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 (cCH) patients (n = 28) in comparison to age and sex-matched healthy individuals (n=28) employing structural MRI and resting-state functional MRI (rs-fMRI). 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 cCH patients from healthy individuals (p<0.05, uncorrected). Specifically, all the significant structures/areas had increased volumes in cCH 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 cCH patients from healthy individuals. The rs-fMRI data analyses showed that cCH 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 cCH 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 cCH 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.

Neurostimulation Treatment in Chronic Cluster Headache—a Narrative Review

Purpose of Review In this narrative review, the current literature on neurostimulation methods in the treatment of chronic cluster headache is evaluated. These neurostimulation methods include deep brain stimulation, vagus nerve stimulation, greater occipital nerve stimulation, sphenopalatine ganglion stimulation, transcranial magnetic stimulation, transcranial direct current stimulation, supraorbital nerve stimulation, and cervical spinal cord stimulation. Recent Findings Altogether, only nVNS and SPG stimulation are supported by at least one positive sham-controlled clinical trial for preventive and acute attack (only SPG stimulation) treatment. Other clinical trials either did not control at all or controlled by differences in the stimulation technique itself but not by a sham-control. Case series report higher responder rates. Summary The evidence for these neurostimulation methods in the treatment of chronic cluster headache is poor and in part contradictive. However, except deep brain stimulation, tolerability and safety of these methods are good so that in refractory situations application might be justified in individual cases.

Great occipital nerve long-acting steroid injections in cluster headache therapy: an observational prospective study

Background Injections targeting the occipital nerve are used to reduce headache attacks and abort cluster bouts in cluster headache patients. There is no widely accepted agreement over the optimal technique of injection, type and doses of steroids and/or anesthetics to use, as well as injection regimens. The aim of this study was to verify the effectiveness and safety of greater occipital nerve long-acting steroid injections in the management of episodic and chronic cluster headache. Methods We conducted a prospective observational cohort study on episodic (ECH) and chronic cluster headache patients (CCH). ECH were included in the study at the beginning of a cluster period. Three injections with 60 mg methylprednisolone were performed on alternate days. We registered the frequency and intensity of attacks three days before and 3, 7 and 30 days after the treatment, the latency of cluster relapse, adverse events, scores evaluating anxiety (Zung scale), depression (Beck’s Depression Scale) and quality of life (Disability Assessment Schedule II, 12-Item Self-Administered Version). Primary outcome was the interruption of the cluster after the three injections. Responders conducted a follow-up period of 12 months. Results We enrolled 60 patients, 47 with ECH and 13 with CCH. We observed a complete response in 47.8% (22/46) of episodic and 33.3% (4/12) of chronic patients. Moreover, a partial response (reduction of at least 50% of attacks) was obtained in further 10.8% (5/46) of episodic and in 33.3% (4/12) of chronic patients at 1 month. Median pain-free period was of 3 months for CCH responders. Only mild adverse events were reported in 38.3% (23/58) cases. Conclusions We suggest three greater occipital nerve injections of 60 mg methylprednisolone on alternate days as useful therapy in episodic and chronic cluster headache. This leads to a long pain-free period in chronic forms. Adverse effects are mild and support its use as first choice. Trial registration The study was inserted in AIFA observational studies register.