Neurosarcoidosis
Overview
Sarcoidosis is a multisystem disease process whose pathogenesis involves formation of an inflammatory lesion known as a granuloma. Most patients with sarcoidosis do not have any symptoms; the disease often is detected on routine chest radiograph. Symptoms, if present, include cough, shortness of breath, and arthritis. The lungs are affected most frequently, but the eyes, nervous system, heart, kidneys, bones, and joints also may be affected. Sarcoidosis is a disease of unknown etiology. Involvement of the central nervous system is referred to as neurosarcoidosis. Neurosarcoidosis is an uncommon but severe, sometimes life-threatening, manifestation of sarcoidosis. It generally occurs only if the disease has had substantial systemic involvement, and signs of neurologic involvement usually are seen in patients known to have active disease. Strictly neurologic forms are seen in fewer than 10% of patients.
Symptoms
The list of signs and symptoms mentioned in various sources for Neurosarcoidosis includes the 31 symptoms listed below: * Weak facial muscles * Impaired vision * Impaired hearing * Headache * Hallucination * Seizures * Memory loss * Agitation * Memory loss * Mood changes * Dysphagia * Psychiatric problems * Adrenal insufficiency - if hypothalamus involved * Irregular menstruation - if hypothalamus involved * Central diabetes insipidus - if hypothalamus involved * Hypothyroidism - if hypothalamus involved * Increased urination - if pituitary gland involved * Excessive thirst - if pituitary gland involved * Irregular menstruation - if pituitary gland involved * Fatigue - if pituitary gland involved * Dementia * Confusion * Loss of sense of smell * Loss of sense of taste * Dizziness * Impaired speech * Behavioral changes * Loss of sensation * Abnormal sensations * Loss of movement * Weakness
Causes
The causes of sarcoidosis are not clear. The present evidence suggests that active sarcoidosis results from an exaggerated cellular immune response to either foreign or self-antigens. T-helper cells proliferate, resulting in an exaggerated response. The T-helper lymphocytes undergo differentiation to a Th1-type cell under the influence of interleukin-4 (IL-4) and co-stimulator CD28. The Th1 cell induces IL-2 and interferon gamma (IFN-gamma) on the macrophages, followed by a cascade of chemotactic factors that promote formation of granuloma. IFN-gamma increases the expression of major histocompatability class (MHC) class II on macrophages, and activated macrophages receptors carry an Fc receptor of immunoglobulin G (IgG) which potentiates their phagocytosis function. Tissue destruction results and granuloma formation is thought to be a secondary process. Several hypotheses have been proposed to explain the mechanism: (1) a persistent antigen (either foreign or self) triggers the T-helper cell response; (2) response of the suppressor arm of the immune response is inadequate, preventing T-helper cells from shutting down; or (3) a possible inherited or acquired (genetic) difference in response genes leads to the exaggerated response. In addition to the exaggerated cellular immune response, active sarcoid shows hyperglobulinemia, with antibodies against several infectious agents (eg, Mycobacterium tuberculosis) as well as IgM anti–T-cell antibodies. However, no evidence exists to suggest that these antibodies play a role in disease pathogenesis; rather, their presence seems to be due to a nonspecific polyclonal stimulation of B cells by activated T cells at the site
Diagnosis
The diagnosis of neurosarcoidosis often is difficult. Definitive diagnosis can only be made by biopsy (surgically removing a tissue sample). Because of the risks associated with brain biopsies, they are avoided as much as possible. Other investigations that may be performed in any of the symptoms mentioned above are computed tomography (CT) or magnetic resonance imaging (MRI) of the brain, lumbar puncture, electroencephalography (EEG) and evoked potential (EP) studies. If the diagnosis of sarcoidosis is suspected, typical X-ray or CT appearances of the chest may make the diagnosis more likely; elevations in angiotensin-converting enzyme and calcium in the blood, too, make sarcoidosis more likely. In the past, the Kveim test was used to diagnose sarcoidosis. This now obsolete test had a high (85%) sensitivity, but required spleen tissue of a known sarcoidosis patient, an extract of which was injected into the skin of a suspected case.[1] Only biopsy of suspicious lesions in the brain or elsewhere is considered useful for a definitive diagnosis of neurosarcoid. This would demonstrate granulomas (collections of inflammatory cells) rich in epithelioid cells and surrounded by other immune system cells (e.g plasma cells, mast cells). Biopsy may be performed to distinguish mass lesions from tumours (e.g. gliomas).[1] MRI with gadolinium enhancement is the most useful neuroimaging test. This may show enhancement of the pia mater or white matter lesions that may resemble the lesions seen in multiple sclerosis.[1] Lumbar puncture may demonstrate raised protein level, pleiocytosis (i.e. increased presence of both lymphocytes and neutrophil granulocytes) and oligoclonal bands. Various other tests (e.g. ACE level in CSF) have little added value.
Prognosis
Of the phenomena occurring in neurosarcoid, only facial nerve involvement is known to have a good prognosis and good response to treatment. Long-term treatment is usually necessary for all other phenomena.
Treatment
Neurosarcoidosis, once confirmed, is generally treated with glucocorticoids such as prednisolone. If this is effective, the dose may gradually be reduced (although many patients need to remain on steroids long-term, frequently leading to side-effects such as diabetes or osteoporosis). Methotrexate, hydroxychloroquine, cyclophosphamide, pentoxifylline, thalidomide and infliximab have been reported to be effective in small studies. In patients unresponsive to medical treatment, radiotherapy may be required. If the granulomatous tissue causes obstruction or mass effect, neurosurgical intervention is sometimes necessary. Seizures can be prevented with anticonvulsants, and psychiatric phenomena may be treated with medication usually employed in these situations