Simona Talamanca

Cyclical changes of cortical excitability and metaplasticity in migraine: evidence from a repetitive transcranial magnetic stimulation study.

Summary Insight is provided into the pathophysiological mechanisms underlying the abnormal regulation of cortical function and its periodicity in episodic and chronic migraine. ABSTRACT The primary brain dysfunctions leading to the onset of a migraine attack remain largely unknown. Other important open questions concern the mechanisms of initiation, continuation, and termination of migraine pain, and the changes in brain function underlying migraine transformation. Brief trains of high‐frequency repetitive transcranial magnetic stimulation (rTMS), when applied to the primary motor cortex at suprathreshold intensity (≥120% of resting motor threshold [RMT]), elicit in healthy subjects a progressive, glutamate‐dependent facilitation of the motor evoked potentials (MEP). Conversely, in conditions of increased cortical excitability, the rTMS trains induce inhibitory MEP responses likely mediated by cortical homeostatic mechanisms. We enrolled 66 migraine‐without‐aura patients, 48 migraine‐with‐aura patients, 14 patients affected by chronic migraine (CM), and 20 healthy controls. We assessed motor cortical response to 5‐Hz rTMS trains of 10 stimuli given at 120% RMT. Patients with episodic migraine were studied in different phases of the migraine cycle: interictal, preictal, ictal, and postictal states. Results showed a facilitatory MEP response during the trains in patients evaluated in the preictal phase, whereas inhibitory responses were observed during and after a migraine attack, as well as in CM patients. In the interictal phase, different responses were observed, depending on attack frequency: facilitation in patients with low and inhibition in those with high attack recurrence. Our findings suggest that changes in cortical excitability and fluctuations in the threshold for inhibitory metaplasticity underlie the migraine attack recurrence, and could be involved in the process of migraine transformation.

Abnormal facilitatory mechanisms in motor cortex of migraine with aura

Experimental evidence suggests impairment of inhibitory intracortical circuits in migraine, while not much is known about activity of facilitatory intracortical circuits. In the present work we evaluated the effects of high frequency‐repetitive transcranial magnetic stimulation (hf‐rTMS) on the activity of facilitatory circuits of motor cortex in 18 patients affected by migraine with aura and 18 healthy subjects. Trains of 10 stimuli were applied to the motor cortex at 5‐Hz frequency with recording of the EMG traces from the contralateral abductor pollicis brevis muscle (APB). Two intensities of stimulation (110% and 130% of resting motor threshold) were used in order to explore whether motor cortex excitability was differently modulated. Twelve patients underwent hf‐rTMS both before and during prophylactic treatment with levetiracetam. Results showed that rTMS delivered at 110% intensity of stimulation at rest had a facilitatory effect on MEP size in untreated patients, while left MEP unchanged in controls. Conversely, when rTMS was applied at 130%, we observed MEP potentiation in healthy subjects and paradoxical MEP inhibition in migraineurs. In treated patients, levetiracetam inhibited MEP size at both 110% and 130% intensity of stimulation. Our findings reveal an opposite response of migraine motor cortex to 5‐Hz rTMS when it is delivered at different stimulation intensities, providing evidence of both hyper‐responsivity and self‐limiting hyperexcitability capacity, in line with studies supporting the concept that under conditions of cortical hyperexcitability inhibitory mechanisms of homeostatic plasticity could be activated.

Transcranial direct current stimulation preconditioning modulates the effect of high-frequency repetitive transcranial magnetic stimulation in the human motor cortex

Experimental studies emphasize the importance of homeostatic plasticity as a mean of stabilizing the properties of neural circuits. In the present work we combined two techniques able to produce short‐term (5‐Hz repetitive transcranial magnetic stimulation, rTMS) and long‐term (transcranial direct current stimulation, tDCS) effects on corticospinal excitability to evaluate whether and how the effects of 5‐Hz rTMS can be tuned by tDCS preconditioning. Twelve healthy subjects participated in the study. Brief trains of 5‐Hz rTMS were applied to the primary motor cortex at an intensity of 120% of the resting motor threshold, with recording of the electromyograph traces evoked by each stimulus of the train from the contralateral abductor pollicis brevis muscle. This interventional protocol was preconditioned by 15 min of anodal or cathodal tDCS delivered at 1.5 mA intensity. Our results showed that motor‐evoked potentials (MEPs) increased significantly in size during trains of 5‐Hz rTMS in the absence of tDCS preconditioning. After facilitatory preconditioning with anodal tDCS, 5‐Hz rTMS failed to produce progressive MEP facilitation. Conversely, when 5‐Hz rTMS was preceded by inhibitory cathodal tDCS, MEP facilitation was not abolished. These findings may give insight into the mechanisms of homeostatic plasticity in the human cerebral cortex, suggesting also more suitable applications of tDCS in a clinical setting.

