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 (lt50 WBC/mm)
• protein (lt100 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 Bells 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 (41), 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

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