Neuromuscular diseases are treated not only with drugs aiming to reverse the cause, such as the immunosuppressants in autoimmune neuropathies, myopathies, and myasthenia gravis (MG), but also with therapies that ameliorate symptoms such as those of painful neuropathy or dysautonomia. Treatments also consist of using methods that provide comfort, increase mobility, and improve the quality of life.
The therapeutic plan has to be individualized so that it involves a team approach and also aims to manage complications, such as respiratory insufficiency, swallowing problems, and cardiac disease, which occur, for example, in some muscular dystrophies.
An important consideration is the prevention and proper management of perioperative complications, for example, in those with MG who undergo thymectomy or other surgeries, during which weakness may increase and cause respiratory failure. Patients with channelopathies and those with metabolic and congenital myopathies are predisposed to develop attacks of malignant hyperthermia syndrome. These patients should be properly monitored and receive both precautionary measurements and treatment for the attacks.
Patients with motor neuron diseases such as amyotrophic lateral sclerosis (ALS) and those with severe myopathies may benefit from noninvasive ventilation as a conservative approach, but some may require tracheostomy for respiratory assistance. This might also be necessary during a myasthenic crisis. Percutaneous endoscopic gastrostomy is also frequently necessary for feeding, particularly in ALS, and should be performed before there is significant respiratory failure.
Patients with muscular dystrophies are treated with tendon stretching and physical therapy which play an important role in management, as do proper exercise programs. Tendon releases and scoliosis surgeries are done according to their severity when patients have an acceptable vital capacity. In our center, surgery for scoliosis is performed in curvatures of over 20 degrees with vital capacity over 50% of the predicted values for the body size.
Patients with Duchenne’s muscular dystrophy and those with limb–girdle dystrophies that affect the heart can benefit from angiotensin-converting enzyme inhibitors , beta-blockers, or mineralocorticoid receptor antagonists. Some might benefit from pacemaker and/or implantable defibrillators. Those with Becker’s muscular dystrophy with prominent cardiac disease may sometimes need cardiac transplantation.
There are several important complications in myotonic dystrophy that require symptomatic therapy. These include gastrointestinal dysmotility and cardiac arrhythmia, which may require pacemaker placement. Patients may also develop respiratory insufficiency, show an increased sensitivity to anesthesia, and prove difficult to wean off the ventilator after surgery.
Those with chronic peripheral neuropathies require management to prevent the development of foot ulcers from deformities and decreased pain perception. Proper use of orthosis, such as ankle–foot orthosis, and sometimes osteotomies are important choices in their management. The active participation of physical medicine and rehabilitation specialists is very valuable, and physical therapy and rehabilitation play a very valuable, and physical therapy and rehabilitation play a very important role in the management of patients with neuromuscular diseases.
It must be emphasized the role of stretching exercises and to maintain ambulation to preserve muscle function and also emphasize the need for proper bracing with the contribution of an occupational therapist and orthotists as well as other ambulator assistances and a wheelchair with adjustments.
We must also emphasize the important role of exercise to maintain function in these disorders.
Specific treatments are discussed in individual cases in this book. The remainder of this chapter covers the management of pain and dysautonomia, the treatment of disorders of neuromuscular transmission, and the use of immunosuppressants and newer genetic therapies.
Treatment of Painful Neuropathies
Pain is a common complaint in patients with neuropathies, particularly those that affect small fibers, such as nociceptive C fibers and small myelinated A-delta fibers. Pain is a major problem in diabetics.
The symptoms of painful neuropathies include burning, aching, lancinating pains, and pins/needles paresthesias. Patients may also have allodynia and hyperalgesia.
The pathogenesis of neuropathic pain includes multiple central and peripheral mechanisms. For example, there is increased sensitization of primary nociceptive afferents and increasing axonal excitability with ectopic discharges and ephaptic transmission. There could also be the formation of neuromas and alteration of the expression of ionic channels causing increasing nerve excitability.
