Sarcoidosis is a multi-system inflammatory disorder of unknown cause, characterized by the formation of abnormal collections of inflamed cells known as noncaseating granulomas. Neuropathy is damage to the peripheral nerves, resulting in symptoms like weakness, numbness, and pain. Sarcoidosis can definitively cause neuropathy, a manifestation that is a key feature of neurosarcoidosis. Neurologic involvement, including neuropathy, is estimated to occur in 5% to 15% of all sarcoidosis patients.
The Pathological Connection Between Sarcoidosis and Nerve Damage
The primary mechanism by which sarcoidosis damages nerves centers on the formation and location of granulomas. These inflammatory clusters directly infiltrate the nerve structure, often affecting the protective outer layers known as the perineurium and epineurium. This direct invasion causes mechanical disruption and inflammation, resulting in damage to the nerve fibers, a process known as axonal degeneration.
Granulomas also cause nerve damage through secondary effects, particularly compression and reduced blood flow. A granulomatous mass can physically compress the nerve, interfering with electrical signal transmission. Furthermore, inflammation can trigger a condition called vasculitis, which is the inflammation of small blood vessels supplying the nerves with oxygen and nutrients. This restriction of blood flow, or ischemia, starves the nerve tissue and accelerates damage.
Neuropathy in sarcoidosis can be broadly categorized based on the type of nerve fiber affected. Large-fiber neuropathy, which affects the thicker, myelinated sensory and motor nerves, is often directly linked to the physical presence of granulomas in the nerve tissue. In contrast, small-fiber neuropathy affects the thin nerves responsible for pain, temperature, and autonomic functions. This is sometimes thought to be a secondary effect of chronic cytokine-mediated inflammation rather than direct granuloma infiltration. The non-granulomatous small-fiber involvement is sometimes referred to as “parasarcoidosis” to distinguish it from the direct nerve destruction.
Clinical Manifestations of Neurosarcoidosis Neuropathy
Neuropathy resulting from sarcoidosis can present in several distinct ways, affecting either the cranial nerves or the peripheral nerves throughout the body. Cranial nerve involvement is the most frequent neurologic manifestation, affecting 60% to 70% of neurosarcoidosis cases. The most commonly affected is the facial nerve, which results in a sudden weakness or paralysis on one side of the face, often mimicking Bell’s palsy. This facial weakness can sometimes occur on both sides of the face simultaneously or sequentially, which is a presentation highly suggestive of neurosarcoidosis.
Other cranial nerves can be affected, leading to sensory and motor deficits. Involvement of the vestibulocochlear nerve can cause issues with hearing loss, ringing in the ears (tinnitus), or problems with balance and vertigo. Damage to the optic nerve may result in visual disturbances, blurry vision, or blindness.
Peripheral neuropathy, involving nerves outside the brain and spinal cord, is common and often presents as small-fiber neuropathy. Patients typically experience burning, tingling, or shooting pain, especially in the feet. Since small fibers also control autonomic functions, patients may experience associated symptoms like an abnormal heart rate, difficulty with sweating, or gastrointestinal issues.
Large-fiber involvement typically manifests as a sensorimotor polyneuropathy, causing a combination of weakness and sensory loss. This type of damage can lead to muscle weakness and stiffness, loss of reflexes, and an inability to feel deep sensations. A less common but specific presentation is mononeuropathy multiplex, which involves damage to two or more specific, separate nerves in different areas of the body. This type of damage often results in an asymmetric pattern of weakness and sensation loss, rather than the symmetrical “stocking-glove” pattern seen in other neuropathies.
Identifying and Treating Nerve Involvement
Identifying nerve involvement requires clinical assessment and specialized diagnostic testing to confirm the disease and rule out other causes of neuropathy. Electromyography (EMG) and nerve conduction studies (NCS) are standard electrophysiological tests used to evaluate peripheral nerve and muscle function. These tests help determine if the damage affects the nerve’s protective sheath (demyelination) or the core wire (axonal damage).
Magnetic resonance imaging (MRI) of the brain and spine is an indispensable tool, especially for detecting inflammation in the central nervous system and cranial nerves. A lumbar puncture, which collects cerebrospinal fluid, can show signs of inflammation within the nervous system and help exclude infectious causes. If small-fiber neuropathy is suspected, a skin biopsy may be performed to assess the density of nerve fibers in the skin, providing objective confirmation of the diagnosis.
The definitive diagnosis of neurosarcoidosis ideally relies on a biopsy of the affected nerve or tissue, confirming the presence of noncaseating granulomas. Since biopsying neurological tissue can be difficult or risky, treatment is often initiated based on a high clinical suspicion and supportive test results. The goal of treatment is to suppress the underlying inflammatory response causing the nerve damage.
Corticosteroids, such as prednisone, are the first-line treatment and are considered the cornerstone of therapy for active neurosarcoidosis. These powerful anti-inflammatory drugs work quickly to reduce the swelling and infiltration of the granulomas. For patients whose symptoms are severe, progressive, or do not respond adequately to corticosteroids, second-line immunosuppressive therapies are often used. These agents, including methotrexate, cyclophosphamide, and TNF-alpha inhibitors (e.g., infliximab), modulate the immune system to prevent further nerve damage.