Sciresol Sciresol https://jmsh.ac.in/ Journal of Medical Sciences and Health 10.46347/jmsh.v8i3.22.267 CASE REPORT A Rare Cause of Headache in A Middle-Aged Patient A rare cause of headache Balagopal Krishnan krishnan.balagopal@gmail.com 1 Nadarajah Jeyaseelan 2 Eldho Maria 3 Consultant, Department of Neurology, MOSC Medical College Kolenchery, Kochi India Interventional Neuroradiologist, Department of Radiology, MOSC Medical College Kolenchery, Kochi India Junior Resident, Department of Neurology, MOSC Medical College Kolenchery, Kochi India 8 3 286 2022 Abstract

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a genetic disease that commonly presents with migraine with aura, ischemic episodes, cognitive decline, and psychiatric manifestations. It is caused by mutations in the NOTCH3 gene with autosomal dominant inheritance. We report a 45-year-old male who presented with recurrent episodes of migraine over the last fifteen years and a history of migraine in his family members. A review of his imaging suggested CADASIL as a possible diagnosis. He underwent genetic testing which showed a positive NOTCH3 mutation. This report aims to highlight the importance of considering CADASIL as a cause of familial migraine.

Keywords CADASIL Migraine Stroke <bold id="strong-197fe61fe3c0467abf200e5b1445e646">History</bold>

This 45-year-old patient born of a non-consanguineous marriage presented to the outpatient department with a history of recurrent episodes of hemicranial headache associated with preceding aura ,nausea and photophobia. On questioning, there was a history of similar headaches in his father and elder sister. Clinical examination revealed no focal neurological deficits. Considering the clinical history suggestive of migraine headaches and positive family history, the possibilities of Familial Hemiplegic Migraine and CADASIL were also considered. Imaging done - MRI Brain -showed multiple hyperintense areas on T2 FLAIR sequences involving the subcortical and periventricular white matter (Figure 1) including the anterior temporal lobes. Diffusion weighted imaging (DWI) showed no areas of restriction while susceptibility weighted imaging (SWI) sequences (Figure 2) showed evidence of micro bleed in right basal ganglia.

MRI T2 FLAIR sequences showing A. multiple hyperintensities involving the subcortical and periventricular regions B. Typical involvement of anterior temporal poles Discussion

Considering the clinical history and imaging findings, the possibility of a CADASIL was considered. The patient underwent a clinical exome sequencing which was positive for NOTCH3 mutation on chromosome 19, confirming the diagnosis. CADASIL is the most common monogenic disorder presenting in young adults in their thirties with episodes of migraine headache with aura. 1 This is followed by recurrent episodes of subcortical stroke which can lead to progressive cognitive decline. 2 Less common features include depression, mood disturbances, seizures, encephalopathy and parkinsonism. 3 Imaging shows characteristic features on MRI and diagnosis is made by genetic analysis showing the characteristic NOTCH3 mutation. 4 The overall life expectancy is reduced in these patients due to multiple strokes causing cognitive decline, and cardiac events. Early diagnosis and initiation of anti-platelet agents can help in stroke prevention though effect on long term outcomes in still unclear.

A. Diffusion weighted imaging (DWI) showing no areas of restriction B. Susceptibility weighted imaging (SWI) showing microbleed in right basal ganglia



<bold id="strong-0a7001896b324192afeec5244fc56efa">Abbreviations</bold>

CADASIL - Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy

MRI - Magnetic Resonance Imaging

FLAIR - Fluid Attenuated Inversion Recovery

SWI - Susceptibility Weighted Imaging

 Acknowledgements

The authors wish to thank their friends and family

Conflict of interest

None

 Funding

None

References Joutel Anne Corpechot Christophe Ducros Anne Vahedi Katayoun Chabriat Hugues Mouton Philippe Alamowitch Sonia Domenga Valérie Cécillion Michaelle Maréchal Emmanuelle Maciazek Jacqueline Vayssière Céline Cruaud Corinne Cabanis Emmanuel-Alain Ruchoux Marie Madeleine Weissenbach Jean Bach Jean François Bousser Marie Germaine Tournier-Lasserve Elisabeth Notch3 mutations in CADASIL, a hereditary adult-onset condition causing stroke and dementia Nature 1996 383 6602 707 710 0028-0836 Springer Science and Business Media LLC https://doi.org/10.1038/383707a0 Chabriat H Joutel A Dichgans M Tournier-Lasserve E Bousser M G Cadasil Lancet Neurol 2009 8 7 643 653 https://doi.org/10.1016/s1474-4422(09)70127-9 Mizuno T Mizuta I Watanabe-Hosomi A Mukai M Koizumi T Clinical and Genetic Aspects of CADASIL Fronters in Aging Neuroscience 2020 12 91 1 10 https://doi.org/10.3389%2Ffnagi.2020.00091 Malandrini A Gaudiano C Gambelli S Berti G Serni G Bianchi S Federico A Dotti M T Diagnostic value of ultrastructural skin biopsy studies in CADASIL Neurology 2007 68 17 1430 1432 0028-3878 Ovid Technologies (Wolters Kluwer Health) https://doi.org/10.1212/01.wnl.0000264018.46335.c8