Date of Award

8-2024

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

School of Nursing

Committee Chair/Advisor

Luigi Boccuto, MD

Committee Member

Sara M. Sarasua, PhD

Committee Member

Kendra Allison, PhD

Committee Member

Laina Lusk, MMSc, LCGC

Committee Member

Ingo Helbig, MD

Abstract

CACNA1A-related Hemiplegic Migraine (HM) is a rare neurodevelopmental disorder characterized by paroxysmal episodes of hemiparesis/hemiplegia with or without headache. The presentation of CACNA1A-related HM can range from mild HM events in neurotypical individuals to life-threatening prolonged periods of hemiplegia with cerebral edema in individuals with baseline neurodevelopmental features. CACNA1A-related HM has been studied extensively in its familial form, Familial Hemiplegic Migraine type 1 (FHM1), but the often more severe disorder attributed to de novo variants, Sporadic Hemiplegic Migraine type 1 (SHM1), has had limited description. Genetic resources and the 3rd edition of the International Classification of Headache Disorders (ICHD-3) definition refer to FHM1, and by omitting SHM1, the severe end of the phenotype is not always illustrated. Severe HM events are potentially life-threatening, requiring rapid appropriate treatment to prevent life-altering adverse outcomes. However, the severity of symptoms during HM events, in combination with baseline neurodevelopmental traits, can lead to suspicion of other disorders and delay treatment, putting the patient at risk.

Therefore, a better clinical characterization at baseline and during HM events and a description over time, was necessary to improve earlier diagnosis and rapid appropriate treatment. Additionally, with only anecdotal evidence for current therapies to manage and prevent HM events, surrogate endpoints were needed for future clinical trials. These goals were achieved through a systematic literature review, a longitudinal exploration of the disorder, and establishing a Disease Concept Model. This dissertation research has increased the generalizable knowledge of CACNA1A-related HM, hopefully improving diagnostic considerations and treatment practices for patients.

Supplementary Document 2.xlsx (35 kB)
Data Collection Spreadsheet for SHM1 Systematic Literature Review

Supplementary Document 3.xlsx (15 kB)
SHM1 Phenotype during HM attacks Spreadsheet

Supplementary Document 4.xlsx (17 kB)
SHM1 Phenotype outside of HM attacks Spreadsheet

Supplementary Document 6 and 7.xlsx (15 kB)
CACNA1F Scoping Review Phenotypes Spreadsheet and Variants

Supplementary Document 2.xlsx (30 kB)
Initial Coding Tree

Supplementary Document 3.xlsx (10 kB)
Saturation Table

Author ORCID Identifier

0000-0002-1132-3097

Available for download on Sunday, August 31, 2025

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