Demyelinating and Thrombotic Diseases of the Central Nervous System: Common Pathogenic and Triggering Factors

INTRODUCTION Demyelinating diseases of the central nervous system (CNS) affect prevalently young adults and represent the main cause of neurological disability after trauma in this population (1). Multiple sclerosis (MS), acute disseminated encephalomyelitis (ADEM), and neuromyelitis optica (NMO) are the most common inflammatory-demyelinating disorders of the CNS (1, 2). Multiple sclerosis shares several features with antiphospholipid syndrome (APS) including the clinical presentation, the relapsing–remitting course, the higher incidence in females of childbearing age, and the presence of similar white matter (WM) lesions at MRI (3). Likewise, both neurological symptoms and MRI lesions may overlap in ADEM and in the initial presentation of APS (4). Therefore, MS, ADEM, and APS are part of the reciprocal differential diagnosis (2). APS represents also one of the main risk factors for cerebral venous thrombosis (CVT) (5), which is not usually included in the differential diagnosis of demyelinating diseases. However, several reports in literature have described an association between CVT and MS (6–9). Although an accurate differential diagnosis is desirable for ensuring a more targeted therapy, the examination of the shared features between thrombotic and demyelinating diseases of the CNS would help to understand their common pathogenic mechanisms. SPECIFICITY AND SIMILARITIES OF THROMBOTIC AND DEMYELINATING DISEASES CEREBRAL VENOUS THROMBOSIS Cerebral venous thrombosis of dural sinus and/or large veins is considered as a rare form of cerebrovascular disease (0.5–1% of all strokes) (5, 10, 11), though a previous pathological study found higher prevalence of CVT (9.3%) in 182 consecutive autopsies (12). Although firstly recognized as an infective disease, CVT is now considered as a non-septic condition (11). Infections, however, mainly parameningeal, are recognized as a common cause of CVT in children (up to 40% of cases) (5). Other predisposing factors include both acquired (APS, pregnancy, puerperium, oral contraceptives, surgery, head trauma, dehydratation, cancer, and parameningeal infections) and genetic (deficiency of antithrombinIII, protein C and S, factor V Leiden positivity) conditions (5). CVT can occur at any age but it is more common in young people: in the largest cohort study, it has been reported that 78% of cases occur in patients younger than 50 years (13). The diagnosis of CVT is challenging in routine practice because the clinical manifestations may mimic several other diseases and may be restricted to isolated headache in up to 25% of patients (5). No laboratory parameters are diagnostic of CVT or can rule out it, as, for instance, a normal d-dimer level. Brain MRI frequently shows non-specific lesions, such as hemorrhages, infarcts, edema, and diffuse brain swelling or may be normal in up to 25% of cases. Gradient-echo and susceptibility-weighted MR imaging may increase CVT diagnostic sensitivity, especially in the early thrombotic stages (5). The overall prognosis of CVT is better than that of arterial stroke, with complete recovery in about two-thirds of cases (11).