For generations, the neuromuscular disorder care community has focused on establishing the correct diagnosis and providing supportive care. As the pathophysiology and genetics of these conditions became better understood, novel treatments targeting the disease mechanism were developed. This has led to some significant disease-modifying and supportive treatments for several neuromuscular disorders. The current treatments for amyotrophic lateral sclerosis (ALS), neuromuscular junction disorders, inflammatory myopathies, and myotonia are reviewed. Additionally, investigational treatments for ALS, Duchenne muscular dystrophy, and spinal muscular atrophy are discussed.
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Pompe disease is a heterogeneous hereditary neuromuscular disorder with an effective treatment.
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Riluzole remains the only disease-modifying treatment for amyotrophic lateral sclerosis (ALS) that is approved by the Food and Drug Administration; however, readily available symptomatic treatments can provide relief from the often-distressing symptoms associated with ALS and improve quality of life for the patient.
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Autoimmune inflammatory myopathies, except inclusion body myositis, characteristically respond with rapid improvement after the initiation of corticosteroid treatment.
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Treatments available for the neuromuscular junction disorders vary based on the underlying genetic or autoimmune abnormality, and should be individualized to avoid significant adverse events and provide the most efficacious disease management.
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New and promising gene-based drug therapies for Duchenne muscular dystrophy and spinal muscular atrophy are currently in clinical trial.
Introduction
Neuromuscular disorders are a collection of well-defined acquired or inherited clinical conditions that affect neuromuscular function. The clinical conditions are a highly heterogeneous group that can affect skeletal muscle, motor neurons, peripheral nerves, and neuromuscular junctions. In the past few decades, there has been a significant increase in the understanding of the pathophysiology of neuromuscular disorders whether attributable to a genetic etiology or an autoimmune process. With the better understanding of disease mechanisms leading to neuromuscular weakness, researchers have attempted to develop therapeutic interventions directly affecting the pathophysiology of the various disorders. Although the development of therapeutic interventions has been slow, the potential for significant therapeutic modalities remains promising.
Pharmacologic management of Pompe disease
Pompe disease, also referred to as acid maltase deficiency (or glycogen storage disease type II), is a rare autosomal recessive disorder caused by deficiency of the glycogen-degrading lysosomal enzyme acid alpha-glucosidase (GAA). Lysosomal GAA catalyzes the breakdown of glycogen into glucose, and the GAA deficiency in Pompe disease results in the accumulation of lysosomal and nonlysosomal glycogen in multiple tissues. In the infantile-onset form of Pompe disease, GAA enzyme activity is either completely or nearly completely absent (typically <1% of normal activity). Some residual enzyme activity (approximately 2%–40% of normal activity) is present in most children and adults with the late-onset form. Infantile-onset Pompe disease is a progressive, multisystemic disorder that causes hypotonia, cardiomyopathy, respiratory deficiency, and feeding difficulties in the first year of life. The disease affects cardiac, skeletal, and smooth muscles and the pulmonary and gastrointestinal systems, as well as anterior horn cells. Death owing to cardiopulmonary failure typically occurs in the first year of life, with rare survival past 2 years. Late-onset Pompe disease is also a multisystemic disease; it may manifest at any time after 12 months of age. Its clinical presentation includes progressive muscle weakness, especially in the trunk and lower limbs; respiratory symptoms with restrictive lung disease pattern; and progression to respiratory insufficiency because of diaphragmatic and intercostal muscle involvement. Respiratory complications are the most frequent cause of death in the late-onset Pompe disease.
