Project ID NS-MH2026_11

ThemeNS-MH

Co Supervisor 1A Dr Francesca Puledd Institute of Psychiatry, Psychology & Neuroscience, School of Neuroscience, Wolfson Sensory, Pain and Regeneration CentreEmail

Co Supervisor 1B Prof Peter J. Goadsby Institute of Psychiatry, Psychology & Neuroscience, School of Neuroscience, Wolfson Sensory, Pain and Regeneration CentreEmail

Mapping metabolic and functional changes in visual snow syndrome and migraine using ultra-high-resolution neuroimaging

Scientific basis: Visual snow syndrome (VSS) is an under-recognized neurological disorder, for which there is neither a clear understanding of the underlying pathophysiology nor adequate treatment. VSS is characterized by a constant perception of small flickering dots in the entire visual field, associated with a combination of visual symptoms: afterimages, sensitivity to light, entoptic phenomena and difficulty seeing at night. The high co-occurrence of VSS and migraine has meant some consider visual snow as part of the migraine spectrum. However, the two conditions represent clearly separate entities, evidenced by the ineffectiveness of migraine treatments in alleviating VSS symptoms. It is essential to unravel the brain mechanisms underlying VSS to advance towards effective treatments for affected patients, and to adequately distinguish VSS from migraine.

Overarching aims and design: The objective of this study is to use proton spectroscopy (1H-MRS) at ultra-high-field (7-Tesla, 7T) to study brain metabolism of primary and associative visual areas in VSS. We will investigate visual cortex metabolism both at rest and in an active brain state by implementing a standard visual cortex functional 1H-MRS (fMRS) paradigm. VSS patients (n=15) aged >18 will be recruited online advertisement to patient groups; an equal number of age and gender matched episodic migraine patients (MO), as well as healthy controls (HC), will be recruited respectively from headache clinics and through King’s circulars. VSS patients will be matched in migraine features (e.g. photophobia, aura, medication use) to the migraine group. Subjects with contraindications to ultra-high-field MRI (vertigo, large tattoos, metal implants etc.) will be excluded.

Skills development: The student will develop expertise in advanced neuroimaging and MRS analysis.

Deliverables: At year 1, the student will learn the technique and start recruitment. Through Years 2 and 3 they will complete neuroimaging investigations. In Year 4, they will finalize neuroimaging analysis and thesis writing.

Representative Publications

1. Abnormal Glutamatergic and Serotonergic Connectivity in Visual Snow Syndrome and Migraine with Aura. Puledda F, Dipasquale O, Gooddy BJM, Karsan N, Bose R, Mehta MA, Williams SCR, Goadsby PJ. Ann Neurol. 2023 Nov;94(5):873-884. doi: 10.1002/ana.26745. Epub 2023 Aug 8. PMID: 37466404 2. Localised increase in regional cerebral perfusion in patients with visual snow syndrome: a pseudo-continuous arterial spin labelling study. Puledda F, Schankin CJ, O’Daly O, Ffytche D, Eren O, Karsan N, Williams SCR, Zelaya F, Goadsby PJ. J Neurol Neurosurg Psychiatry. 2021 Sep;92(9):918-926. doi: 10.1136/jnnp-2020-325881. Epub 2021 Jul 14. 3. Visual snow syndrome: A clinical and phenotypical description of 1,100 cases. Puledda F, Schankin C, Goadsby PJ. Neurology. 2020 Feb 11;94(6):e564-e574. doi: 10.1212/WNL.0000000000008909. Epub 2020 Jan 15.

“1. A Controlled Trial of Erenumab for Episodic Migraine. Goadsby PJ, Reuter U, Hallström Y, Broessner G, Bonner JH, Zhang F, Sapra S, Picard H, Mikol DD, Lenz RA. N Engl J Med. 2017 Nov 30;377(22):2123-2132. doi: 10.1056/NEJMoa1705848. 2. Efficacy of Atogepant in Chronic Migraine With and Without Acute Medication Overuse in the Randomized, Double-Blind, Phase 3 PROGRESS Trial. Goadsby PJ, Friedman DI, Holle-Lee D, Demarquay G, Ashina S, Sakai F, Neel B, Gandhi P, Dabruzzo B, Smith JH, Liu Y, Trugman JM. Neurology. 2024 Jul 23;103(2):e209584. doi: 10.1212/WNL.0000000000209584. Epub 2024 Jun 26. 3. Phase 3 randomized, placebo-controlled, double-blind study of lasmiditan for acute treatment of migraine. Goadsby PJ, Wietecha LA, Dennehy EB, Kuca B, Case MG, Aurora SK, Gaul C. Brain. 2019 Jul 1;142(7):1894-1904. doi: 10.1093/brain/awz134.”