- Barney J Stern, MD
Barney J Stern, MD
- Professor of Neurology
- University of Maryland
- Section Editors
- Michael J Aminoff, MD, DSc
Michael J Aminoff, MD, DSc
- Editor-in-Chief — Neurology
- Section Editor — Medical Neurology
- Professor of Neurology
- University of California, San Francisco School of Medicine
- Talmadge E King, Jr, MD
Talmadge E King, Jr, MD
- Editor-in-Chief — Pulmonary and Critical Care Medicine
- Section Editor — Interstitial Lung Disease
- Dean, School of Medicine
- Vice Chancellor, Medical Affairs
- University of California San Francisco
Neurologic complications occur in approximately 5 to 10 percent of patients with sarcoidosis [1-4]. Neurosarcoidosis is a diagnostic consideration in patients with known sarcoidosis who develop neurologic complaints and in patients presenting de novo with a constellation of findings consistent with the disease [5,6]. Approximately 50 percent of patients with neurosarcoidosis present with neurologic difficulties at the time sarcoidosis is first diagnosed. One-third of those with neurosarcoidosis have or develop more than one neurologic manifestation of their disease.
The diagnosis and management of neurosarcoidosis will be reviewed here. General issues related to sarcoidosis and its pathogenesis are discussed separately. (See "Clinical manifestations and diagnosis of pulmonary sarcoidosis" and "Pathogenesis of sarcoidosis".)
Any portion of the central or peripheral nervous system can be affected by sarcoidosis. Common syndromes include:
●Cranial mononeuropathy. Peripheral facial nerve palsy develops in 25 to 50 percent of patients with neurosarcoidosis [2,6,7]. The facial nerve palsy can be unilateral or bilateral (simultaneous or sequential) and recurrent. Optic neuropathy and cranial nerve VIII dysfunction can lead to intermittent or progressive visual, auditory, or vestibular dysfunction . (See "Optic neuropathies", section on 'Sarcoidosis'.)
●Neuroendocrine dysfunction typically occurs with hypothalamic inflammation, resulting in polyuria or disturbances in thirst, sleep, appetite, temperature, or libido. Hypothalamic or pituitary lesions may also cause thyroid, gonadal, or adrenal abnormalities [6,9]. (See "Causes of hypopituitarism".)
One such manifestation, polyuria, can result from one or more factors in patients with sarcoidosis. Direct hypothalamic involvement can lead to central diabetes insipidus or primary polydipsia, while hypercalcemia (due to production of calcitriol by activated macrophages) can cause nephrogenic diabetes insipidus . (See "Hypercalcemia in granulomatous diseases".) Thus, patients with sarcoidosis and polyuria may require a water restriction test to establish the correct diagnosis. (See "Diagnosis of polyuria and diabetes insipidus".)
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- Joseph FG, Scolding NJ. Sarcoidosis of the nervous system. Pract Neurol 2007; 7:234.
- Terushkin V, Stern BJ, Judson MA, et al. Neurosarcoidosis: presentations and management. Neurologist 2010; 16:2.
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- Joseph FG, Scolding NJ. Neurosarcoidosis: a study of 30 new cases. J Neurol Neurosurg Psychiatry 2009; 80:297.
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- Navi BB, DeAngelis LM. Sarcoidosis presenting as brainstem ischemic stroke. Neurology 2009; 72:1021.
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- Reda HM, Taylor SW, Klein CJ, Boes CJ. A case of sensory ataxia as the presenting manifestation of neurosarcoidosis. Muscle Nerve 2011; 43:900.
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- SHAMBAUGH GE, CIRKSENA WJ, NEWCOMER KL. CARPAL TUNNEL SYNDROME AS MANIFESTATION OF SARCOIDOSIS. Arch Intern Med 1964; 114:830.
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- Zajicek JP, Scolding NJ, Foster O, et al. Central nervous system sarcoidosis--diagnosis and management. QJM 1999; 92:103.
- Sherman JL, Stern BJ. Sarcoidosis of the CNS: comparison of unenhanced and enhanced MR images. AJNR Am J Neuroradiol 1990; 11:915.
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- Scott TF. Cerebral herniation after lumbar puncture in sarcoid meningitis. Clin Neurol Neurosurg 2000; 102:26.
- Peeples DM, Stern BJ, Jiji V, Sahni KS. Germ cell tumors masquerading as central nervous system sarcoidosis. Arch Neurol 1991; 48:554.