Alglucosidase Alfa
Disease-specific enzyme replacement treatment (ERT) strategy for Pompe disease was first attempted in 1973. Highly purified, placenta-derived GAA enzyme was administered by intravenous infusion, taking advantage of the lysosome’s ability to internalize exogenously delivered proteins by endocytosis. Initial attempts at ERT encountered problems of immunogenicity, and there was limited availability of purified GAA for practical and sustainable enzyme delivery. In 1979, the 28-kb gene for GAA was identified on chromosome 17, and in the 1990s, new recombinant DNA technology became available, enabling the production of enough recombinant human acid alpha-glucosidase (rhGAA) to allow ERT clinical trials to be conducted. In 2006, alglucosidase alfa (MYOZYME, Genzyme Corporation, Cambridge, MA) was approved by the US Food and Drug Administration (FDA) and the European Medicines Agency and became the first disease-specific treatment for Pompe disease. The approval was based on the results of a pivotal clinical trial of ERT with alglucosidase alfa in 18 infants showing significant benefit. The ERT with rhGAA improved ventilator-free survival, cardiomyopathy, growth, and motor function in patients with infantile-onset Pompe disease compared with outcomes expected for patients without treatment.
The results of the first randomized, double-blind, placebo-controlled study of ERT, known as the Late-Onset Treatment Study (LOTS), led to the FDA approval in 2010 of LUMIZYME (Genzyme Corporation) for the treatment of late-onset Pompe disease in the United States. Those who qualified for the study were randomly assigned in a ratio of 2:1 to receive biweekly infusions of alglucosidase alfa (20 mg/kg, based on body weight) or placebo. The LOTS trial was conducted in 90 patients 8 years or older (range, 10–70 years). The 2 coprimary end points were distance walked during a 6-minute walk test (6MWT) and the percent of predicted forced vital capacity (FVC) in the upright position. At week 78, statistically significant findings in favor of alglucosidase alfa were noted in both the 6MWT and percentage of predicted upright FVC results. All of the secondary and tertiary end points favored the treatment group, but only the MEP results reached statistical significance. Similar frequencies of adverse events, serious adverse events, and treatment-related adverse events occurred in patients in both the treatment and placebo groups. Anaphylactic reactions occurred only in patients receiving ERT (5%, 3 of 60 treated). All of the alglucosidase alfa recipients tested negative for immunoglobulin G (IgG) anti-GAA antibodies at start of the trial, but all seroconverted by week 12. The study findings indicate that alglucosidase alfa has a positive effect on the disease process or processes that produce impaired ambulation and respiratory insufficiency in late-onset Pompe disease, but treatment carries a risk of serious potential complications, including anaphylactic reactions. Because 5% of patients in the treatment group of the LOTS trial developed an anaphylactic reaction, caution is recommended during home-based infusion and patients treated with alglucosidase alfa who have persistently high antibody titers should be closely monitored until the effect of the antibodies is more fully understood. Several treatment recommendation guidelines for Pompe disease are available.
In the United States, LUMIZYME is available only through a restricted distribution program: the LUMIZYME ACE (Alglucosidase Alfa Control and Education) Program. The program is a risk evaluation and mitigation strategy program designed to mitigate the potential risk of rapid disease progression in patients with infantile-onset Pompe disease and patients with late-onset disease who are younger than 8 years, for whom the safety and efficacy of LUMIZYME have not been evaluated in randomized, controlled studies. The LUMIZYME ACE Program acts to ensure that “the known risks of anaphylaxis and severe allergic reactions associated with the use of alglucosidase alfa are communicated to patients and prescribers and to ensure that potential risks of severe cutaneous and systemic immune-mediated reactions to alglucosidase alfa are communicated to patients and prescribers.” Moreover, prescribers, health care facilities, and patients treated in the United States must enroll in the LUMIZYME ACE Program before alglucosidase alfa will be authorized for shipment, and prescribers and health care facilities at which ERT infusions will be conducted must complete the LUMIZYME ACE Program online certification ( www.lumizyme.com/ace/default.asp ).
The completion and successes of the infantile and late-onset Pompe trial with subsequent FDA approval of ERT as treatment for Pompe disease are tremendous achievements. Much work remains to be completed, however, including more basic research improving our understanding of the links between GAA enzyme deficiency, glycogen deposition, lysosomal function, and the various phenotypic presentations. For the future, other potential therapeutic approaches are also being explored that include small molecule pharmacologic chaperones, gene therapy (adeno-associated virus), and new-generation ERT with improved targeted delivery capabilities.