Central sensitization occurs in the spinal cord and brain. Their mechanisms include the release of cytokines and other inflammatory mediators with increased excitability of spinal sensory neurons and decreased activity of inhibitory neurons. Neuronal damage is caused by an increased activity of the AMPA and glutamate receptors and by the accumulation of calcium through the AMPA receptors. In chronic pain there is an increased expression of micro-opioid receptors and increased activity of substance P through the N -methyl- d -aspartic acid (NMDA) receptors, facilitating excitatory responses. There is also evidence of increased connections of nonnociceptive A-beta fibers to nociceptive neurons in the lamina II of the spinal cord.
Sympathetic neuronal sprouting occurs in the posterior root ganglia with increased sensitization of C terminals and the release of inflammatory mediators from sympathetic nerve terminals.
Finally, connections of sensory pathways with the limbic system might contribute to the emotional effects of chronic pain.
Drugs used to Treat Chronic Pain
The rational approach for the management of chronic neuropathic pain includes the use of a combination of therapies that act in different areas of pain generation, including central and peripheral sensitization ( Fig. 3-1 ).
First-line drugs are those whose benefit has been demonstrated with well-controlled clinical trials; these include tricyclic antidepressants, gabapentin, duloxetine, and pregabalin (see Fig. 3-1 ). These drugs can be used alone or in combination, for example, tricyclics in addition to gabapentin. Other therapies can be initiated when there is no response to first-line drugs. ( Table 3-1 lists common drugs used in painful neuropathy, their side effects, and mechanisms of action.)
| Drug | Mechanism | Side Effects |
|---|---|---|
| Antidepressants | ||
| Tricyclics and tetracyclics | 5-HT and NE reuptake inhibitors, Na + channel blockage | Sedation, cholinergic effects, glaucoma, dryness, constipation, psychosis, arrhythmias, and seizures; desipramine produces fewer cholinergic effects, nortriptyline fewer cardiac effects |
| Duloxetine | 5-HT and NE reuptake inhibitor | Sedation, cognitive dysfunction, nausea, and minor cholinergic effects |
| Venlafaxine | 5-HT and NE reuptake inhibitor | Sedation, psychosis, lowers seizure threshold, insomnia, nervousness; used in the treatment of tobacco addiction, and weight loss |
| Anticonvulsants | ||
| Gabapentin | Ca 2+ channel agonist | Dryness, cognitive dysfunction, and weight gain |
| Carbamazepine | Modulator of Ca 2+ channel, blocks Na + channel | Sedation, dizziness, hyponatremia, liver toxicity, and leukopenia |
| Phenytoin | Blocks Na + channels | Hirsutism, osteopenia, anemia, rash, liver toxicity, neuropathy, and gingival hyperplasia |
| Pregabalin | Ca 2+ channel blocker | Dizziness, weight gain, cognitive dysfunction, and swelling |
| Topiramate | Na + channel blocker | Glaucoma, kidney stones, sedation, and weight loss |
| Lamotrigine | Na + channel stabilization, glutamate release inhibitor, modulate Ca 2+ , K + currents | Rash, Stevens–Johnson syndrome, needs slow titration, and liver toxicity |
| Mexiletine | Na + channel blocker | Leukopenia, arrhythmia |
| Analgesics | ||
| Opiates (hydroxycodone, oxycodone, codeine) | Opioid agonists, bind opioid receptors, and mainly μ receptors | Sedation, dry mouth, nausea, constipation, respiratory depression, confusion, and addiction |
| Tramadol | Micro-opioid receptor agonist | Seizures, addictive potential, and nausea |
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Tricyclic Antidepressants
These are serotonin (5-HT) and norepinephrine (NE) reuptake inhibitors with some effect on dopa reuptake. The tricyclics have a cyclical structure similar to phenothiazines, but with different mechanisms of action. The first tricyclic used was imipramine , which is metabolized to desipramine , while another tricyclic, nortriptyline , is a metabolite of amitriptyline.
Tricyclics are absorbed in the gut, bind to albumin, and are metabolized in the liver. Their effects in chronic pain include blockade of sodium channels, suppression of ectopic discharges, alterations of central NE and 5-HT reuptake, and central nociceptive modulation.
