Alessandro Viganò

Transcranial Direct Current Stimulation (tDCS) of the visual cortex: a proof-of-concept study based on interictal electrophysiological abnormalities in migraine

BackgroundPreventive pharmacotherapy for migraine is not satisfactory because of the low efficacy/tolerability ratio of many available drugs. Novel and more efficient preventive strategies are therefore warranted. Abnormal excitability of cortical areas appears to play a pivotal role in migraine pathophysiology. Transcranial direct current stimulation (tDCS) is a non-invasive and safe technique that is able to durably modulate the activity of the underlying cerebral cortex, and is being tested in various medical indications. The results of small open studies using tDCS in migraine prophylaxis are conflicting, possibly because the optimal stimulation settings and the brain targets were not well chosen. We have previously shown that the cerebral cortex, especially the visual cortex, is hyperresponsive in migraine patients between attacks and provided evidence from evoked potential studies that this is due to a decreased cortical preactivation level. If one accepts this concept, anodal tDCS over the visual cortex may have therapeutic potentials in migraine prevention, as it is able to increase neuronal firing.ObjectiveTo study the effects of anodal tDCS on visual cortex activity in healthy volunteers (HV) and episodic migraine without aura patients (MoA), and its potentials for migraine prevention.MethodsWe recorded pattern-reversal visual evoked potentials (VEP) before and after a 15-min session of anodal tDCS over the visual cortex in 11 HV and 13 MoA interictally. Then 10 MoA patients reporting at least 4 attacks/month subsequently participated in a therapeutic study, and received 2 similar sessions of tDCS per week for 8 weeks as migraine preventive therapy.ResultsIn HV as well as in MoA, anodal tDCS transiently increased habituation of the VEP N1P1 component. VEP amplitudes were not modified by tDCS. Preventive treatment with anodal tDCS turned out to be beneficial in MoA: migraine attack frequency, migraine days, attack duration and acute medication intake significantly decreased during the treatment period compared to pre-treatment baseline (all p < 0.05), and this benefit persisted on average 4.8 weeks after the end of tDCS.ConclusionsAnodal tDCS over the visual cortex is thus able to increase habituation to repetitive visual stimuli in healthy volunteers and in episodic migraineurs, who on average lack habituation interictally. Moreover, 2 weekly sessions of anodal tDCS had a significant preventive anti- migraine effect, proofing the concept that the low preactivation level of the visual cortex in migraine patients can be corrected by an activating neurostimulation. The therapeutic results indicate that a larger sham-controlled trial using the same tDCS protocol is worthwhile.

Pearls and pitfalls: Electrophysiology for primary headaches

Background Primary headaches are functional neurological diseases characterized by a dynamic cyclic pattern over time (ictal/pre-/interictal). Electrophysiological recordings can non-invasively assess the activity of an underlying nervous structure or measure its response to various stimuli, and are therefore particularly appropriate for the study of primary headaches. Their interest, however, is chiefly pathophysiological, as interindividual, and to some extent intraindividual, variations preclude their use as diagnostic tools. Aim of the work This article will review the most important findings of electrophysiological studies in primary headache pathophysiology, especially migraine on which numerous studies have been published. Results In migraine, the most reproducible hallmark is the interictal lack of neuronal habituation to the repetition of various types of sensory stimulations. The mechanism subtending this phenomenon remains uncertain, but it could be the consequence of a thalamocortical dysrythmia that results in a reduced cortical preactivation level. In tension-type headache as well as in cluster headache, there seems to be an impairment of central pain-controlling mechanisms but the studies are scarce and their outcomes are contradictory. The discrepancies between studies might be as a result of methodological differences as well as patients’ dissimilarities, which are also discussed. Conclusions and perspectives Electrophysiology is complementary to functional neuroimaging and will undoubtedly remain an important tool in headache research. One of its upcoming applications is to help select neurostimulation techniques and protocols that correct best the functional abnormalities detectable in certain headache disorders.

