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Neurologic sarcoidosis

Neurologic sarcoidosis
Literature review current through: Jan 2024.
This topic last updated: Feb 11, 2020.

INTRODUCTION — 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 [7]. (See "Clinical manifestations and diagnosis of sarcoidosis" and "Pathology and pathogenesis of sarcoidosis".)

CLINICAL FEATURES — Any portion of the central or peripheral nervous system can be affected by sarcoidosis. Patients presenting with neurosarcoidosis may have no systemic features of the disease. In one case series, nonneurologic symptoms were present in less than one-fourth of patients and were most commonly anterior uveitis, cough and dyspnea, renal impairment, rash, and polyarthritis [6].

Cranial mononeuropathy — Peripheral facial nerve palsy develops in 25 to 50 percent of patients with neurosarcoidosis [2,6,8]. The facial nerve palsy can be unilateral or bilateral (simultaneous or sequential) and recurrent. Optic neuropathy [9] and cranial nerve VIII dysfunction can lead to intermittent or progressive visual, auditory, or vestibular dysfunction [10]. (See "Optic neuropathies", section on 'Sarcoidosis'.)

Hypothalamic or pituitary involvement — 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 [6,11]. (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 [12] (see "Hypercalcemia in granulomatous diseases"). Thus, patients with sarcoidosis and polyuria may require a water restriction test to establish the correct diagnosis. (See "Evaluation of patients with polyuria".)

Brain and spinal cord involvement

Granulomatous inflammation in a perivascular distribution can involve the brain and produce focal or generalized seizures, or a restricted or generalized encephalopathy/vasculopathy [6,8]. Patients can present with cognitive or behavioral problems and/or focal neurologic deficits referable to the anatomic area involved. In rare cases, this manifests as a focal cerebral infarction [13].

A myelopathy or radiculopathy can occur if granulomatous inflammation affects the spinal cord [6,8,14,15]. The lesions are typically perivascular, can be extramedullary or intramedullary, and can involve the cauda equina.

Communicating or noncommunicating hydrocephalus may develop acutely or subacutely. Asymptomatic ventricular enlargement may be incidentally detected by imaging studies [16]. Sudden death can rarely result from acute obstruction to cerebrospinal fluid (CSF) flow, and neurologic deterioration can follow a lumbar puncture (LP).

Meningeal involvement can take the form of either an acute aseptic meningitis or a chronic meningitis. Meningeal mass lesions also can develop.

Peripheral neuropathy — Peripheral neuropathic presentations include a mononeuropathy, mononeuritis multiplex, and generalized sensory, sensorimotor, and motor polyneuropathies [17]. The symptoms can be acute, subacute, or chronic; electromyography usually reveals an axonal neuropathy. In addition, an acute generalized demyelinating motor neuropathy similar to the Guillain-Barré syndrome also has been described [18] (see "Guillain-Barré syndrome in adults: Treatment and prognosis") Perhaps the most unrecognized neuropathy presentation is that of a small fiber disorder manifesting as impaired perception of distal limb pain and temperature, often associated with paresthesias and hyperesthesia/dysesthesia, and autonomic dysfunction. When severe, symptoms and signs can extend to the torso [19].

Carpal tunnel syndrome appears to be more common among patients with sarcoidosis than the general population [20-22]. (See "Carpal tunnel syndrome: Pathophysiology and risk factors".)

Myopathy — Muscle involvement includes asymptomatic microscopic nodules, isolated palpable nodules, an acute or chronic proximal myopathy, and muscle atrophy [23].

DIAGNOSTIC APPROACH — Neurosarcoidosis is a diagnostic consideration in patients with known sarcoidosis who develop neurologic findings, although an intercurrent infection or malignancy must be excluded. Patients who develop a neurologic illness consistent with neurosarcoidosis but who are not known to have sarcoidosis present a diagnostic challenge.

Differential diagnosis — The time course and details of presentation sometimes assist in differentiating neurosarcoidosis from other diseases, but many illnesses can present in a manner indistinguishable from neurosarcoidosis. Some representative situations include:

Cranial nerve dysfunction – A patient with a peripheral facial nerve palsy may have an idiopathic Bell's palsy or a facial neuropathy associated with Lyme disease (see "Clinical manifestations of Lyme disease in adults", section on 'Neurologic manifestations'). An optic neuropathy may be indistinguishable from a multiple sclerosis-associated optic neuritis or neuromyelitis optica. Chronic infections, such as tuberculosis, and carcinomatous or lymphomatous meningitis should be considered in patients with multiple cranial nerve palsies.

