eMedicine Specialties > Neurology > Inflammatory and Demyelinating Diseases

Neurosarcoidosis: Differential Diagnoses & Workup

Author: Gabriel Bucurescu, MD, MS, Staff Neurologist, Neurology Service, Philadelphia Veterans Affairs Medical Center
Coauthor(s): Amer Suleman, MD, Consultant in Electrophysiology and Cardiovascular Medicine, Department of Internal Medicine, Division of Cardiology, Medical City Dallas Hospital
Contributor Information and Disclosures

Updated: Jul 29, 2009

Differential Diagnoses

Chronic Inflammatory Demyelinating Polyradiculoneuropathy
Pituitary Tumors
Craniopharyngioma
Polyarteritis Nodosa
Diabetic Neuropathy
Primary CNS Lymphoma
HIV-1 Associated Distal Painful Sensorimotor Polyneuropathy
Sarcoidosis and Neuropathy
Inclusion Body Myositis
Systemic Lupus Erythematosus
Infectious Myositis
Tuberculous Meningitis
Leptomeningeal Carcinomatosis
Tuberous Sclerosis
Lumbar Puncture (CSF Examination)
Wegener Granulomatosis
Metabolic Neuropathy
Multiple Sclerosis
Neurosyphilis

Other Problems to Be Considered

Brain tumors

Workup

Laboratory Studies

  • Findings of cerebrospinal fluid (CSF) analysis are normal in 30% of cases, specifically in patients with cranial nerve and peripheral nerve involvement. When CSF analysis findings are abnormal, they reflect a nonspecific pattern with high protein level (>0.5 g/L), high leukocyte count (>5 cells/µL), usually lymphocytosis, and normal or low glucose level; this combination coupled with negative cytology and culture results support the diagnosis of neurosarcoidosis. Sometimes serial CSF analyses may be necessary. In one study of 68 patients, the CSF leukocyte count was in the range of 5-220 cells/µL.
  • Levels of angiotensin-converting enzyme (ACE), lysozyme, and beta2-microglobulin can be elevated in the CSF in more than half the patients; changes in these markers can parallel the clinical course.
  • High IgG, Ig index, and oligoclonal bands have been reported in the CSF. Studies of subpopulations of T lymphocytes have shown a high T4/T8 ratio, which can help in differentiating sarcoidosis from multiple sclerosis.
  • Hypochromic microcytic anemia of chronic disease can be seen.
  • Endocrine studies should be performed whenever involvement of the pituitary-hypothalamic axis is suspected. This includes thyroid function tests, prolactin, testosterone, growth hormone, luteinizing hormone, follicle-stimulating hormone, corticotropin-releasing hormone, estradiol, urine osmolality determination, and insulinlike growth factor.
  • Creatine kinase, erythrocyte sedimentation rate, and aldolase may be useful in cases of myopathy.
  • Calcium levels, liver enzymes may be helpful.
  • Antineutrophil cytoplasmic antibody (C-ANCA) titers may be needed to differentiate from Wegener granulomatosis.

Imaging Studies

  • Both a CT scan and an MRI of the brain and spine are indispensable in assessing nervous system involvement.
    • The MRI has become the modality of choice because of the superior images obtained.
    • The use of gadolinium and fluid-attenuated inversion recovery (FLAIR) has increased the sensitivity of an MRI.
    • Some series have shown that gadolinium enhancement demonstrated leptomeningeal involvement in cases that unenhanced images might have missed. The enhancement can follow the contour of the brain, extending into the cortical sulci. Gadolinium also can leak into the contiguous CSF because of disruption of capillary endothelial tight junctions of the arachnoid matter. A thick and ragged pial enhancement is indicative of invasion along perivascular spaces, leading to a meningoencephalovasculopathy. Enhancement of linear and nodular areas from the pial surface into the white matter indicates infiltration along Virchow-Robin spaces.
    • In the FLAIR technique, the signal from the CSF is suppressed, and mild or heavy T2 weighting (long TE) is used to detect lesions. This technique is of value in detecting low-contrast lesions. It also can be used to improve the accuracy of detecting T2 prolongation in the temporal lobe in cases of mesial temporal sclerosis. The nulling of the CSF signal maximizes the sensitivity of the sequence to changes in the T1 of the CSF. The FLAIR technique is valuable in diffusion weighting and is especially sensitive to contrast enhancement. It also can be combined with fat suppression.
  • An MRI may demonstrate the following:
    • Periventricular high-signal lesions on T2-weighted images
    • Multiple supratentorial and infratentorial brain lesions
    • Solitary intra-axial mass
    • Solitary extra-axial mass
    • Leptomeningeal enhancement
    • Optic nerve enhancement (see Media files 3-7)

