MS: including the relatively rapid onset of symptoms, a relapsing–remitting course, fatigue, depression, HA, ocular symptoms, autonomic dysfunction, evidence of brainstem or cerebellar symptoms (including slurring of speech), seizure-like activity. Higher cortical features may be spared early in the disease, but may be affected later in the days; female predominance; On MRI, lesions primarily affecting the white matter of the brain and spinal cord are found; corpus callosum is commonly affected; lesions may or may not enhance with contrast; CSF is normal mostly except for mild elevation of protein, Oligoclonal Bands, and leucocytes, mostly Monocytes; Visual or auditory evoked potential; 

Other Demylinating disease

B12 Deficiency

SLE

Lyme Disease: Affects CNS in 15 % of the time; this diagnosis should always be considered if white mater lesions are present; B/L CN VII is the key feature; Lymphocytic meningitis can occur; painful radiculitis can occur; rarely focal encephalomyelitis or myelopathy can occur. 

HIV: progressive apathy, depression, psychomotor retardation, and memory loss can occur; There is often focal subcortical involvement, with infection of macrophages in the subcortical white matter and the basal ganglia.

Maligancy: glioma (Gliomas can in- filtrate the corpus callosum) or a lymphoma (Lymphoma of the central nervous system tend to affect the deep structures, including the corpus callosum) 

MELAS: typically begin before 40 yr but can occur after that; encephalomyopathy, seizures, and dementia often occur with headaches and vomiting; DM is frequently seen; Stroke affect cortical and sub-cortical white matter, but do not confer the vascular area; 

Case 36-2005: A 61-Year-Old Woman with Seizure, Disturbed Gait, and Altered Mental Status (DDx of MELAS)

Migraine: White-matter abnormalities called “unidentified bright objects” are associated with migraine; The number of white-matter abnormalities in- creases with an increasing frequency of migraines; 

Cerebral Vasculopathies 

Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy: Subcortical ischemic strokes, particularly in the anterior temporal lobes, begin in the fifth or sixth decade, often in the absence of traditional vascular risk factors; Psychiatric symptoms, dementia, and migraine headaches are common; MRI shows multiple subcortical infarcts, with diffuse leukoencephalopathy; 

Cerebral Vasculitis: 

Susac’s syndrome, also known as retinoco- chleocerebral vasculopathy, is a microangiopathy that affects the brain, retinal arteries, and cochlea, causing headaches, personality changes, dementia, bilateral branch retinal artery occlusions, and deaf- ness. It occurs predominantly in women 20 to 40 years of age and is thought to be immune-medi- ated. Chronic lesions, described as “snowball le- sions,” can be confluent and can affect large areas of the corpus callosum; Patients with primary angiitis of the central nervous system have an elevated erythrocyte sedimenta- tion rate, a characteristic angiographic appearance, and evidence of inflammation in the cerebrospinal fluid; 

Binswanger’s disease, or subcortical leukoencephalopathy : progressive subcortical white-matter disease associated with progressive cognitive and motor decline; 4th - 7th decade; HTN; small discrete infarcts and larger areas of diffuse and incomplete infarction and demyelination with thickening and hyalinization of arterioles

Lacunar infarcts are deep white-matter infarcts, typically less than 15 mm in diameter, that are due to occlusion of a penetrating artery; The occlusion may be caused by multiple processes, most commonly hypertension, diabetes, advanced age, ischemic heart disease, and cigarette smoking;