Parenchymal lesions – Parenchymal granulomatous masses can masquerade as an astrocytoma or other primary or metastatic brain tumors. Multiple small white matter areas of increased T2 signal on magnetic resonance imaging (MRI) are a nonspecific finding and can be associated with multiple sclerosis or other inflammatory disorders. Spinal cord inflammation should prompt an evaluation for neuromyelitis optica.

Ten cases of progressive multifocal leukoencephalopathy complicating sarcoidosis were described in one report; only eight had received immunosuppressive therapy, usually glucocorticoids alone [24]. Symptoms and MRI findings were mistakenly attributed to neurosarcoidosis in eight patients, perhaps contributing to the high case-fatality rate of 57 percent. (See "Progressive multifocal leukoencephalopathy (PML): Epidemiology, clinical manifestations, and diagnosis".)

Encephalopathy – The encephalopathy/vasculopathy of sarcoidosis can be difficult to distinguish from syphilis or central nervous system (CNS) vasculitis (see "Primary angiitis of the central nervous system in adults"). Other rare, recently recognized, diagnostic considerations include autoimmune astrocytopathy [25] and common variable immunodeficiency [26].

Meningeal disease – Sarcoidosis-associated aseptic meningitis is indistinguishable from that caused by viral infections, including HIV, or by tuberculosis or syphilis. A granulomatous meningeal mass may look like a meningioma on imaging studies. Immunoglobulin G4 (IgG4) pachymeningitis is a diagnostic consideration if there is prominent dural enhancement [27].

Peripheral neuropathy – Other causes of neuropathy need to be considered depending upon the type of neuropathy present. Acquired etiologies of neuropathy include toxin exposure, metabolic abnormalities, and inflammatory disorders. Patients often have diabetic neuropathy from glucocorticoid-induced hyperglycemia.

Muscle weakness – Polymyositis and other causes of acquired muscle weakness need to be considered if a myopathic process is identified. (See "Approach to the patient with muscle weakness".)

With the passage of time and with observation of the clinical course, some diagnostic considerations become more or less tenable. As an example, an immunosuppressed patient who remains relatively well over one to two years is unlikely to be suffering from an infection or malignancy. If deterioration occurs in conjunction with glucocorticoid therapy, complications of chronic glucocorticoid use, such as steroid-induced diabetes mellitus, myopathy, or epidural lipomatosis, may be contributing to the patient's decline. Opportunistic infections, such as cryptococcal meningitis or progressive multifocal leukoencephalopathy, can also occur in the immunosuppressed individual (see "Clinical manifestations and diagnosis of Cryptococcus neoformans meningoencephalitis in patients without HIV"). If deterioration in disease occurs after a period of clinical stability, an intercurrent problem should be considered initially, rather than an exacerbation of sarcoidosis.

Clinical evaluation — If neurosarcoidosis is suspected, the patient should be evaluated for evidence of extraneural disease because obtaining nerve tissue for diagnostic evaluation is often difficult. Glucocorticoids can eliminate evidence of systemic inflammation, and the diagnostic evaluation should be pursued in a rapid fashion while withholding immunosuppressive therapy unless severe illness mandates its use.

The search for extraneural sarcoidosis should include a thorough evaluation of the skin, lymph nodes, and lungs (see "Clinical manifestations and diagnosis of sarcoidosis"). Other tests that may be useful are:

Ophthalmologic examination.

Conjunctival biopsy has a low yield and is not recommended for the routine evaluation of patients for neurosarcoidosis [28].

Endoscopic nasal and sinus examination.

A chest x-ray or computed tomographic scan of the chest to look for hilar adenopathy or parenchymal changes consistent with pulmonary sarcoidosis. Positive findings suggestive of sarcoidosis on chest imaging have been reported in 24 to 68 percent of individuals who present with neurologic sarcoidosis [6,8].

