|Lambert-Eaton syndrome (LEMS)
Fluctuating, fatiguable muscle weakness of eye, bulbar, respiratory and limb muscles
|Initial Management of Myasthenic crisis|
- Exhausted, Poor resp effort, poor cough/cannot clear secretions
- Can be cyanosed, Low FVC
- May be due to MG or excess anticholinesterases. Involve ITU
- ABC, Intubated and ventilate and hold all medications
- MG will respond to edrophonium chloride, 2 mg by IV injection
- If worsening MG then Plasma exchange or IV Immunoglobulins
- Autoimmune attack on nicotinic Ach receptors causing fatiguable weakness
- 90% have Ab to the nicotinic acetylcholine receptor (AChR)
- Ab to the Muscle-specific protein kinase (musk) protein
- Ab to Titin and Ryanodine also seen with thymomas
- Leads to complement-mediated damage and a reduction of receptors
- There is therefore a REDUCTION in postsynaptic response to Ach.
- Rheumatoid arthritis, Pernicious anaemia
- Systemic lupus erythematosus, Sarcoidosis, Sjogren's disease
- Polymyositis, Ulcerative colitis, Pemphigus
- Fluctuating weakness worsens with exercise - fatigability
- Most develop eye signs - diplopia and ptosis [pupil unaffected].
- An eyelid twitch response (Cogan's lid twitch) is characteristic
- Respiratory muscle involvement can lead to intubation and ventilation
- Difficulty in chewing, abnormal smile, dysarthria, and dysphagia are also common.
- Bulbar speech and even dysphagia
- Acute illness such as surgery or infections can worsen symptoms
- Pregnancy - Worsens in 1st trimester of pregnancy and then improves. Transient neonatal myasthenia due to maternal abs in fetus
- Myasthenic crises : Profound respiratory muscle weakness leads to respiratory failure. Needs intubated and ventilated. Stop anti cholinesterases as cause excess secretions. Steroids can make it worse. Plasmapheresis or IVIG may be useful acutely especially in myasthenic crises
- Lambert-Eaton syndrome (LEMS), Botulism
- Drug induced myasthenia - penicillamine, aminoglycosides
- Chronic progressive external ophthalmoplegia
- Serum anti-acetylcholine receptor (ACh-R) antibody testing: first-line investigation for non-urgent patients seen in 90%.
- Thyroid function: for all patients.iv
- Serum anti-muscle-specific kinase (MuSK) antibody testing: for all patients negative for ACh-R antibodies.
- Neurophysiology: May help to establish the diagnosis in seronegative patients with suspected myasthenia gravis. It should be performed by a practitioner with experience of myasthenia gravis. Repetitive nerve stimulation is the initial test; if negative, consider single-fibre electromyography.v Focus the testing on symptomatic muscles. Repetitive nerve stimulation may demonstrate a reduction in the amplitude of the compound muscle action potential from the fourth stimulation when a nerve is subjected to repetitive supramaximal electrical stimulations at a frequency of 3 Hz. The measurement of decrement is made between the first and the fourth responses which should be greater than 10%. Single fibre electromyography is the most sensitive test (>95%) for diagnosing myasthenia gravis. In this test, the action potentials generated by closely adjacent muscle fibres of the same motor unit are recorded with a fine electrode. When a motor unit is activated, the action potentials reaching muscle fibres are not all synchronous. Single-fiber electromyography is highly accurate in confirming myasthenia gravis by detecting 'jitter'
- Tensilon test : Edrophonium chloride (Tensilon). Cardiac monitor and resuscitation equipment in case of bradycardia /asystole. The patient may need Atropine. Edrophonium chloride 1 mg iv test dose given and if not problems then 2 mg iv given with determination of clinical improvement in motor power. Further edrophonium up to 10 mg in total may be given. This test is particularly useful in myasthenia gravis patients with ocular symptoms. Onset less than one minute. Last 5 minutes.
- Ice cube test - placed over the eyelid with ptosis and after 30 seconds improves. Decreased temperature reduces the activity of cholinesterase
- Give Pyridostigmine bromide 60 mg PO which has a longer duration of action and is often used in patients with generalized symptoms.
- MR scan of brain: Patients with negative serology and neurophysiology, and symptoms compatible with ocular myasthenia may have a structural brain disease.
