Neurosarcoidosis

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.