Serum angiotensin converting enzyme (ACE) assay, which may be helpful if elevated; however, an elevated serum ACE is not specific for sarcoidosis, and the ACE concentration may not necessarily be elevated if the patient has isolated neurosarcoidosis.

In occasional cases, a magnetic resonance, gallium, or fluorodeoxyglucose positron emission tomographic scan may highlight otherwise occult areas of inflammation that might be amenable to biopsy.

Neurodiagnostic testing — Neurologic evaluation, including consideration of a biopsy site, is especially important if no extraneural tissue is available for biopsy. Unfortunately, no neurodiagnostic tests are pathognomonic for neurosarcoidosis. However, neurodiagnostic tests help define the extent of disease and eliminate other diagnostic considerations, particularly infection and malignancy. Furthermore, a presumptive diagnosis of neurosarcoidosis is often made on the basis of MRI and lumbar puncture (LP) results in the appropriate clinical setting [29].

Neuroimaging — The imaging procedure of choice for CNS disease is contrast-enhanced MRI [8,11,30]. Meningeal or parenchymal enhancement suggests active inflammation with disruption of the blood-brain barrier, and parenchymal or meningeal masses and hydrocephalus are easily identified. Involvement of the optic nerve or other cranial nerves can be documented, and spinal cord and cauda equina inflammation is well seen on targeted images. Multiple parenchymal nodules may actually represent inflammation extending along the Virchow-Robin spaces deep into the brain or spinal cord. In one series of 29 patients with neurosarcoidosis, approximately 40 percent demonstrated meningeal enhancement and/or multiple white matter lesions on MRI [29].

The MRI signs that are suggestive of spinal cord sarcoidosis include dorsal subpial gadolinium enhancement extending >2 vertebral segments and persistent enhancement in spite of >2 months of treatment [31].

Lumbar puncture — Cerebrospinal fluid (CSF) abnormalities occur frequently in patients with CNS sarcoidosis [6,8]:

The CSF opening pressure is elevated in approximately 10 percent of patients, and the total protein is increased in two-thirds of patients, typically up to 250 mg/dL. A pleocytosis is present in approximately 50 percent of patients.

Glucose can be normal or low, as can be seen in CNS infections or carcinomatous meningitis.

A predominantly mononuclear cell pleocytosis is common.

The IgG index can be elevated, and oligoclonal bands may be present.

The CSF ACE concentration is occasionally elevated, but reliable normal values are lacking and CSF ACE may also be increased with infection or carcinomatous meningitis. The CSF ACE concentration can be elevated if the serum ACE level is increased and there is a leaky blood-brain barrier.

CSF soluble interleukin 2 receptor (sIL-2r) levels can be elevated in CNS sarcoidosis; however, this test is not widely available and is not used routinely in the diagnosis of neurosarcoidosis. In one report, levels greater than 150 picograms/mL suggested neurosarcoidosis (61 percent sensitivity and 93 percent specificity) in comparison with healthy controls and other inflammatory diseases, such as multiple sclerosis and CNS vasculitis [32]. sIL-2r levels can be elevated in the setting of infection.

The presence of diffuse leptomeningeal enhancement is associated with an abnormal CSF profile. Patients with active disease tended to have higher CSF cell counts and total protein and hypoglycorrhachia [33].

Caution should be applied in performing an LP in patients with neurosarcoidosis if there is evidence of increased intracranial pressure. A funduscopic examination to exclude papilledema and an MRI to exclude ventricular enlargement, cerebral edema, and a mass lesion should precede LP [34].

Other tests — Other diagnostic tests, such as electroencephalography, evoked potentials, and angiography, are occasionally indicated to further characterize disease involvement or exclude other conditions. Nerve conduction studies (NCS) and electromyography (EMG) can help localize and characterize neuromuscular lesions, depending on the clinical syndrome.

Although false-positive reactions to the Kveim-Siltzbach test are reported to be rare, the test has limited utility and is no longer used [6]. The test is not standardized, it is not universally available, and there are concerns regarding the transmission of HIV and hepatitis. (See "Pathology and pathogenesis of sarcoidosis".)

Biopsy — If the diagnosis remains in doubt, meningeal, brain, or spinal cord biopsy is occasionally indicated. Extraneural tissue biopsy from other clinically affected organs is generally preferable when possible, as it is less risky; skin, lymph node, and lung (transbronchial) biopsies can be of high yield [6,8]. Muscle and peripheral nerve biopsy, including an epidermal biopsy with quantitative nerve terminal analysis and sweat gland innervation to document small fiber sensory neuropathy [35], can all be easily performed for the appropriate syndrome.