Side effects and benefits of different tricyclics vary. The most common include constipation, orthostatic hypotension (OH), dry mouth, other cholinergic symptoms, and weight gain. They can precipitate attacks of narrow-angle glaucoma or cause urinary retention, particularly in patients with prostatic hypertrophy. These drugs should not be used concomitantly with monoamine oxidase (MAO) inhibitors.
Because of their sedative effects, tricyclics are usually given at nighttime for insomnia and nocturnal symptoms. Nortriptyline has fewer cardiovascular effects, such as arrhythmias, particularly in the elderly, while desipramine is less sedating and has fewer anticholinergic effects (see Table 3-1 ). The usual dosage of amitriptyline is 10–150 mg, nortriptyline 10–150 mg, desipramine 25–150 mg, and imipramine 50–200 mg.
Atypical Antidepressants, Selective Serotonin, and Norepinephrine Reuptake Inhibitors
Venlafaxine is a 5-HT and NE reuptake inhibitor antidepressant also useful in chronic pain syndrome. Side effects include nausea, diarrhea, and sedation. The drug is used in dosages of 75–225 mg a day.
Bupropion is a nontricyclic antidepressant that inhibits NE and dopamine reuptake. The drug is used in dosages of 150–300 mg a day for chronic pain. It has also been used for tobacco addiction. Bupropion causes less sexual dysfunction than other antidepressants but might produce hypertension and lower the threshold for seizures. The drug is eliminated primarily by the liver and its metabolism could be affected by other drugs.
Duloxetine hydrochloride is a selective 5-HT and NE reuptake inhibitor introduced recently to treat painful diabetic neuropathy usually in dosages of 60 mg twice a day (higher doses can be used). This drug is eliminated mainly by hepatic metabolism in the P450 system. Side effects include minor cholinergic symptoms, nausea, vomiting, and constipation. Duloxetine may interfere with MAO inhibitors and may produce mild cognitive dysfunction and sedation, similar to tricyclics. Because this drug metabolizes in the liver and kidney, it should be taken with caution in patients with liver or kidney failure.
Selective 5-HT reuptake inhibitors such as fluoxetine may help diminish depression but do not have proven effects in pain.
Anticonvulsants
Anticonvulsants have been used extensively in neuropathic pain because of their action of diminishing peripheral and spinal cord pain–mediated mechanisms.
Carbamazepine is closely related to tricyclics and acts by inhibiting sodium channels. The drug is used in doses of 200 mg three times a day, but the dosage should be adjusted slowly by titration, because the drug can cause dizziness and sedation, which is increased according to plasma levels, but tolerability varies. Side effects include not only dizziness but also sedation, hyponatremia, liver toxicity, and particularly aplastic anemia and agranulocytosis. Some patients might develop a rash. Carbamazepine is metabolized in the liver, and its metabolites are eliminated by the kidneys. In chronic users, levels should be monitored and dosage may need to be increased, because the drug is a self-inducer of its metabolism.
Oxcarbazepine is structurally similar to carbamazepine but has different pharmacokinetic and pharmacodynamic properties. It slows the recovery state of voltage-activated sodium channels, inhibits calcium channels, and reduces glutaminergic transmission, thus affecting central and peripheral mechanisms of pain. Oxcarbazepine has fewer bone marrow depressive effects than carbamazepine but can produce significant hyponatremia and sedation.
Phenytoin has some effect in pain reduction by blocking sodium channels and, because of its long half-life, can be used in single daily dosages, usually of 300 mg adjusted according to blood levels. Phenytoin is metabolized in the liver by the P450-enzyme system and its levels are affected by other drugs that utilize this system. Side effects of phenytoin are common, for example, hirsutism, gingival hyperplasia, mild peripheral neuropathy, bone marrow suppression, rash, Stevens–Johnson syndrome, macrocytic anemia and vitamin D deficiency, liver disease, and, rarely, cerebellar degeneration.
Valproic acid is a carboxylic acid derivative that potentiates gabaminergic neuronal activity. It benefits patients with chronic pain by potentiating inhibitory pathways. Its starting dose is 15 mg/kg, increased up to 60 mg/kg, adjusting according to blood levels. The usual doses are 250–500 mg three times a day. Side effects include tremor, obesity, hair loss, skin rash, and liver dysfunction. Valproic acid should not be used in patients with liver disease. The drug could also cause bone marrow suppression and can produce teratogenic effects. The metabolism of valproic acid could be influenced by other drugs.
