Understanding_Guillain_Barr__syndrome.4
- 1. JAAPA Journal of the American Academy of Physician Assistants www.JAAPA.com 19 CME G uillain-Barré syndrome (GBS) is an acute general- ized polyneuropathy affecting 1 to 2 out of 100,000 people per year. More men than women are affected (1.25:1), and the syndrome may occur in patients of any age, typically affecting patients ages 40 to 50 years, although incidence is increased by 20% for every 10-year increase in age.1 GBS can be classified into three main subtypes: • Acute inflammatory demyelinating polyneuropathy, the most common type and the focus of this article • Axonal, acute motor axonal neuropathy and acute motor sensory axonal neuropathy • Miller Fisher syndrome. Symptoms of acute inflammatory demyelinating polyneu- ropathy evolve rapidly, and are characterized by progressive ascending weakness and diminished or absent deep tendon reflexes.2 The degree of weakness varies from minimal dif- ficulty walking to complete paralysis including the facial, respiratory, and bulbar (tongue and swallowing) muscles. CAUSES GBS usually develops after a triggering event. Infections Campylobacter jejuni, one of the most com- mon causes of gastroenteritis worldwide, causes 30% to 35% of GBS cases.3 Other infectious triggers include cytomegalovirus, Mycoplasma pneumoniae, Haemophilus influenzae, Epstein-Barr virus, and HIV. GBS also occurs in patients with lymphoma, Hodgkin disease, and systemic Robert Estridge practices at the Cleveland Clinic in Cleveland, Ohio. Mariana Iskander is a hospitalist in the Neurological Institute at the Cleveland Clinic in Cleveland, Ohio. The authors have disclosed no potential conflicts of interest, financial or otherwise. DOI: 10.1097/01.JAA.0000466585.10595.f5 Copyright © 2015 American Academy of Physician Assistants Understanding Guillain-Barré syndrome Robert Estridge, PA-C; Mariana Iskander, PA-C ABSTRACT Guillain-Barré syndrome (GBS) is a rapidly progressive peripheral neuropathy that most commonly presents with ascending symmetrical weakness and diminished or absent deep tendon reflexes. Because weakness may affect the diaphragm and cause respiratory distress, 10% to 30% of patients require mechanical ventilation. Symptoms prog- ress and peak about 4 weeks after onset. Patients generally require hospitalization for respiratory and cardiac monitor- ing, as well as supportive care and treatment. The treat- ments of choice are IV immunoglobulin and plasmapheresis. Even after treatment, as many as 20% of patients have persistent neurologic symptoms, and up to 3% of patients die of autonomic issues. Keywords: Guillain-Barré syndrome, polyneuropathy, plasmapheresis, Campylobacter jejuni, IVIG, autonomic dysfunction Learning objectives List the pathophysiology, signs, and symptoms of GBS. Describe the important aspects of diagnosis and management of patients with GBS. FIGURE 1. An oligodendrocyte repairing damaged myelin sheaths of a motor neuron ©CAROL&MIKEWERNER/VISUALSUNLIMITED,INC. Copyright © 2015 American Academy of Physician Assistants
- 2. 20 www.JAAPA.com Volume 28 • Number 7 • July 2015 CME lupus erythematosus; these cases occur more frequently than can be attributed to chance alone.3 Other causes A small percentage of patients develop GBS after another triggering event such as immunization, surgery, trauma, or bone marrow transplantation. One study based on a vaccine used in the 1970s found that the H1N1 influenza vaccine increased the risk of developing GBS in 2 per 1 million people vaccinated.4 PATHOPHYSIOLOGY GBS appears to be an autoimmune response in which the immune system attacks the peripheral nervous system. Infections such as C. jejuni express lipooligosaccharides in the bacterial wall; these molecules are similar to gan- gliosides, and antiganglioside antibodies produced by the body attack the nerve and destroy the myelin sheath. Exactly which antibodies are stimulated and which area of the nerve is targeted may explain the different subtypes of GBS.4 SIGNS AND SYMPTOMS The most prominent symptom experienced by patients with GBS is