Neurosarcoidosis

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Neurosarcoidosis

  1. 1. Neurosarcoidosis Duc Tran, M.D. September 2003
  2. 2. General <ul><li>Multisystem granulomatous disease </li></ul><ul><li>Etiology unknown </li></ul><ul><li>Lungs, heart, bone, nervous system </li></ul><ul><li>1909 – Uveoparotid fever/cranial nerve palsies </li></ul><ul><li>Incidence 0.85% whites, 2.4% blacks </li></ul><ul><li>Children – more common in whites. Usually better prognosis </li></ul><ul><li>Prevalence 40/100,000 </li></ul><ul><li>Mortality 1-5%. Usually secondary to respiratory failure </li></ul>
  3. 3. Clinical <ul><li>Lungs involved most often (90%) </li></ul><ul><li>Lymph nodes (33%) </li></ul><ul><li>Liver (50-80%) </li></ul><ul><li>Skin (25%) </li></ul><ul><li>Eyes </li></ul><ul><li>Musculoskeletal (25-39%) </li></ul><ul><li>Endocrine </li></ul>
  4. 4. Genetics <ul><li>Higher prevalence first generation relatives </li></ul><ul><li>Familial clustering of cases </li></ul><ul><li>HLA-B8 UK, Italian, Czech </li></ul><ul><li>HLA-DR17 Scandinavian </li></ul><ul><li>Polymorphisms C-C chemokine receptor (monocyte chemoattractant protein) </li></ul>
  5. 5. Etiology <ul><li>HHV-8 </li></ul><ul><li>HIV </li></ul><ul><li>Mycobacterium </li></ul><ul><li>Borrelia </li></ul><ul><li>Propionibacterium acnes </li></ul><ul><li>Aluminum, beryllium, zirconium </li></ul>
  6. 6. Immunology <ul><li>Accumulation activated T cells and macrophages </li></ul><ul><li>Release of interferon gamma, interleukin-2, cytokines </li></ul><ul><li>Interaction sarcoid antigen with specific T cell receptor and antigen presenting cell to trigger inflammatory response </li></ul>
  7. 7. Pathology <ul><li>Noncaseating epitheliod cell granuloma </li></ul><ul><li>Accumulation of CD4 </li></ul><ul><li>Multinucleated giant cells may be present </li></ul><ul><li>Inflammation similar in all organs affected </li></ul><ul><li>Fibrosis leads to tissue damage </li></ul>
  8. 8. Neurologic Involvement <ul><li>Frequency 5-16% </li></ul><ul><li>Occurs at later age than systemic </li></ul><ul><li>Majority have systemic disease </li></ul><ul><li>Neurologic symptoms presenting features 50% cases </li></ul><ul><li>Acute – isolated CN or aseptic meningitis </li></ul><ul><li>Chronic – parenchymal, multi CN, hydrocephalus, PNS </li></ul>
  9. 9. Neurologic Involvement <ul><li>Series 68 pts CNS involvement 62% (optic, CN palsies increased rate to 72%. </li></ul><ul><li>Spinal 28% </li></ul><ul><li>Posterior Fossa 21% </li></ul><ul><li>Cognitive decline 10% </li></ul>
  10. 10. Manifestations <ul><li>Encephalopathy (14-30%) anxiety, dementia, vascular dementia </li></ul><ul><li>Mass lesions (3-26%). </li></ul><ul><li>Hypothalamic (10-26%) </li></ul><ul><li>Meningitis (8-40%). </li></ul><ul><li>Hydrocephalus (6-17%). </li></ul><ul><li>Seizures (18-34%) </li></ul><ul><li>Posterior Fossa (9-26%). </li></ul><ul><li>Spinal Cord (3-10%). </li></ul><ul><li>Peripheral Nerve (6-40%) </li></ul><ul><li>Muscle (9-23%) </li></ul>
  11. 11. Diagnosis <ul><li>Verification of systemic sarcoid </li></ul><ul><li>CT – hyperdense, enhance with contrast. Periventricular white matter lesions common </li></ul><ul><li>MRI sensitivity (82%). </li></ul><ul><li>PET </li></ul><ul><li>Gallium scans </li></ul><ul><li>VEP/BAEP </li></ul><ul><li>Kviem-Siltzbach (KT) 67-92% </li></ul><ul><li>Serum ACE may correlate with clinical disease </li></ul><ul><li>Biopsy if feasible </li></ul>
  12. 12. Diagnosis <ul><li>CSF nonspecific </li></ul><ul><li>CSF 80% abnormal </li></ul><ul><ul><li>elevated cell count (<50 WBC/mm) </li></ul></ul><ul><ul><li>protein (<100 mg%) </li></ul></ul><ul><ul><li>elevated pressure </li></ul></ul><ul><ul><li>decreased glucose </li></ul></ul><ul><li>CSF ACE level elevated 50% cases. ?Use (usually elevated with elevated protein) </li></ul><ul><li>IgG Index/Oliogoclonal Bands reported </li></ul><ul><li>Elevated CD4/CD8 ratio </li></ul><ul><li>Lysozyme/B2m elevated in half of patients </li></ul>
  13. 13. Diagnosis <ul><li>Multiple Sclerosis </li></ul><ul><li>Idiopathic Bell’s Palsy </li></ul><ul><li>Granulomatous Infections </li></ul><ul><li>Lyme </li></ul><ul><li>Vasculitis </li></ul><ul><li>Neoplasms </li></ul><ul><li>Meningeal Carcinomatosis </li></ul><ul><li>HIV/AIDS </li></ul><ul><li>Herpes Encephalitis </li></ul>
  14. 14. Cranial Nerve <ul><li>37-61% </li></ul><ul><li>Facial nerve most often involved </li></ul><ul><li>CN VIII, Optic, Trigeminal </li></ul><ul><li>Other CNs less often involved leading to anosmia, disturbance of ocular movements, pharygeal/vocal cord involvement </li></ul>
