Mesocorticolimbic system abnormalities in chronic cluster headache patients: A neural signature?

BACKGROUND: Converging evidence suggests that anatomical and functional mesocorticolimbic abnormalities support the chronicization of pain disorders. METHODS: We mapped structural and functional alterations of the mesocorticolimbic system in a sample of chronic cluster headache patients (n = 28) in comparison to age and sex-matched healthy individuals (n = 28) employing structural MRI and resting-state functional MRI. RESULTS: Univariate logistic regression models showed that several of the examined structures/areas (i.e., the bilateral nucleus accumbens, ventral diencephalon, hippocampus, and frontal pole, and the right amygdala) differentiated chronic cluster headache patients from healthy individuals (p < 0.05, uncorrected). Specifically, all the significant structures/areas had increased volumes in chronic cluster headache patients compared to healthy individuals. The examination of the groups suffering from left and right-sided cranial attacks showed a lateralization effect: ipsilateral to the pain ventral diencephalic regions and contralateral to the pain nucleus accumbens discriminated chronic cluster headache patients from healthy individuals. The resting-state functional MRI data analyses showed that chronic cluster headache patients compared to CTRL individuals present robust reduced functional connectivity in the right frontal pole-right amygdala pathway (p < 0.05, FDR-corrected). CONCLUSION: Our results showed that chronic cluster headache patients present anatomical and functional maladaptation of the mesocorticolimbic system, with functional data indicating a possible prefrontal areas' failure to modulate the mesolimbic structures. These results were opposite to what we hypothesized based on the previous literature on chronic pain conditions.Future studies should assess whether the observed mesocorticolimbic abnormalities are due to the neuroprotective effects of the assumed medications, or to the frequent comorbidity of CH with neuropsychiatric disorders or if they are a genuine neural signature of CH and/or chronic cluster headache condition.

Chronic cluster headache: A study of the telencephalic and cerebellar cortical thickness.

PURPOSE: Previous studies on brain morphological alterations in chronic cluster headache revealed inconsistent findings. METHOD: The present cross-sectional explorative study determined telencephalic and cerebellar cortex thickness alterations in a relatively wide sample of chronic cluster headache patients (n = 28) comparing them to matched healthy individuals. RESULTS: The combination of two highly robust state-of-the-art approaches for thickness estimation (Freesurfer, CERES), strengthened by functional characterization of the identified abnormal regions, revealed four main results: chronic cluster headache patients show 1) cortical thinning in the right middle cingulate cortex, left posterior insula, and anterior cerebellar lobe, regions involved in nociception's sensory and sensory-motor aspects and possibly in autonomic functions; 2) cortical thinning in the left anterior superior temporal sulcus and the left collateral/lingual sulcus, suggesting neuroplastic maladaptation in areas possibly involved in social cognition, which may promote psychiatric comorbidity; 3) abnormal functional connectivity among some of these identified telencephalic areas; 4) the identified telencephalic areas of cortical thinning present robust interaction, as indicated by the functional connectivity results, with the left posterior insula possibly playing a pivotal role. CONCLUSION: The reported results constitute a coherent and robust picture of the chronic cluster headache brain. Our study paves the way for hypothesis-driven studies that might impact our understanding of the pathophysiology of this condition.

Migraine and rare neurological disorders.

Although migraine is generally considered an idiopathic and isolated neurological condition, it may also represent the presenting symptom of several uncommon heritable and acquired neurological diseases contributing to the recognition of such conditions. Migraine may indeed present with atypical characteristics or prolonged duration and may be associated with specific neuroradiological findings that may help in identifying the underlying condition. However, features of migraine in rare diseases are usually little known because of the lack of systematic studies. The aim of this paper is to provide clinicians with an updated review on specific clinical and neuroradiological features of migraine in uncommon neurological diseases that may be helpful to their diagnosis and treatment. Therefore, the early diagnosis of these uncommon diseases is crucial for patients' clinical management and for the implementation of therapeutic approaches aimed at targeting the underlying disease pathogenic mechanisms. Thus, when investigating patients affected by migraine, physicians should always be aware about rare causes of migraine that if misdiagnosed could seriously impact patients' outcome. Given these relevant implications, future studies specifically assessing features of migraine in uncommon diseases are mandatory.

Cluster headache: insights from resting-state functional magnetic resonance imaging.

The comprehension of cluster headache (CH) has greatly benefited from the tremendous progress of the neuroimaging techniques over the last 20 years. Since the pioneering study of May et al. (1998), the neuroimaging results have indeed revolutionized the conception of this disease, now considered as a dysfunction of the central nervous system. Clinical, neuroendocrinological, and neuroimaging studies strongly suggested the involvement of the hypothalamus as the generator of cluster headache attacks. However, the latency of the improvement and the inefficacy of the hypothalamic deep brain stimulation (DBS) in the acute phase suggested that the hypothalamus might play a modulating role, pointing to the presence of some dysfunctional brain networks, normalized or modulated by the DBS. Despite the great importance of possible dysfunctional hypothalamic networks in cluster headache pathophysiology, only quite recently the scientific community has begun to explore the functional connectivity of these circuits using resting-state functional magnetic resonance imaging. This is a neuroimaging technique extensively employed to investigate the functional connectivity among separated regions of the brain at rest in the low-frequency domain (< 0.1 Hz). Here, we present a review of the few resting-state functional magnetic resonance imaging studies investigating the hypothalamic network contributing to a deeper comprehension of this neurological disorder. These studies seem to demonstrate that both the hypothalamus and the diencephalic-mesencephalic junction regions might play an important role in the pathophysiology of CH. However, future studies are needed to confirm the results and to clarify if the observed dysfunctional networks are a specific neural fingerprint of the CH pathophysiology or an effect of the severe acute pain. It will be also crucial to clarify the neural pathways of the chronicization of this disorder.

Clinical and psychosocial features of frequent relapsers (FR) among patients with chronic migraine and medication overuse.

The objective was to characterize frequent relapsers (FR)-i.e. those requiring two or more withdrawals in a 3-year period-in a sample of 188 patients with chronic migraine with medication overuse (CM-MO). We tested differences between FR and non-FR for age, gender, employment status, days with headache, headache severity, type of overused medication, BDI-II, WHODAS 2.0 and MSQ. 30.8% of participants were FR: they were more frequently treated as inpatients and living alone, had a lower education, higher disability and lower QoL, higher frequency and intensity of headaches, and higher depression scores. Clinicians should address whether CM-MO patients submitted to withdrawal had recently underwent other similar interventions.