Elisa Iacovelli

Differences in short-term primary motor cortex synaptic potentiation as assessed by repetitive transcranial magnetic stimulation in migraine patients with and without aura

&NA; To find out more about glutamatergic and gabaergic transmission in migraine, in this study we investigated glutamate‐dependent short‐term synaptic potentiation and GABA‐dependent inhibitory cortical interneuron excitability as assessed by 5 Hz‐rTMS delivered over primary motor cortex (M1) (motor evoked potential, MEP, amplitude facilitation and cortical silent period, CSP, duration lengthening) in migraine patients with (MA) and without aura (MwoA) and healthy controls. We studied 37 patients with migraine (19 MA and 18 MwoA) and 19 healthy control subjects. 5 Hz‐rTMS was delivered at 120% resting motor threshold to the hand motor area of the left hemisphere with the target muscle at rest and during contraction. Three of the MA patients were also tested at the end of visual aura during a spontaneous migraine attack. ANOVA showed that the MEP significantly increased in size and CSP significantly lengthened during 5 Hz‐rTMS in the three groups tested. The 5 Hz‐rTMS‐induced MEP facilitation differed significantly being highest in MA patients. In the three patients tested both ictally and interictally the MEP increased during the interictal session but remained unchanged when the visual aura ended. Our study shows that the neurophysiological feature that differentiates MA patients from MwoA patients and healthy controls is an abnormal M1 susceptibility to 5 Hz‐rTMS both outside and during the attack suggesting that glutamate‐dependent short‐term M1 cortical potentiation patterns differ in migraine with and without aura.

Acute and chronic effects of ethanol on cortical excitability

OBJECTIVE We designed this study to find out whether 5Hz repetitive transcranial magnetic stimulation (rTMS) would disclose changes in cortical plasticity after acute intake of ethanol and in patients with chronic alcohol consumption. METHODS Ten stimuli-5Hz-rTMS trains were applied over the primary motor cortex in 10 healthy subjects before and after acute ethanol intake and in 13 patients with chronic ethanol abuse, but negative blood ethanol levels when studied. The motor evoked potential (MEP) amplitude and the cortical silent period (CSP) duration during the course of rTMS trains were measured. Short-interval intracortical inhibition (3ms) and intracortical facilitation (10ms) were studied by paired-pulse TMS in 4 healthy subjects and 4 patients. RESULTS In healthy subjects before and after acute ethanol intake, 5Hz-rTMS produced a significant increase in the MEP size and CSP duration during rTMS. The first CSP in the train was significantly longer after than before ethanol intake. In patients 5Hz-rTMS failed to produce the normal MEP facilitation but left the CSP increase unchanged. CONCLUSIONS Acute and chronic ethanol intake alters cortical excitability and short-term plasticity of the primary motor cortex as tested by the MEP size facilitation and CSP lengthening after 5Hz-rTMS. SIGNIFICANCE This finding suggests that rTMS is a valid tool for investigating the effects of ethanol on cortical plasticity in humans.

Dynamic changes in thalamic microstructure of migraine without aura patients: a diffusion tensor magnetic resonance imaging study.

The thalamus seems to be profoundly involved in the cyclical recurrence of migraine clinical and neurophysiological features. Here possible structural changes in the thalamus of migraineurs were searched for by means of diffusion tensor (DT) magnetic resonance imaging (MRI). This MRI technique provides quantitative data on water molecule motion as a marker of tissue microstructure.

Evidence for brain morphometric changes during the migraine cycle: A magnetic resonance-based morphometry study

Neurophysiological investigations have demonstrated that there are unique fluctuations in the migraine brain functional activity between the ictal and interictal periods. Here we investigated the possibility that there are fluctuations over time also in whole brain morphometry of patients affected by episodic migraine without aura (MO). Twenty-four patients with untreated MO underwent 3T MRI scans during (n = 10) or between attacks (n = 14) and were compared to a group of 15 healthy volunteers (HVs). We then performed voxel-based-morphometry (VBM) analysis of structural T1-weighted MRI scans to determine if changes in brain structure were observed over the course of the migraine cycle. Interictally, MO patients had a significantly lower gray matter (GM) density within the right inferior parietal lobule, right temporal inferior gyrus, right superior temporal gyrus, and left temporal pole than did HVs. Ictally, GM density increased within the left temporal pole, bilateral insula, and right lenticular nuclei, but no areas exhibited decreased GM density. These morphometric GM changes between ictal and interictal phases suggest that abnormal structural plasticity may be an important mechanism of migraine pathology. Given the functional neuroanatomy of these areas, our findings suggest that migraine is a condition associated with global dysfunction of multisensory integration and memory processing.

Cannabinoid-induced effects on the nociceptive system: A neurophysiological study in patients with secondary progressive multiple sclerosis

Although clinical studies show that cannabinoids improve central pain in patients with multiple sclerosis (MS) neurophysiological studies are lacking to investigate whether they also suppress these patients’ electrophysiological responses to noxious stimulation. The flexion reflex (FR) in humans is a widely used technique for assessing the pain threshold and for studying spinal and supraspinal pain pathways and the neurotransmitter system involved in pain control.

Abnormal sensorimotor plasticity in migraine without aura patients.

