Primary Angiitis of the Central Nervous System (PACNS)

Table of Contents

  1. Disorder
  2. Epidemiology
  3. Differential Diagnosis
  4. Clinical Symptoms
  5. Pathology
  6. Diagnosis
  7. Management
  8. References

Disorder

  • PACNS, also known as primary central nervous system vasculitis, is a rare inflammatory vasculopathy initiated within the brain and spine

  • Incidence of 2.4 per 1,000,000 person-years

  • Sex Distribution: No difference

  • Factors associated with higher mortality: Ischemic strokes on imaging, advanced age, cognitive impairment at initial presentation

Differential Diagnosis

  • Reversible Cerebral Vasoconstriction Syndrome (RCVS)

  • Intracranial Atherosclerosis

  • Intravascular Lymphoma

  • Moyamoya Disease/Syndrome

  • Secondary Cerebral Vasculitis

  • Infections

Pathophysiology

Diagnostic Criteria

Core Clinical Characteristics:

  1. Optic Neuritis

  2. Acute myelitis

  3. Area postrema syndrome (presenting feature in 10%)

  4. Acute brainstem syndrome

  5. Symptomatic narcolepsy or acute diencephalic clinical syndrome with NMOSD-typical diencephalic MRI lesions

  6. Symptomatic cereral syndrome with NMOSD-typical brain lesions

Diagnostic Criteria for NMOSD with AQP4-IgG:

  1. ≥ 1 core clinical characteristic

  2. Positive test for AQP4-IgG (cell-based assay strongly recommended, or best test available)

  3. Alternative Diagnoses excluded

Diagnostic Criteria for NMOSD without AQP4-IgG or unknown AQP4-IgG status

  1. ≥ 2 core clinical characteristics meeting the following requirements

    • ≥ 1 core clinical characteristic must be

      • Optic Neuritis

      • Acute Myelitis with longitudinally extensive transverse myelitis (LETM)

      • Area postrema syndrome

      • Fulfillment of additional MRI requirements, as applicable

    • Dissemination in space (2 or more different core clinical characteristics)

  2. Negative test for AQP4-IgG using best available assay or testing unavailable

  3. Alternative diagnoses excluded

MRI requirements for NMOSD without AQP4-IgG or unknown AQP4-IgG status

  1. Acute Optic Neuritis: requires brain MRI with…

    • Normal findings or nonspecific white matter lesions OR

    • T2-hyperintense lesion or T1-weighted gadolinium-enhancing lesion extending over >1/2 optic nerve length or involving optic chiasm

  2. Acute Myelitis: requires associated intramedullary MRI lesion extending over ≥ 3 contiguous segments (LETM) or ≥ 3 contiguous segments of focal spinal cord atrophy in patients with history compatible with acute myelitis

  3. Area postrea syndrome: requires associated dorsal medulla/area postrema lesions

  4. Acute brainstem syndrome: requires associated periependymal brainstem lesions

Diagnostic Workup

  • Serum: 
    • Anti-Aquaporin-4 IgG

      • Detected in ~80% of patients

      • Most accurate test is a cell-based flow cytometric assay (Sensitivity 60 - 80%, Specificity >99%)

      • Enzyme-linked Immunosorbent Assay (ELISA) for AQP4 may create diagnostic uncertainty as false positive low-titers may occur

      • Should not be tested directly after plasma exchange or during immunosuppressive therapies as false negative results can occur

  • Cerebrospinal Fluid (not necessary for the diagnosis but may be helpful to distinguish between MS or other similar conditions):
    • Anti-Aquaporin-4 IgG

      • Testing in CSF is relatively insensitive

    • Cell count

      • Pleocytosis (lymphocyte predominate) is commonly seen

    • Oligoclonal bands

      • Not usually present

    • Elevated protein is commonly seen
  • Imaging: 
    • MRI with & without contrast
      • Orbits

        • Predilection for optic chiasm and adjacent posterior optic nerve

        • May involve the full length of the optic nerve or a small segment

      • Brain

        • Area postrema (dorsal medulla) inflammatory lesion (lesion is small and may be difficult to detect on MRI)

        • Diencephalon inflammatory lesion

        • Inflammatory lesions in the cerebrum

      • Spine (Cervical, Thoracic, Lumbar)

        • Longitudinally extensive transverse myelitis (characteristic of NMOSD)

        • Short segment transverse myelitis (as seen in MS) occurs in 15% of sentinel myelitis attacks

Acute Therapy

Preventive Immunotherapy

References

Epidemiology

  1. IV glucocorticoids

    • IV methylprednisolone 1 gram Daily for 3-5 days

    • Studies have shown response to initial therapy is usually suboptimal (~19% remission rate) and requires a 2nd treatment for which PLEX is usually added to IV glucocorticoid administration

  2. Adjunctive Plasma Exchange (PLEX)

    • Often used for patients with severe symptoms or vision loss poorly responsive to glucocorticoids however, it should likely always be used in conjunction with IV steroids for greater chance at remission.

    • Every other day PLEX for 5-7 sessions

*IV Immunoglobulin has not proven to be beneficial in acute NMOSD attacks and so are rarely used in this setting

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