Guillain Barre Syndrome
Guillain Barré syndrome (GBS) is an autoimmune disorder. In GBS, the immune system specifically attacks the nerves. GBS is usually triggered by a viral or bacterial infection. Rarely, viral or bacterial components (proteins) can appear to look similar to your body’s proteins. When this happens, the immune system becomes confused and starts to attack its own body. When the nerves are attacked by the immune system, this can result in GBS. GBS isn't contagious and it's not passed down through families (it is not an inherited disease).
Symptoms of GBS may include the following:
Numbness or tingling in the hands or feet.
Muscle weakness (usually starts in the feet and moves upward).
Heart rate or blood pressure problems.
Diagnosis of GBS is based on the patient history, neurological electrophysiological, and cerebrospinal fluid (CSF) examinations.
Cerebrospinal fluid examination
CSF examination is mainly used to rule out causes of weakness other than GBS and should be performed during the initial evaluation of the patient. The classic finding in GBS is the combination of an elevated CSF protein level and a normal CSF cell count which is known as albumin-cytological dissociation. However, protein levels are normal in 30–50% of patients in the first week after disease onset and 10–30% of patients in the second week. Therefore, normal CSF protein levels do not rule out a diagnosis of GBS. Marked pleocytosis (>50 cells/μl) suggests other pathologies, such as leptomeningeal malignancy or infectious or inflammatory diseases of the spinal cord or nerve roots. Mild pleocytosis (10–50 cells/μl), though compatible with GBS, should still prompt clinicians to consider alternative diagnoses, such as infectious causes of polyradiculitis.
Electrophysiological studies provide evidence of PNS dysfunction and can distinguish between the subtypes of GBS: acute inflammatory demyelinating polyradiculoneuropathy (AIDP), acute motor axonal neuropathy (AMAN), and acute motor-sensory axonal neuropathy (AMSAN). Electrophysiological measurements might be normal when performed early in the disease course (within 1 week of symptom onset) or in patients with initially proximal weakness, mild disease, slow progression, or clinical variants. In these patients, a repeat electrodiagnostic study 2–3 weeks later can be helpful. In patients with MFS, results of electrodiagnostic studies are usually normal or demonstrate only a reduced amplitude of sensory nerve action potentials.
Although GBS affects the peripheral nervous system, CSF is a potential source for biomarkers (characteristic molecules/traits of a process/disease), because of its close contact with the nerve roots. Alterations in protein expression, post-translational modification, or turnover within the nervous system may be reflected in corresponding changes in CSF protein levels. Hp and HSp70 are significantly increased, and Cystatin C is downregulated in the CSF of patients with GBS. However, these biomarkers cannot differentiate AIDP type of GBS from AMAN type. The other biomarkers in GBS include myelin sheath associated glial (glia are the supporting cells in the nervous system) and neuronal markers (neuron specific enolase, 14-3-3 proteins, S100B, Hypocretin-1), and immunologic markers (TNF-α, chemokines).
Although most patients with GBS recover spontaneously, all of them need to be hospitalized for disease-modifying immunotherapy and multispecialty supportive care because of the unpredictable, potentially life-threatening and severely disabling course of GBS.
Studies have established plasma exchange (PE) (blood plasma is a yellowish liquid component of blood that is freed from blood cells but contains proteins and other constituents of whole blood in suspension) and intravenous immunoglobulin (IVIg) as the disease-modifying treatment of GBS.
Plasma exchange (PE)
Brettle et al. (1978) first drew attention to the improved outcome in a patient with GBS following plasma exchange. There is no consensus over the optimal number of exchanges in patients with different grades of disability. The complications of PE comprise hypotension (lower than normal blood pressure), septicemia (infection in the blood), hypocalcemia (lower than normal calcium levels in the blood), and abnormal clotting.
Intravenous immunoglobulin (IVIg)
It is used extensively in the treatment of immunologically mediated disorders. The benefits of IVIg in treating GBS were first reported by Kleyweg et al (1988). The absolute contraindications to IVIg treatment include selective IgA deficiency, and anaphylaxis (life-threatening, severe allergic response to a drug) from previous Ig infusion, while the relative contraindications comprise cardiac (heart) and renal (kidney) failure. The common adverse effects to IVIg include malaise, fever, chills, headache, nausea, vomiting, and rashes.
The American Academy of Neurology (AAN) guideline (reaffirmed last in 2016) on immunotherapy (immunotherapy for a disease works by activating or suppressing the body’s natural immune system; Immunotherapies which elicit or amplify an immune response are termed activation immunotherapies, while those that reduce or suppress are termed suppression immunotherapies) for GBS concludes:
Treatment with plasma exchange (PE) or intravenous immunoglobulin (IVIg) hastens recovery from GBS.
PE and IVIg are equally effective in patients with advanced GBS symptoms.
PE may carry a greater risk of side effects and is more difficult to administer.
Combining the two treatments is not recommended.
Steroid (corticosteroid) treatment is not beneficial in treating GBS.
The emerging biologic therapeutic agents for GBS include anti-C5 monoclonal antibody (eculizumab), anti-C1q monoclonal antibody, anti-T cell monoclonal antibody, anti-CD2 monoclonal antibody, anti-L-selectin monoclonal antibody, anti-CD20 monoclonal antibody (rituximab), anti-CD52 monoclonal antibody (alemtuzumab) and cytokine targets. However, none of these has been approved by the U.S. food and drug administration (FDA), to date.
The FDA has granted fast track designation to ANX005, a novel treatment for GBS. ANX005 is a clinical-stage investigational monoclonal antibody intended to treat patients with autoimmune and neurodegenerative disorders and formulated for IV administration. A phase 1b clinical trial of ANX005 has been completed and the company is planning for later-stage clinical trials in GBS. The blood-nerve barrier (BNB), which is adversely affected in immune-mediated neuropathies, such as GBS, is the focus of ongoing research in therapeutics for GBS. Future therapies include selective targeting of endoneurial endothelial cell-expressed intercellular adhesion molecule-1 (ICAM-1) (molecular substances essential to BNB integrity) for local delivery of proven therapeutics using nano therapy. These therapies that alter the BNB integrity are showing potential in ongoing research as clinically viable alternatives to the current standard of care for GBS.