White Matter Disease / CNS vasculitis DDX

White Matter Disorders : Introduction
White Matter Disorders in a patient with DM 
White Matter Disorders in HIV patient with low CD4 counts

White Matter Disorder : Introduction

Brain consists of 
  • Gray Matter : Nerve Cell
  • White Matter : Nerve fiber and myelin sheath
Pathophysiology: Any damage to the white matter can cause white matter disorders
  • Hypomyelination disorders: If myelin was never made or made in insufficient amount (childhood illness) eg. hypomyelination of prematurity
  • Demyelinating Disorders: 
    • If myelin was made normally, but subsequently gets damaged, and disintegrated. eg. MS, ADEM
    • If structure and function of myelin is impaired due to hereditary disorders. eg. Leukodystrophy
  • Vacoules are formed in the myelin sheath eg. 
  • Scar tissues are formed in the nerve fiber 
Diagnosis: White matter disorder is a radiological diagnosis, and includes many diseases, and presentation. Few examples are discussed below.

White Matter Disorders in a patient with DM 
Case Based Learning 

51 yo F with DM, HTN, HLD presented for AMS. Details of history not known.  MRI shows the following. Unclear of diagnosis of MS. LP is done. No inflammatory cells, or oligoclonal band is seen. Working diagnosis is microvascular disease. 

CPK, Lactic Acid is elevated on admission. HIV is negative. B12 level is normal. MMA and Homocystein is not checked. 

What is the DDx. 



Further work up reveals absence of proteinuria, and retinopathy. 
MMA and Homocysteine, 


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


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;  eiosinophilic material accumulates between the smooth-muscle cells

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; 

White Matter Disorders in HIV with low CD4 counts

Clinical Question
26 yo AAM with 1 mth history of worsening of mental status. HIV of ??? duration. MRI shows global volume loss with white matter disease. LP is normal. CD 4 count is 7. Viral load is very high. 

DDx. of white matter diseases in a HIV patient includes the following

DDx of white matter disease in this patient (with low CD4 counts) includes the following 

  • EEG shows diffuse slowing. Normal EEG does not rule out delirium
  • Can cause psychotic symptoms
  • Fluctuating mental status is the key
  • Substance abuse
    • Alcohol:
    • Drug use:
HIV-associated Dementia
  • HIV Dementia Scale (with scores of 10 or less indicat- ing HIV-associated dementia) 
  • The typical presentation is a progressive dementia with subcortical features (apathy, inattention, and loss of retentive memory) and abnormalities of motor function, such as psychomotor slowing 
  • AIDS Mania: When psychosis (prominent agitation, irritability, and delusions) occurs in patient with HIV-associated dementia
  • The extent of the cognitive impairment will require reexamination with a full battery of neuropsychological tests after his acute illness has resolved 
Primary Psychiatry Disorder
  • A first episode of schizophrenia is unlikely, since the onset of schizophrenia is typically not sudden but instead involves a prodromal period of several years, with gradual loss of function and social competence
  • Reactive Psychosis: the very sudden onset of psychosis during the course of a day or so has been called “reactive psychosis,” in response to stressors 
Infection and Malignancy in HIV host
  • Toxo: Not seen in MRI
  • Cryptococcal: LP CSF cell count can be normal, but CSF antigen was negative
  • CMV: CMV in blood and CSF PCR was negative. Yet, cannot rule out when CD4 is that low. Retinal exam will be useful as well. 
  • M Tb: Less likely based on MRI and CSF but cannot be ruled out. 
  • PMLE: MRI rules out
  • Lymphoma : MRI rules out
  • B12 deficiency
  • Thiamine Deficiency
  • Olanzapine, an antipsychotic agent.  proven efficacy and relatively low risk of causing extrapyramidal symptoms and tar dive dyskinesia, which are highly prevalent among patients with HIV. 
  • HIV-associated damage to the dopaminergic basal ganglia system and increased plasma levels of antipsychotic agents because of interactions with antiret- roviral drugs puts hiv patient at risk of extrapyramidal symptoms 
  • Dysfunction of the basal ganglia also heightens the risk for neuroleptic malignant syndrome in hiv, which has been well documented to occur in patients with HIV 
  • Refernces:

ACR 2016  Dr. Tracey Cho

ACR 2016  Dr. Tracey Cho

ACR 2016  Dr. Tracey Cho

More reading on the above cases.