Neurosarcoidosis

Definition

Neurosarcoidosis refers to an autoimmune disorder of unknown cause, which causes deposition of inflammatory lesions called granulomas in the central nervous system .

Description

Sarcoidosis is a multisystem disease of unknown cause. It is thought that the disorder is caused by an inflammatory reaction in the body which forms a lesion called a granuloma. Neurosarcoidosis is characterized by formation of granulomas in the central nervous system. The granulomas consist of inflammatory cells (lymphocytes, mononuclear phagocytes) which function during inflammatory reactions. The disorder is often unrecognized since most patients do not exhibit symptoms. Typically the disease is diagnosed by routine chest x ray. If symptoms are present they usually include respiratory problems (shortness of breath, cough) since the lungs are affected most frequently.

Neurological description

Patients can have a broad range of clinical signs and symptoms that typically could involve mononeuropathy, peripheral neuropathy , or central nervous system involvement. Mononeuropathy problems can include facial nerve palsy, impaired taste and smell, blindness (or other eye problems such as double vision, visual field defects, blurry vision, dry/sore eyes), or speech problems (impaired swollowing or hoarseness). Patients can also develop vertigo, weakness of neck muscles and tongue deviation and atrophy.

Peripheral nerve involvement

Neurosarcoidosis can cause damage to peripheral nerves that can affect motor nerves (responsible for movement of muscles) and sensory nerves (responsible for sensation). Symptoms of sensory loss include loss of sensation and abnormal sensation (numb, painful, tingling sensations) over the thorax (chest) and the areas where stockings and gloves are usually worn. Motor neurosarcoidosis is characterized by weakness that can progress to immobility and joint stiffness.

Central nervous system (CNS) involvement can affect the pituitary gland, cerebellum , or cerebral cortex. The spinal cord is rarely involved. Signs and symptoms of CNS involvement can include polyuria, polydipsia, obesity, impotence, amenorrhea, confusion/amnesia (short and long term memory), meningitis, and seizures (focal seizures).

Demographics

Sarcoid disorders are more prevalent in African Americans, and in the United States there seems to be a variable prevalence within different states. The prevalence is much higher in the southeastern United States among both Caucasian and African Americans. The prevalence is high in Puerto Rico, reaching approximately 175 cases per 100,000 persons. The frequency for neurological involvement for all cases of sarcoid disease is 5%. However, neurological involvement has been reported to occur in up to 5% to 16% of cases. Internationally the incidence of sarcoid varies widely. In Spain the incidence is low (0.04 per 100,000) whereas in Sweden the incidence is high, representing 64 cases per 100,000 persons. Studies reveal the prevalence in London is 27 per 100,000 and 97 per 100,000 among Irish men. In the Caribbean, studies indicate that the prevalence is as high as 200 per 100,000 in men from the West Indies and 13% of individuals from Martinique.

There does not seem to be a racial predilection for the development of sarcoid neuropathy. Sarcoid disease is uncommon in Chinese, Inuits, Southeast Asians, Canadian Indians, New Zealand Maoris and native Japanese. Death from neurosarcoidosis is unusual. About 66% of patients with neurosarcoidosis have self-limited monophasic illness. Approximately 33% have a chronic remitting and relapsing course. Neurosarcoidosis commonly occurs in adults aged 25-50 years. Neurosarcoidosis is not common in children, but if it does occur, it affects children age 9-15 years. The clinical signs in children are different than in adults. When neurosarcoidosis is present in children over the age of eight, there is usually a triad of signs which include arthritis, uveitis, and cutaneous nodules. In children ocular (eye) problems occur in approximately 100% of cases, which typically manifest as iritis and/or anterior vitreitis. For all cases, if the nervous system is involved it usually occurs within two years of disease onset.

Causes and symptoms

The causes of sarcoid disease are not clear. Current evidence suggests that sarcoidosis is due to the abnormal proliferation of a certain cell called a T-helper cell, which functions to help immune cells attack a foreign substance. The abnormal proliferation of T-helper cells is thought to result from an exaggerated response to a foreign substance or to self cells (a condition referred to as autoimmunity, in which for unknown reasons, the body's natural defense cells attack normal cells in organs).

