Gullian Barre Syndrome

Guillain-Barré syndrome (GBS) is a heterogeneous group of immune-mediated peripheral neuropathies which presents as evolving polyradiculoneuropathy preceded by a triggering event (often an infection). Cross-reactivity between the pathogen and the nerve tissue sets up the autoimmune response. It typically manifests as a symmetric motor paralysis with or without sensory and autonomic disturbances. The progressive phase of this syndrome is followed by a plateau phase of persistent, unchanging symptoms. Improvement begins within days of the plateau and the time to resolution of symptoms varies among patients.

Patients commonly report a respiratory tract infection or gastroenteritis that resolved when the neuropathy began. Campylobacteriosis is the most common precipitant in GBS.  Other antecedent infections include cytomegalovirus, HIV, Epstein-Barr virus, and varicella-zoster virus.

Typical Presentation

• Weakness (Proximal>Distal, Legs>Arms) accompanied by tingling dysesthesias in the extremities 
• Areflexia few days of symptom onset.
• Cranial nerve involvement may affect airway maintenance, facial muscles, eye move- ments, and swallowing. 
• Shoulder, Back, Thigh Pain (severe, occurring with even the slightest of movements)

The patient with Guillain-Barré syndrome typically presents with weakness accompanied by tingling dysesthesias in the extremities.

Types of GBS
GBS has five distinct subtypes which can be distinguished electrodiagnostically and pathologically. 

1. Acute inflammatory demyelinating polyradiculoneuropathy (AIDP)

• Autoimmune disorder, antibody mediated
• Triggered by antecedent viral or bacterial infection Electrophysiologic findings demonstrate demyelination. Inflammatory demyelination may be accompanied by axonal
• nerve loss.
• Remyelination occurs after the immune reaction stops.

2. Acute motor axonal neuropathy (AMAN)

• Pure motor axonal form of neuropathy 
• 2/3rd of patients are seropositive for campylobacteriosis.
• Electrophysiologic studies are normal in sensory nerves
• Reduced or absent in motor nerves. 
• Recovery is typically more rapid. High proportion of pediatric patients

3. Acute motor sensory axonal neuropathy (AMSAN)

• Wallerian-like degeneration of myelinated motor and sensory fibers 
• Minimal inflammation and demyelination
• Similar to AMAN except AMSAN affects sensory nerves and roots 
• Typically affects adults

4. Miller Fisher syndrome

• Rare disorder
• Rapidly evolving ataxia, areflexia, mild limb weakness, and ophthalmoplegia
• Sensory loss unusual, but proprioception may be impaired. Demyelination and inflammation of cranial nerve III and VI, spinal ganglia, and peripheral nerves
• Reduced or absent sensory nerve action potentials, tibial H reflex is usually absent.
• Resolution occurs in one to three months.

5. Acute panautonomic neuropathy

• Rarest of all the variants
• Sympathetic, parasympathetic nervous systems are involved. Cardiovascular involvement is common (postural hypotension, tachycardia, hypertension, dysrhythmias). 
• Blurry vision, dry eyes, anhidrosis, gastrointestinal pseudo-obstruction, and urinary retention 
• Recovery is gradual and often incomplete. 
• Often combined with sensory features

Diagnosis
GBS is the most common type of rapidly evolving, generalized peripheral nervous system disorder. However, there are several mimics that must be considered.

Diagnostic Criteria for Typical Guillain-Barré Syndrome Features required for diagnosis

• Progressive weakness in both arms and legs Areflexia

Features strongly supporting the diagnosis

• Progression of symptoms over days, up to four weeks
• Relative symmetry of symptoms
• Mild sensory symptoms or signs
• Cranial nerve involvement, especially bilateral weakness of facial muscles
• Recovery beginning two to four weeks after progression ceases 
• Autonomic dysfunction
• Absence of fever at onset
• High concentration of protein in cerebrospinal fluid, with fewer than 10 cells per cubic millimeter 
• Typical electrodiagnostic features

Features excluding diagnosis

• Diagnosis of botulism, myasthenia, poliomyelitis, or toxic neuropathy Abnormal porphyrin metabolism
• Recent diphtheria
• Purely sensory syndrome, without weakness

Differential Diagnosis Guillain-Barré Syndrome

• Basilar artery occlusion (asymmetric limb paresis)
• Botulism (descending paralysis)
• Heavy metal intoxication (confusion, psychosis, organic brain syndrome)
• Hypophosphatemia (irritable, apprehensive, hyperventilation, normal cerebrospinal fluid)
• Metabolic myopathies (cerebral and cerebellar symptoms) 
• Myasthenia gravis (weakness and fatigue that improves with rest) 
• Neoplastic meningitis (asymmetric spastic paralysis)
• Neurotoxic fish poisoning (spontaneous recovery within 24 hours) 
• Paraneoplastic neuropathy (chronic)
• Poliomyelitis (purely motor disorder with meningitis)
• Polymyositis (chronic, affects proximal limb muscles)
• Spinal cord compression (asymmetric)
• Tick paralysis (sensory changes absent, normal cerebrospinal fluid) 
• Transverse myelitis (abrupt bilateral leg weakness, ascending, sensory)
• Vasculitic neuropathies (mononeuropathy)

The diagnosis of GBS is based on typical clinical features, electrodiagnostic examination and examination of the cerebrospinal fluid (CSF) can aid in the diagnosis. Characteristic CSF findings consist of elevated protein without pleocytosis (abnormal number of cells in the CSF). 

