Nursing 203 Myasthenia Gravis and Guillain Barre syndrome Exam 4
cholinergic crisis
Cholinergic Crisis (rare) - muscles bombarded w/ACh Rapidly developing muscle weakness, dysphagia and respiratory distress→resp failure Cause: overdosage of anticholinesterase med Diagnosed only after adequate oxygenation and ventilation are assured Tensilon test differentiates myasthenia crisis vs cholinergic crisis Treatment: for bradycardia - atropine (anticholinergic) Respiratory support & airway protection
corticosteroids for MG
Corticosteroids - Prednisone taken alternate days Suppress immune response, ↓antibody production Initial higher daily dose. Taper as Sx improve. The goal of immunosuppressive therapy is to reduce the production of the antibody. 2. Thus Corticosteroids suppress the patients immune response, thus decreasing the antibody production. As the corticosteroid dose is gradually increased the anticholinesterase dosage is lowered.
symptoms of GB
Increasing muscle weakness → paralysis Symmetrical and ascending progression Minimal sensory changes In "stocking glove pattern" No effect on cognitive level or LOC
nursing diagnosis for GB
Ineffective breathing & impaired gas exchange Impaired physical mobility Imbalanced nutrition Impaired verbal communication Fear & anxiety
Guillain Barre Syndrome
autoimmune attack of the myelin of the peripheral nerves resulting in acute, rapid segmental demyelination of peripheral and some cranial nerves, producing ascending weakness with dyskinesia hyporeflexia paresthesias GB: bottom up
incidence of GB
3,500 in U.S. & Canada yearly Males more than females All age groups 80-90% have spontaneous recovery Death occurs in 5% cases
IV immune globulin and thymectomy
5. IV immune globulin (IVIG) nearly as effective as Plasmapheresis - unknown mechanism 6. Thymectomy Surgical removal of the thymus gland - 50% won't need medication after 1 yr
recovery stage of GB
Recovery Stage takes days to years Recovery is in reverse order (from head downward) 30% have some residual effects after 3 yrs
Myasthenia gravis diagnostics
Acetylcholinesterase inhibitor test - Tensilon Test (short acting acetylcholinesterase inhibitor) is injected IV in increments. 30 seconds later facial muscle weakness & ptosis dramatically resolve for ~5 mins (+test) Acetylcholine receptor antibody titer Repetitive nerve stimulation tests - show successive ↓ muscle contraction w/repeated stimulation MRI - enlarged thymus (90% cases)
Symptoms in acute GB stage
Acute stage - from onset to 2-3 weeks Symmetrical paresthesias/weakness/paralysis of LEs moves upward and peaks around day 14. Autonomic nervous system dysfunction - BP, HR, sweating, flush, urinary retention Cranial nerve involvement Respiratory failure - 30-50% pts Tingling, muscle cramps, hypersensitivity "stocking glove pattern"
meds that worsen MG
Antibiotics Cardiovascular, including beta-blockers Antiseizure Psychotropics Morphine Quinine Novocaine risks/ benefits
Pathophysiology of Myasthenia Gravis
Antibodies interfere with transmission of neurotransmitter: Acetylcholine to receptor sites on muscles Muscles don't receive signal from nerves to move Pathophysiology Myasthenia gravis is a disorder of neuromuscular transmission. In order to understand what causes MG, we must first describe what constitutes normal neuromuscular transmission. Normal Neuromuscular Transmission Acetylcholine (ACh) is synthesized in the nerve terminal by action of the enzyme choline acetyltransferase. ACh is then stored in vesicles, forming a quantum, containing about 10,000 molecules of ACh. Quanta of ACh are released into the nerve terminal by calcium dependent exocytosis - the fusing of the vesicles with the outer membrane wall. ACh then binds to the post-synaptic ACh receptor, resulting in a transient increase in membrane permeability to Na, K, Ca, and Mg, leading to an Endplate potential (EPP). Spacial and temporal summation of the EPPís are usually sufficient to reach threshold and cause a muscle membrane action potential. Acetycholinesterase and diffusion deactivates the ACh and terminates neuromuscular transmission. Acetylcholine Receptor Antibody The culprit in MG is an abnormally created antibody which has activity against the acetylcholine receptor, which is why MG is classified as an autoimmune disease. The AChR antibody is polyclonal and is present in 85-95% of MG cases. The antibody blocks neuromuscular transmission by several mechanisms - blockade of receptor sites by steric hindrance, destruction of AChR (complement mediated), and crosslinking of AChR which causes increased turnover by endocytosis (from 5-6 days to 2.5 days). These effects collectively decrease the number of acetylcholine molecules binding to receptors, therefore decreasing the number of EPP's, and decreasing the likelihood of the muscle fiber reaching threshold depolarization and contracting. The resulting decrease in the number of muscle fibers firing is what causes weakness. Structural Changes The chronic inflammation of MG causes several changes in the structure of the Neuromuscular Junction which also inhibit transmission and contribute to weakness. These include flattening out of the junctional folds, spreading out of AChR and Acetylcholinesterase, a 66% decrease in number of AChR, and an increased junctional gap. Thymus The thymus gland plays some role in the pathogenesis of MG, although it is not yet clear exactly what this role is. Evidence for the thymus playing a role includes the fact that the thymus contains myoid cells which can express AChR. B and T lymphocytes taken from MG thymus are reactive to AChR. 65% of patients with MG are found to have thymic dysplasia and 15% of cases are associated with thymoma. Finally, there is definite clinical improvement if the thymus gland is removed. Some speculate that there might also be a viral trigger, although this has not been proven. This means that a viral infection may cause an autoimmune response against AChR through molecular mimicry, or a chance similarity between proteins on the virus and the ACh receptor.
