Neurosarcoidosis. Walter Royal, III, MD Professor of Neurology and Anatomy and Neurobiology University of Maryland School of Medicine
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1 Neurosarcoidosis Walter Royal, III, MD Professor of Neurology and Anatomy and Neurobiology University of Maryland School of Medicine
2 Sarcoidosis A granulomatous disease of unknown etiology and no current FDAapproved treatment approach
3 Sarcoid Granuloma Joseph. Pract Neurol 2007; 7: Boos et al. 2013, Vol 4, Article 437.
4 Sarcoidosis: Disease Epidemiology Prevalence of sarcoidosis: 40 per 100,000 Most commonly presents at age years Familial risk / Heritability Familial cases ~ 3 fold increased risk to sibs and offspring Twin study heritability estimate 0.66 (95% CI 0.45 to 0.80) Differences in prevalence and severity across different race-ethnicities Courtesy of B. Stern, MD
5 Diagnosis of Systemic Sarcoidosis Elevated serum ACE activity Hypercalcemia Hypercalciuria Elevated immunoglobulins Anergy Chest X-ray Thoracic CT PFT s including D CO Ophthalmologic exam Retinal vasculitis Conjunctival granulomas Endoscopic nasal exam Whole-body gallium scan Muscle MRI Whole-body FDG PET scan Courtesy of B. Stern, MD
6 Sarcoidosis: Frequency of Organ Involvement and Treatment (N=1248) Judson MA. Resp Med. 113 (2016)
7 Neurosarcoidosis Neurological complications of sarcoidosis occur in approximately 5-10% of patients with sarcoidosis. Patients with known systemic sarcoidosis can develop neurological symptoms and signs. Patients without known sarcoidosis can develop neurological findings consistent with neurosarcoidosis. Approximately 50% of neurosarcoidosis patients present with neurological disease at the time of their sarcoidosis diagnosis. Courtesy of B. Stern, MD
8 Neurosarcoidosis: Clinical Manifestations Cranial neuropathies 1, 2, 5, 7, 8 Meningeal disease Acute aseptic meningitis Chronic meningitis Mass lesion Hydrocephalus CNS disease Endocrinopathy Mass lesion(s) Encephalopathy / microvasculopathy Seizures Stroke Vegetative dysfunction Spinal cord Nerve roots Cauda equina syndrome Neuropathy Mononeuropathies Axonal or demyelinating Sensory, motor, sensorimotor Small fiber sensory neuropathy +/- autonomic neuropathy Myopathy Polymyositis Nodule(s) Courtesy of B. Stern, MD
9 Ethnicity and Sarcoidosis Incidence African Americans 39 per 100,000 Caucasians 5 per 100,000 Lifetime risk African Americans Women 2.7% Men 2.1% Caucasians Women 1.0% Men 0.7% Mirsaeidiet al. Chest 2015; 147(2):
10 Annual Average, Age-adjusted Sarcoidosis Incidence (Detroit, MI, ) Rybicki et al. J Epidemiol. 1997;145:3.
11 Annual Average, Age-specific Sarcoidosis Incidence (Detroit, MI, ) Rybicki et al. J Epidemiol. 1997;145:3.
12 Multiple Cause of Death in Caucasians and African Americans with Sarcoidosis in the United States (1999 to 2010) Mirsaeidi et al. Chest 2015; 147(2):
13 Symptom Frequency and MRI Findings in Neurosarcoidosis (N=48 Patients) Scott et al. Arch Neurol/Vol 64, May 2007
14 Para-Neurosarcoidosis Possibly related to high circulating cytokine levels Small fiber polyneuropathy Sensory neuropathy Impaired pin and temperature sensibility Often painful Autonomic neuropathy Brain Fog Fatigue Courtesy of B. Stern, MD
15 Neurodiagnostic Investigations Brain and spine MRI -/+ contrast FDG PET Brain hyper- or hypo-metabolism CSF protein, glucose, mononuclear pleocytosis IgG index, + OCB ACE
16 MRI Lesions in Neurosarcoidosis Extra-axial mass lesion Spinal cord lesion (T1-T7) Pawate et al. Q J Med 2009; 102:
17 Neurosarcoidosis: Approaches to treatment No rigorous studies have been performed Only case series and expert opinion are available Treatment decisions guided by The prior clinical course The expected natural history Response to previous therapy Adverse effects from treatment
18 Concerns Related to Current Treatment Approaches Frequent requirement for a prolonged treatment course Unwanted, serious side effects Common incomplete clinical response
19 Potential Long-Term Complications Cryptococcal and tuberculous meningitis Toxoplasmosis Progressive multifocal leukoencephalopathy Listeria monocytogenes infection Spinal epidural lipomatosis Corticosteroid-induced myopathy Lymphoma Inclusion body myositis
20 68 Year-old Woman with Progressive Cognitive Decline Davis et al. The Neurologist
21 CD68 SV40 Davis et al. The Neurologist
22 A: Myocardium B: Lung apex C: Mediastinal lymph node D: Brain (LFB stain) Davis et al. The Neurologist
23 Conclusion Sarcoidosis is a potentially severe disease that disparately impacts African Americans in society. Further studies are required to elucidate pathogenetic factors that are associated with risk and to guide the development of safe and effective therapies.
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