Biopsy to establish the diagnosis, rather than empiric therapy, should be considered if there is no defined systemic disease. Biopsy, in an attempt to uncover an alternative neurologic diagnosis, should also be considered for patients with known systemic sarcoidosis and neurologic disease who are progressively deteriorating despite therapy [36].

TREATMENT — There have been no randomized, double-blind, placebo-controlled treatment trials for neurosarcoidosis, but there is a consensus that these patients should be treated with glucocorticoids [37]. Treatment strategies with alternative agents have also been proposed (algorithm 1). Sarcoidosis is typically a systemic disease, and treatment should address the burden of disease in all involved organs.

Glucocorticoids — Glucocorticoids are the first-line agents for the treatment of neurosarcoidosis, and the dose and duration of therapy should be dictated by disease severity and response to therapy (see "Treatment of pulmonary sarcoidosis: Initial approach"). Different regimens are generally utilized depending upon the site of neurologic involvement:

Patients with a peripheral facial nerve palsy or aseptic meningitis are often treated with prednisone 0.5 mg/kg per day for two weeks, and for a slightly longer duration by some physicians

Patients with a myopathy or neuropathy are usually treated with prednisone 0.5 mg/kg per day for four weeks and their response assessed

A meningeal or parenchymal mass lesion, encephalopathy/vasculopathy, or symptomatic hydrocephalus often requires prednisone 1 to 1.5 mg/kg per day for four weeks before any benefit is appreciated

Severely incapacitated or rapidly deteriorating patients may respond to intravenous methylprednisolone 20 mg/kg per day for three days followed by prednisone 1 to 1.5 mg/kg per day for two to four weeks

A slow prednisone taper should be considered in patients who are severely compromised or for whom a chronic course is likely. One useful approach is to allow the patient to stabilize or improve with four weeks of treatment and then to decrease the prednisone dose by 5 mg every two weeks as tolerated by symptoms. Exacerbations are most common when a prednisone dose of 10 mg/day is approached; thus, the dose should be decreased by 1 mg decrements every one to two weeks when the dose is near this level.

Acute deterioration is unusual if glucocorticoids are tapered in this fashion and patients are closely monitored. If the patient's symptoms recur, the prednisone dose should be doubled if the deterioration occurred at a dose of prednisone above 10 mg/day, or increased to 10 to 20 mg/day if a relapse occurred at lower doses.

Frequent clinical evaluation and periodic assessment of the extent of magnetic resonance imaging (MRI) enhancement (if enhancement was present on pretreatment scans) are generally helpful as glucocorticoids are weaned; monitoring of nerve conduction velocities and the electromyogram (EMG) is occasionally useful. By contrast, titrating therapy to normalize cerebrospinal fluid (CSF) parameters is not recommended, because excessive immunosuppression frequently results from this practice.

Other immunomodulatory therapies — Patients who deteriorate in spite of aggressive glucocorticoid treatment, who cannot tolerate glucocorticoids, or who have a primary contraindication to glucocorticoid treatment may benefit from alternative therapies [37-39]. Expert opinion suggests that alternative therapies be considered early in the course of treatment for patients on high-dose glucocorticoid treatment and with manifestations likely to require prolonged treatment such as those with parenchymal inflammation, hydrocephalus, or optic neuropathy. There have been no prospective studies comparing various alternative treatments with one another in patients with neurosarcoidosis. A decision about the specific agent should be based upon ease of use, cost, and the desire to avoid the complications of a particular drug. There is little rigorous evidence that use of an alternative agent will result in a better functional clinical outcome than "optimal" glucocorticoid therapy, although 10 to 30 percent of patients improve to a greater extent than with glucocorticoid monotherapy [38,39]. Many patients treated with alternative agents respond most favorably if they are maintained on a modest glucocorticoid regimen (prednisone 10 to 20 mg/day). (See "Treatment of pulmonary sarcoidosis refractory to initial therapy".)