Cerebral responses and role of the prefrontal cortex in conditioned pain modulation: an fMRI study in healthy subjects

The mechanisms underlying conditioned pain modulation (CPM) are multifaceted. We searched for a link between individual differences in prefrontal cortex activity during multi-trial heterotopic noxious cold conditioning and modulation of the cerebral response to phasic heat pain. In 24 healthy female subjects, we conditioned laser heat stimuli to the left hand by applying alternatively ice-cold or lukewarm compresses to the right foot. We compared pain ratings with cerebral fMRI BOLD responses. We also analyzed the relation between CPM and BOLD changes produced by the heterotopic cold conditioning itself, as well as the impact of anxiety and habituation of cold-pain ratings. Specific cerebral activation was identified in precuneus and left posterior insula/SII, respectively, during early and sustained phases of cold application. During cold conditioning, laser pain decreased (n=7), increased (n=10) or stayed unchanged (n=7). At the individual level, the psychophysical effect was directly proportional to the cold-induced modulation of the laser-induced BOLD response in left posterior insula/SII. The latter correlated with the BOLD response recorded 80s earlier during the initial 10-s phase of cold application in anterior cingulate, orbitofrontal and lateral prefrontal cortices. High anxiety and habituation of cold pain were associated with greater laser heat-induced pain during heterotopic cold stimulation. The habituation was also linked to the early cold-induced orbitofrontal responses. We conclude that individual differences in conditioned pain modulation are related to different levels of prefrontal cortical activation by the early part of the conditioning stimulus, possibly due to different levels in trait anxiety.

Topiramate modulates habituation in migraine: evidences from nociceptive responses elicited by laser evoked potentials

BackgroundLack of habituation during repetitive stimulation is the most consistent interictal abnormality of cortical information processing observed in migraine. Preventive migraine treatments might act by stabilizing cortical excitability level and thus the habituation to external stimuli.MethodsWe examined the effects of preventive treatment with topiramate on migraineur’s habituation to nociceptive stimulation. Scalp potentials were evoked by Nd-YAP Laser stimulation of the hand dorsum and supraorbital region in 13 patients with migraine without aura (MO) and 15 healthy volunteers (HV). The exam was repeated in MO before and after treatment.ResultsWe observed a lack of habituation and lower initial amplitudes in MO compared to HV. These abnormalities reached statistical significance for N1 LEPs component, generated in the secondary somatosensory cortex (SII), but not for N2/P2 complex, generated in the insula and anterior cingulated cortex (ACC). Topiramate normalized the N1 habituation pattern in MO, with a significant correlation between clinical effects and normalization of neurophysiological responses.ConclusionsOur results indicate a modulating action of topiramate on cortical processing of sensorial stimuli, mainly regarding the sensory-discriminative component of pain, elaborated by SII, without a significant effect on the affective dimension of pain, in which the ACC has an important role.

Alice in Wonderland Syndrome: A Clinical and Pathophysiological Review

Alice in Wonderland Syndrome (AIWS) is a perceptual disorder, principally involving visual and somesthetic integration, firstly reported by Todd, on the literary suggestion of the strange experiences described by Lewis Carroll in Alice in Wonderland books. Symptoms may comprise among others aschematia and dysmetropsia. This syndrome has many different etiologies; however EBV infection is the most common cause in children, while migraine affects more commonly adults. Many data support a strict relationship between migraine and AIWS, which could be considered in many patients as an aura or a migraine equivalent, particularly in children. Nevertheless, AIWS seems to have anatomical correlates. According to neuroimaging, temporoparietal-occipital carrefour (TPO-C) is a key region for developing many of AIWS symptoms. The final part of this review aims to find the relationship between AIWS symptoms, presenting a pathophysiological model. In brief, AIWS symptoms depend on an alteration of TPO-C where visual-spatial and somatosensory information are integrated. Alterations in these brain regions may cause the cooccurrence of dysmetropsia and disorders of body schema. In our opinion, the association of other symptoms reported in literature could vary depending on different etiologies and the lack of clear diagnostic criteria.

