Sarcoidosis is an autoimmune disease of unknown cause characterized by the formation of noncaseating granulomas. It can affect multiple organ systems, although pulmonary involvement is most common. Ocular and neurologic involvement can be the presenting symptom of sarcoidosis, or can occur in patients with known systemic sarcoidosis. For obvious reasons, evaluation of the patient with known sarcoidosis and neurologic symptoms will differ from that outlined here, which applies to patients presenting with neurologic or ocular symptoms but without a prior sarcoidosis diagnosis.
Patients may present with decreased vision and floaters, resulting from granulomatous inflammation of the posterior chamber, iris, sclera, or conjunctiva. An orbital inflammatory syndrome with edema, erythema, and proptosis can also occur. Facial weakness is the most common cranial neuropathy seen; optic neuritis, eye movement abnormalities, hearing loss, and anosmia may also occur from cranial nerve involvement. Leptomeningeal involvement can also cause radiculitis or communicating hydrocephalus. Hypothalamic involvement may lead to increased thirst and polyuria (from diabetes insipidus) or sexual dysfunction. When brain parenchyma is affected, seizures, encephalopathy, or focal neurologic deficits may occur. Perivascular inflammation may lead to a vasculopathy; rarely, infarction or hemorrhage may ensue. Spinal cord involvement may present as myelitis, including a longitudinally extensive transverse myelitis with a predilection for the surface of the cord. Enhancement of the spinal cord may be multifocal or exhibit a “trident sign”—a crescent-shaped posterior enhancement accompanied by central canal enhancement leading to a three-pronged appearance. Very rarely, sarcoidosis may be associated with a neuropathy or myopathy.
The majority of patients will have abnormal cerebrospinal fluid (CSF), with elevated protein and a mononuclear pleocytosis the most common findings. Elevated opening pressure (~ 10%) and low CSF glucose (10%–20%) may occur, but are uncommon. Elevated CSF angiotensin converting enzyme is not sensitive, but is specific if found (> 90%). When abnormal CSF is present, thorough testing to exclude alternative infectious or inflammatory diagnoses should be pursued.
Biopsy of affected nervous system tissue provides definitive diagnosis of neurosarcoidosis. However, biopsy of ocular, brain, or spinal cord lesions is often high risk. A diagnosis of probable neurosarcoidosis can be made in a patient with the above neurological manifestations and a positive biopsy of non–nervous system tissue, which is more easily sampled. Since pulmonary involvement is common, a chest computed tomography (CT) scan should be performed looking for hilar adenopathy. When present, pulmonary biopsy can usually be performed safely with good diagnostic yield.
If chest CT is unrevealing, consider fluorodeoxyglucose-positron emission tomography (FDG-PET) to look for other sites of systemic involvement that might be amenable to biopsy. If none are found, then biopsy of brain (or other affected neural tissue, such as meninges) should be considered.
Treatment of the patient with neurosarcoidosis should begin with corticosteroids. A short course of intravenous high-dose steroids should be used for patients with severe neurologic symptoms, otherwise oral prednisone may be used. The duration of oral steroid treatment varies based on the extent and severity of neurologic involvement, but most cases should receive at least 1 month of high-dose prednisone before considering dose reduction. Steroid taper should be slow and adjusted based on the patient’s clinical response. Alternative immunosuppressants can be considered in patients intolerant of or unable to taper off steroids.