Primary and secondary CNS vasculitis

CNS vasculitis often affects previously healthy patients. If the inflammation solely targets the blood vessels of the brain and/or spinal cord in these patients, the disease is then referred to as primary CNS vasculitis or Primary Angiitis of the CNS (PACNS). 

All patients require a careful assessment for an associated systemic illness such as an infection, rheumatic disease or malignancy. Patients who develop CNS vasculitis in the context of an underlying illness are considered to have Secondary CNS Vasculitis.  

Diagnosing CNS Vasculitis: Calabrese Criteria

The diagnosis of primary CNS vasculitis requires:

  • A newly acquired focal or diffuse neurological deficit and/or psychiatric symptom plus
  • Angiographic and/or brain biopsy evidence of CNS vasculitis in the absence of an underlying systemic condition known to cause or mimic the findings

Patients are diagnosed with secondary CNS vasculitis if they have evidence of:

  • Any newly acquired focal and/or diffuse neurological and/or psychiatric deficit plus
  • Angiography and/or brain biopsy evidence of CNS vasculitis in the presence of an underlying systemic condition such as an infection, rheumatic disease

Secondary CNS vasculitis can be caused by a large number of underlying conditions. Infection is the most common cause for secondary CNS vasculitis. A thorough evaluation for an underlying systemic condition is required when a patient presents with newly acquired neurological and/or psychiatric deficit. 

Causes of Secondary CNS Vasculitis

The following is a non-exhaustive and non-limiting list of possible causes of secondary CNS vasculitis:

Infectious/post-infectious

  • Bacterial
    • Mycobacterium tuberculosis
    • Streptococcus pneumoniae
    • Salmonella species
    • Mycoplasma pneumoniae
    • Treponema pallidum
    • Other
  • Spiorochete
    • Borrelia burgdorferi
  • Viral
    • Varicella zoster virus
    • HIV
    • Hepatitis C virus
    • Cytomegalovirus
    • Epstein-Barr virus
    • Parvovirus B19
    • Enterovirus
    • West Nile virus
    • Other
  • Fungal
    • Actinomycosis
    • Candida albicans
    • Aspergillus
    • Other

Systemic rheumatic diseases

  • Systemic lupus erythematosus
  • Systemic vasculitis
    • Anti-neutrophil cytoplasmatic antibodies (ANCA) associated vasculitis
      • Granulomatosis with Polyangiitis (GPA, formerly known as Wegener's granulomatosis)
      • Microscopic polyangiitis (MPA)
      • Eosinophilic Granulomatosis with Polyangiitis (EGPA, formerly known as Churg–Strauss syndrome)
    • Polyarteritis nodosa (PAN)
    • Kawasaki disease
    • Takayasu's arteritis
    • Henoch-Schoenlein purpura (HSP)
  • Behçet's syndrome 
  • Sjögren's syndrome
  • Juvenile Dermatomyositis
  • Scleroderma

Systemic inflammatory diseases 

  • Inflammatory bowel disease
  • Hemophagocytic lymphohistiocytosis (HLH)

Other systemic diseases or exposures

  • Graft-versus-host diseases
  • Radiation
  • Drug-induced CNS vasculitis
  • Haemoglobinopathies
  • Malignancies
  • Other

The list bellow is modified from M. Twilt ., The spectrum of CNS vasculitis in children and adults. Nat Rev Rheumatol. 2011 Dec 20;8(2):97-107.

Differential diagnosis and mimics of Angiography-Positive CNS Vasculitis

Noninflammatory CNS vasculopathies:

  • Dissection
  • Thrombembolic disease
  • Intracranial atherosclerosis.
  • Hemoglobin disorders
  • Antiphospholipid antibody (aPL) syndrome
  • Fibromuscular dyplasia
  • Genetic collagen vascular disorders(Marfan Syndrome, Ehlers-Danlos Syndrome, others)
  • Moyamoya disease

Conditions associated with cerebral vasospasms:

  • Channelopathies including familiar hemiplegic migraine and calcium channelopathy
  • Reversible cerebral vasoconstrictive syndrome (RCVS)
  • Idiopathic vasospasms

Genetic syndromes with associated vasculopathy:

  • Neurofibromatosis type 1 (NF1)
  • Down’s syndrome
  • Posterior fossa malformations–hemangiomas–arterial anomalies–cardiac defects–eye abnormalities–sternal cleft and supraumbilical raphe syndrome (PHACES)
  • Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)
  • Fabry disease
  • Homocysteinuria

Atherosclerosis (Adults)

Other syndromes with associated cerebral vasculopathy:

  • Cogan syndrome (vasculopathy plus inflammatory eye disease [interstitial keratitis] and vestibular auditory dysfunction)
  • Susac syndrome (noninflammatory vasculopathy resulting in retinopathy, hearing loss and encephalopathy)

Differential diagnosis of Angiography-Negative CNS Vasculitis

Nonvasculitic inflammatory brain diseases:

  • Demyelinating diseases (acute demyelinating encephalomyelitis, multiple sclerosis, idiopathic or demyelinating optic neuritis)
  • Antibody-mediated inflammatory brain diseases (anti-NMDAR encephalitis, antibody-mediated limbic encephalitis, neuromyelitis optica, Hashimoto’s encephalitis, post-mycoplasma encephalitis, celiac-disease-associated encephalitis, Paediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections or PANDAS)
  • Granulomatous inflammatory brain diseases (Neurosarcoidosis)

Infections

  • Syphillis
  • Tuberculosis
  • JC Virus
  • Other bacterial, viral or parasitic

Metabolic diseases with associated inflammatory or ischemic brain lesions:

  • Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS)
  • Rolandic mitochondrial encephalomyopathy (ROME)
  • Polymerase gamma deficiency (POL-γ)
  • Malignancies
  • Angiocentric lymphoma

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