MG etiology
Antibodies responsible for destruction of acetylcholine receptors 80% persons w/MG also have abnormal thymus gland
anticholinesterase drugs
Anticholinesterase drugs pyridostigmine (Mestinon) neostigmine (Prostigmine) Inhibit breakdown of acetylcholine @ neuromuscular junction. Dosage is increased gradually until maximal benefit is obtained. Adverse effects:GI sxs, increased oropharyngeal secretions and muscle twitching. meds for MG Anticholinesterase drugs-Mestinon-provides symptomatic relief by increasing the relative concentration of available acetylcholine at the neuromuscular junction. Dosage is increased gradually until maximal benefit (improved strength, less fatigue) are obtained. Adverse effects: abdominal pain, diarrhea, nausea and increased oropharyngeal secretions. The goal of immunosuppressive therapy is to reduce the production of the antibody. 2. Thus Corticosteroids suppress the patients immune response, thus decreasing the antibody production. As the corticosteroid dose is gradually increased the anticholinesterase dosage is lowered.
myasthenia Gravis and symptoms
Autoimmune disorder Defect in nerve conduction at neuromuscular junction Symptoms: Chronic fatigue Varying degrees of muscle weakness, especially in face & throat
myasthenia gravis symptoms
Fatigue & weakness Profound weakness of eye & periorbital muscles Ptosis or diplopia initial symptom 2/3 pts Can progress. (HEAD DOWNWARD): Eyesmouththroatchestlimbs Purely a motor disorder with no effect on sensation or coordination MG is characterized by fluctuating weakness increased by exertion. Weakness increases during the day and improves with rest. Presentation and progression vary. Extraocular muscle (EOM) weakness or ptosis is present initially in 50% of patients and occurs during the course of illness in 90%. Bulbar muscle weakness is also common, along with weakness of head extension and flexion. Weakness may involve limb musculature with myopathic like proximal weakness greater than distal muscle weakness. Isolated limb muscle weakness as the presenting symptom is rare and occurs in fewer than 10% of patients. Patients progress from mild to more severe disease over weeks to months. Weakness tends to spread from the ocular to facial to bulbar muscles and then to truncal and limb muscles. On the other hand, symptoms may remain limited to the EOM and eyelid muscles for years. Rarely, patients with severe, generalized weakness may not have associated ocular muscle weakness. The disease remains ocular in only 16% of patients. About 87% of patients generalize within 13 months after onset. In patients with generalized disease, the interval from onset to maximal weakness is less than 36 months in 83% of patients. Intercurrent illness or medication can exacerbate weakness, quickly precipitating a myasthenic crisis and rapid respiratory compromise. Spontaneous remissions are rare. Long and complete remissions are even less common. Most remissions with treatment occur during the first 3 years of disease.
Diagnosis of Guillain Barre
History & physical Symmetric ascending weakness Hx of viral illness previous few weeks CSF - high protein EMG - lack of nervous stimulation Nerve conduction study - demonstrates demyelination
how is MG diagnosed?
How is myasthenia gravis diagnosed? Unfortunately, a delay in diagnosis of one or two years is not unusual in cases of myasthenia gravis. Because weakness is a common symptom of many other disorders, the diagnosis is often missed in people who experience mild weakness or in those individuals whose weakness is restricted to only a few muscles. The first steps of diagnosing myasthenia gravis include a review of the individual's medical history, and physical and neurological examinations. The signs a physician must look for are impairment of eye movements or muscle weakness without any changes in the individual's ability to feel things. If the doctor suspects myasthenia gravis, several tests are available to confirm the diagnosis. A special blood test can detect the presence of immune molecules or acetylcholine receptor antibodies. Most patients with myasthenia gravis have abnormally elevated levels of these antibodies. However, antibodies may not be detected in patients with only ocular forms of the disease. Another test is called the edrophonium test. This approach requires the intravenous administration of edrophonium chloride or Tensilon(r), a drug that blocks the degradation (breakdown) of acetylcholine and temporarily increases the levels of acetylcholine at the neuromuscular junction. In people with myasthenia gravis involving the eye muscles, edrophonium chloride will briefly relieve weakness. Other methods to confirm the diagnosis include a version of nerve conduction study which tests for specific muscle fatigue by repetitive nerve stimulation. This test records weakening muscle responses when the nerves are repetitively stimulated, and helps to differentiate nerve disorders from muscle disorders. Repetitive stimulation of a nerve during a nerve conduction study may demonstrate decrements of the muscle action potential due to impaired nerve-to-muscle transmission. A different test called single fiber electromyography (EMG), in which single muscle fibers are stimulated by electrical impulses, can also detect impaired nerve-to-muscle transmission. EMG measures the electrical potential of muscle cells. Muscle fibers in myasthenia gravis, as well as other neuromuscular disorders, do not respond as well to repeated electrical stimulation compared to muscles from normal individuals. Computed tomography (CT) or magnetic resonance imaging (MRI) may be used to identify an abnormal thymus gland or the presence of a thymoma. A special examination called pulmonary function testing - which measures breathing strength - helps to predict whether respiration may fail and lead to a myasthenic crisis.