Pharmacologic management of Pompe disease
Pompe disease, also referred to as acid maltase deficiency (or glycogen storage disease type II), is a rare autosomal recessive disorder caused by deficiency of the glycogen-degrading lysosomal enzyme acid alpha-glucosidase (GAA). Lysosomal GAA catalyzes the breakdown of glycogen into glucose, and the GAA deficiency in Pompe disease results in the accumulation of lysosomal and nonlysosomal glycogen in multiple tissues. In the infantile-onset form of Pompe disease, GAA enzyme activity is either completely or nearly completely absent (typically <1% of normal activity). Some residual enzyme activity (approximately 2%–40% of normal activity) is present in most children and adults with the late-onset form. Infantile-onset Pompe disease is a progressive, multisystemic disorder that causes hypotonia, cardiomyopathy, respiratory deficiency, and feeding difficulties in the first year of life. The disease affects cardiac, skeletal, and smooth muscles and the pulmonary and gastrointestinal systems, as well as anterior horn cells. Death owing to cardiopulmonary failure typically occurs in the first year of life, with rare survival past 2 years. Late-onset Pompe disease is also a multisystemic disease; it may manifest at any time after 12 months of age. Its clinical presentation includes progressive muscle weakness, especially in the trunk and lower limbs; respiratory symptoms with restrictive lung disease pattern; and progression to respiratory insufficiency because of diaphragmatic and intercostal muscle involvement. Respiratory complications are the most frequent cause of death in the late-onset Pompe disease.
Alglucosidase Alfa
Disease-specific enzyme replacement treatment (ERT) strategy for Pompe disease was first attempted in 1973. Highly purified, placenta-derived GAA enzyme was administered by intravenous infusion, taking advantage of the lysosome’s ability to internalize exogenously delivered proteins by endocytosis. Initial attempts at ERT encountered problems of immunogenicity, and there was limited availability of purified GAA for practical and sustainable enzyme delivery. In 1979, the 28-kb gene for GAA was identified on chromosome 17, and in the 1990s, new recombinant DNA technology became available, enabling the production of enough recombinant human acid alpha-glucosidase (rhGAA) to allow ERT clinical trials to be conducted. In 2006, alglucosidase alfa (MYOZYME, Genzyme Corporation, Cambridge, MA) was approved by the US Food and Drug Administration (FDA) and the European Medicines Agency and became the first disease-specific treatment for Pompe disease. The approval was based on the results of a pivotal clinical trial of ERT with alglucosidase alfa in 18 infants showing significant benefit. The ERT with rhGAA improved ventilator-free survival, cardiomyopathy, growth, and motor function in patients with infantile-onset Pompe disease compared with outcomes expected for patients without treatment.
The results of the first randomized, double-blind, placebo-controlled study of ERT, known as the Late-Onset Treatment Study (LOTS), led to the FDA approval in 2010 of LUMIZYME (Genzyme Corporation) for the treatment of late-onset Pompe disease in the United States. Those who qualified for the study were randomly assigned in a ratio of 2:1 to receive biweekly infusions of alglucosidase alfa (20 mg/kg, based on body weight) or placebo. The LOTS trial was conducted in 90 patients 8 years or older (range, 10–70 years). The 2 coprimary end points were distance walked during a 6-minute walk test (6MWT) and the percent of predicted forced vital capacity (FVC) in the upright position. At week 78, statistically significant findings in favor of alglucosidase alfa were noted in both the 6MWT and percentage of predicted upright FVC results. All of the secondary and tertiary end points favored the treatment group, but only the MEP results reached statistical significance. Similar frequencies of adverse events, serious adverse events, and treatment-related adverse events occurred in patients in both the treatment and placebo groups. Anaphylactic reactions occurred only in patients receiving ERT (5%, 3 of 60 treated). All of the alglucosidase alfa recipients tested negative for immunoglobulin G (IgG) anti-GAA antibodies at start of the trial, but all seroconverted by week 12. The study findings indicate that alglucosidase alfa has a positive effect on the disease process or processes that produce impaired ambulation and respiratory insufficiency in late-onset Pompe disease, but treatment carries a risk of serious potential complications, including anaphylactic reactions. Because 5% of patients in the treatment group of the LOTS trial developed an anaphylactic reaction, caution is recommended during home-based infusion and patients treated with alglucosidase alfa who have persistently high antibody titers should be closely monitored until the effect of the antibodies is more fully understood. Several treatment recommendation guidelines for Pompe disease are available.