      MRI of the brain in a 37-year-old man with neuros...

      MRI of the brain in a 37-year-old man with neurosarcoidosis who had complete loss of vision in the right eye for 2 months and occasional blurry vision in the left. T1-weighted sagittal image shows intact optic nerves.

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      MRI of the brain in a 37-year-old man with neuros...

      MRI of the brain in a 37-year-old man with neurosarcoidosis who had complete loss of vision in the right eye for 2 months and occasional blurry vision in the left. T1-weighted sagittal image shows intact optic nerves.

    • Spinal cord intramedullary mass resembling demyelinating disease
  • Chest radiograph reveals sarcoidosis (see Media files 8-9).

    Early chest radiograph findings in sarcoidosis.

    Early chest radiograph findings in sarcoidosis.

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    Early chest radiograph findings in sarcoidosis.

    Early chest radiograph findings in sarcoidosis.



    Advanced chest radiograph findings in sarcoidosis.

    Advanced chest radiograph findings in sarcoidosis.

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    Advanced chest radiograph findings in sarcoidosis.

    Advanced chest radiograph findings in sarcoidosis.

  • Fluorodeoxyglucose positron emission tomography (PET) imaging may show areas of hypermetabolism or hypometabolism in the CNS, and this information may be compared to a systemic PET scan in patients with systemic sarcoidosis, thus establishing a firmer diagnosis.

Other Tests

  • EMG/nerve conduction studies can be used to confirm neuropathy.
    • Findings include slowing of motor nerve conduction velocities; abnormal sensory nerve conduction consisting of absent potentials, reduced amplitude, and mild slowing; mixed compound nerve action potentials may be seen as well.
    • The most characteristic electrodiagnostic finding is mononeuropathy multiplex, showing axonal degeneration and segmental demyelination.
    • With treatment and clinical improvement, motor, sensory, and mixed nerve conduction tend to improve.
    • In cases of myopathy, the EMG shows myopathic potentials.
  • Evoked potential (EP) studies may be of value in supporting the diagnosis and monitoring the course of the disease. Visual evoked potentials (VEPs) and brainstem auditory evoked potentials (BAEPs) tend to be abnormal in about one third of the patients with neurosarcoidosis. Somatosensory evoked potentials tend to show abnormalities less frequently. All 3 modalities of EPs can show abnormalities in patients before the appearance of clinical signs.
  • Visual field testing

Procedures

  • Nerve and muscle biopsy can help confirm the diagnosis.
    • In asymptomatic patients, biopsies show granulomas surrounded by normal muscle. This is the most common type of involvement and is seen in 50-80% of asymptomatic patients. A recent case report of neurosarcoidosis (sarcoid brainstem encephalitis) demonstrated nemaline rods in every muscle examined.
    • Because the granulomas can be scarce, a large sample should be taken.
    • Granulomas are not specific for neurosarcoidosis and can be seen in patients with tuberculosis, fungal infections, collagen vascular disorders, or carcinoma.
    • In symptomatic patients, nodules are less frequent. In some cases, noncaseous granulomatous myositis or chronic myopathic changes can be seen.
    • Peripheral nerve biopsies may show segmental demyelination, degenerating nerve roots with inflammatory cells, axonal degeneration, and mechanical destruction of nerves by granulomas.
  • Brain biopsy may be required in selected cases with isolated brain involvement; in other cases the patient's history, MRI scans, and chest radiograph may be sufficient for arriving at the correct diagnosis.
  • Blood vessel biopsies of both arteries and veins can show involvement of the vessel wall, most frequently in the perforating arteries.
  • Ventriculoperitoneal shunting may be needed in cases of hydrocephalus.