immune suppressants for MG
Immune suppressants: azathioprine (Imuran) cyclophosphamide (Cytoxan) cyclosporine (Neoral) Reserved for patients who fail to respond to the other meds
Prevalence of Myasthenia Gravis
In U.S. ~60,000 cases No racial predominance Strikes younger women (20-40 yrs) and older men (>60yrs) Epidemiology The incidence of MG is 5 -10 cases per million population per year, which results in a prevalence in the US of 25,000 cases. MG is considered a sporadic disease, meaning that it seems to strike at random and it does not run in families. There is no racial predominance, but in people who present with MG at < 40 years old, 75% are women. Those > 40 years old are 60% men. This pattern is often summarized by stating that MG is a disease of young women and old men.
Nursing Management for Myasthenia Gravis
Medication management - must take ON TIME! Assist with energy conservation Tape eye shut short intervals, artificial tears, alternate eye patch Meals coincide w/peak effect of meds; Aspiration precautions Help client to identify/avoid triggers Support the client in coping with lifestyle & body image changes
mestinon for MG
Mestinon-provides symptomatic relief by increasing the relative concentration of available acetylcholine at the neuromuscular junction. Dosage is increased gradually until maximal benefit (improved strength, less fatigue) are obtained. Adverse effects: abdominal pain, diarrhea, nausea and increased oropharyngeal secretions.
Recovery from Guillain Barre Syndrome
Most make complete recovery If prolonged paralysis, need REHAB Outpatient rehab Home rehab Guillain Barre Syndrome Foundation International
myasthenic crisis
Myasthenic Crisis Sudden exacerbation of muscular weakness Rapidly developing muscle weakness, dysphagia and respiratory distress→resp failure Triggers: infection, med change, surgery, pregnancy, high environmental temp Treatment: Plasmapheresis and/or IVIG Respiratory support & airway protection Nutritional support if intubated long time usually ICU
weakness in MG
Not being able to move or barely able Worsens over day, especially if using affected muscles Worsens w/emotional upset, viral respiratory infection, thyroid problems, ↑body temp, menses, pregnancy
Therapeutic Measures for Guillain-Barre
Plasmapheresis exchange of plasma High dose IV immunoglobulin Supportive care - can quickly progress to medical emergency Careful monitoring (respiratory, BP, cardiac) Nutritional support Prevent complications DVT, PE Skin breakdown
ptosis
Ptosis of eyelids with sustained upward gaze 30-60 seconds MG
plasmapheresis
Plasmapheresis Pt's plasma exchanged. Temporary reduction in the circulating antibodies. Improves symptoms in 75% of patients for few wks while other therapy started 3. Cytotoxic medication though the precise mechanism of action is not understood. Azathioprine (Imuran), cyclophosphamide (Cytoxan), and cyclosporine reduce the circulating anti acetylcholine receptor antibody titers. These agents are reserved for patients who fail to respond to the other meds. 4. Plasmapheresis: Plasma exchange (Plasmapheresis) is a technique used to treat exacerbations. The patients plasma and plasma components are removed through a centrally placed large-bore double-lumen catheter. The blood cells and antibody-containing plasma are separated; then the cells and the plasma substitute are reinfused. Plasma exchange produces a temporary reduction in the titer of circulating antibodies. Plasma exchange improves symptoms in 75% of patients, although improvement lasts only a few weeks unless Plasmapheresis is continued or other forms of treatment such as immunosuppressant with corticosteroids are initiated. IV immune globulin (IVIG) has been shown to be nearly as effective as Plasmapheresis in controlling symptom exacerbation.. However, neither therapy is a cure nor does it stop the production of acetylcholine receptor antibodies.
etiology of GB
Probable Immune response to respiratory or gastrointestinal viral or bacterial infection Widespread outbreak during 1976-1977 swine flu vaccination program Camphylobacter infection in hens - flu vaccine grown in chicken eggs
cholinergic crisis treatment
Treatment: for bradycardia - atropine (anticholinergic) Respiratory support & airway protection
MG tiggers and treatment
Triggers: infection, med change, surgery, pregnancy, high environmental temp Treatment: Plasmapheresis and/or IVIG Respiratory support & airway protection Nutritional support if intubated long time usually ICU
what is a myasthenic crisis
What are myasthenic crises? A myasthenic crisis occurs when weakness affects the muscles that control breathing, creating a medical emergency and requiring a respirator for assisted ventilation. In patients whose respiratory muscles are weak, crises - which generally call for immediate medical attention - may be triggered by infection, fever, an adverse reaction to medication, or emotional stress.