In the United States, LUMIZYME is available only through a restricted distribution program: the LUMIZYME ACE (Alglucosidase Alfa Control and Education) Program. The program is a risk evaluation and mitigation strategy program designed to mitigate the potential risk of rapid disease progression in patients with infantile-onset Pompe disease and patients with late-onset disease who are younger than 8 years, for whom the safety and efficacy of LUMIZYME have not been evaluated in randomized, controlled studies. The LUMIZYME ACE Program acts to ensure that “the known risks of anaphylaxis and severe allergic reactions associated with the use of alglucosidase alfa are communicated to patients and prescribers and to ensure that potential risks of severe cutaneous and systemic immune-mediated reactions to alglucosidase alfa are communicated to patients and prescribers.” Moreover, prescribers, health care facilities, and patients treated in the United States must enroll in the LUMIZYME ACE Program before alglucosidase alfa will be authorized for shipment, and prescribers and health care facilities at which ERT infusions will be conducted must complete the LUMIZYME ACE Program online certification ( www.lumizyme.com/ace/default.asp ).
The completion and successes of the infantile and late-onset Pompe trial with subsequent FDA approval of ERT as treatment for Pompe disease are tremendous achievements. Much work remains to be completed, however, including more basic research improving our understanding of the links between GAA enzyme deficiency, glycogen deposition, lysosomal function, and the various phenotypic presentations. For the future, other potential therapeutic approaches are also being explored that include small molecule pharmacologic chaperones, gene therapy (adeno-associated virus), and new-generation ERT with improved targeted delivery capabilities.
Pharmacologic management of amyotrophic lateral sclerosis
Amyotrophic lateral sclerosis (ALS) remains a challenging condition to treat, and current medical treatments have only a modest effect on disease progression. ALS progressively causes muscle weakness and eventually respiratory failure. Mechanical ventilation can prolong life significantly, but this option is rarely used in North America because of patient preferences and sometimes because of economic concerns. The nonpharmacologic interventions of noninvasive ventilation and gastrostomy tubes provide prolonged life expectancy.
Riluzole
The only medication proven to slow ALS is riluzole. Its major pharmacologic effect in ALS is serving as a glutamate receptor blocker, thereby preventing excitotoxicity. The medication also has a sodium channel blocking effect of uncertain relevance to ALS. Riluzole has a modest benefit in animal models of ALS. In human trials, survival was prolonged by 2 to 3 months. Riluzole has failed to demonstrate any benefits on strength or breathing function. The modest survival benefit that has been demonstrated was shown in patients in a relatively early stage of disease and a trial of patients with more advanced disease did not demonstrate a survival advantage with riluzole. Patients with more advanced disease may not benefit from the medication or the benefit was too small to be detected in the trial of 168 patients. Despite riluzole’s clear effect on patients with early ALS, the drug is not uniformly used in North America, with only 59% of patients taking the drug.
Riluzole is dosed at 50 mg daily for the first week and then 2 times daily thereafter. Elevated liver enzymes occurs 2.62 times more often in patients taking riluzole versus placebo. Monitoring liver enzymes is advisable before treatment and after 1 month, followed by testing every 3 to 6 months. More common limiting side effects include gastrointestinal discomfort and diarrhea. Riluzole binds to food in the stomach. To ensure maximal absorption, it should be administered apart from meals.