bilateral, ascending, symmetrical weakness of the limbs. In 90% of patients, weakness starts in the legs and advances proximally. Between 10% and 30% of patients require mechanical ventilation secondary to respiratory muscle weakness.5 Between 50% and 89% of patients report pain in addition to weakness, especially with movement. Pain is described as severe, deep aching or cramping in the back or legs. It is often worse at night and may be difficult to control.6 Weakness typically peaks at 2 weeks for 50% of patients, and by 4 weeks for 90% of patients.7 Weakness is consid- ered a significant factor in the diagnosis of GBS. The patient’s reflexes are diminished to absent. Autonomic symptoms affect 70% of patients, most com- monly causing cardiac dysrhythmias, but also causing BP instability. Other autonomic symptoms include paralytic ileus, abnormal sweating, orthostasis, and urinary reten- tion.8,9 Facial diparesis occurs in 50% of patients. The lower cranial nerves also are frequently involved, causing bulbar weakness that makes it difficult for patients to manage secretions and maintain an airway; these patients may initially be thought to have brainstem ischemia.3 Monitor patients with GBS closely for signs of respira- tory failure, and perform frequent bedside measurements of vital capacity and negative inspiratory force. Signs of impending respiratory arrest and the need for endotracheal intubation are: • Forced vital capacity less than 20 mL/kg • Maximum inspiratory pressure less than 30 cm H2 O • Maximum expiratory pressure less than 40 cm H2 O or a reduction of more than 30% in vital capacity.10 DIAGNOSIS The differential diagnosis of GBS includes acute myelopa- thy, arsenic poisoning, botulism, cytomegalovirus, critical illness neuropathy or myopathy, diphtheria, Lyme polyra- diculitis, myasthenia gravis, organophosphate or paralytic shellfish poisoning, poliomyelitis, porphyria, severe hypo- phosphatemia, thallium poisoning, vasculitis neuropathy, and West Nile virus. Diagnostic criteria for GBS are listed in Table 1. Patients with GBS classically have elevated protein levels (as high as 1,800 mg/dL compared with the normal range of 15 to 45 mg/dL) and normal white blood cell (WBC) counts in the cerebrospinal fluid (CSF), a condition known as albu- minocytologic dissociation.3 Protein levels in the CSF may be normal in early GBS; however, by the end of the second week of symptoms, protein levels in the CSF are elevated in 90% of patients.4 One study of 474 patients found higher-than-normal CSF protein concentrations in 49% of patients on the first day and 53% of patients in the first 3 days.11 This percentage typically increases as the syndrome progresses, so clinicians should not rely solely on elevated protein levels in the CSF for diagnosis, especially early in the course of GBS. Interestingly, MRI of the lumbosacral spine, which can be used to rule out other diagnoses, may reveal gadolinium enhancement of the lumbosacral nerve roots, aiding the diagnosis of GBS.12 TREATMENT Treatment typically focuses on supportive care and mon- itoring the patient’s respiratory, cardiac, and electrolyte status. Supportive care The following recommendations are in agreement with a 2005 expert review of supportive care for patients with GBS, and are based on observational studies and expert opinion: • Immunizations are not recommended during the acute phase of GBS and are not suggested for a period of 1 year or more after the onset of GBS. • After 1 year, immunizations need not be withheld, but the need for the immunization should be reviewed on an individual basis.10 Key points GBS is an acute inflammatory demyelinating poly- neuropathy characterized by motor difficulty, diminished to absent reflexes, and possible cranial nerve involvement. In 70% of patients, GBS develops after an infection, most commonly C. jejuni. Diagnostic testing shows increased CSF protein. Respiratory difficulties or cardiac dysrhythmias require patients to be hospitalized for supportive care. Treatment with IVIG or plasmapheresis can improve symptoms. Copyright © 2015 American Academy of Physician Assistants
