Intracerebral haemorrhage in multiple sclerosis: assessing the impact of disease-modifying medications

Abstract

Multiple Sclerosis (MS) is a complex autoimmune disorder that significantly impacts the central nervous system, leading to a range of complications. While intracranial haemorrhage (ICH) is a rare but highly morbid complication, more common CNS complications include progressive multifocal leukoencephalopathy (PML) and other CNS infections. This severe form of stroke, known for its high morbidity and mortality rates, presents a critical challenge in the management of MS. The use of disease-modifying drugs (DMDs) in treating MS introduces a nuanced aspect to patient care, with certain medications like Dimethyl Fumarate and Fingolimod showing potential in reducing the risk of ICH, while others such as Alemtuzumab and Mitoxantrone are associated with an increased risk. Understanding the intricate relationship between these DMDs, the pathophysiological mechanisms of ICH, and the individualised aspects of each patient's condition is paramount. Factors such as genetic predispositions, existing comorbidities, and lifestyle choices play a crucial role in tailoring treatment approaches, emphasising the importance of a personalised, vigilant therapeutic strategy. The necessity for ongoing and detailed research cannot be overstated. It is crucial to explore the long-term effects of DMDs on ICH occurrence and prognosis in MS patients, aiming to refine clinical practices and promote patient-centric, informed therapeutic decisions. This approach ensures that the management of MS is not only comprehensive but also adaptable to the evolving understanding of the disease and its treatments.

Keywords: Blood–brain barrier; CNS immunity; Disease-modifying drugs; Intracerebral haemorrhage; Multiple sclerosis; Neuroinflammation; Neurological complications; Pharmacotherapy in MS.

Fig. 1

Prisma flow diagram

Fig. 2

Pathophysiology of Intracerebral Haemorrhage in Multiple Sclerosis Patients. ICH Intracerebral haemorrhage, BBB Blood–brain barrier, CSF Cerebrospinal fluid, ICAM-1 Intercellular adhesion molecule 1, TNF-α Tumour necrosis factor alpha, T cells: T Lymphocytes, B cells: B Lymphocytes, ROS Reactive oxygen species, IL-6 Interleukin 6, NF-κB Nuclear factor kappa-light-chain-enhancer of activated B cells

Fig. 3

Disease-modifying drugs with protective effect against intracerebral haemorrhage in multiple sclerosis patients. DMD Disease-modifying drugs, ICH Intracerebral haemorrhage, MS Multiple sclerosis, Nrf2 Nuclear factor erythroid-2-related factor 2, S1P Sphingosine 1-1-phosphate, S1PR Sphingosine 1-1-phosphate receptor

Fig. 4

Disease-modifying drugs associated with increased ICH risk in MS patients. Abbreviations: AML Acute myelocytic leukaemia, APL Acute promyelocytic leukaemia, CD-52 Cluster of differentiation-52, DBP Diastolic blood pressure, DMD Disease-modifying drugs, ICH Intracerebral haemorrhage, ITP Immune thrombocytopenic purpura, MS Multiple sclerosis, RRMS Relapsing–remitting multiple sclerosis, SBP Systolic blood pressure, SPMS Secondary progressive multiple sclerosis, TRAL Therapy-related acute leukaemia, TSP Thrombospondin