- Image anterior mediastinum (CT or MRI) to exclude thymoma (found in 12% of patients with myasthenia gravis)
- Thymus scanning: All patients with suspected myasthenia, irrespective of distribution (ocular/generalised) or serology (seropositive/negative), should undergo thymus imaging. The modality (CT or MRI) should be decided locally.
- ACh-R/MuSK seropositive/seronegative
- Thymoma/no thymoma
- Ocular /generalised
- Congenital: (may mimic seronegative autoimmune myasthenia)
- Possible myasthenia but tests negative: consider a muscle disorder or refer to myasthenia expert for management.
Avoid in those who have true Myasthenia or muscle weakness
Drugs can worsen MG - always check all drugs
Aminoglycosides, Phenytoin, Lignocaine, Beta Blockers, Quinidine
Can impair Ach release
Creates antibodies to the Ach receptor
Weakness that is similar to MG
- Pyridostigmine should be part of the initial treatment in most patients with MG. Pyridostigmine dose should be adjusted as needed based on symptoms. The ability to discontinue pyridostigmine can be an indicator that the patient has met treatment goals and may guide the tapering of other therapies. Corticosteroids or IS therapy should be used in all patients with MG who have not met treatment goals after an adequate trial of pyridostigmine. Pyridostigmine 30 to 60 mg orally 4h initially has an onset of effect is 30 minutes and duration is 4 hours
- Steroids e.g. Prednisolone 5 mg given on alternate days as a single dose slow increasing dose by 5 mg every 3 doses for ocular MG. A dose of 10 mg alternate days is given for systemic disease increasing by 10 mg every 3 doses to a maximum of 100 mg/alternate days. The Max dose for ocular MG is 50 mg on alternate days. Patients with MuSK-MG appear to respond well to corticosteroids and to many steroid-sparing IS agents. They tend to remain dependent on prednisone despite concomitant treatment with steroid-sparing agents.
- Non-steroidal immunosuppressive agents used include azathioprine, cyclosporine, mycophenolate mofetil, methotrexate, and tacrolimus.
- Severe Patients with refractory MG should be referred to a physician or a centre with expertise in the management of MG. In addition to the previously mentioned IS agents, the following therapies may also be used in refractory MG:
- a. Chronic IVIg and chronic PLEX (see IVIg and PLEX);
- b. Cyclophosphamide
- c. Rituximab, for which evidence of efficacy is building, but for which formal consensus could not be reached.
- Surgery: Thymectomy for thymoma. Thymectomy should be considered in all those with myasthenia gravis and can reduce the dose or duration of immunotherapy, or if patients fail to respond to an initial trial of immunotherapy or have intolerable side effects from that therapy. Because of the long delay in onset of effect, thymectomy for MG is an elective procedure. It should be performed when the patient is stable and deemed safe to undergo a procedure where postoperative pain and mechanical factors can limit respiratory function. All patients with MG with thymoma should undergo surgery to remove the tumour. Removal of the thymoma is performed to rid the patient of the tumour and may not produce improvement in MG. All thymus tissue should be removed along with the tumour. Further treatment of thymoma will be dictated by histologic classification and the degree of surgical excision. Incompletely resected thymomas should be managed after surgery with an interdisciplinary treatment approach (radiotherapy, chemotherapy).
- Plasmapheresis or IVIG may be useful acutely especially in myasthenic crises. Many patients with MuSK-MG respond poorly to ChEIs, and conventional pyridostigmine doses frequently induce side effects MuSK-MG responds well to PLEX, while IVIg seems to be less effective. Rituximab should be considered as an early therapeutic option in patients with MuSK-MG who have an unsatisfactory response to initial immunotherapy.
- Pregnancy: Oral pyridostigmine is the first-line treatment during pregnancy. IV ChEIs may produce uterine contractions and should not be used during pregnancy. Thymectomy should be postponed until after pregnancy as the benefit is unlikely to occur during pregnancy. Chest CT without contrast can be performed safely during pregnancy, although the risks of radiation to the fetus need to be carefully considered. Unless there is a compelling indication, postponement of diagnostic CT until after delivery is preferable. Prednisone is the IS agent of choice during pregnancy. Provided that their myasthenia is under good control before pregnancy, the majority of women can be reassured that they will remain stable throughout pregnancy. If worsening occurs, it may be more likely during the first few months after delivery. Magnesium sulfate is not recommended for the management of eclampsia in MG because of its neuromuscular blocking effects; barbiturates or phenytoin usually provide adequate treatment.
- Avoid penicillamine, aminoglycosides, tetracyclines, phenytoin