- 3. Understanding Guillain-Barré syndrome JAAPA Journal of the American Academy of Physician Assistants www.JAAPA.com 21 Annual influenza vaccination is considered beneficial for most patients who have a history of GBS that is not pro- voked by influenza vaccination, and who have risk factors for severe influenza complications (for example, older age or immunosuppression). The two main treatments for GBS are plasma exchange (PLEX) and IV immunoglobulin (IVIG). PLEX First described as a treatment for GBS more than 30 years ago, PLEX filters pathogenic substances from the blood and removes the offending antibodies behind the pathophysiology of neural destruction. PLEX also can be used to treat antiphospholipid antibody syndrome, mul- tiple sclerosis, myasthenia gravis, neuromyelitis optica, and rhabdomyolysis. Long-term effects of PLEX include immunosuppression and transfusion reactions. Some immediate adverse reac- tions include symptoms associated with hypocalcemia (seen in about 20% of patients), as well as allergic reactions including urticaria or pruritus.13 Treatment with PLEX has significantly reduced patients’ need for mechanical ventilation from 27% to 14%.2 PLEX also has increased the rate of recovery and reduced the need for ambulatory assistive devices. Five PLEX treatments are typical for patients with GBS.2 IVIG This treatment began more than 50 years ago when pooled human plasma was used to treat measles and hepatitis. Since then, clinicians have used IVIG to treat Kawasaki disease, idiopathic thrombocytopenic purpura, and chronic inflammatory demyelinating polyneuropathy.14 IVIG is thought to have multiple mechanisms of action, which are not totally understood. One theory proposes that IVIG provides an antigen that blocks autoantibodies from binding to B lymphocytes. IVIG’s multiple other mechanisms are related to T-cells (reducing the production of interleukin), and complement system (antibodies against C3 and C4), and will not be discussed in detail here.15 IVIG protects patients against infection and suppresses inflammatory and immune-mediated processes. The stan- dard dose is 0.4 g/kg/day for 5 days. This procedure is most beneficial if started within 2 weeks of symptom onset, although it has been shown to be beneficial if started within 4 weeks of symptom onset.4 Trials analyzing the efficacy of IVIG versus PLEX have concluded that they are of equivalent efficacy.10 Due to the incidence of adverse reactions to PLEX, IVIG has become more widely used as a first-line treatment for GBS.4,7 Other treatments Corticosteroids have not been shown to be helpful, but rather, have been shown to delay recov- ery from GBS, although they are used when the symptoms become chronic.16 Sodium channel blockers are being studied for the treat- ment of GBS. These drugs may significantly protect nerve axons from damage.2 PROGNOSIS About 85% of patients with GBS achieve a full recovery within several months to a year. Fatigue is the most com- mon and persistent symptom after treatment.5 Other less- common residual difficulties include weakness of the lower leg muscles, numbness of the feet and toes, and mild bifacial weakness. Five percent to 10% of patients who improved with treatment will have a relapse within 3 days to 3 weeks after completing treatment. If the patient responded to the initial therapy, the same treatment may be used, or an alternative treatment may be tried; either can be successful (for example, PLEX or IVIG).12 Even with treatment, however, 3% to 5% of patients with GBS die, most often from cardiac arrest related to autonomic dysfunction, acute respiratory distress syndrome, pulmonary embolism, or infection.12 CONCLUSION GBS typically causes acute, rapid, and progressive ascend- ing motor weakness. Early recognition and treatment are crucial, especially for patients who need mechanical ven- tilation. Most patients are admitted to the hospital for cardiac and respiratory monitoring. The two therapeutic options for GBS that have been shown to be the most effective in improving symptoms are