Sjögren’s syndrome (SS) is a systemic autoimmune disorder primarily recognized for attacking moisture-producing glands, leading to chronic dry eyes and dry mouth. However, SS is a multi-system disease, meaning it can cause inflammation and damage throughout the body, including the nervous system. Neurological involvement affects up to 20% of patients and can sometimes appear before the classic dryness symptoms. Sjögren’s affects both the central nervous system (CNS)—the brain and spinal cord—and the peripheral nervous system (PNS)—the nerves outside the central axis.
The Autoimmune Process Behind Neurological Involvement
The immune system’s misdirected attack is the underlying cause of neurological damage in Sjögren’s syndrome through chronic inflammation and autoantibody activity. Immune cells, specifically T- and B-lymphocytes, infiltrate and damage nervous tissues, leading to neuroinflammation.
Chronic inflammation creates a toxic environment for nerve cells and fibers. The sustained release of inflammatory signaling molecules, such as cytokines, can disrupt the blood-brain barrier, which normally protects the CNS. This breach allows immune cells to enter the brain and spinal cord, promoting inflammation and direct neural injury.
Autoantibodies also play a destructive role. While the classic anti-SSA/Ro and anti-SSB/La antibodies are commonly associated with Sjögren’s, other autoantibodies may directly target nerve tissue or blood vessels. This targeted attack can lead to vasculitis, the inflammation of blood vessel walls, causing restricted blood flow and damage to nerve fibers in the brain and periphery.
Central Nervous System Manifestations
Damage to the central nervous system (CNS) results in a range of diffuse and focal symptoms. Cognitive dysfunction, often described as “brain fog,” is the most common CNS complaint, involving difficulties with higher-order functions. Patients frequently report problems with memory, attention, concentration, and executive function, which can significantly impair daily life.
Inflammation in the brain and spinal cord can manifest as severe, focal events. Myelitis, or inflammation of the spinal cord, causes weakness, numbness, and sensory changes below the affected area, sometimes progressing to paralysis or bladder control issues. This inflammation may present acutely or progress slowly over weeks to months.
Optic neuritis, the inflammation of the optic nerve, is another CNS manifestation that can cause severe vision loss. Sjögren’s can also cause aseptic meningitis or encephalitis, forms of inflammation affecting the brain or its surrounding membranes. Vasculitis in the brain’s blood vessels may lead to stroke-like events or the development of white matter lesions resembling those seen in multiple sclerosis.
Peripheral Nervous System Complications
Neurological effects outside the brain and spinal cord involve the peripheral nervous system (PNS), including the nerves extending to the limbs and organs. Peripheral neuropathy is a common complication of Sjögren’s, often presenting as sensory disturbances. These include tingling, numbness, and burning pain, frequently starting in the hands and feet in a “stocking-glove” distribution.
Small fiber neuropathy (SFN) is a specific type involving damage to the small nerve fibers responsible for pain and temperature sensation. SFN can cause intense neuropathic pain, often described as a burning or lancinating sensation. Unlike large fiber neuropathies, SFN often presents with normal nerve conduction study results, requiring specialized testing for diagnosis.
The disease can also affect the autonomic nervous system, which controls involuntary bodily functions. Autonomic neuropathy may lead to symptoms like lightheadedness upon standing due to blood pressure regulation issues, abnormal heart rate, or gastrointestinal motility problems. Cranial neuropathies, such as trigeminal neuralgia which causes facial pain, are also observed.
Identifying and Treating Neurological Sjögren’s
Diagnosis of neurological involvement in Sjögren’s requires a combination of clinical evaluation and specialized testing. Magnetic resonance imaging (MRI) of the brain and spine is used to look for signs of inflammation, such as white matter lesions or myelitis. For peripheral nerve damage, doctors use nerve conduction studies (NCS) and electromyography (EMG) to assess the function of larger nerve fibers.
For small fiber neuropathy, the gold standard diagnostic test is a skin biopsy to measure the density of intra-epidermal nerve fibers. A lumbar puncture, or spinal tap, may also be performed to analyze cerebrospinal fluid for inflammatory markers and to rule out other conditions. The diagnosis can be challenging because some patients with neurological Sjögren’s may not have the classic SSA/SSB antibodies.
Treatment strategies are tailored to the specific type and severity of the neurological damage. For active inflammation in the CNS or severe, progressive neuropathy, immunosuppressive therapies are often necessary. These treatments may include corticosteroids or other immunosuppressants and biologics aimed at modulating the overactive immune response. For chronic symptoms, such as neuropathic pain, symptomatic treatments like anti-seizure medications and pain relievers are used to improve the patient’s quality of life.