Histologic Findings

Noncaseating granulomas are seen in affected tissues (see Media files 10-11).


Noncaseating granuloma surrounded by epithelioid ...

Noncaseating granuloma surrounded by epithelioid cells, from the medulla oblongata. Also shown are nodular inflammatory infiltrates consisting of multinucleated giant cells, macrophages, and lymphocytes (hematoxylin and eosin, 40x).

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Noncaseating granuloma surrounded by epithelioid ...

Noncaseating granuloma surrounded by epithelioid cells, from the medulla oblongata. Also shown are nodular inflammatory infiltrates consisting of multinucleated giant cells, macrophages, and lymphocytes (hematoxylin and eosin, 40x).



Noncaseating granuloma in medulla oblongata showi...

Noncaseating granuloma in medulla oblongata showing the granuloma surrounded by epithelioid cells and nodular inflammatory infiltrates (hematoxylin and eosin, 20x).

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Noncaseating granuloma in medulla oblongata showi...

Noncaseating granuloma in medulla oblongata showing the granuloma surrounded by epithelioid cells and nodular inflammatory infiltrates (hematoxylin and eosin, 20x).

More on Neurosarcoidosis

Overview: Neurosarcoidosis
Differential Diagnoses & Workup: Neurosarcoidosis
Treatment & Medication: Neurosarcoidosis
Follow-up: Neurosarcoidosis
Multimedia: Neurosarcoidosis
References
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Further Reading

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Keywords

sarcoidosis of nervous system, sarcoidosis, granuloma, central nervous system, lymphocytes, mononuclear phagocytes, iritis, anterior vitreitis

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Contributor Information and Disclosures

Author

Gabriel Bucurescu, MD, MS, Staff Neurologist, Neurology Service, Philadelphia Veterans Affairs Medical Center
Gabriel Bucurescu, MD, MS is a member of the following medical societies: American Academy of Neurology, American Clinical Neurophysiology Society, and American Epilepsy Society
Disclosure: Nothing to disclose.

Coauthor(s)

Amer Suleman, MD, Consultant in Electrophysiology and Cardiovascular Medicine, Department of Internal Medicine, Division of Cardiology, Medical City Dallas Hospital
Amer Suleman, MD is a member of the following medical societies: American College of Physicians, American Heart Association, American Institute of Stress, American Society of Hypertension, Federation of American Societies for Experimental Biology, Royal Society of Medicine, and Society of Cardiac Angiography and Interventions
Disclosure: Nothing to disclose.

Medical Editor

Amy A Pruitt, MD, Associate Professor of Neurology, University of Pennsylvania; Attending Neurologist, Hospital of the University of Pennsylvania
Amy A Pruitt, MD is a member of the following medical societies: American Academy of Neurology
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Florian P Thomas, MD, MA, PhD, Drmed, Director, Spinal Cord Injury Unit, St Louis Veterans Affairs Medical Center; Director, National MS Society Multiple Sclerosis Center; Professor, Department of Neurology and Psychiatry, Associate Professor, Institute for Molecular Virology, and Department of Molecular Microbiology and Immunology, St Louis University
Florian P Thomas, MD, MA, PhD, Drmed is a member of the following medical societies: American Academy of Neurology, American Paraplegia Society, and National Multiple Sclerosis Society
Disclosure: Nothing to disclose.

CME Editor

Selim R Benbadis, MD, Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, University of South Florida School of Medicine, Tampa General Hospital
Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, and American Medical Association
Disclosure: Nothing to disclose.

Chief Editor

Nicholas Y Lorenzo, MD, Chief Editor, eMedicine Neurology; Consulting Staff, Neurology Specialists and Consultants
Nicholas Y Lorenzo, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Neurology
Disclosure: Nothing to disclose.

 
 
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