Clinical Correlates of Longitudinal Hypothalamic-Pontine Functional Changes in Migraine Patients
Roberta Messina1, Paola Valsasina2, Laura Zanandrea1, Ilaria Cetta4, Bruno Colombo3, Maria Rocca5, Massimo Filippi6
1Neuroimaging Research Unit, Division of Neurscience, and Neurology Unit, 2Neuroimaging Research Unit, Division of Neuroscience, 3Neurology Unit, IRCCS San Raffaele Scientific Institute, 4Neurology Unit, 5Neuroimaging Research Unit, Division of Neuroscience, and Neurology Unit, 6Neuroimaging Research Unit, Division of Neuroscience, Neurology Unit, Neurorehabilitation Unit, and Neurophysiology Service, IRCCS San Raffaele Scientific Institute; Vita-Salute San Raffaele University
Objective:
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.
Background:
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.
Design/Methods:
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.
Results:
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.
Conclusions:
Interictal migraine patients experience a prominent inhibitory influence of the pons over the hypothalamus and vice versa 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.