Summary Impaired paired associative stimulation (PAS)‐induced long‐term synaptic plasticity characterizes migraine without aura patients between attacks. We suggest that the malfunctioning in PAS‐induced effects in migraine reflects low cortical preactivation, which prevents short‐term and longer‐term changes in cortical synaptic effectiveness. ABSTRACT The period between migraine attacks is characterized by paradoxical responses to repetitive sensory and transcranial magnetic stimulation (TMS). Abnormal long‐term cortical functional plasticity may play a role and can be assessed experimentally by paired associative stimulation (PAS), in which somatosensory peripheral nerve stimuli are followed by TMS of the motor cortex. Changes in motor‐evoked potential (MEP) amplitudes were recorded in 16 migraine without aura patients (MO) and 15 healthy volunteers (HV) before and after PAS, which consisted of 90 peripheral electrical right ulnar nerve stimulations and subsequent TMS pulses over the first dorsal interosseous (FDI) muscle activation site with a delay of 10 ms (excitability depressing) or 25 ms (excitability enhancing). As a control experiment of the 31 subjects studied, 8 (4 MO and 4 HV) also underwent PAS10 earlier, the recording of somatosensory high‐frequency oscillations (HFOs) reflecting thalamocortical activation (early HFOs). Although PAS10 reduced MEP amplitudes in HV (−17.7%), it significantly increased amplitudes in MO (+35.9%). Although in HV MEP amplitudes were significantly potentiated (+55.1) after PAS25, only a slight, nonsignificant increase was observed in MO (+18.8%). In the control experiment, performed on 8 subjects pooled together, Pearsons correlation showed an inverse relationship between the percentage of MEP amplitude changes after PAS10 and early HFO amplitudes (r = −0.81; P = .01). Because we observed that the more deficient the long‐term PAS‐induced change, the more the thalamocortical activation decreased, we hypothesize that the abnormalities in long‐term cortical plasticity observed in the interictal period between migraine episodes could be due to altered thalamic control.

Botulinum toxin type A for the treatment of sialorrhoea in amyotrophic lateral sclerosis: A clinical and neurophysiological study

Abstract Botulinum toxin type A (BoNT/A) has been proposed as an alternative treatment for sialorrhoea in patients with amyotrophic lateral sclerosis (ALS). In an open-label prospective study, BoNT/A was injected into the parotid glands bilaterally using anatomic landmarks in 26 ALS patients with bulbar symptoms. Two weeks after injection the severity of sialorrhoea and the related disability were evaluated subjectively and objectively. A group of healthy subjects acted as controls for saliva production. Patients also underwent electrophysiological tests to evaluate possible toxin effects in the nearby non-injected muscles by comparing the amplitude of compound motor action potentials (cMAPs) elicited by electrical stimulation and recorded from the orbicularis oculi and masseter muscles. After BoNT/A injections, of the 26 patients treated, 23 reported that the severity of sialorrhoea improved and the disabling symptoms diminished. Cotton roll weight also decreased after BoNT/A injection, suggesting a reduction in saliva production. Two patients complained of dry mouth. BoNT/A injection left the cMAP amplitude unchanged, suggesting that botulinum toxin does not significantly affect the non-injected facial and masticatory muscles. In conclusion, intraparotid anatomically-guided BoNT/A injection is an effective, easy, and safe treatment for sialorrhoea in patients with bulbar symptoms related to ALS.

Neuroimaging in cluster headache and other trigeminal autonomic cephalalgias

The central nervous system mechanisms involved in trigeminal autonomic cephalalgias, a group of primary headaches characterized by strictly unilateral head pain that occurs in association with ipsilateral craniofacial autonomic features, are still not comprehensively understood. However, functional imaging methods have revolutionized our understanding of mechanisms involved in these primary headache syndromes. The present review provides a brief overview of the major modern functional neuroimaging techniques used to examine brain structure, biochemistry, metabolic state, and functional capacity. The available functional neuroimaging data in cluster headache and other TACs will thus be summarized. Although the precise brain structures responsible for these primary headache syndromes still remain to be determined, neuroimaging data suggest a major role for posterior hypothalamus activation in initiating and maintaining attacks. Furthermore, pathophysiological involvement of the pain neuromatrix and of the central descending opiatergic pain control system was observed. Given the rapid advances in functional and structural neuroimaging methodologies, it can be expected that these non-invasive techniques will continue to improve our understanding into the nature of the brain dysfunction in cluster headache and other trigeminal autonomic cephalalgias.

Recurrent leukoencephalopathy in a cocaine abuser

We report the case of a cocaine abuser who presented two consecutive episodes of acute leukoencephalopathy, documented by serial MRI, with favourable outcome. Clinical findings and brain imaging led to the diagnosis of cocaine-induced toxic leukoencephalopathy and other possible mimickers have been excluded on the basis of clinical assessment. The patients unexpected recovery on neurological and neuropsychological examination, despite initially severe neurological symptoms, is striking and differs from more common reports of a rapid progression to death. Of note, case presented in the peculiar form of recurrent episodes of acute leukoencephalopathy, with favourable outcome, which, to our knowledge, has not been described yet. We speculate about the aetiology of this condition, which is still poorly understood.

Influence of the corticospinal tract on the cutaneous silent period: A study in patients with pyramidal syndrome

The cutaneous silent period (CSP) is a brief transient suppression of the voluntary muscle contraction that follows a noxious cutaneous nerve stimulation. In this study we investigated the influence of the corticospinal tract on this spinal inhibitory reflex. In patients with pyramidal syndrome and in a group of healthy subjects we delivered painful electrical finger stimulation during sustained contraction of the ipsilateral abductor digiti minimi muscle. The CSP latency and duration and the background electromyographic (EMG) activity were measured and compared between-groups. The compound motor action potential amplitude and F-wave latency were also measured after electrical stimulation of the ulnar nerve at the wrist. The CSP latency was significantly longer in patients than in healthy subjects. None of the other variables differed in patients and healthy subjects. Our findings suggest that corticospinal projections influence the CSP latency probably by modulating the balance of excitability in the underlying circuits.