Specific cognitive and psychological alterations are more strongly linked to increased migraine disability than chronic migraine diagnosis
Authors: Castro Zamparella Tatiana , Carpinella Mariela , Peres Mario , Cuello Florencia Patricia , Maza Pilar , Van Gansen Melanie , Filipchuk Marcelo , Balaszczuk Verónica , Maldonado Carolina , Scarnato Pablo , Conci Magris Diego , Lisicki Marco 
Published: March 2024

Abstract
Introduction
The efficiency of The International Classification of Headache Disorders (ICHD-3) in reflecting patients’ disability has recently been questioned. This prompts consideration that clinical features beyond pain may more accurately indicate the extent of underlying brain impairment than the mere frequency of headache days. Important cognitive dysfunctions and psychological impairment have been reported in burdensome cases of migraine, and the presence of these alterations has been associated with biological changes in the nervous system. This study aimed to compare migraine-related disability within a specific patient group, classified using ICHD-3 criteria or classified based on findings from a neuropsychological evaluation using machine learning. Additionally, a complementary voxel-based morphometry (VBM) comparison was conducted to explore potential neuroanatomical differences between the resulting groups.

Patients and methods
The study included episodic and chronic migraine patients seeking consultation at a specialized headache department. A neuropsychological evaluation protocol, encompassing validated standardized tests for cognition, anxiety, depression, perceived stress, and headache-related impact (HIT-6) and disability (MIDAS), was administered. Results from this evaluation were input into an automated K-means clustering algorithm, with a predefined K=2 for comparative purposes. A supplementary Voxel-based Morphometry (VBM) evaluation was conducted to investigate neuroanatomical contrasts between the two distinct grouping configurations.

Results
The study involved 111 participants, with 49 having chronic migraine and 62 having episodic migraine. Seventy-four patients were assigned to cluster one, and 37 patients were assigned to cluster two. Cluster two exhibited significantly higher levels of depression, anxiety, and perceived stress, and performed worse in alternating and focalized attention tests. Differences in HIT-6 and MIDAS scores between episodic and chronic migraine patients did not reach statistical significance (HIT-6: 64.39 (±7,31) vs 62.92 (±11,61); p= 0. 42 / MIDAS: 73.63 (±68,61) vs 84.33 (±63,62); p=0.40). In contrast, patients in cluster two exhibited significantly higher HIT-6 (62.32 (±10,11) vs 66.57 (±7,21); p=0.03) and MIDAS (68.69 (±62,58) vs 97.68 (±70,31); p=0.03) scores than patients in cluster one. Furthermore, significant differences in grey matter volume between the two clusters were noted, particularly involving the precuneus, while differences between chronic and episodic migraine patients did not withstand correction for multiple comparisons.

Conclusions
The classification of migraine patients based on neuropsychological characteristics demonstrates a more effective separation of groups in terms of disability compared to categorizing them based on the chronic or episodic diagnosis of ICHD-3. These findings could reveal biological changes that might explain differences in treatment responses among apparently similar patients.