Gabapentin is a gamma-aminobutyric acid (GABA) agonist with very weak antiepileptic activity but has significant effects on chronic pain. It is well tolerated and is eliminated mainly in the kidney, so it is not affected by other drugs that are metabolized in the liver. It competes with l -type amino acids for active transport, has a high affinity binding to the alpha-2-delta subunit of the voltage-activated calcium channels, inhibits sodium channels, and increases 5-HT concentrations. Daily dosages can be raised to 3600 mg a day or even higher, according to clinical response and side effects. Common side effects include dizziness, drowsiness, edema, and weight gain; significant cognitive dysfunction occurs with higher doses.
Lamotrigine is an anticonvulsant that not only stabilizes sodium channels and inhibits glutamate release but also has an effect on calcium and potassium currents. The drug is efficient in chronic pain management and is well tolerated. The usual dosages can vary from 200 to 600 mg daily. The most significant side effect is rash which can be severe, and some patients develop Stevens–Johnson syndrome. The risks can be diminished with slow titration. Lamotrigine metabolizes in the liver and can be affected by other drugs such as valproic acid. Cognitive dysfunction is minimal.
Topiramate works by inhibiting voltage-gated calcium and sodium channels by enhancing GABA receptors and antagonizing glutamate receptors. It is particularly useful in the treatment of diabetic neuropathy ; side effects include loss of appetite and weight, somnolence, diarrhea, and dizziness. There is a risk of kidney stones, and the drug can precipitate attacks of glaucoma. Dosages vary from 100 to 400 mg a day given in divided doses.
Pregabalin is a new antiepileptic that acts preferentially, binding to the alpha-2-delta subunit of the voltage-gated calcium channels. Its antiepileptic effects are weak but it has a proven beneficial effect in painful neuropathies. Pregabalin is eliminated primarily by the kidneys; only 9% is metabolized in the liver. Side effects include dryness, dizziness, weight gain, somnolence, edema, and infections. It can cause decreased cognitive function. The drug should be given with caution in patients with liver and kidney disease. The usual dosages are 75–150 mg two times a day.
Other Treatments
Antiarrhythmic agents such as tocainide and mexiletine have a peripheral effect, blocking sodium channels and thereby producing significant pain relief. These drugs have also been used in the treatment of myotonia and in patients with muscle spasms of neurogenic origin. Tocainide is no longer used because of its toxic effects. Opioids and other pain medications such as oxycodone and others are useful, but can cause addiction, and should be used with caution. Medical marijuana is now being used increasingly in the treatment of chronic pain. The main metabolites tetrahydroxy cannabinol and cannabidiol and other cannabinoids appear to be very useful in the management of chronic peripheral neuropathy pain.
Methadone is a 5-HT and NE reuptake inhibitor as well as an NMDA receptor antagonist and is very helpful in the management of pain that should be used with caution, because of addiction, and particularly should be given by pain specialists. Levorphanol is a synthetic opioid with NMDA receptor antagonism and is used in painful neuropathies. Tapentadol is a centrally acting drug that has a very strong analgesic effect with opioid and adrenergic features and has been proven to be helpful in diabetic neuropathy.
Opioid analgesics are not only useful mainly in acute pain management but are also prescribed in some chronic pain syndromes, although these drugs cause addiction. Side effects include sedation and cholinergic symptoms, such as constipation and nausea. Tramadol is a nonnarcotic, centrally acting synthetic analgesic that has a low addicting potential compared with hydroxycodone or oxycodone. Tramadol is used in doses of 50 mg four times a day starting with slow titration. Higher dosages can be used; it may lower the threshold for seizures, cause constipation, and produce dryness and respiratory problems. Other opiates can also be used in severe pain, but they have higher addictive effects.
NMDA antagonists such as dextromethorphan provide mild relief in painful neuropathy and have side effects similar to tramadol.