During physical examination patients may exhibit weakness, absence of tendon reflexes, lack of sensation in a stocking and glove distribution, atrophy of muscles, and focal mononueropathies that may affect the cranial nerves (causing problem with hearing, vision, smell, balance, or paralysis of facial muscles). Some patients may develop Heerfordt syndrome characterized by fever, uveitis, swelling of the parotid gland, and facial palsy.

Diagnosis

Blood analysis is essential since patients may have increased erythrocyte sedimentation rate (ESR) or anemia (hypochromic microcytic type). Blood analysis can provide information concerning multiple organs (kidney, liver, blood) and this is important since sarcoidosis is a multisystem disease (affects many different organs in the body). CT and MRI scans are important in assessing neurosarcoidosis. MRI is the imaging tool of choice in cases of neurosarcoidosis, because of the high quality superior images obtained. The presence of a mass or lesion in the CNS can be visualized by MRI images. To confirm the diagnosis it is necessary to take a biopsy of either muscle or nerve tissue. Examination of the tissue specimen with a microscope reveals the characteristic granuloma within tissues.

Treatment team

The effects of neurosarcoidosis can involve several symptoms from different organ systems. The treatment team consists of a neurologist , neurosurgeon, endocrinologist, rheumatologist, and pulmonologist.

Treatment

There is no definitive treatment, but corticosteroids remain the standard treatment. The most commonly used oral corticosteroid is prednisone, which works to decrease inflammatory actions in the body that are responsible for granuloma formation. Doses are usually tapered down. Additionally, patients can be given immunosuppressant agents (e.g., cyclosporine) which can suppress autoimmune responses (which are responsible for granuloma formation). Surgery is rare and reserved for cases that require removal of a mass (space-occupying lesion) in the brain.

Recovery and rehabilitation

Neurosarcoidosis is a slowly chronic disease with a progressive course, which is fatal in about 50% of patients. Follow-up visits with a neurologist every three to six months are advisable. During visits the neurologist will monitor progress and make recommendations.

Clinical trials

There are several studies currently active concerning sarcoidosis. The National Heart, Lung and Blood Institute Drug study are conducting clinical research trials with patients who have lung involvement (pulmonary sarcoidosis). Contact Pauline Barnes, RN (1-877-644-5864) or visit their website: <http://www.sarcoidresearch.org>.

Prognosis

Spontaneous resolution of neurosarcoidosis can occur but it is not common. Many patients with neurosarcoidosis have a slow chronic and progressive course with intermittent exacerbations. Neurosarcoidosis responds to steroid therapy, but long-term outcome of neurologic impairment is unknown.

Special concerns

Sarcoidosis is difficult to diagnose, and sometimes a delay can cause patients to get sicker before proper treatment is initiated. On rare occasions a patient may even die because the diagnosis was not suspected. Caution must be taken to exclude other diseases before a final diagnosis is made. Additionally, before corticosteroid therapy is initiated, the clinician must rule out an infectious cause.

Resources

BOOKS

Goldman, Lee et al. Cecil's Textbook of Medicine 21st ed. Philadelphia: WB. Saunders Company, 2000.

Noble, John., et al eds. Textbook of Primary Care Medicine 3rd ed. St. Louis: Mosby, Inc., 2001.

PERIODICALS

Nikhar, N.K. Sarcoidosis and Neuropathy.

Suleman, Amer. Neurosarcoidosis.

WEBSITES

National Organization for Rare Disorders (NORD). <http://www.rarediseases.org>.

ORGANIZATIONS

Sarcoidosis Research Institute. 3475 Central Avenue, Memphis, TN 38111. (901) 766-6951; Fax: (901) 744-7294. paula@sarcoidosisresearch.org. <http://www.sarcoidosisresearch.org>.

Laith Farid Gulli, M.D.

Nicole Mallory, M.S., PA-C