Mycophenolate mofetil, azathioprine, methotrexate, cyclophosphamide, and leflunomide are immunosuppressive agents that have been used to treat neurosarcoidosis [6,39-44]. In one small case series, mycophenolate mofetil was effective for treating disease affecting the central nervous system (CNS) but not sarcoid myopathy [45]. A retrospective multicenter study compared methotrexate and mycophenolate mofetil in preventing a relapse in patients with neurosarcoidosis [46]. Methotrexate treatment was associated with 0.2 relapses per year whereas mycophenolate mofetil was associated with 0.6 relapses per year. Adverse effects were more common with methotrexate than with mycophenolate mofetil. Dosing of azathioprine and cyclophosphamide should be targeted to achieve hematologic endpoints. We recommend lowering the total white blood cell count to approximately 3500 or the lymphocyte count to 1000 per mm3. Rituximab has been observed to be beneficial in refractory patients [47]; this author has observed benefit in several patients. Patient response to any specific drug cannot be predicted, and one should try two or three agents before concluding that the patient's disease is refractory.

Infliximab is a chimeric human-murine antihuman antibody that specifically blocks the effect of tumor necrosis factor-alpha (TNF-alpha). Observational studies suggest that infliximab may be useful in selected patients with pulmonary and extrapulmonary sarcoidosis refractory to glucocorticoid therapy [48-53]. In one series of seven patients with glucocorticoid-refractory neurosarcoidosis, treatment with infliximab (with mycophenolate mofetil in six patients) was associated with symptom relief, regression of neurologic deficits, and a decrease in disease activity on MRI [54]. Another series reported stabilization and improvement in four patients with CNS manifestations of neurosarcoidosis [55]. A retrospective multicenter study of 66 patients with CNS sarcoidosis treated with infliximab for a median of 1.5 years found a beneficial MRI treatment response in 82.1 percent of patients with imaging follow-up. Clinical improvement was evident in 77.3 percent of patients. In 16 patients in remission when infliximab was discontinued, a recurrence developed in nine (56 percent) [56]. Use of infliximab requires an intravenous infusion (5 mg/kg of ideal body weight) initially, and periodically thereafter as the clinical course is monitored. Adalimumab is an injectable TNF-alpha antagonist that may be efficacious in the treatment of small fiber neuropathy [57,58]. Intravenous immunoglobulin is another option for the treatment of small fiber neuropathy [59]. (See "Treatment of pulmonary sarcoidosis refractory to initial therapy".)

Surgical considerations — Resection of a CNS mass lesion is rarely indicated, and patients may deteriorate following attempted resection of a mass. If biopsy of a mass lesion is consistent with sarcoidosis, resection usually should be deferred while appropriate medical management is pursued. If a mass lesion persists or enlarges despite "optimal" immunosuppressive therapy, resection may need to be considered.

A ventricular drain can be life-saving in patients with acute hydrocephalus [6]. Placement of a ventriculoperitoneal shunt is indicated for symptomatic hydrocephalus despite the fact that the presence of a foreign object in an immunocompromised patient predisposes to infection. Immunosuppressive therapy should continue immediately following shunt placement to treat the underlying inflammatory process. Inflammation due to neurosarcoidosis often leads to shunt obstruction, necessitating multiple shunt revisions.

Radiation therapy — Cranial or spinal irradiation has been used for refractory disease and should be considered if patients fail glucocorticoid therapy and trials of at least two alternative agents [60]. The modality has also occasionally been required for patients with acute, life-threatening disease. Immunosuppression is generally continued during radiation therapy, albeit at less intense levels.

General measures — Endocrinologic deficiencies should be corrected [11]. Hypothalamic hypothyroidism should be excluded if a patient has CNS disease beyond a single cranial nerve deficit. This requires measurement of the T4 concentration, since serum thyrotropin (TSH) concentrations may be normal or low (see "Diagnosis of and screening for hypothyroidism in nonpregnant adults"). Testosterone deficiency is often clinically silent and should be sought in patients with symptoms or other signs of hypothalamic or pituitary disease. Treatment of an otherwise occult testosterone deficiency may help preserve muscle and bone mass.

Patients who require prolonged glucocorticoid therapy may benefit from early dietary counseling and an exercise program to mitigate weight gain and debilitation. Intervention to prevent excessive bone loss is appropriate. (See "Prevention and treatment of glucocorticoid-induced osteoporosis".)