Skin patches of the local anesthetic lidocaine and capsaicin are topical therapies for pain. Capsaicin depletes substance P in nerve terminals. Magnets and other nonspecific treatments, such as acupuncture, may also be helpful and is free of side effects, because of poor absorption; side effects may include skin irritation.
Topical lidocaine is a therapeutic method used to treat postherpetic neuralgia but can be used to treat chronic pain from neuropathy. High-frequency spinal cord stimulation produces substantial pain relief in diabetic polyneuropathy.
Treatment of Autonomic Dysfunction
Patients with peripheral neuropathy and other neuromuscular disorders might also develop symptoms of dysautonomia which include orthostatic hypotension (OH), constipation, bladder problems, and sexual dysfunction.
OH is treated with a commonsense approach, including proper hydration and by increasing fluid and caffeine intake during the day. Pressurized stockings are also helpful. Drugs that cause OH should be discontinued or used in lower doses.
Midodrine hydrochloride is the drug most frequently used for OH. It is metabolized to desglymidodrine, an alpha-1 agonist that increases vascular tone and blood pressure. Because of this, a potential side effect is supine hypertension that can be severe at night. For this reason, it should be given with caution, avoiding late-night dosages, and patients taking it should sleep with their heads elevated. The usual dosage is 2.5–10 g four times a day. Other similar drugs, such as phenylpropanolamine and ephedrine , are sometimes used in patients who cannot take midodrine.
Fludrocortisone is a potent mineralocorticoid that is used in a dosage of 0.1–0.2 mg two times a day. Side effects include hyperglycemia, fluid retention, edema, hypertension, hypokalemia, and, rarely, hypomagnesemia.
Droxidopa in doses of 100–600 mg three times a day has been very useful and is a synthetic precursor of NE that induces peripheral brain and arterial vasoconstriction. The main side effects of concern include hypertension.
Other treatments include erythropoietin that might help by increasing blood expansion and is used in those with mild anemia. Oteoclide , which can be given in subcutaneous injections, is used in those with severe postprandial hypotension, in dosages of 0.2 mg/kg subcutaneously three times a day with meals. Desmopressin is a potent V2 renal vasopressor receptor agonist that produces nocturnal antidiuretic effects. It therefore can be used in patients with severe disease and nocturnal polyuria in a dosage of 10–40 μg transnasal every night.
Pyridostigmine also helps OH by increasing transmission in sympathetic ganglion.
Decreased esophageal and intestinal motility and constipation are treated with proper hydration. Pyridostigmine can be helpful.
Metoclopramide is an anticholinergic and antidopamine agent that acts mainly in GI 5-HT receptors; it is sometimes of benefit in those with decreased esophageal motility. The drug is used in dosages of 5–10 mg three times a day. It can produce dryness, nausea, vomiting, and, particularly, confusion, dystonia, and parkinsonism. It can precipitate malignant neuroleptic syndrome. Proper use of stool softeners, bisacodyl, and senna can be helpful for constipation.
Urinary Symptoms
Urinary retention and particularly urinary incontinence can be caused by detrusor hyperreflexia which is treated with the anticholinergic oxybutynin in doses of 2.5–15 mg three times a day, or tolterodine in doses of 1–4 mg three times a day. Both drugs have extended-release forms. Desmopressin can be used because of its antidiuretic effects, particularly in those with nocturnal enuresis.
Sexual dysfunction in males is treated with a commonsense approach, including avoidance of drugs that can decrease libido and psychotherapeutic measurements.
Sildenafil citrate and similar drugs work by inhibiting cyclic guanosine monophosphate, which is a specific phosphodiesterase inhibitor that produces vasodilation of the corporae smooth muscle. They have several side effects, which include change in color perception, facial flushing, headaches, and, rarely, optic nerve damage. They might decrease platelet aggregability and have the potential to cause intracranial hemorrhage. This drug can also cause severe cardiovascular complications, particularly in patients with heart disease, and can potentiate vasodilation and hypotension caused by nitrates.
Other treatment includes vacuum constriction devices, urethral suppositories, and intracavernous injections of vasoactive drugs.
