M. Bracaglia

Migraine improvement during short lasting ketogenesis: a proof-of-concept study.

Ketogenesis is a physiological phenomenon due to starvation or a ketogenic diet (KD), a drastic restricted carbohydrate dietary regimen that induces lipid metabolism and ketone body synthesis. Two patients whose migraines disappeared only during, and not outside, cycles of very‐low‐calorie KD performed to reduce their weight were recently observed. To confirm our observation, in a dietitian clinical setting two parallel groups of migraineurs, one receiving a 1‐month very‐low‐calorie KD prescription followed by a 5‐month standard low‐calorie diet (SD) and the other a 6‐month SD, were followed.

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.

Drug-induced changes in cortical inhibition in medication overuse headache:

Background: We investigated whether chronic headache related to medication overuse (MOH) is associated with changes in brain mechanisms regulating inhibitory cortical responses compared with healthy volunteers and episodic migraineurs recorded between attacks, and whether these changes differ according to the drug overused. Subjects and Methods: We studied 40 MOH patients whose symptoms were related to triptans alone, non-steroidal anti-inflammatory drugs (NSAIDs) or both medications combined, 12 migraineurs and 13 healthy volunteers. We used high-intensity transcranial magnetic stimulation over the primary motor cortex to assess the silent period from contracted perioral muscles. Results: In MOH patients the cortical silent period differed according to the type of headache medication overused: in patients overusing triptans alone it was shorter than in healthy volunteers (44.7 ± 14.2 vs. 108.1 ± 30.1 ms), but similar to that reported in migraineurs (59.9 ± 30.4 ms), whereas in patients overusing NSAIDs alone or triptans and NSAIDs combined duration of silent period was within normal limits (80.6 ± 46.4 and 103.8 ± 47.2 ms). Conclusions: Compared with episodic migraineurs, MOH patients overusing triptans have no significant change in cortical inhibition, whereas those overusing NSAIDs have an increase in cortical inhibitory mechanisms. We attribute these changes to medication-induced neural adaptation promoted by changes in central serotonin neurotransmission.

Lateral inhibition in the somatosensory cortex during and between migraine without aura attacks: Correlations with thalamocortical activity and clinical features

Background We studied lateral inhibition in the somatosensory cortex of migraineurs during and between attacks, and searched for correlations with thalamocortical activity and clinical features. Participants and methods Somatosensory evoked potentials (SSEP) were obtained by electrical stimulation of the right median (M) or ulnar (U) nerves at the wrist or by simultaneous stimulation of both nerves (MU) in 41 migraine without aura patients, 24 between (MO), 17 during attacks, and in 17 healthy volunteers (HVs). We determined the percentage of lateral inhibition of the N20–P25 component by using the formula [(100)–MU/(M + U)*100]. We also studied high-frequency oscillations (HFOs) reflecting thalamocortical activation. Results In migraine, both lateral inhibition (MO 27.9% vs HVs 40.2%; p = 0.009) and thalamocortical activity (MO 0.5 vs HVs 0.7; p = 0.02) were reduced between attacks, but not during. In MO patients, the percentage of lateral inhibition negatively correlated with days elapsed since the last migraine attack (r = −0.510, p = 0.01), monthly attack duration (r = −0.469, p = 0.02) and severity (r = −0.443, p = 0.03), but positively with thalamocortical activity (r = −0.463, p = 0.02). Conclusions We hypothesize that abnormal migraine cycle-dependent dynamics of connectivity between subcortical and cortical excitation/inhibition networks may contribute to clinical features of MO and recurrence of attacks.

Cortical functional correlates of responsiveness to short-lasting preventive intervention with ketogenic diet in migraine: a multimodal evoked potentials study

BackgroundHere, we aim to identify cortical electrofunctional correlates of responsiveness to short-lasting preventiveintervention with ketogenic diet (KD) in migraine.MethodsEighteen interictal migraineurs underwent visual (VEPs) and median nerve somatosensory (SSEPs) evokedpotentials before and after 1 month of KD during ketogenesis. We measured VEPs N1-P1 and SSEPs N20-P25 amplitudes respectively in six and in two sequential blocks of 100 sweeps as well as habituation as theslope of the linear regression between block 1 to 6 for VEPs or between 1 to 2 for SSEPs.ResultsAfter 1-month of KD, a significant reduction in the mean attack frequency and duration was observed (all P< 0.001). The KD did not change the 1st SSEP and VEP block of responses, but significantly inducednormalization of the interictally reduced VEPs and SSEPs (all p < 0.01) habituation during the subsequentblocks.ConclusionsKD could restore normal EPs habituation curves during stimulus repetition without significantly changing theearly amplitude responses. Thus, we hypothesize that KD acts on habituation regulating the balancebetween excitation and inhibition at the cortical level.

The use of illicit drugs as self-medication in the treatment of cluster headache: Results from an Italian online survey.