PROGNOSIS — Patients with neurosarcoidosis can have a monophasic illness (approximately two-thirds of patients), a relapsing-remitting course, or progressive disease punctuated by episodic deteriorations [6,61,62]. Historically, approximately 10 percent of patients die as a direct result of the inflammatory process or its treatment; current management strategies have substantially improved patient survival. These high-risk patients typically have central nervous system (CNS) parenchymal disease or hydrocephalus and are often profoundly immunocompromised due to treatment. Patients with sarcoidosis are at risk for cancer, particularly lymphoma, by virtue of the disease or treatment with immunosuppressive drugs other than glucocorticoids.

The long-term course of neurosarcoidosis has not been clearly defined. Nevertheless, some generalizations are possible based upon observations of treated individuals:

Patients with a peripheral facial nerve palsy tend to improve over two to four weeks. Most other cranial mononeuropathies follow a similar course [8].

Optic neuropathy can improve over several weeks, but some patients have a progressive course ending in blindness [8].

Aseptic meningitis usually resolves over several weeks, although an asymptomatic chronic pleocytosis can persist.

Meningeal or parenchymal mass lesions often exhibit a prolonged course, although some mass lesions resolve over time.

Endocrinopathies rarely improve with immunosuppression; as a result, chronic hormonal replacement therapy is usually necessary.

Hypothalamic vegetative symptoms can respond to treatment but rarely resolve spontaneously.

The encephalopathy/vasculopathy of sarcoidosis is typically progressive albeit with periods of improvement and deterioration.

Seizure control is usually not difficult as long as the underlying inflammatory process is controlled [63].

Ventricular enlargement can be asymptomatic or can cause acute or chronic deterioration.

Peripheral neuropathic and myopathic illness tends to be chronic and progressive, although remissions are possible.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Sarcoidosis".)

SUMMARY AND RECOMMENDATIONS

Neurologic complications potentially affecting any portion of the central or peripheral nervous system occur in approximately 5 to 10 percent of patients with sarcoidosis and can be the presenting feature. Common syndromes include a cranial mononeuropathy, neuroendocrine dysfunction, a focal or multifocal encephalopathy, myelopathy, hydrocephalus, aseptic meningitis, peripheral neuropathy, or myopathy. (See 'Clinical features' above.)

Diagnostic evaluation requires distinguishing neurosarcoidosis from a variety of other inflammatory, neoplastic, and infectious conditions. (See 'Differential diagnosis' above.)

A thorough evaluation for systemic sarcoidosis (eg, chest imaging, positron emission tomography scan) can expedite the evaluation by providing tissue that is accessible for biopsy. In the absence of systemic sarcoidosis, testing that may be helpful includes magnetic resonance imaging (MRI) of the affected area, cerebrospinal fluid (CSF) evaluation (with expected findings described above), and serum angiotensin converting enzyme (ACE) level. None of these tests have perfect sensitivity and specificity. (See 'Clinical evaluation' above and 'Neurodiagnostic testing' above.)

Biopsy should be considered in all patients in whom diagnosis remains in doubt, as treatment is prolonged and associated with complications. (See 'Biopsy' above.)

We suggest glucocorticoid therapy as the first treatment in a patient with neurosarcoidosis (Grade 2B). The dose and duration are determined by the severity of the illness and treatment response, with some suggested guidelines outlined above. (See 'Glucocorticoids' above.)

Patients who deteriorate in spite of aggressive glucocorticoid treatment, who cannot tolerate glucocorticoids, who have a primary contraindication to glucocorticoid treatment, or who are predicted to have chronic, aggressive disease may benefit from alternative therapies. Benefits have been observed with mycophenolate mofetil, azathioprine, methotrexate, cyclophosphamide, infliximab, or adalimumab, to mention a few select drugs. (See 'Other immunomodulatory therapies' above.)

Radiation can be attempted in patients with central nervous system (CNS) disease refractory to medical treatment. (See 'Radiation therapy' above.)

Patients with neurosarcoidosis can have a monophasic illness (approximately two-thirds of patients), a relapsing-remitting course, or progressive disease punctuated by episodic deteriorations. (See 'Prognosis' above.)

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Topic 4834 Version 12.0

References

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