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Neurosarcoidosis

Neurosarcoidosis. Duc Tran, M.D. September 2003. General. Multisystem granulomatous disease Etiology unknown Lungs, heart, bone, nervous system 1909 – Uveoparotid fever/cranial nerve palsies Incidence 0.85% whites, 2.4% blacks Children – more common in whites. Usually better prognosis

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Neurosarcoidosis

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  1. Neurosarcoidosis Duc Tran, M.D. September 2003

  2. General • Multisystem granulomatous disease • Etiology unknown • Lungs, heart, bone, nervous system • 1909 – Uveoparotid fever/cranial nerve palsies • Incidence 0.85% whites, 2.4% blacks • Children – more common in whites. Usually better prognosis • Prevalence 40/100,000 • Mortality 1-5%. Usually secondary to respiratory failure

  3. Clinical • Lungs involved most often (90%) • Lymph nodes (33%) • Liver (50-80%) • Skin (25%) • Eyes • Musculoskeletal (25-39%) • Endocrine

  4. Genetics • Higher prevalence first generation relatives • Familial clustering of cases • HLA-B8 UK, Italian, Czech • HLA-DR17 Scandinavian • Polymorphisms C-C chemokine receptor (monocyte chemoattractant protein)

  5. Etiology • HHV-8 • HIV • Mycobacterium • Borrelia • Propionibacterium acnes • Aluminum, beryllium, zirconium

  6. Immunology • Accumulation activated T cells and macrophages • Release of interferon gamma, interleukin-2, cytokines • Interaction sarcoid antigen with specific T cell receptor and antigen presenting cell to trigger inflammatory response

  7. Pathology • Noncaseating epitheliod cell granuloma • Accumulation of CD4 • Multinucleated giant cells may be present • Inflammation similar in all organs affected • Fibrosis leads to tissue damage

  8. Neurologic Involvement • Frequency 5-16% • Occurs at later age than systemic • Majority have systemic disease • Neurologic symptoms presenting features 50% cases • Acute – isolated CN or aseptic meningitis • Chronic – parenchymal, multi CN, hydrocephalus, PNS

  9. Neurologic Involvement • Series 68 pts CNS involvement 62% (optic, CN palsies increased rate to 72%. • Spinal 28% • Posterior Fossa 21% • Cognitive decline 10%

  10. Manifestations • Encephalopathy (14-30%) anxiety, dementia, vascular dementia • Mass lesions (3-26%). • Hypothalamic (10-26%) • Meningitis (8-40%). • Hydrocephalus (6-17%). • Seizures (18-34%) • Posterior Fossa (9-26%). • Spinal Cord (3-10%). • Peripheral Nerve (6-40%) • Muscle (9-23%)

  11. Diagnosis • Verification of systemic sarcoid • CT – hyperdense, enhance with contrast. Periventricular white matter lesions common • MRI sensitivity (82%). • PET • Gallium scans • VEP/BAEP • Kviem-Siltzbach (KT) 67-92% • Serum ACE may correlate with clinical disease • Biopsy if feasible

  12. Diagnosis • CSF nonspecific • CSF 80% abnormal • elevated cell count (<50 WBC/mm) • protein (<100 mg%) • elevated pressure • decreased glucose • CSF ACE level elevated 50% cases. ?Use (usually elevated with elevated protein) • IgG Index/Oliogoclonal Bands reported • Elevated CD4/CD8 ratio • Lysozyme/B2m elevated in half of patients

  13. Diagnosis • Multiple Sclerosis • Idiopathic Bell’s Palsy • Granulomatous Infections • Lyme • Vasculitis • Neoplasms • Meningeal Carcinomatosis • HIV/AIDS • Herpes Encephalitis

  14. Cranial Nerve • 37-61% • Facial nerve most often involved • CN VIII, Optic, Trigeminal • Other CNs less often involved leading to anosmia, disturbance of ocular movements, pharygeal/vocal cord involvement

  15. Meningeal Involvement • 60% of cases • Aseptic meningitis • Meningeal mass lesion • Obstructive or communicating hydrocephalus • Cranial neuropathies from basilar meningitis

  16. Parenchymal Disease • Clinical features depend on location • Hypothalmic – impairment of neuroendocrine system (thyroid, adrenal, sexual dysfucntion, sleep, temperature, electrolyte balance, appetite) • Mass lesions

  17. Encephalitis/Seizures • Delirium, psychiatric, memory disturbance • TIAs/vasculopathy • Seizures 20% of patients – generalized or focal • Seizures associated with poorer prognosis

  18. Peripheral System • PN – 15-18% of cases • Axonal sensorimotor most common • Mononeuritis multiplex, polyradiculopathy, GBS • Most are assymptomatic • Epineurium/perineurium involvement axonal degeneration • Endoneurium involvement demyelinating neuropathy

  19. Peripheral System • Muscle involvement is common. • Symptomatic – less 1% of systemic cases • Acute or chronic myopathy, myositis, intramuscular nodules, pseudohypertrophy • More common in women (4:1), especially postmenopausal

  20. Corticosteroids • Mainstay of treatment • Proposed mechanism • Inhibition of lymphocyte/mononuclear phagocytic activity • Inhibition of transcription of proinflammatory cytokines • Downregulation of cellular receptors • Interference with collagen synthesis • May not change natural history

  21. Treatment • Cyclosporine. • Azathioprine. • Methotrexate. • Cyclophosphamide • Radiation.. • Surgery

  22. Treatment • Tacrolimus (Prograf) – macrolide immunosuppresant. Inhibit T-cell activation • Sirolimus (Rapamune) – macrolide immunosuppressant. • Anticytokine therapy • Anticellular adhesion molecules • Gene therapy targeting proinflammatory cytokines

  23. Treatment • Consider combination therapy, refractory cases • Isolated facial palsies – favorable outcome • Certain cases, e.g. parenchymal involvement, may require longer course of treatment • Consider biopsy of intracranial lesions • Before initiating therapy • Refractory to treatment • Diagnosis unclear

  24. Treatment • Shunt in selected cases • Surgical resection rarely curative • Seizure control • Peripheral involvement treat if symptomatic

  25. Prognosis • Monophasic, relapsing, progressive • 2/3 neurologic symptoms may improve with treatment • Depends on location of involvement • 72% deterioration with spinal cord 18 months or more • Acute or subacute presentations have better prognosis than chronic • 1/3 may relapse • Mortality 8-12% if neurological involvement

  26. References • Zajicek JP. Neurosarcoidosis. Current Opinion in Neurology. 2000; 13:323-325. • Oksanen V. Neurosarcoidosis. Sarcoidosis. 1994; 11:76-79. • Gullapalli D, Phillips LH. Neurologic Manifestations of Systemic Disease. Neurologic Clinics. 2002; 20(1). • Mana J. Magnetic Resonance Imaging and Nuclear Imaging in Sacoidosis. Current Opinions in Pulmonary Medicine. 2002; 8(5): 457-463. • Scott TF. Neurosacoidosis: Progress and Clinical Aspects. Neurology. 1993; 43:8-12. • Kang S, Suh JH. Radiation Therapy for Neurosarcoidosis: Report of Three Cases from a Single Institution. Radiation Oncology Investigations. 1999; 7:309-312. • Nowak DA, Widenka DC. Neurosarcoidosis: a review if its intracranial manifestations. Journal Neurology. 2001; 248:363-372. • Zajicek JP, Scolding NJ, et al. Central Nervous System Sarcoidosis-diagnosis and management. Quarterly Journal of Medicine. 1999; 92:103-111.

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