Treatment
1. Supportive care (Analgesia, Fluids/Electrolytes, Physical Therapy, Nutrition, DVT Prophylaxis, Ventilation)
2. Specific therapy (IVIg, Plasmapheresis)

If patients advance past the acute phase of illness, most will recover function. However, the neuropathy can advance so rapidly that endotracheal intubation and mechanical ventilation may be necessary within 24 hours of symptom onset. Therefore, all patients who have GBS should be admitted to a hospital for close observation for respiratory compromise, cranial nerve dysfunction, and autonomic instability. 

Indications to Consider Intubation

• Forced vital capacity <20 mL per kg
• Maximal inspiratory pressure <30 cm H2O
• Maximal expiratory pressure <40 cm H2O
• Progression is noted with a reduction of more than 30 per cent in vital capacity, maximal inspiratory pressure, or maximal expiratory pressure

Other predictors of subsequent mechanical ventilation:
(1) time from GBS onset to hospital admission of less than seven days
(2) inability to lift the elbows or head above the bed
(3) inability to stand
(4) ineffective coughing
(5) increased liver enzyme levels

Specific treatment should be initiated soon after diagnosis. High-dose intravenous immunoglobulin (IVIg; 400 mg per kg daily for five days) or plasmapheresis can be initiated. IVIg and plasmapheresis are considered as equally effective therapies. 

Disadvantages of plasmapheresis include its rare complications, such as sepsis, that are believed to be caused by depletion of immunoglobulins. If fresh frozen plasma is used as replacement fluid, there is a risk of acquiring viral infections such as hepatitis and HIV. IVIg treatment has advantages over plasmapheresis because it is easier to administer, has significantly fewer complications, and is more comfortable for the patient. 

Despite its benefits, there are side effects from this IVIg therapy such as congestive heart failure and renal insufficiency. Patients may develop fever, myalgia, headache, nausea, and vomiting, but these “influenza-like” symptoms are self-limiting. A history of previous anaphylaxis to IVIg is a contraindication to repeat treatment. 

Corticosteroids were once believed to be useful in the treatment of GBS because of its immune-mediated inflammatory mechanism. However, a Cochrane Database Review of randomized trials, which included 195 patients treated with corticosteroids compared with controls, showed no difference in the outcome. Corticosteroids no longer have a role in GBS treatment.

Approximately 85 per cent of patients with GBS achieve a full and functional recovery within six to 12 months. 

Take Home:

• Guillain-Barré syndrome (GBS) is a heterogeneous group of immune-mediated peripheral neuropathies which presents as evolving polyradiculoneuropathy. It typically presents as Ascending Symmetrical Weakness (Proximal>Distal, Legs>Arms) accompanied by tingling dysesthesias in the extremities, Areflexia, Cranial nerve lesions and Shoulder, Back, Thigh Pain 
• Patients commonly report a respiratory tract infection or gastroenteritis that resolved when the neuropathy began. Campylobacteriosis is the most common precipitant in GBS.  
• Therefore, all patients who have GBS should be admitted to a hospital for close observation for respiratory compromise, cranial nerve dysfunction, and autonomic instability. 
• Treatment of GBS includes Supportive care (Analgesia, Fluids/Electrolytes, Physical Therapy, Nutrition, DVT Prophylaxis, Ventilation) and Specific therapy (IVIg, Plasmapheresis)

References:

• Lindenbaum Y, Kissel JT, Mendell JR. Treatment approaches for Guillain-Barré syndrome and chronic inflammatory demyelinating polyradiculoneuropathy. Neuro Clin 2001;19:187-204.
• Hughes RA, Wijdicks EF, Barohn R, Benson E, Cornblath DR, Hahn AF, et al. Practice parameter: immunotherapy for Guillain-Barré syndrome: report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2003;61:736-40.

• Hughes RA, van Der Meche FGA. Corticosteroids for treating Guil- lain-Barré syndrome. Cochrane Database Syst Rev 2003;(4): CD001446. Review.
• Zochodne DW. Autonomic involvement in Guillain-Barré syndrome: a review. Muscle Nerve 1994;17:1145-55
• Newswanger DL, Warren CR. Guillain-Barré syndrome. American family physician. 2004 May 15;69(10).

Posted by:

              

     Lakshay Chanana

     

     ST4 Trainee

     Royal Infirmary of Edinburgh

     Department of Emergency Medicine

     Edinburgh

     Scotland

     @EMDidactic