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Neurosarcoidosis

Summary

  • Neurosarcoidosis is a granulomatous inflammatory disorder affecting the central and/or peripheral nervous system in 5-10% of patients with systemic sarcoidosis
  • Clinical presentation varies widely including cranial neuropathies, meningitis, hydrocephalus, myelopathy, and hypothalamic-pituitary dysfunction
  • Imaging typically demonstrates leptomeningeal enhancement, parenchymal lesions, and/or cranial nerve involvement with characteristic basal predominance

Pathophysiology

  • Non-caseating granulomas composed of epithelioid histiocytes and multinucleated giant cells
  • CD4+ T-cell mediated inflammatory response with release of inflammatory cytokines (IL-2, TNF-alpha)
  • Granulomas can affect:
    • Leptomeninges (most common)
    • Brain parenchyma
    • Cranial nerves
    • Hypothalamic-pituitary axis
    • Spinal cord
  • Mechanism of injury includes:
    • Direct granulomatous infiltration
    • Vascular compromise from perivascular inflammation
    • Compression from mass effect

Demographics

  • Affects 5-10% of patients with systemic sarcoidosis
  • Isolated neurosarcoidosis without systemic involvement occurs in 10-17% of cases
  • Peak incidence: 25-40 years of age
  • Female predominance (female:male ratio approximately 1.5:1)
  • Higher prevalence in African Americans and Northern Europeans
  • African Americans tend to have more severe disease

Diagnosis

  • Clinical presentation:
    • Cranial neuropathies (50-75%), especially facial nerve palsy
    • Headache and meningeal signs
    • Endocrinopathies from hypothalamic-pituitary involvement
    • Seizures
    • Cognitive dysfunction
    • Myelopathy
  • Laboratory findings:
    • Elevated serum ACE (limited sensitivity ~25-50%)
    • Elevated serum calcium
    • CSF analysis: lymphocytic pleocytosis, elevated protein, low glucose, elevated ACE
    • Oligoclonal bands present in 20-40%
  • Histopathologic confirmation:
    • Biopsy showing non-caseating granulomas
    • Neural tissue biopsy often required for definitive diagnosis
  • Diagnostic criteria (Zajicek criteria):
    • Definite: positive neural tissue biopsy
    • Probable: compatible clinical/imaging findings with systemic sarcoidosis
    • Possible: compatible clinical/imaging findings without histologic confirmation

Imaging

  • MRI Brain:
    • T2: hyperintense parenchymal lesions, predominantly periventricular and subcortical white matter
    • T1: isointense to hypointense parenchymal lesions
    • T1+C: nodular or linear leptomeningeal enhancement, particularly basilar cisterns; enhancing parenchymal lesions; cranial nerve enhancement
    • FLAIR: hyperintense parenchymal lesions; leptomeningeal hyperintensity
    • DWI: typically no restricted diffusion unless acute infarction from vasculitis
    • SWI: may show microhaemorrhages in chronic cases
  • MRI Spine:
    • T2: intramedullary hyperintense lesions, often longitudinally extensive
    • T1+C: leptomeningeal enhancement; nodular or patchy cord enhancement; nerve root enhancement
  • Patterns of involvement:
    • Leptomeningeal (30-40%): basilar predominance
    • Pachymeningeal (less common): dural thickening and enhancement
    • Parenchymal (35-50%): multiple non-specific white matter lesions
    • Cranial nerves: optic nerve and facial nerve most common
    • Hypothalamic-pituitary: infundibular thickening and enhancement
    • Hydrocephalus: communicating from leptomeningeal involvement
  • Advanced imaging:
    • FDG-PET: increased uptake in active lesions; useful for monitoring treatment response
    • Gallium-67 scintigraphy: historical use, largely replaced by PET

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  • A 60-year-old patient presented with a tinnitus and facial weakness.
  • MRI showed T2-hypointense enahncing disease surrounded by oedema.
  • A diagnosis of neurosarcoidosis was made following biopsy of thoracic disease.

Treatment

  • First-line therapy:
    • High-dose corticosteroids (prednisolone 1 mg/kg/day or IV methylprednisolone for severe disease), then slow taper over months
  • Steroid-sparing agents (for relapsing or steroid-dependent disease):
    • Methotrexate
    • Azathioprine
    • Mycophenolate mofetil
  • Refractory disease:
    • Rituximab
    • Infliximab (TNF-alpha inhibitor)
    • Cyclophosphamide
  • Symptomatic management:
    • Anticonvulsants for seizures
    • Ventriculoperitoneal shunt for hydrocephalus
    • Hormone replacement for hypothalamic-pituitary dysfunction

Differential diagnosis

Differential diagnosis Differentiating feature
Multiple sclerosis Periventricular lesions perpendicular to ventricles (Dawson fingers); calloso-septal interface lesions; short spinal cord lesions; no leptomeningeal enhancement
CNS lymphoma Homogeneously enhancing periventricular or corpus callosum mass; marked restricted diffusion on DWI; no basal predilection of meningeal enhancement
Tuberculous meningitis Predominantly basilar leptomeningeal enhancement with calcifications; tuberculomas show ring enhancement; similar to neurosarcoidosis on imaging
CNS vasculitis Beading pattern on MRA/conventional angiography; cortical and subcortical infarcts in multiple vascular territories
Leptomeningeal carcinomatosis Nodular subarachnoid/dural deposits along cranial nerves and spinal roots; associated parenchymal metastases
IgG4-related disease Nodular hypertrophic pachymeningitis; pituitary/infundibular thickening with enhancement; orbital and skull base involvement
Glioma Progressive solitary intraparenchymal mass with irregular or ring enhancement; elevated choline/creatine on MR spectroscopy