Clinical Correlates of Longitudinal Hypothalamic-Pontine Functional Changes in Migraine Patients (S41.008)

<h3>Objective:</h3> To explore longitudinal hypothalamic-pontine resting state (RS) effective connectivity (EC) changes in migraine patients and investigate their association with disease progression over the years. <h3>Background:</h3> The hypothalamus and pons play a pivotal role in migraine pathophysiology. Whether longitudinal hypothalamic-pontine RS EC changes could influence migraine disease activity has never been investigated. <h3>Design/Methods:</h3> RS functional magnetic resonance imaging were acquired from 92 headache-free episodic migraine patients and 73 controls. Twenty-three migraine patients and 23 controls were reexamined after 4 years. RS EC of bilateral pons and hypothalamus was performed using SPM12 and dynamic causal modelling. Longitudinal RS EC differences between groups were investigated using parametric empirical bayes models. <h3>Results:</h3> During the follow-up, 35% of patients reported an increased migraine attack frequency. Over the follow-up, migraine patients developed a higher inhibitory EC within the left pons, from the right pons to the ipsilateral hypothalamus, from the left hypothalamus to the ipsilateral and contralateral pons, and from the left pons to the ipsilateral and contralateral hypothalamus. Migraine patients experienced also a higher excitatory EC from the right pons to the left pons. At follow-up, greater headache impact correlated to higher inhibitory EC from the left pons to the ipsilateral and contralateral hypothalamus, while higher migraine attack frequency was associated with higher inhibitory left hypothalamic-left pontine EC. During the follow-up, the increased left pontine-right hypothalamic inhibitory EC was significantly associated to an increased migraine attack frequency. Lower inhibitory RS EC from the left pons to the left and right hypothalamus at baseline predicted clinical worsening over the years. <h3>Conclusions:</h3> Interictal migraine patients experience a prominent inhibitory influence of the pons over the hypothalamus and <i>vice versa</i> that could affect migraine progression over the years. An altered hypothalamic-pontine inhibitory activity may be a prognostic marker for migraine worsening after 4 years. <b>Disclosure:</b> Dr. Messina has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Lundbeck . Dr. Messina has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Eli Lilly. Dr. Messina has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Bromatech. Paola Valsasina has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for ACCMED. Dr. Zanandrea has nothing to disclose. Dr. Cetta has nothing to disclose. Bruno Colombo has nothing to disclose. Maria Assunta Rocca has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bayer, Biogen, Bristol Myers Squibb, Celgene, Genzyme, Merck Serono, Novartis, Roche, and Teva. The institution of Maria Assunta Rocca has received research support from Italian Ministry of Health, MS Society of Canada and Fondazione Italiana Sclerosi Multipla. Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Bayer, Biogen Idec, Merck-Serono, Novartis, Roche, Sanofi Genzyme, Takeda, and Teva Pharmaceutical Industries. Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Bayer, Biogen Idec, Merck-Serono, Novartis, Roche, Sanofi Genzyme, Takeda, and Teva Pharmaceutical Industries. Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Springer Nature. The institution of Dr. Filippi has received research support from Biogen Idec, Merck-Serono, Novartis, Roche, Teva Pharmaceutical Industries, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla, and ARiSLA (Fondazione Italiana di Ricerca per la SLA).