Inflammatory neuropathy refers to a group of autoimmune disorders where the body’s immune system mistakenly attacks the peripheral nervous system (PNS), causing inflammation and damage to the nerves outside the brain and spinal cord. This attack leads to motor and sensory symptoms, ranging from mild tingling to debilitating muscle weakness. These inflammatory conditions significantly impact a person’s quality of life by causing pain, fatigue, and impaired physical function.
Understanding the Pathophysiology
The nervous system is divided into the central nervous system (CNS) and the peripheral nervous system (PNS). Inflammatory neuropathies specifically target the PNS, where immune system components, such as T-cells and antibodies, infiltrate the nerve structure. Peripheral nerves are protected by the blood-nerve barrier, which is breached during the autoimmune attack.
The damage can manifest in two primary ways: demyelination or axonal injury. Demyelinating neuropathy occurs when the immune system targets the myelin sheath. The immune components, including T-cells and macrophages, strip this protective coating, severely slowing down or blocking the electrical impulses.
Axonal neuropathy occurs when the immune response directly attacks the nerve fiber, or axon. This type of damage is often more severe and can result from antibodies targeting specific molecules like gangliosides, which are abundant on the axon surface. Autoantibodies can also target proteins at the nodes of Ranvier, the small gaps in the myelin sheath, causing a specific form of nerve damage called nodopathy.
Antibodies and T-cells work together to initiate this inflammatory cascade. T-cells, specifically activated CD4+ T-cells, recruit macrophages to the site of the peripheral nerve, where they strip the myelin sheath. Meanwhile, specific antibodies, sometimes triggered by a prior infection through a process called molecular mimicry, bind to nerve components and activate a complement cascade, leading to direct destruction of the nerve structure.
Key Classifications of Inflammatory Neuropathy
Inflammatory neuropathies are categorized based on their clinical course, the nerves they affect, and the resulting pattern of symptoms. The three most commonly recognized types are differentiated primarily by the speed of onset and the distribution of weakness.
Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) is characterized by a persistent and progressive course, with symptoms worsening over a period of at least eight weeks. The typical presentation involves symmetric weakness in both the proximal muscles (hips and shoulders) and the distal muscles (hands and feet), often accompanied by sensory symptoms like numbness and tingling. The disease course can be progressive or relapsing-remitting, where symptoms improve and then return.
Guillain-Barré Syndrome (GBS) stands in contrast to CIDP due to its acute onset, with symptoms rapidly progressing to their maximum severity within four weeks. The classic clinical picture involves an ascending, symmetric weakness that often begins in the legs and feet and moves upward to the arms and upper body. GBS can become life-threatening if the weakness affects the respiratory muscles, requiring immediate medical intervention.
Multifocal Motor Neuropathy (MMN) is a distinct type defined by its chronic, slowly progressive, and asymmetric weakness, typically starting in the arms or hands. A key distinguishing feature of MMN is that it is a purely motor neuropathy, meaning it causes muscle weakness, cramping, and twitching without significant sensory loss. MMN is often associated with high titers of specific autoantibodies, such as anti-GM1 ganglioside antibodies, which target motor nerves.
Establishing a Diagnosis
Diagnosing inflammatory neuropathy involves a combination of clinical evaluation and specialized neurological tests designed to pinpoint the location and nature of the nerve damage. Nerve Conduction Studies (NCS) and Electromyography (EMG) are instrumental in this process, helping to distinguish between damage to the myelin sheath and damage to the axon itself.
NCS measures how quickly and effectively electrical signals travel along the nerve. Demyelination is identified by prolonged distal latency, significantly slowed conduction velocity, and the presence of conduction blocks, where the signal fails to pass a segment of the nerve. Conversely, axonal damage is primarily indicated by a reduction in the amplitude of the electrical signal, reflecting a loss of functioning nerve fibers.
A Cerebrospinal Fluid (CSF) analysis, performed via a lumbar puncture, looks for a classic finding called albuminocytologic dissociation, particularly in GBS and CIDP. This phenomenon is characterized by elevated protein levels in the CSF, the fluid surrounding the brain and spinal cord, with a normal white blood cell count. The high protein level results from the disruption of the blood-nerve barrier at the nerve roots.
Blood tests are also performed to search for specific autoantibodies that suggest a particular inflammatory neuropathy subtype. For example, the presence of anti-GM1 antibodies strongly supports a diagnosis of Multifocal Motor Neuropathy or an axonal variant of GBS. Detecting antibodies against the ganglioside GQ1b is highly suggestive of the Miller-Fisher syndrome, a variant of GBS.
Current Treatment Modalities
The primary goal of treating inflammatory neuropathy is to suppress the immune system’s attack on the nerves and reduce inflammation. The main therapeutic interventions are immune-modulating therapies, which include Intravenous Immunoglobulin (IVIg) and Plasma Exchange (PLEX).
Intravenous Immunoglobulin (IVIg) involves infusing a concentrated solution of antibodies derived from the plasma of thousands of healthy donors. IVIg works by neutralizing harmful autoantibodies, inhibiting the complement cascade that damages the nerves, and modulating the overall immune response. IVIg is widely used for all three main types—GBS, CIDP, and MMN—and is often preferred due to its relative ease of delivery via a peripheral vein.
Plasma Exchange (PLEX), also known as plasmapheresis, physically removes the patient’s plasma containing pathogenic autoantibodies and replaces it with a substitute solution, such as albumin. The patient’s blood is separated by a machine and then returned to the body without the harmful plasma components. PLEX is typically used as an acute treatment for GBS and CIDP, offering significant short-term improvement, but it is a more invasive and time-consuming procedure than IVIg.
Corticosteroids, such as prednisone or dexamethasone, are potent anti-inflammatory drugs that suppress the immune response and are frequently used in CIDP. These medications are typically administered orally or through intravenous pulse therapy and can lead to long-term remission by reducing the inflammatory response in the peripheral nerves. Other immunosuppressant drugs, including azathioprine or methotrexate, may be used as maintenance therapy, often in combination with IVIg or corticosteroids, to sustain remission and minimize the frequency of other treatments.