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Clinical, pathophysiological, and therapeutic study of new daily persistent headache syndromes

Cheema, Sanjay; (2025) Clinical, pathophysiological, and therapeutic study of new daily persistent headache syndromes. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

This thesis concerns new daily persistent headache (NDPH), which is little studied in comparison to episodic headache disorders; as well as one of its major differential diagnoses, spontaneous intracranial hypotension (SIH). Chapters 2 and 3 include a comprehensive systematic review and meta-analysis of the existing literature on NDPH; followed by a description of the largest cohort of NDPH to date (n=366). Compared to patients with chronic daily headache which has transformed from an episodic disorder, patients with NDPH were statistically less likely to be female, less likely to have migrainous and cranial autonomic symptoms, and less likely to overuse acute medications, suggesting it is a distinct disorder. Chapters 4 and 5 include open-label treatment studies of onabotulinumtoxinA (n=58) and calcitonin gene-related peptide (CGRP) monoclonal antibody therapy (n=48) in NDPH. Approximately 1/3 patients with NDPH responded to onabotulinumtoxinA, similarly to CM. Less than 1/4 responded to CGRP monoclonal antibody therapy, which was less effective in NDPH than CM. Chapter 6 is a biomarkers study examining serum levels of 30 cytokines and chemokines in NDPH. IL-6 was raised in both NDPH and CM compared to controls, but no other differences were seen, challenging the role of neuroinflammation in NDPH. Chapter 7 presents the results of two surveys regarding SIH, a differential diagnosis of NDPH which is now becoming better understood. A patient survey showed that SIH is amongst the most disabling known conditions, impacting mobility, activities of daily living, financial circumstances, and employment; but is often misdiagnosed or diagnosed late. A healthcare professional survey highlighted lack of awareness of SIH in non-specialists and variable management pathways. Chapter 8 presents the process and results of developing a comprehensive multidisciplinary consensus clinical guideline for best practice in diagnosis and treatment of SIH.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Clinical, pathophysiological, and therapeutic study of new daily persistent headache syndromes
Language: English
Additional information: Copyright © The Author 2025. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
URI: https://discovery.ucl.ac.uk/id/eprint/10204071
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