Serotonergic Correlation with Anger and Aggressive Behavior in Acute Stroke Patients: An Intensity Dependence of Auditory Evoked Potentials (IDAP) Study

Anger and aggressive behavior (AB) are two of the main post-stroke behavioral manifestations, which could imply both an anger trait (TA) or a state condition of anger (SA). Serotonergic system is thought to play an inhibitory control on aggressive impulse. Nevertheless, whether 5HT has the same role in TA and in SA, is still debated. Intensity dependence of auditory evoked potentials (IDAP) is thought to be inversely related to the central 5HT tone. The aim of this study was to evaluate, in acute stroke patients, the 5HT system involvement in AB by IDAP. Consecutive stroke patients were evaluated and compared with healthy controls. The Spielberger Trait Anger Scale (STAS) was used to assess AB, SA and TA. Patients with AB and TA showed a significantly increased IDAP value, whereas patients with SA had a significantly lower IDAP; this indicates an increased 5HT tone. In acute stroke patients with AB, there is a decreased central 5HT tone. Surprisingly, we found an opposite 5HT feature between patients with TA and those showing SA, suggesting that the hypothesis of aggression based on 5HT deficiency requires further investigations. This might open new strategies in the treatment of post-stroke AB.

A multidisciplinary approach to the functional abnormalities of the migrainous brain and non-invasive interventions to treat them

Background Migraine is characterized pathophysiologically by an interictal habituation deficit of information processing, responsible for cortical hyperresponsiveness, which normalizes during attacks [1]. Furthermore, descending pain control systems (DPCSs) can be impaired in episodic and chronic migraine [3,4]. Noninvasive neuromodulation of the cerebral cortex may be effective in migraine prophylaxis [2] including, in chronic migraine, modulation of the dorsolateral prefrontal cortex (DLPFC) that is part of the DPCSs [5].

Hemodynamic Features of Non-Aneurysmal Subarachnoid Hemorrhage in a Case of Familial Moyamoya Disease: A Transcranial Doppler Ultrasound Study

Willis circle with absence of the ACAs and of L-MCA and multiple tortuous vessels branching from the R-MCA (‘moyamoya vessels’). No aneurysms or vascular malformations were found ( fig. 1 ). Based on these findings, the patient was diagnosed with MMD. No neurological deficits were noted on the patient’s physical examination. Upon admission, we performed a Carotid Duplex ultrasound and a TCD, which showed an increase in mean blood flow velocity of R-MCA. This was initially attributed to vasospasm and nimodipine therapy was started. We also performed a progressive TCD follow-up; hemodynamic parameters of the first ultrasound examination as well as those from TCD follow-up are summarized in table 1 (we exclusively reported follow-up values from the R-MCA, which were the only ones that showed significant changes through time). The patient had a very favorable outcome and is currently asymptomatic. Particularly interesting is the monitoring of hemodynamic state of brain vessels done in our case. According to previous studies performed on asymptomatic MMD patients [6] , we found at T0 that both the ICAs showed normal flow velocity and low resistance, while the remaining intracranial vessels showed a consistent hemodynamic pattern in terms of high flow velocity and low resistance. This pattern re

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.

Paroxysmal hemicrania-tic syndrome: a new case report

An association of Paroxysmal Hemicrania (PH) with Trigeminal Neuralgia (TN) was described in eight patients [1,2] and has been called the PH-tic syndrome [3]. Case report. A 52-year-old man presented with a 5-year history of excruciating and burning pain, involving the left ophthalmic trigeminal branch, lasted 30 to 60 seconds, occurred 2 to 5 times a day, without any autonomic sign. Triggering factors included touching, washing face or brushing the teeth. Carbamazepine (600 mg/day) produced marked improvement. Any attempt to reduce the dose resulted in pain recurrence. While the previous pain was in remission by carbamazepine, he complained of a second type of pain that lasted 15 to 30 minutes and occurred up to 8 times per day. The strictly unilateral pain occurred in the left orbit, forehead, temple, nose and was described as severe and sharp with autonomic signs. There were no triggers. Indomethacin (150 mg/day) completely resolved attacks. His past medical history was significant for atrial fibrillation, hypertension and glaucoma; neurological examination and blood analysis were normal. Brain magnetic resonance showed silent lacunar infarcts, while magnetic cerebral angiography was normal. Trigeminal reflexes were also normal. In order to assess the possible involvement of the small myelinated and unmyelinated trigeminal fibers, we recorded, using a Nd:YAP laser stimulator, laser evoked potentials (LEPs) after supraorbital stimulation that showed a normality of A-delta and C fibers activation of the affected compared to the normal side. At the time of LEPs the patient was TN and PH off-indomethacin pain-free.