Impaired Glutamatergic Neurotransmission in Migraine With Aura? Evidence by an Input–Output Curves Transcranial Magnetic Stimulation Study

(Headache 2011;51:726‐733)

Different forms of trigeminal autonomic cephalalgias in the same patient: description of a case

The trigeminal autonomic cephalalgias (TACs), including cluster headache, paroxysmal hemicrania and SUNCT, are characterized by the cardinal combination of short-lasting unilateral pain and autonomic phenomena affecting the head. Hemicrania continua (HC) shares many clinical characteristics with TACs, including unilateral pain and ipsilateral autonomic features. Nevertheless, HC is separately classified in the revised International Classification of Headache Disorders (ICHD-II). Here, we describe the case of a 45-year-old man presenting an unusual concurrence of different forms of primary headaches associated with autonomic signs, including subsequently ipsilateral cluster headache, SUNCT and HC. This report supports the theory that common mechanisms could be involved in pathophysiology of different primary headache syndromes.

Reduced threshold for inhibitory homeostatic responses in migraine motor cortex? A tDCS/TMS study.

Neurophysiological studies in migraine have reported conflicting findings of either cortical hyper‐ or hypoexcitability. In migraine with aura (MwA) patients, we recently documented an inhibitory response to suprathreshold, high‐frequency repetitive transcranial magnetic stimulation (hf‐rTMS) trains applied to the primary motor cortex, which is in contrast with the facilitatory response observed in the healthy subjects. The aim of the present study was to support the hypothesis that in migraine, because of a condition of basal increased cortical responsivity, inhibitory homeostatic‐like mechanisms of cortical excitability could be induced by high magnitude stimulation. For this purpose, the hf‐rTMS trains were preconditioned by transcranial direct current stimulation (tDCS), a noninvasive brain stimulation technique able to modulate the cortical excitability state.

MRI abnormalities following repeated and incoming seizures

Neuroimaging, an important diagnostic tool frequently used in the evaluation of patients with epilepsy, has mainly the aim to identify structural abnormalities needing a treatment and to contribute to the definition of the aetiology. Brain magnetic resonance imaging (MRI) in epilepsy is more sensitive than computerized tomography (CT) scan for detecting abnormalities. Status epilepticus (SE) and repeated incoming seizures may determine extensive and transient or long lasting pronounced MRI changes. We describe a case of a 41-year-old woman with a history of brain neoplasm, whose contrast-enhanced MRI images following repeated and incoming seizures were characterized either by reversible and irreversible abnormalities.

Reversible posterior leukoencephalopathy syndrome in a patient with thrombotic thrombocytopenic purpura

Thrombotic thrombocytopenic purpura (TTP) is an autoimmune disorder characterised by fever, microangiopathic haemolytic anaemia, renal insufficiency, and thrombocytopenia. Neurological involvement, a prominent component of TTP, is characterised by a variety of brain lesions which include reversible cerebral oedema or magnetic resonance imaging (MRI) features of reversible posterior leukoencephalopathy syndrome (RPLS). TTP is frequently associated with deficiency of the von Willebrand factor-cleaving protease, ADAMTS13.Here, we report a case of TTP with severe acute encephalopathy. Posterior leukoencephalopathy and brainstem oedema with triventricular hydrocephalus were observed on MRI. The low activity of ADAMTS13 was not observed and ADAMTS-13 antibodies were absent. Neurological symptoms and patient’s condition were completely resolved by plasma exchange therapy in addition to high dose of methylprednisolone.

O047. The sound-induced flash illusions reveal visual cortex hyperexcitability in cluster headache

Objectives Pathophysiology of cluster headache (CH) is not wellknown. Although posterior hypothalamus has been suggested to play a pivotal role, evidence exists of a more diffuse involvement of the central nervous system including brainstem and cerebral cortex. In this regard, we recently observed increased motor cortical excitability in episodic CH patients both outside and inside bout [1]. The sound-induced flash illusions (SIFI) represent an example of multisensory integration, and provide a tool to indirectly explore the excitability state of the visual cortex [2]. SIFI are classified as “fission” and “fusion” illusions. When one visual stimulus (flash) is accompanied by two or more auditory stimuli (beeps), it is often perceived as multiple flashes (fission illusion). Conversely, fusion illusion occurs when subjects perceive less number of flashes when these are presented with only one beep. On such bases, here we used SIFI to explore excitability of visual cortex in CH patients.

EHMTI-0220. Cortical excitability in episodic cluster headache

Methods Twenty-five patients with episodic CH and thirteen healthy subjects underwent an experimental session where we evaluated, in both hemispheres, motor-cortical response to: 1) single-pulse TMS: i.e. motor threshold (MT); input-output (IO) curves and cortical silent period (CSP) and 2) paired-pulse TMS: i.e. intracortical facilitation (ICF) and short intracortical inhibition (SICI). Thirteen patients were evaluated outside bout, while the remaining twelve patients were inside bout at the time of recording.