Other Symptomatic Treatments in Neuromuscular Disorders
Management of neuromuscular disorders also includes treatment and control of secondary symptoms that are not uncommon in patients with severe weakness, including sialorrhea in ALS and other motor neuron diseases from poor swallowing. This can be treated with anticholinergic drugs such as glycopyrrolate in doses of 1–2 mg three times a day and benztropine and trihexyphenidyl in doses of 2 mg three times a day. Dosages can be increased with caution; side effects include constipation, dryness, and confusion. These drugs can precipitate attacks of glaucoma . Scopolamine patches and tricyclics can also be used to decrease sialorrhea.
Antispasticity drugs are frequently used to treat patients with prominent upper motor neuron disorders. These include baclofen , a GABA agonist that is used in doses of 10–20 mg four times a day, but this can be increased up to 200 mg per day as tolerated. Baclofen metabolizes in the liver and interacts with other drugs. Side effects include sedation, dizziness, and liver toxicity. Rapid withdrawal can cause hallucinations. A potential problem, as with other muscle relaxants, is the possibility of increasing weakness.
Tizanidine is a centrally acting alpha 2-adrenergic agonist that relieves spasticity by increasing presynaptic inhibition of the motor neurons. The usual starting dosage is 2–4 mg three times a day, increasing to 36 mg a day as tolerated. Tizanidine not only is metabolized in the liver and has interactions with other drugs that utilize the P450 system but is also eliminated in the kidney. Its excretion might be affected in patients with kidney disease. The most significant side effects are sedation and dizziness, but the drug can also cause hypotension, as it has a mechanism of action similar to the antihypertensive clonidine and, rarely, can cause liver failure.
Quinine sulfate , a commonly used muscle relaxant, is also a sodium channel blocker. It is used for peripheral muscle cramps in doses of 260–375 mg a day. It is contraindicated in myasthenia gravis (MG), can produce thrombocytopenia, dizziness, and tinnitus, and could precipitate arrhythmias.
Benzodiazepines are centrally acting GABA agonists. The drug used most commonly is diazepam . It has sedating effects and can be addictive. Diazepam can be used in dosages of 5–10 mg three times a day. This and other benzodiazepines are metabolized in the liver, and their metabolism is affected by other drugs. Side effects include sedation and increased muscle weakness.
Dantrolene is a peripherally acting muscle relaxant that works via inhibition of the release of calcium by the sarcoplasmic reticulum in muscle; the usual dosages are 25–50 mg three times a day. This drug is helpful not only in spasticity but also in the prevention and treatment of attacks of malignant hyperthermia in the dosage of 2 mg/kg IV every 5 minutes until the attack is controlled. We have found the drug to be beneficial in the treatment of muscle spasms, particularly in myopathies. Dantrolene is metabolized mainly in the liver and affects the metabolism of other drugs. It can cause severe sedation and, rarely, severe liver disease, particularly in young children.
Treatment of Myasthenia Gravis and Other Disorders of Neuromuscular Transmission
The first-line therapy of MG includes the use of anticholinesterase drugs. Other treatments include immunosuppressants, plasma exchange, and gamma globulin infusions, discussed in the section on immunosuppressants. These are used in patients with generalized myasthenia and those with disabling ocular myasthenia who do not respond to anticholinesterase drugs.
Thymectomy is an effective treatment, particularly in those with generalized myasthenia, even if there is no evidence of thymoma. In our center we first stabilize the patient prior to thymectomy, particularly with the use of plasmapheresis 2–3 weeks prior to surgery, depending on the clinical presentation. In patients with significant weakness, corticosteroids are initiated at least 1 month prior to thymectomy. Thymectomy has not been proven beneficial in controlled studies, but the evidence is very suggestive that this is an important therapeutic option. Most recommend a total or a transsternal thymectomy, and this is the approach in our center. Proper management during the pre- and perioperative period is important to prevent complications.
Pyridostigmine (Mestinon) is the most common anticholinesterase drug used to treat MG. Its pharmacologic effects are produced by inhibition of cholinesterase, the enzyme that metabolizes the neurotransmitter acetylcholine at the neuromuscular junction and the autonomic ganglia. It is given in doses of 60–120 mg every 4 hours; the dosage should be regulated according to the symptoms. A time-released preparation is also available but is not frequently used because of unpredictable absorption, though some give it in dosages of 180 mg three times a day. This preparation is used sometimes only at night to prevent early morning weakness. It should not be broken or split.
