Maha Yektay Farahmand - Institutionen för kliniska vetenskaper, Lund

Title: Basal ganglia calcifications and cerebrovascular disease 

Main supervisor: Professor Arne G Lindgren 

Reviewers:   Professor Erik Lundström, Uppsala University

Assoc Professor Catarina Lundin, Lund University

Abstract

Background

Small vessel disease (SVD) is common in ischemic and hemorrhagic stroke and related to several findings on neuroimaging. Several case reports suggest an association between familial basal ganglia calcifications (BCGs) in Fahr's disease and SVD. However, the association between BCGs, SVD and stroke as a potential phenotype of Fahr's disease remain unclear, and BCGs in stroke patients are often regarded as incidental.

Research questions

The project aims to: (1) investigate the prevalence of SVD and clinical features in Fahr’s disease indicating stroke/TIA; (2) identify new genetic causes of cerebrovascular disease linked to BGCs; (3) determine the proportion of stroke/TIA patients with BGCs on CT scans and its relation to SVD-related stroke; and (4) explore if BGCs can improve SVD subtype classification.

Preliminary results

Paper I: In two Swedish families with novel truncating PDGFB variants we found SVD in all mutation carriers. In family members with clinical and/or radiological signs of stroke/TIA we found no classical vascular risk factors. 

Paper III: Analyses of CT and MRI scans of 1,430 stroke patients and 1,000 controls detected 144 patients and 75 control subjects with BGCs. BGCs were frequently linked to imaging markers of SVD in both groups. An association between BGC and stroke was observed but no significant association between BGCs and stroke due to small artery occlusion.

Significance

Understanding the role of subtle BGCs and their association with SVD on neuroimaging may improve the diagnostic yield for many patients with TIA/stroke. In patients with monogenic mechanisms to stroke—an often difficult to diagnose mechanism to stroke—identifying a BGCs-SVD link could uncover underlying pathophysiological pathways. This insight may improve diagnostic precision and support development of targeted interventions.

Published studies 

Yektay Farahmand M, Wasselius J, Englund E, Braverman I, Puschmann A, Ilinca A. Small vessel disease in primary familial brain calcification with novel truncating PDGFB variants. Neurol Neurochir Pol. 2024;58(1):94-105.