfunctions in migraine, we have studied the R2 component of the nociceptive specific blink reflex (nBR) after conditioning by supraorbital or index finger stimuli in 14 untreated migraine without aura patients (MO) between attacks and in 15 healthy volunteers. We determined the R2 recovery curve at increasing inter-stimulus intervals between 50 and 600 ms. The nBR was conditioned by a paired supraorbital stimulus and, in another session, by an ipsilateral electrical shock delivered to the index finger. The R2 nBR recovery curves were normal in MO patients for both the supraorbital and peripheral conditioning. These results do not favour persistent interictal sensitization in the spinal trigeminal sensory system. They also suggest that the control exerted by descending brainstem pathways on medullary R2 interneurones is normal in migraine between attacks.

Les potentiels évoqués visuels dans la maladie de Parkinson

Summary Visual evoked potentials were studied in 23 patients with Parkinsons disease at varying stages, and in 23 normal subjects of the same age. The latency of the P wave is increased in the Parkinson group in a significant manner and becomes more marked as the disease progresses. The difference in latency between the potentials evoked by stimuli applied to both eyes is also significantly increased in Parkinsons disease. The interpretation of these results remains obscure, but « peripheralretinal and « centralmechanisms are probably involved. From a practical point of view, these results demonstrate that increases in latency of visual evoked potentials are not always due to localized demyelinization. Study of visual evoked potentials could be of value when investigating patients with Parkinsons disease.

Réflexes du muscle soléaire évoqués par la stimulation du nerf tibial postérieur versus réflexe tendineux chez l'homme

Summary The characteristics of the reflex response evoked in the soleus muscle after stimulation of the posterior tibial nerve at the ankle were contrasted with the achilleus tendon reflex in 14 healthy volunteers and in a group of selected neurological patients. The following features were examined : conditions of stimulation including stimulation frequency ; appearance of reflex activity in muscles other than soleus, effect of the vibratory stimulation, interactions with voluntary contraction. Moreover, a reflex response is described in the soleus following stimulation of the sural nerve. The results have shown a marked jitter in latencies of the responses, a pattern of coactivation of antagonistic muscles, a clear increase of amplitude under vibration or voluntary contraction, normal responses both in spasticity and in S1 radiculopathy with achilleus areflexia. All these data differ from those observed with the tendon jerk of the same amplitude and differentiate the two responses. It is concluded that the reflex evoked by stimulation of the tibial nerve at the ankle is a polysynaptic response of cutaneous origin.

Anodal transcranial direct current stimulation of the visual cortex for migraine prevention: a proof-of-concept study

Prophylaxis is challenging in migraine because of the low efficiency/tolerability ratio of most drugs [1]. Abnormal excitability of the cerebral cortex seems implicated in migraine pathophysiology [2]. Transcranial direct current stimulation (tDCS) can durably modify the activity of a target cortex and thus be a promising treatment [3]. We have shown that the cerebral cortex, namely the visual cortex, is hyperreactive in migraineurs between attacks and hypothesized that this may be related more to a decreased preactivation level than to hyperexcitability per se [2]. Anodal, rather than cathodal, tDCS might be the stimulation modality of choice in migraine.

EHMTI-0217. Neurophysiological study of tdcs effects in healthy volunteers

Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation technique able to activate (anode) or to inhibit (cathode) the underlying cortex. It could be of interest for the preventive treatment of migraine that is associated with interictal changes in cortical responsivity. To optimize neuromodulation protocols, however, studies of their physiological effects on the normal human brain are necessary.

EHMTI-0238. Why narcissus was probably no migraineur: a study of visually induced analgesia

Results In HV, gazing at the face reflection decreased significantly CHEPs latency (N2) and amplitude (P1-N2 and N2-P2), and increased P1-N2 habituation. Conversely, the mirror considerably decreased trigeminal CHEPs habituation in MO. Pain perception assessed by visual analogue scale was not modified either by the mirror, or between groups. The mirror decreased CHEPs parameters in the wrist numerically but not significantly in both groups. Conclusions The visually induced analgesia phenomenon using a mirror is demonstrated by a decrease of thermonociceptive potentials in HV in trigeminal and peripheral areas. In interictal migraineurs, forehead VIA is significantly impaired and gazing at the mirror strongly decreases the trigeminal habituation to thermal nociceptive stimulation. This study suggests a connectivity dysfunction between visual and trigeminal pain networks. No conflict of interest.