eMedicine Specialties > Neurology > Inflammatory and Demyelinating Diseases
Neurosarcoidosis: Treatment & Medication
Updated: Jul 29, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Medical Care
Neurosarcoidosis has no known cure. Treatment alleviates symptoms that are severe or progressive. The disease can follow a monophasic, relapsing, or chronic course.
- Immunosuppression is the principal method of controlling the disease, and corticosteroids are the cornerstone of therapy. Spontaneous remission has been observed, but long-term therapy often is required. In cases of exacerbation, intravenous pulsed methylprednisolone followed by oral taper may be necessary. Relapses may respond poorly, however, requiring chronic steroid therapy.
- A retrospective report of 26 patients with refractory neurosarcoidosis monitored for a mean of 81.2 months demonstrated steroid sparing in 10 of 26 patients and clinical improvement in 15 of 26 patients treated with alternative medications, including azathioprine (AZA; 14 courses), cyclophosphamide (CYA; 14 courses), cyclosporine (CTX; 3 courses), chloroquine (CHL; 1 course), methotrexate (MTX; 3 courses), and irradiation (3 courses). Positive response to a course of therapy was recorded in 8 of 14 patients who received AZA, 11 of 14 who received CYA, 2 of 3 who received CTX, 3 of 3 treated with irradiation, 1 of 3 who received MTX, and in the only patient given CHL. On the basis of this experience, the authors believed that AZA and CYA should be used as the alternative agents of choice in corticosteroid-resistant neurosarcoidosis and that MTX should be reserved for patients who either do not respond to or are intolerant of those alternative agents. AZA has been used as an alternative to corticosteroids when the adverse effects are intolerable, but reports in the literature are sparse.
- CTX has been reported to lead to improvement in some patients. It has been successful in controlling the disease in patients undergoing transplantation. In one series, the response rate was 75%, but the patients had relapses once the therapy was stopped.
- MTX can be used as a steroid-sparing agent. It is generally well tolerated, with minimal adverse effects except for potential liver toxicity. Thus, patients on long-term dosing need to have careful monitoring of liver function, including liver biopsies. In one study, the remission rate for patients on MTX was 61%.
- CYA use has been more limited. Short-term therapy has not been associated with good response. Therapy lasting at least several months is needed to determine efficacy. In one study, intermittent intravenous CYA was associated with better compliance and lower risk of malignancy, especially bladder malignancy; however, bladder toxic effects did occur. Patients showed improvement in the course of the disease.
- CHL and hydroxychloroquine also have been used. In a study by Sharma et al, CHL and hydroxychloroquine were effective in controlling neurological sarcoidosis in those patients who did not respond to corticosteroids or developed severe adverse effects. Ten of 12 patients had their symptoms stabilized or controlled.
- Recently, a single case was reported of treatment with antimetabolite cladribine (2-chlorodeoxyadenosine). Used in only one patient with aggressive suprasellar disease, it resulted in loss of vision. Results were encouraging, however, and this antimetabolite could be considered in cases refractory to other agents.
- Several recent cases of refractory neurosarcoidosis treated with thalidomide, a tumor necrosis factor-α (TNF-α) inhibitor, have been reported. Treatment ranged from 4 weeks to 6 months.5
- One case report of optic neuropathy treated with infliximab, a TNF-α antagonist, was recently reported in the literature.
- Radiation: Some patients clearly demonstrate symptomatic benefits from low-dose radiation if the brain is involved. Since the adverse effects of low-dose cranial irradiation are minimal, using radiation therapy may be prudent for patients whose disease is refractory to steroids or who have adverse effects to high-dose steroids.
- Neuropathy and myopathy: Patients may require extended steroid therapy. The prognosis with peripheral neuropathy is more favorable than with central nervous system involvement.
- Dementia: Treatment should comprise safety intervention and assistance.
- Hypopituitarism: Patients require incorporation of hormone replacement therapy.
- Psychosis: Risperidone and other antipsychotic drugs have been used for the treatment of psychosis associated with neurosarcoidosis.
Surgical Care
Removal of the space-occupying lesions in the brain has little or no benefit and should be attempted only in extreme cases. Hydrocephalus may require shunting.
Consultations
- Rheumatologist
- Endocrinologist
- Neurosurgeon
- Pulmonologist
Diet
No special dietary preferences/recommendations are given.
Activity
- Physical therapy is of some benefit for patients with involvement of the feet.
- Specific activity recommendations should be given on a case-by-case basis to decrease predilection to falls.
Medication
Immunosuppression with corticosteroids is the mainstay of treatment.
Corticosteroids
These agents have anti-inflammatory properties and cause profound and varied metabolic effects. Corticosteroids modify the body's immune response to diverse stimuli.
Prednisone (Deltasone, Orasone, Meticorten)
Immunosuppressant for treatment of autoimmune disorders; may decrease inflammation by reversing increased capillary permeability and suppressing PMN activity. Stabilizes lysosomal membranes and suppresses lymphocytes and antibody production. Helps in general treatment of sarcoidosis; use lowest possible maintenance dose.
