Neurology/Neurosurgery Grand Rounds December, 2016 on "A Review on Neurosarcoidosis".

1. A REVIEW ON
NEUROSARCOIDOSIS
NARESH MULLAGURI MD, PGY4
NEUROLOGY AND NEUROSURGERY GRANDROUNDS - 12/2016
UNIVERSITY OF MISSOURI HEALTHCARE
COLUMBIA-MISSOURI

2. DISCLOSURES

3. REASON FOR DOING THIS REVIEW
• Lot of unknowns starting from etiology to management. No randomized controlled
trials till date.
• A challenge for both subspecialties in diagnosing and managing patients.
• It is a great mimicker in our world. To raise awareness of the condition.

4. OBJECTIVES
• Historical account
• Definition
• Epidemiology
• Clinical manifestations
• Diagnosis and Monitoring
• Management
• Prognosis

5. Historical account

6. Definition of Sarcoidosis

7. Neurosarcoidosis
• Pathologically characterized by the presence of non-caseating
granulomas composed of compact clusters of activated
Macrophages and other epithelioid cells surrounded by T
lymphocytes.

8. Other conditions that cause granulomas
inflammation

9. Types of Antigens
Infections:
Propionibacterium acnes
Mycobacteria
Environmental:
Pesticides, mold, metallic
particles
Genetic:
Annexin A11 gene
polymorphism involved in
apoptosis

10. Neurosarcoidosis
• Develops clinically in 5% of patients with Sarcoidosis. Asymptomatic involvement is
higher in autopsy studies upto 15%.
• Nervous system dysfunction can be a presenting feature of Sarcoidosis in 50-70% of
patients with Neurosarcoidosis.
• Isolated Neurological involvement without systemic disease can occur in 10-17% of the
Neurosarcoidosis patients.
• Any part of the nervous system can be involved.
• 1/3 of the patients have refractory illness that is associated with considerable morbidity
and possible mortality.

11. EPIDEMIOLOGY

12. Clinical Features of Neurosarcoidosis
• Cranial Neuropathy 50-75%
• Parenchymal Disease 25-45%
• Aseptic Meningitis 10-20%
• Hydrocephalus 10%
• Peripheral Neuropathy 5-10%
• Small fiber Neuropathy – recent addition.
• Myopathy 10%

13. Differential Diagnosis of Neurosarcoidosis

14. Cranial Neuropathies
Facial Nerve - 30-40% of cases have bilateral involvement (simultaneous or sequential).
most of the patients will have complete resolution in few weeks.
Optic Nerve - Recovery may not be complete. May involve long segments of the Optic
Nerve including chiasm and tracts. Can be intermittant or progressive.
Vestibulocochlear Nerve – Severe and often acute hearing loss and severe vestibular
dysfunction.
Trigeminal Nerve – Less commonly facial numbness and Trigeminal Neuralgia like
symptoms.
** The lesions can be nuclear and infra-nuclear. The cranial nerves can also be involved
secondary to skull base inflammation.
25-50% 0f NS patients

15. Meningitis(Aseptic)
• Sub-acute or chronic meningitis.
• Mostly involves basal regions and
Leptomeninges.
• Usually presents with Headache and
hydrocephalus(both communicating and non-
communicating)
• Cranial nerve and hypothalamic pituitary axis
dysfunction.

16. Neurosarcoidosis – Myelopathic form
Distribution of Lesions
• Mostly involves Cervicothoracic regions.
• Both Parenchymal and Leptomeningeal lesions
• Cauda equina syndrome.
Symptoms:
• Subjective weakness with intact strength on the
exam.
• Patchy, non-contiguous sensory loss due to the
patchy involvement of the leptomeninges,
parenchyma and radicles of the nerves.
• Bladder and bowel symptoms are common.
• Mostly result in severe disability ending up in
severe spinal cord atrophy.

17. Intracranial Lesions

18. Neuroendocrine Symptoms
• Affects the hypothalamic-pituitary
axis.
• Causes Central Hypothyroidism,
Hypogonadism, Hyperprolactinemia,
DI both central and nephrogenic and
SIADH.
• Symptoms : Changes in menstrual
periods, excessive tiredness,
excessive thirst and high urine
output. Hypothalamic vegetative
dysfunction.

19. Headache and Seizures
• Secondary to Acute or Chronic
Meningitis or mass lesions.
• Due to Opportunistic infections
resulting from chronic
immunosuppression.
• Optic Neuritis, Trigeminal
Neuralgia.
• Exacerbation of chronic Migraines

20. Neurovascular manifestations

21. Neuropsychiatric Manifestations

22. Neuromuscular manifestations

23. Neuropathy types and symptoms

25. Neurosarcoidosis – Neuropathy

26. Neuromuscular – Muscle involvement

27. Differential Diagnosis

28. Parenchymal Lesions
• Granulomatous masses can masquerade as an
Astrocytoma, primary or secondary brain tumor
• Multiple white matter T2 hyperintensities on MRI are non-
specific and are associated with MS or other inflammatory
disorders.
• 10 cases of PML complicating sarcoidosis were described
in one report, among them only 8 had received
immunotherapy, usually corticosteroids alone. Symptoms
and MRI findings are mistakenly attributed to
Neurosarcoidosis in eight patients, perhaps contributing
to the high fatality rate of 57%.
MS
PML

29. Vasculopathy
Can mimic Syphilis or CNS vasculitis

30. Meningeal Disease

31. Peripheral Nerve Lesions

32. Clinical Evaluation

33. Where to look

35. Gallium scan "panda" sign: A gallium scan demonstrates the
"panda" sign of increased radiotracer uptake in the lacrimal,
parotid, and salivary glands bilaterally.

37. Neurodiagnostic testing

38. Lumbar Puncture

39. CSF soluble Interleukin-2 receptor levels

40. Other test relevant for the clinical
presentation
• EEG
• Evoked potentials
• Angiography
• NCS/EMG can help localize the lesions
• Calcium levels

41. Kveim-Slitzbach test

42. Diagnostic Criteria for Neurosarcoidosis

43. Biopsy
Schaumann
body/Conchoidal
bodies
Concentric Calcium oxylate and
protein inclusions in Langhans
giant cells

44. Treatment – No randomized controlled trials

45. Corticosteroids taper

46. Adverse Effects of Steroids

47. Immunomodulatory therapies

48. Surgical Interventions

49. Radiation Therapy

50. Treatment

51. General Measures

52. Prognosis

53. Take home points

54. Suggested reading
• Sarcoidosis Michael C. Iannuzzi, M.D., Benjamin A. Rybicki, Ph.D., and Alvin S.
Teirstein, M.D – NEJM 2007
• https://www.uptodate.com/contents/neurologic-sarcoidosis/abstract/39
• Katz JM et al. Pathogenesis and treatment of Optic Neuritis in Neurosarcoidosis, a
unique therepeutic response to Infliximab – Arc. Neurology 2003
• Treatment of Neurosarcoidosis with infliximab and Mycophenolate – Moravan M,
Segal BM. Neurology 2009, 72:337
• Role of radiotherapy in the treatment of Neurosarcoidosis. AM J Clin Oncology 2003;
26:e115. Menninger et al.
• Hoitsma E, Faber CG et al. Improvement of small fiber Neuropathy in a patient with
Sarcoidosis after treatment with Infliximab. Sarcoidosis Vasc Diffuse Lung Disease
2006; 23:73
• Continuum Neurology of systemic disease 2013, Minneap, MN