Background Cluster headache (CH) patients often receive unsatisfactory treatment and may explore illicit substances as alternatives. We aimed to explore this use of illicit drugs for CH treatment. Methods We invited CH patients from an Internet-based self-help group to complete a questionnaire regarding their therapeutic use of illicit substances. Results Of the 54 respondents, 29 were classified as chronic and 39 were drug-resistant cases. Fifty patients had previously tried subcutaneous sumatriptan, 40 had tried O2, and 48 had tried at least one prophylactic treatment. All 54 patients specified that they were dissatisfied with conventional treatments. Thirty-four patients had used cannabinoids, 13 cocaine, 8 heroin, 18 psilocybin, 12 lysergic acid amide (LSA), and 4 lysergic acid diethylamide (LSD). Discussion Some patients with intractable CH decided to try illicit drugs concomitantly with cessation of medical care. Most of these patients found suggestions for illicit drug use on the Internet. Many patients seemed to underestimate the judicial consequences of, and had an overestimated confidence in the safety of, such illicit treatments. Physicians are often not informed by patients of their choice to use illicit drugs. This leads to questions regarding the true nature of the physician-patient relationship among dissatisfied CH patients.

Lateralized nociceptive blink reflex habituation deficit in episodic cluster headache: Correlations with clinical features

Background We previously observed impaired habituation mechanisms of the conventional blink reflex (BR) in patients with episodic cluster headache (ECH) during the bout, studying only the affected side. Here, we have studied the nociceptive-specific BR (nBR) both on the affected and non-affected sides, and in relation to clinical features. Participants and methods We recorded nBR in 18 ECH patients during the bout, and in 18 healthy volunteers (HVs). We compared pain threshold, area, and habituation of the nBR, recorded both for the affected and non-affected sides. Results In patients, the pain threshold on the affected side was lower than that of the non-affected side (p = 0.009), and lower than in HVs (p = 0.038). Reflex area was decreased on both sides (p < 0.05) compared with HVs, whereas habituation was significantly impaired only on the affected side (p = 0.025 vs. HVs; p = 0.003 vs. non-affected). The habituation slope was positively correlated with the number of days since the onset of the bout and the daily attack frequency. Conclusions Our data reflect lateralized pathological variations in craniofacial nociception in ECH patients over the course of the cluster period. We hypothesized that this is due to malfunctioning of mechanisms that regulate hypothalamic activity and descending aminergic controls.

O025. Excitability of the motor cortex in migraine changes with the distance from the last attack

Background Single-pulse transcranial magnetic stimulation studies of motor cortex have the advantage of relying on an objective measure, the motor evoked potential (MEP) recorded in peripheral muscles, to non-invasively explore the cortical excitability. Previously, thresholds for MEP were found to be normal, increased or even reduced in migraine. In the present study, we investigated whether the level of cortical excitability changes with the distance from the last migraine attack could explain these inconsistent results.

58. Clinical efficacy of short-lasting ketogenic diet in migraine might be due to a general normalization of cortical hyperresponsivity rather than to a direct modulation of the brainstem activity

We previously reported that a short-lasting period of ketogenic diet (KD) regimen can help to prevent migraine and can normalize its interictally abnormal cortical hyperresponsivity. Here, we aimed to verify whether cerebral cortex is the primary site of KD-related changes or if the latter are the expression of ketones ability to modulate brainstem subcortical structures. We simultaneously recorded the nociceptive specific blink (nBR, a marker of the brainstem trigeminal activity) and cortical pain-related evoked potentials (PREP) elicited by the stimulation of right the supraorbital division of the trigeminal nerve in 18 migraine without aura patients before and after 1-month of KD, during ketogenesis. We measured nBR R2 component as well as PREP amplitude habituations over 2 blocks of 5 averaged responses. We confirmed the ability of 1-month KD of significantly decreasing mean attack frequency and duration. KD significantly induced normalization of the interictally reduced PREP habituation (pre: +1.8, post: −9.1), while nBR habituation remained unchanged. Here, we provided evidence that the clinical efficacy of a short-lasting KD regimen in migraine can be principally due to a general normalization of the interictal cortical dysfunction, and not to a direct modulation of the subcortical brainstem activation.

EHMTI-0182. Positive family history of migraine predisposes to a reduced migraineurs visual cortical reactivity

Results We recruited 85 patients with and 24 without a positive family history of migraine. Patients who had one parent affected (mother or father) had significantly lower N75-P100 VEP amplitude blocks overall than those had no parents affected, the latter resulting not different from HV. Lack of VEP N75-P100 amplitude habituation was found in overall migraineurs compared with HV, irrespectively of whether they had a parent affected or not. Conclusion These findings suggest that familial occurrence of migraine may predispose to a general reduced cortical reactivity to visual stimulation. No conflict of interest.