- Stern BJ, Corbett J. Neuro-ophthalmologic Manifestations of Sarcoidosis. Curr Treat Options Neurol 2007; 9:63.
- Agbogu BN, Stern BJ, Sewell C, Yang G. Therapeutic considerations in patients with refractory neurosarcoidosis. Arch Neurol 1995; 52:875.
- Scott TF, Yandora K, Valeri A, et al. Aggressive therapy for neurosarcoidosis: long-term follow-up of 48 treated patients. Arch Neurol 2007; 64:691.
- Stern BJ, Schonfeld SA, Sewell C, et al. The treatment of neurosarcoidosis with cyclosporine. Arch Neurol 1992; 49:1065.
- Sharma OP. Neurosarcoidosis: a personal perspective based on the study of 37 patients. Chest 1997; 112:220.
- Lower EE, Broderick JP, Brott TG, Baughman RP. Diagnosis and management of neurological sarcoidosis. Arch Intern Med 1997; 157:1864.
- Doty JD, Mazur JE, Judson MA. Treatment of corticosteroid-resistant neurosarcoidosis with a short-course cyclophosphamide regimen. Chest 2003; 124:2023.
- Tikoo RK, Kupersmith MJ, Finlay JL. Treatment of refractory neurosarcoidosis with cladribine. N Engl J Med 2004; 350:1798.
- Androdias G, Maillet D, Marignier R, et al. Mycophenolate mofetil may be effective in CNS sarcoidosis but not in sarcoid myopathy. Neurology 2011; 76:1168.
- Bomprezzi R, Pati S, Chansakul C, Vollmer T. A case of neurosarcoidosis successfully treated with rituximab. Neurology 2010; 75:568.
- Pritchard C, Nadarajah K. Tumour necrosis factor alpha inhibitor treatment for sarcoidosis refractory to conventional treatments: a report of five patients. Ann Rheum Dis 2004; 63:318.
- Morcos Z. Refractory neurosarcoidosis responding to infliximab. Neurology 2003; 60:1220.
- Katz JM, Bruno MK, Winterkorn JM, Nealon N. The pathogenesis and treatment of optic disc swelling in neurosarcoidosis: a unique therapeutic response to infliximab. Arch Neurol 2003; 60:426.
- Pettersen JA, Zochodne DW, Bell RB, et al. Refractory neurosarcoidosis responding to infliximab. Neurology 2002; 59:1660.
- Carter JD, Valeriano J, Vasey FB, Bognar B. Refractory neurosarcoidosis: a dramatic response to infliximab. Am J Med 2004; 117:277.
- Hoitsma E, Faber CG, van Santen-Hoeufft M, et al. Improvement of small fiber neuropathy in a sarcoidosis patient after treatment with infliximab. Sarcoidosis Vasc Diffuse Lung Dis 2006; 23:73.
- Moravan M, Segal BM. Treatment of CNS sarcoidosis with infliximab and mycophenolate mofetil. Neurology 2009; 72:337.
- Santos E, Shaunak S, Renowden S, Scolding NJ. Treatment of refractory neurosarcoidosis with Infliximab. J Neurol Neurosurg Psychiatry 2010; 81:241.
- Marques IB, Giovannoni G, Marta M. Mononeuritis multiplex as the first presentation of refractory sarcoidosis responsive to etanercept. BMC Neurol 2014; 14:237.
- Wijnen PA, Cremers JP, Nelemans PJ, et al. Association of the TNF-α G-308A polymorphism with TNF-inhibitor response in sarcoidosis. Eur Respir J 2014; 43:1730.
- Menninger MD, Amdur RJ, Marcus RB Jr. Role of radiotherapy in the treatment of neurosarcoidosis. Am J Clin Oncol 2003; 26:e115.
- Luke RA, Stern BJ, Krumholz A, Johns CJ. Neurosarcoidosis: the long-term clinical course. Neurology 1987; 37:461.
- Allen RK, Sellars RE, Sandstrom PA. A prospective study of 32 patients with neurosarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis 2003; 20:118.
- Krumholz A, Stern BJ, Stern EG. Clinical implications of seizures in neurosarcoidosis. Arch Neurol 1991; 48:842.
- CLINICAL FEATURES
- DIAGNOSTIC APPROACH
- Differential diagnosis
- Clinical evaluation
- Neurodiagnostic testing
- - Neuroimaging
- - Lumbar puncture
- - Other tests
- Other immunomodulatory therapies
- Surgical considerations
- Radiation therapy
- General measures
- SUMMARY AND RECOMMENDATIONS