Sarcoidosis is a systemic inflammatory disease characterized by the growth of microscopic collections of immune cells, called granulomas, in various organs throughout the body. Neurosarcoidosis represents a rare manifestation where this inflammatory process affects the central nervous system, including the brain and spinal cord, or the peripheral nervous system. This condition is estimated to occur in about 5% to 15% of individuals diagnosed with sarcoidosis. Diagnosis is often a complex, multi-step process because the symptoms can mimic other neurological disorders, and it frequently requires the exclusion of other possible causes like infections or malignancies.
Understanding Neurosarcoidosis
Sarcoidosis is an immune-mediated disorder resulting in granulomatous inflammation. Granulomas are compact clusters of immune cells, specifically lymphocytes and mononuclear phagocytes, that aggregate in affected tissues. The hallmark of the disease is the presence of non-caseating granulomas, meaning they do not undergo the necrosis seen in conditions like tuberculosis.
The underlying cause remains unknown, but it is theorized to result from a hyperactive immune response. This immune overreaction is thought to be triggered in genetically predisposed individuals by exposure to certain environmental agents, possibly including infectious microorganisms. In neurosarcoidosis, these granulomas directly infiltrate and compress nervous system tissues, causing damage and dysfunction.
The disease can impact any part of the nervous system, including the brain, spinal cord, meninges, or peripheral nerves. While sarcoidosis primarily affects the lungs in most patients, neurological symptoms are the first sign of the disease in 50% to 70% of cases. Less than 10% of patients have isolated neurosarcoidosis where no other organ involvement is initially detected, though up to 84% eventually develop systemic manifestations over time.
Neurological Manifestations and Symptoms
Symptoms depend on the location of granuloma formation within the nervous system. Cranial nerve involvement is the most common manifestation, occurring in 50% to 70% of patients. The facial nerve is most frequently affected, leading to weakness or drooping, which can be recurrent or affect both sides of the face. Granulomas affecting the optic or vestibulocochlear nerves can cause vision changes, eye pain, or hearing loss.
The disease can cause inflammation of the meninges (meningeal sarcoidosis), which are the protective layers surrounding the brain and spinal cord. This inflammation often affects the base of the skull and can result in headaches or, in advanced cases, hydrocephalus (an abnormal buildup of cerebrospinal fluid). Granulomas within the brain tissue (parenchymal disease) can manifest as mass lesions that resemble tumors, leading to seizures, confusion, or changes in cognitive function and behavior.
Spinal cord involvement (myelopathy) is reported in up to 26% of patients. This can lead to weakness, sensory loss, or issues with bowel and bladder control, either from granuloma formation or compression. When the disease affects peripheral nerves outside the central nervous system, patients may experience peripheral neuropathy, manifesting as numbness, tingling, or muscle weakness in the arms and legs.
Identifying and Confirming the Diagnosis
Diagnosing neurosarcoidosis is challenging because no single test can definitively confirm the condition without a tissue biopsy. Diagnosis requires excluding other diseases that cause similar symptoms, such as infections, malignancies, or multiple sclerosis.
Magnetic Resonance Imaging (MRI) of the brain and spine is a standard part of the evaluation. MRI scans can reveal characteristic patterns of inflammation, such as contrast-enhancing lesions in the brain or along the meninges, which are highly suggestive of the disease. However, imaging findings are diverse and can mimic other conditions, requiring careful interpretation.
Analysis of the cerebrospinal fluid (CSF) is another important diagnostic step. Abnormal CSF findings, which occur in a majority of patients, often include a mild elevation in white blood cells (predominantly lymphocytes) and increased protein levels. While these findings confirm inflammation, they are not specific to neurosarcoidosis and are also used to rule out infectious causes.
The most definitive diagnosis requires a tissue biopsy showing the characteristic non-caseating granulomas. Since neurological tissue biopsy carries risks, physicians often first attempt to obtain tissue from a more accessible site, like an enlarged lymph node or skin lesion, to confirm systemic sarcoidosis. If a systemic biopsy is positive and neurological symptoms are consistent, a diagnosis of probable neurosarcoidosis is often made. A diagnosis of definite neurosarcoidosis requires finding the granuloma within the nervous system tissue itself.
Treatment Strategies
Treatment is highly individualized and depends on the location and severity of the neurological involvement, aiming to reduce inflammation and prevent permanent neurological damage.
Corticosteroids, such as prednisone, are the first-line therapy due to their potent, rapid anti-inflammatory effects. They are typically initiated at a high dose and slowly tapered over several months as symptoms improve. Because of the potential for significant long-term side effects, steroid-sparing agents are often introduced early in the treatment course.
These second-line treatments are immunosuppressants that help control the underlying immune system overactivity. Commonly used medications include methotrexate, azathioprine, and mycophenolate mofetil. For cases that do not respond sufficiently to these conventional immunosuppressants, biologic therapies, specifically Tumor Necrosis Factor-alpha (TNF- \(\alpha\)) inhibitors like infliximab, may be used. Other medications, such as anti-seizure drugs, may be used to manage specific symptoms.