Dysimmune
and Inflammatory Neuropathies
Introduction
Dysimmune inflammatory neuropathies or immune-mediated peripheral neuropathies are a heterogenous group of disorders affecting the peripheral nervous system (PNS), due to dysregulation of the immune system. The course of the disease is varying and can be acute, sub-acute, chronic or relapsing-remitting.
Such peripheral neuropathies are generally characterised by progressive muscle weakness and accompanied by sensory deficits and can be caused by immune response against autoantigens in the PNS. There are several types of immune-mediated neuropathies such as Guillain– Barre syndrome (GBS) and its subtypes, chronic inflammatory demyelinating
polyradiculoneuropathy (CIDP), multifocal motor neuropathy (MMN) and paraproteinemic neuropathies.
Given that the main pathophysiology is immunemediated, it would mean that with early detection, potential treatment of neuropathies is possible.
This review aims to highlight the pathophysiological mechanisms, immunological processes and management of these conditions.
CIDP
Chronic Inflammatory Demyelinating Polyneuropathy
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is the most common treatable chronic neuropathy worldwide, with a prevalence ranging from about 1 to 9 cases per 100 000. CIDP typically presents a relapsing or progressive neuropathy with proximal and distal weakness which develops over at least an 8-week period. CIDP is classed as an autoimmune disorder in which a dysimmune response is directed towards components of the peripheral nerve causing demyelination, Node of Ranvier and/or axonal damages. The exact mechanisms underlying the
development of immunopathology remain to be defined. And because of the multiple phenotypic variation and clinical presentation, the identification of the pathogenic mechanisms remains complicated.
While many patients can be successfully treated (plasma derivatives, corticosteroids, plasma exchange, immunosuppressives treatment) with current therapies, some do not respond or have lasting disability.
In Europe, there are centers of expertise for this type of pathology. EPODIN is mobilized to promote access to the best diagnostic and therapeutic standards throughout Europe.
LSS/MADSAM
Lewis Sumner Syndrome: Multifocal acquired demyelinating sensory and motor neuropathy
Lewis-Sumner syndrome (LSS) is a dysimmune peripheral nerve disorder, characterized by a predominantly distal, asymmetric weakness mostly affecting the upper limbs. LSS represents the asymmetric variant of chronic inflammatory demyelinating polyneuropathy (CIDP) with multifocal pattern of motor and sensory loss. There are a few reports of a pure sensory presentation of LSS, without weakness and atrophy. LSS can be considered as an intermediate link between chronic inflammatory demyelinating polyneuropathy and MMN. The most commonly used treatment for Lewis-Sumner syndrome is intravenous immunoglobulin (IVIg) and more recently subcutaneous immunoglobulin (SCIg).
GBS
Guillain-Barré Syndrome
Guillain-Barré syndrome is a disorder of the peripheral nerves (see below) characterised by weakness or even progressive paralysis, most often starting in the legs and sometimes progressing to the breathing muscles and then to the nerves in the head and neck. This syndrome is also known as acute inflammatory polyradiculoneuropathy, or acute post-infectious polyradiculoneuropathy, because it often occurs after an infection. In the majority of cases, sufferers recover their physical abilities within 6 to 12 months.
In Europe, there are centers of expertise for this type of pathology. EPODIN is
mobilized to promote access to the best diagnostic and therapeutic standards throughout Europe.
MMN
Multifocal Motor Neuropathies
MFS
Miller Fisher Syndrome
Miller Fisher syndrome (MFS) is a rare neurological disorder characterized by a triad of symptoms:
Ophthalmoplegia: paralysis or weakness of the muscles that control eye movement, leading to difficulty moving the eyes in different directions.
Ataxia: lack of muscle coordination, resulting in unsteady gait, difficulty with balance, and clumsiness.
Areflexia: absence of reflexes, particularly the deep tendon reflexes, such as the knee-jerk reflex.
These symptoms typically develop over a few days to a week and are often preceded by an infection, most commonly a respiratory or gastrointestinal infection, caused by certain types of bacteria or viruses. Miller Fisher syndrome is considered a variant of Guillain-Barré syndrome (GBS), which is an autoimmune disorder affecting the peripheral nervous system. Both disorders involve the body’s immune system mistakenly attacking the nerves, leading to the characteristic symptoms. However, MFS tends to affect specific nerves in the brainstem and cranial nerves, whereas GBS typically affects the peripheral nerves in the limbs. Treatment for Miller Fisher syndrome may involve supportive care, such as physical therapy, and sometimes intravenous immunoglobulin (IVIG) or plasma exchange therapy to suppress the immune response. Most individuals with MFS experience a gradual recovery over weeks to months, although some may have residual symptoms or complications.
Paraproteinemic
neuropathies
Paraproteinemic neuropathies, also known as monoclonal gammopathy-associated neuropathies, refer to a group of neurological disorders characterized by damage to peripheral nerves (nerves outside of the brain and spinal cord) that is associated with the presence of abnormal proteins called paraproteins or monoclonal gammopathies in the blood.
These paraproteins are abnormal antibodies produced by a single clone of plasma cells (a type of white blood cell) and can be detected through blood tests. The presence of these paraproteins can lead to various neuropathic symptoms, including numbness, tingling, weakness, and pain in the limbs.
There are several subtypes of paraproteinemic neuropathies, including:
Monoclonal gammopathy of undetermined significance (MGUS) neuropathy: MGUS is a condition where there is an abnormal proliferation of plasma cells producing a monoclonal protein, but it doesn’t meet the criteria for multiple myeloma or other plasma cell disorders. MGUS neuropathy occurs when the presence of the monoclonal protein is associated with neuropathic symptoms.
Monoclonal gammopathy-associated neuropathy (MGAN): This subtype includes neuropathies associated with various underlying conditions such as multiple myeloma, Waldenström macroglobulinemia, and other lymphoproliferative disorders where monoclonal proteins are produced.
POEMS syndrome: This is a rare paraneoplastic syndrome that involves Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy, and Skin changes. It is characterized by the presence of a monoclonal protein in addition to other systemic manifestations.
The treatment of paraproteinemic neuropathies depends on the underlying cause and may involve addressing the plasma cell disorder, managing symptoms, and potentially using therapies to reduce the levels of abnormal proteins in the blood. This may include chemotherapy, immunomodulatory drugs, plasma exchange, or other targeted therapies. Physical therapy and supportive care may also be important components of management.