  15. 15. Meningeal Involvement <ul><li>60% of cases </li></ul><ul><li>Aseptic meningitis </li></ul><ul><li>Meningeal mass lesion </li></ul><ul><li>Obstructive or communicating hydrocephalus </li></ul><ul><li>Cranial neuropathies from basilar meningitis </li></ul>
  16. 16. Parenchymal Disease <ul><li>Clinical features depend on location </li></ul><ul><li>Hypothalmic – impairment of neuroendocrine system (thyroid, adrenal, sexual dysfucntion, sleep, temperature, electrolyte balance, appetite) </li></ul><ul><li>Mass lesions </li></ul>
  17. 17. Encephalitis/Seizures <ul><li>Delirium, psychiatric, memory disturbance </li></ul><ul><li>TIAs/vasculopathy </li></ul><ul><li>Seizures 20% of patients – generalized or focal </li></ul><ul><li>Seizures associated with poorer prognosis </li></ul>
  18. 18. Peripheral System <ul><li>PN – 15-18% of cases </li></ul><ul><li>Axonal sensorimotor most common </li></ul><ul><li>Mononeuritis multiplex, polyradiculopathy, GBS </li></ul><ul><li>Most are assymptomatic </li></ul><ul><li>Epineurium/perineurium involvement axonal degeneration </li></ul><ul><li>Endoneurium involvement demyelinating neuropathy </li></ul>
  19. 19. Peripheral System <ul><li>Muscle involvement is common. </li></ul><ul><li>Symptomatic – less 1% of systemic cases </li></ul><ul><li>Acute or chronic myopathy, myositis, intramuscular nodules, pseudohypertrophy </li></ul><ul><li>More common in women (4:1), especially postmenopausal </li></ul>
  20. 20. Corticosteroids <ul><li>Mainstay of treatment </li></ul><ul><li>Proposed mechanism </li></ul><ul><ul><li>Inhibition of lymphocyte/mononuclear phagocytic activity </li></ul></ul><ul><ul><li>Inhibition of transcription of proinflammatory cytokines </li></ul></ul><ul><ul><li>Downregulation of cellular receptors </li></ul></ul><ul><ul><li>Interference with collagen synthesis </li></ul></ul><ul><li>May not change natural history </li></ul>
  21. 21. Treatment <ul><li>Cyclosporine. </li></ul><ul><li>Azathioprine. </li></ul><ul><li>Methotrexate. </li></ul><ul><li>Cyclophosphamide </li></ul><ul><li>Radiation.. </li></ul><ul><li>Surgery </li></ul>
  22. 22. Treatment <ul><li>Tacrolimus (Prograf) – macrolide immunosuppresant. Inhibit T-cell activation </li></ul><ul><li>Sirolimus (Rapamune) – macrolide immunosuppressant. </li></ul><ul><li>Anticytokine therapy </li></ul><ul><li>Anticellular adhesion molecules </li></ul><ul><li>Gene therapy targeting proinflammatory cytokines </li></ul>
  23. 23. Treatment <ul><li>Consider combination therapy, refractory cases </li></ul><ul><li>Isolated facial palsies – favorable outcome </li></ul><ul><li>Certain cases, e.g. parenchymal involvement, may require longer course of treatment </li></ul><ul><li>Consider biopsy of intracranial lesions </li></ul><ul><ul><li>Before initiating therapy </li></ul></ul><ul><ul><li>Refractory to treatment </li></ul></ul><ul><ul><li>Diagnosis unclear </li></ul></ul>
  24. 24. Treatment <ul><li>Shunt in selected cases </li></ul><ul><li>Surgical resection rarely curative </li></ul><ul><li>Seizure control </li></ul><ul><li>Peripheral involvement treat if symptomatic </li></ul>
  25. 25. Prognosis <ul><li>Monophasic, relapsing, progressive </li></ul><ul><li>2/3 neurologic symptoms may improve with treatment </li></ul><ul><li>Depends on location of involvement </li></ul><ul><li>72% deterioration with spinal cord 18 months or more </li></ul><ul><li>Acute or subacute presentations have better prognosis than chronic </li></ul><ul><li>1/3 may relapse </li></ul><ul><li>Mortality 8-12% if neurological involvement </li></ul>
  26. 26. References <ul><li>Zajicek JP. Neurosarcoidosis. Current Opinion in Neurology. 2000; 13:323-325. </li></ul><ul><li>Oksanen V. Neurosarcoidosis. Sarcoidosis. 1994; 11:76-79. </li></ul><ul><li>Gullapalli D, Phillips LH. Neurologic Manifestations of Systemic Disease. Neurologic Clinics. 2002; 20(1). </li></ul><ul><li>Mana J. Magnetic Resonance Imaging and Nuclear Imaging in Sacoidosis. Current Opinions in Pulmonary Medicine. 2002; 8(5): 457-463. </li></ul><ul><li>Scott TF. Neurosacoidosis: Progress and Clinical Aspects. Neurology. 1993; 43:8-12. </li></ul><ul><li>Kang S, Suh JH. Radiation Therapy for Neurosarcoidosis: Report of Three Cases from a Single Institution. Radiation Oncology Investigations. 1999; 7:309-312. </li></ul><ul><li>Nowak DA, Widenka DC. Neurosarcoidosis: a review if its intracranial manifestations. Journal Neurology. 2001; 248:363-372. </li></ul><ul><li>Zajicek JP, Scolding NJ, et al. Central Nervous System Sarcoidosis-diagnosis and management. Quarterly Journal of Medicine. 1999; 92:103-111. </li></ul>

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