Patients who cannot take oral pyridostigmine may be given a parenteral dosage of 1 / 30 of the usual oral dose.
Side effects include muscarinic cholinergic symptoms such as increased secretions, bronchial spasms, diarrhea, and cramps. Pyridostigmine can also increase intraocular pressure. Excessive dosages can cause increased weakness and a cholinergic crisis. Allergic reactions to the bromide in the drug can occur. Pyridostigmine is metabolized mainly in the liver.
Neostigmine is another anticholinesterase drug, although used less frequently. It is given in doses of 15–30 mg every 4 hours; the total daily dose should not exceed 150 mg. Neostigmine can be given intravenously or intramuscularly in doses of 0.5–1.5 mg every 4 hours. This drug is also metabolized in the liver.
Ambenonium chloride is a seldom-used anticholinesterase drug that seems to produce fewer cholinergic side effects. The usual dosage is 7.5 mg but could go up to 15 mg every 6 hours as tolerated.
3–4 Aminopyridine is a potassium channel blocker that enhances acetylcholine release and is used in the treatment of Eaton–Lambert syndrome. The dosage is 5–20 mg four times a day. Side effects include tingling paresthesias, spasms, and seizures at a total dosage of 100 mg or more. Immunotherapy could be beneficial in these patients, particularly for those with idiopathic causes.
Ephedrine is helpful in some congenital myasthenic syndromes. Fluoxetine and quinidine are beneficial in the slow channel myasthenic syndrome.
Immunotherapy
Many neuromuscular disorders have an autoimmune etiology whose treatments require the use of either a single or a combination of immunosuppressant drugs and other therapies such as plasma exchange and gamma globulin infusions. The most frequently prescribed immunotherapeutic drugs are described in the following subsections (summarized in Table 3-2 ).
| Drug | Dosage | Side Effects | Drug Monitoring | Indications | Evidence Level according to the AAN criteria |
|---|---|---|---|---|---|
| 0.5-2 mg/kg po daily then taper | See Box 7-1 | Weight, blood pressure, glucose, bone density, eye examination |
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| Methylprednisolone | 1 g IV q day x 3-5 days as initial treatment then 1 g IV weekly for 1 month before tapering or 500 mg po q week | See Box 7-1 | As above |
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| Therapeutic Plasma Exchange | 500-5000 mL plasma volume per exchange x 4 exchanges | Pneumo-hemothorax, easy bruising or bleeding, hypotension |
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| Methotrexate | 5 mg/week to 25 mg/week po or IV/IM |
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| Mycophenolate mofetil | 2-4 or 5 g daily, divided bid | Gastrointestinal upset, paresthesias, bone marrow suppression, liver toxicity (rare) | CBC weekly to monthly initially then tri-monthly |
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| Cyclophosphamide | 0.5-1 g/m 2 IV q month | Myelosuppression, myelofibrosis, hemorrhagic cystitis, malignancy (especially bladder) | CBC weekly, liver function tests weekly for a month and then every 1 to 3 months, urinalysis every 1 to 3 months |
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| 3-5 mg/kg po q day divided bid | Hypertension, renal insufficiency, CNS toxicity, hirsutism |
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| Tacrolimus | 3-4 mg up to 1 mg/kg po q day divided bid | Same as discussed earlier but less common, diabetes mellitus |
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| Rapamycin | 2-5 mg po q day | Hyperlipidemia | Periodic CMP | dermatomyositis | U |
| Monoclononal Antibodies Rituximab | 0.375 g/m 2 IV weekly x 4 or 1 g IV q other week x2 |
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| Alemtuzumab | Varies |
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| CIDP | U |
| 3-6 mg/kg IV periodically |
| CBC, CMP monthly |
| U |
| Etanercept | 25 mg sq biweekly | As above | As above |
| U |
| Anakinra | 100 mg sq q day |
| CBC, CMP monthly | Inflammatory myopathies | U |
| Interferon-β-1a | 30 μg IM q week |
| CMP, TSH periodically | CIDP | U |
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