IVIG and PLEX. Most patients exhibit near-full functional recovery in about a year, with occasional residual difficul- ties. The syndrome has a 3% to 5% mortality. Reviewing the possible progression of disease and prognosis are keys to the family discussion, and are crucial to setting appro- priate expectations. JAAPA Required: • Progressive weakness in both arms and legs • Areflexia Strongly support: • Symptom progression over days and for up to 4 weeks • Relative symmetry of symptoms • Mild sensory symptoms or signs • Cranial nerve involvement, especially bilateral weakness of facial muscles • Recovery beginning 2 to 4 weeks after symptom progres- sion ceases • Autonomic dysfunction • Absence of fever at onset • High concentration of protein in CSF • Typical electrodiagnostic features Rule out GBS: • Diagnosis of botulism, myasthenia, poliomyelitis, or toxic neuropathy • Abnormal porphyrin metabolism • Recent diphtheria • Purely sensory syndrome, without weakness TABLE 1. Diagnostic criteria for GBS17 Copyright © 2015 American Academy of Physician Assistants
- 4. 22 www.JAAPA.com Volume 28 • Number 7 • July 2015 CME Earn Category I CME Credit by reading both CME articles in this issue, reviewing the post-test, then taking the online test at http://cme.aapa. org. Successful completion is defined as a cumulative score of at least 70% correct. This material has been reviewed and is approved for 1 hour of clinical Category I (Preapproved) CME credit by the AAPA. The term of approval is for 1 year from the publication date of July 2015. REFERENCES 1. Sejvar JJ, Baughman AL, Wise M, Morgan OW. Population incidence of Guillain-Barré syndrome: a systematic review and meta-analysis. Neuroepidemiology. 2011;36(2):123-133. 2. Arcila-Londono X, Lewis RA. Guillain-Barré syndrome. Semin Neurol. 2012;32(3):179-186. 3. Dimachkie MM, Barohn RJ. Guillain-Barré syndrome and variants. Neurol Clin. 2013;31(2):491-510. 4. Walling AD, Dickson G. Guillain-Barré syndrome. Am Fam Physician. 2013;87(3):191-197. 5. Longo DL, Fauci AS, Kasper DL, et al., eds. Harrison’s Principles of Internal Medicine. 18th ed. New York, NY: McGraw-Hill; 2012. 6. Ropper AH, Samuels MA, Klein JP. Diseases of the peripheral nerves. In: Ropper AH, Samuels MA, eds. Adams and Victor’s Principles of Neurology. 9th ed. New York, NY: McGraw-Hill; 2009. 7. Van Der Meché FG, Van Doorn PA, Meulstee J, Jennekens FG. GBS-consensus group of the Dutch Neuromuscular Research Support Centre. Diagnostic and classification criteria for the Guillain-Barré syndrome. Eur Neurol. 2001;45(3):133-139. 8. Zochodne DW. Autonomic involvement in Guillain-Barré syndrome: a review. Muscle Nerve. 1994;17(10):1145-1155. 9. Lunn MP, Willison HJ. Diagnosis and treatment in inflamma- tory neuropathies. J Neurol Neurosurg Psychiatry. 2009;80(3): 249-258. 10. Lawn ND, Fletcher DD, Henderson RD, et al. Anticipating mechanical ventilation in Guillain-Barré syndrome. Arch Neurol. 2001;58(6):893-898. 11. Fokke C, van den Berg B, Drenthen J, et al. Diagnosis of Guillain-Barré syndrome and validation of Brighton criteria. Brain. 2014;137(Pt 1):33-43. 12. Yuki N, Hartung HP. Guillain–Barré syndrome. N Engl J Med. 2012;366(24):229-304. 13. Szczepiorkowski ZM, Winters JL, Bandarenko N, et al. Apheresis Applications Committee of the American Society for Apheresis. Guidelines on the use of therapeutic apheresis in clinical practice—evidence-based approach from the Apheresis Applications Committee of the American Society for Apheresis. J Clin Apher. 2010;25(3):83-177. 14. Darabi K, Abdel-Wahab O, Dzik WH. Current usage of intravenous immune globulin and the rationale behind it: the Massachusetts General Hospital data and a review of the literature. Transfusion. 2006;46(5):741-753. 15. Pierce LR, Jain N. Risks associated with the use of intravenous immunoglobulin. Transfus Med Rev. 2003;17(4):241-251. 16. Ropper AH. The Guillain-Barré syndrome. N Engl J Med. 1992;326(17):1130-1136. 17. Newswanger DL, Warren CR. Guillain-Barré syndrome. Am Fam Physician. 2004;69(10):2405-2410. Copyright © 2015 American Academy of Physician Assistants