Adult
60 mg PO qd
Pediatric
1 mg/kg PO qd
Estrogens may decrease clearance; concurrent digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics
Documented hypersensitivity; viral infection; peptic ulcer disease; hepatic dysfunction; connective tissue infections; fungal or tubercular skin infections; GI disease
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Abrupt discontinuation may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections may occur
Immunosuppressant agents
These agents inhibit immune cell growth and proliferation, decreasing immune system activity.
Thalidomide (Thalomid)
Immunomodulatory agent that acts to inhibit production of TNF-alpha. TNF-alpha is an important mediator in CNS inflammation. It enhances TNF-alpha mRNA degradation. It inhibits the upregulation of IL-6 and downregulates nuclear factor-kB activity. Both of these 2 molecules are elevated during the CNS inflammatory process in neurosarcoidosis.
Adult
50 mg po bid, titrated up to 650 mg/d in 2 divided doses
Pediatric
50 mg po bid
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
Cyclophosphamide (Cytoxan, Neosar)
Antimitotic agent mainly used as steroid-sparing therapy.
Adult
1-5 mg/kg/d IV
Pediatric
2.5-3 mg/kg/d IV for less than 60-90 d (administration for longer periods increases possibility of sterility)
Allopurinol may increase risk of bleeding or infection and enhance myelosuppressive effects; may potentiate doxorubicin-induced cardiotoxicity; may reduce digoxin serum levels and antimicrobial effects of quinolones; chloramphenicol may increase half-life while decreasing metabolite concentrations; may increase effect of anticoagulants; high doses of phenobarbital may increase rate of metabolism and leukopenic activity; thiazide diuretics may prolong CYA-induced leukopenia and neuromuscular blockade by inhibiting cholinesterase activity
Documented hypersensitivity; severely depressed bone marrow function
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Regularly examine hematologic profile (particularly neutrophils and platelets) to monitor for hematopoietic suppression; regularly examine urine for RBCs, which may precede hemorrhagic cystitis
Antimalarials
Chloroquine phosphate and hydroxychloroquine sulfate have been used in the treatment of patients with neurosarcoidosis who either do not respond to corticosteroid therapy or develop unacceptable side effects. In a sarcoidosis clinic at a university teaching hospital, 12 patients with biopsy-proven sarcoidosis, 6 women and 6 men with neurologic involvement aged 20-49 years were administered antimalarials.
Patients had regular clinical evaluation, determination of serum and CSF ACE levels, CT scan or MRI, chest radiography, lung function testing, and slit-lamp examination of the eyes.
Chloroquine or hydroxychloroquine either stabilized or controlled neurologic symptoms in 10 of 12 patients; 2 patients did not respond. CSF abnormalities, including lymphocytosis, were seen in 3 patients.
Chloroquine phosphate (Aralen)
Anti-inflammatory activity by suppressing lymphocyte transformation and may have photoprotective effect.
Adult
250 mg PO bid
Pediatric
Not recommended
Cimetidine may increase serum levels (possibly other 4-aminoquinolones); magnesium trisilicate may decrease absorption of 4-aminoquinolones
Documented hypersensitivity; psoriasis; retinal and visual field changes attributable to 4-aminoquinolones
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in hepatic disease, G-6-PD deficiency, psoriasis, porphyria; not recommended for long-term use in children; perform periodic ophthalmologic examinations; test for muscle weakness; retinopathy, tinnitus, nerve deafness, skin eruption, headache, anorexia, nausea, vomiting, and diarrhea may occur
Hydroxychloroquine (Plaquenil)
Inhibits chemotaxis of eosinophils and locomotion of neutrophils, and impairs complement-dependent antigen-antibody reactions.
Hydroxychloroquine sulfate 200 mg equivalent to 155 mg hydroxychloroquine base and 250 mg chloroquine phosphate.
Adult
200 mg PO bid
Pediatric
Not established
Cimetidine increases serum levels; magnesium trisilicate may decrease absorption
Documented hypersensitivity; psoriasis; retinal and visual field changes attributable to 4-aminoquinolones
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in hepatic disease, G-6-PD deficiency, psoriasis, and porphyria; not recommended for long term in children; perform periodic (6 mo) ophthalmologic examinations; test periodically for muscle weakness
Immunomodulators
These agents can change the immune system or block cytokine effects.
Infliximab (Remicade)
Inhibits the release of tumor necrosis factor alpha (TNA), which is released in high concentrations by alveolar macrophages in active sarcoidosis. The levels of TNA were noted to decrease with corticosteroid and methotrexate treatment, and studies of substances that reduce TNA or block its effect have shown improvement in refractory cases.
Adult
3 mg/kg once in week 1, week 3, and week 5; then once q6wk, IV
Pediatric
Not established
Should be combined with MTX
Patients with heart failure
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Increases rate of tuberculosis; screening is indicated before treatment
More on Neurosarcoidosis |
| Overview: Neurosarcoidosis |
| Differential Diagnoses & Workup: Neurosarcoidosis |
 Treatment & Medication: Neurosarcoidosis |
| Follow-up: Neurosarcoidosis |
| Multimedia: Neurosarcoidosis |
| References |
| « Previous Page | Next Page » |
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Further Reading
Keywords
sarcoidosis of nervous system, sarcoidosis, granuloma, central nervous system, lymphocytes, mononuclear phagocytes, iritis, anterior vitreitis
