Neurosarcoidosis
Neurosarcoidosis refers to sarcoidosis involving the central nervous system. Approximately 5-10% of people with sarcoidosis develop central nervous system involvement. Only 1% of people with sarcoidosis will have neurosarcoidosis alone.
Signs and symptoms
Neurological
Abnormalities of the cranial nerves are present 50-70% of cases. The most common abnormality is involvement of the facial nerve, which may lead to reduced power on one or both sides of the face (65% resp 35% of all cranial nerve cases), followed by reduction in visual perception due to optic nerve involvement. Rarer symptoms are double vision (oculomotor nerve, trochlear nerve or abducens nerve), decreased sensation of the face (trigeminal nerve), hearing loss or vertigo (vestibulocochlear nerve), swallowing problems (glossopharyngeal nerve) and weakness of the shoulder muscles (accessory nerve) or the tongue (hypoglossal nerve). Visual problems may also be the result of papilledema (swelling of the optic disc) due to obstruction by granulomas of the normal cerebrospinal fluid (CSF) circulation.[1]
Seizures (mostly of the tonic-clonic/"grand mal" type) are present in about 15%, and may be the presenting phenomenon in 10%.[1]
Meningitis (inflammation of the lining of the brain) occurs in 3-26% of cases. Symptoms may include headache and nuchal rigidity (being unable to bend the head forward). It may be acute or chronic.[1]
Accumulation of granulomas in particular areas of the brain can lead to abnormalities in the function of that area. For instance, involvement of the internal capsule would lead to weakness in one or two limbs on one side of the body. If the granulomas are large, they can exert a mass effect and cause headache and increase the risk of seizures. Obstruction of the flow of cerebrospinal fluid, too, can cause headaches, visual symptoms (as mentioned above) and other features of raised intracranial pressure and hydrocephalus[1]
Involvement of the spinal cord is rare, but can lead to abnormal sensation or weakness in one or more limbs, or cauda equina symptoms (incontinence to urine or stool, decreased sensation in the buttocks).[1]
Endocrine
Granulomas in the pituitary gland, which produces numerous hormones, is rare but leads to any of the symptoms of hypopituitarism: amenorrhoea (cessation of the menstrual cycle), diabetes insipidus (dehydration due to inability to concentrate the urine), hypothyroidism (decreased activity of the thyroid) or hypocortisolism (deficiency of cortisol).[1]
Mental and other
Psychiatric problems occur in 20% of cases; many different disorders have been reported, e.g. depression and psychosis. Peripheral neuropathy has been reported in up to 15% of cases of neurosarcoidosis.[1]
Other symptoms due to sarcoidosis of other organs may be uveitis (inflammation of the uveal layer in the eye), dyspnoea (shortness of breath), arthralgia (joint pains), lupus pernio (a red skin rash, usually of the face), erythema nodosum (red skin lumps, usually on the shins), and symptoms of liver involvement (jaundice) or heart involvement (heart failure).[1]
Diagnosis
The diagnosis of neurosarcoidosis often is difficult. Definitive diagnosis can only be made by biopsy. Because of the risks associated with brain biopsies, frequently they are not done.
In an individual with known sarcoidosis, the development of suggestive symptoms with collaborative imaging on MRI is often considered enough for diagnosis. The diagnosis is not definitive, in this case, as other conditions may mimic the disease. For instance, cryptococcus is associated with sarcoid patients, even those not on immunosuppressive therapy, and should be a consideration in any person with sarcoidosis who develops neurological symptoms. In addition, some lymphomas cannot be differentiated from sarcoidosis on MRI.
There is no definitive lab test to make the diagnosis, however, several can be helpful. In cerebral spinal fluid, protein concentration is usually elevated, a pleocytosis is present and the glucose may be normal to high. In the CSF, the ACE level is elevated in 50% of neurosarcoid patients and has a specificity greater than 90%. Serum and urine calcium are occasionally elevated.
In individuals found to have brain lesions consistent with sarcoidosis but who have no known systemic involvement, an evaluation for involvement of other organs is warranted. A chest x-ray and possibly a high resolution CT of the lungs should be done as the lungs are most frequently affected by sarcoidosis. In addition, a thorough examination of the skin and lymph nodes should be done. An examination of the eye by an ophthalmologist is also indicated. Any tissue suggestive of sarcoid should be biopsied to help confirm the diagnosis.
If only the brain appears affected, however, a biopsy is not necessarily indicated, depending on the area involved and degree of suspicion. If infection and tumor have been ruled out, the lesions on imaging are suggestive of sarcoid and the symptoms improve on steroids, it may reasonable to make the diagnosis without a biopsy.
Treatment
Because of the rarity of the disease, little evidence exists to guide treatment. High dose steroids are considered the treatment of choice followed by a slow taper. Two thirds of patients will have remission of the disease and not require further treatment.
Recurrent or chronic disease may require long term treatment with steroids which is frequently limited by side effects. In this case, a trial of a non-steroidal immunosuppressive is warranted. Their use has been reported in numerous case studies; however, no randomized controlled studies have been done to show their efficacy. Thalidomide may have a role in treatment as well.