Experimental Pharmacologic Management in ALS
Investigative approaches in early development are covered in a separate article in this issue. Currently there are 2 drugs in phase III trials in the United States: ceftriaxone and dexpramipexole. Both trials will be completed in late 2012. Ceftriaxone is a third-generation cephalosporin that was selected for the treatment of ALS through in vitro screening of available pharmacologic agents. The effect of ceftriaxone pertinent to slowing disease progression in ALS is the upregulation of EAAT2, a glutamate transporter that protects neurons from excitotoxicity. Dexpramipexole is the dextro isomer of pramipexole, and it lacks the racemic pramipexole’s strong dopaminergic effect. The lack of dopaminergic effect makes the drug tolerable at a many fold higher dose. Dexpramipexole has been shown to be neuroprotective in several animal models. A phase II trial in ALS done in 2008 was encouraging, suggesting a slowing of disease progression by 20%.
Pharmacologic Management of Pseudobulbar Affect in ALS
Pseudobulbar affect (PBA) is a symptom that is experienced in about half of patients with ALS. The term refers to a disconnect between emotion and affect that manifests as brief paroxysms of crying or laughing that is out of proportion, or sometimes even opposite, to the experienced emotion. Multiple other names, such as “inappropriate emotional expressive disorder” or “pathologic laughing and crying” and “emotional incontinence” have been proposed for the symptom because PBA is a term that does not describe the symptom. There are several medications used to treat PBA symptoms. Dextromethorphan has the best evidence base with several studies showing an effect in ALS. Dextromethorphan has to be combined with quinidine, which blocks its CYP450 2D6 breakdown to achieve an effective pharmacologic profile. Quinidine also leads to increased plasma levels of other drugs that are metabolized by the CYP450 2D6, but the drug combination otherwise has few side effects. Tricyclic antidepressants (TCAs) are also effective, and in particular amitriptyline with its strong anticholinergic effect is widely used for several indications in ALS care. Last, the selective serotonin reuptake inhibitors (SSRIs) can also be effective, but anecdotally, they are the less effective than dextromethorphan and amitriptyline.
Pharmacologic Management of Symptoms in ALS
Dementia
Dementia or less severe cognitive deficits and behavioral changes occur in about half of patients with ALS, but we lack pharmacologic treatments for the problem. The frontal lobe dysfunction seen in ALS is not helped by a centrally acting reversible acetylcholinesterase inhibitor like donepezil or by N-methyl-D-aspartate receptor blockers like memantine.
Fatigue
Fatigue is another common ALS symptom. Patients may experience low energy level and loss of stamina, often with daytime sleepiness, and difficulty concentrating. Nonpharmacologic management with energy conservation and noninvasive ventilation are useful, but pharmacologic agents can also be used. Modafinil has shown preliminary benefit in improving fatigue in ALS. Modafinil can worsen anxiety, but no other side effects are common. Other options include activating SSRIs, such as fluoxetine, which also are effective against depression, anxiety, and PBA and may even help with weight maintenance.
Depression
Depression is not more common in ALS than in the general population, but it is a problem for a minority of ALS patients. Nonpharmacologic interventions, such as counseling and support groups, can help, but often an antidepressant is indicated. SSRI medications are normally the first-line agent against depression. The doses of TCA used to control other ALS symptoms are generally insufficient to have an effect on depression.
Anxiety
Anxiety often relates to specific fears regarding dying and terminal symptoms, such as shortness of breath. Information and discussion of specific fears can often very effectively alleviate anxiety. When information and reassurance are not enough, then the SSRIs are again useful and form the mainstay of preventive treatment. Benzodiazepines are very effective in acutely reducing anxiety, and also help spasticity and muscle cramps. Benzodiazepines reduce respiratory drive, which can result in respiratory depression and carbon dioxide retention. Patients with near normal breathing function are not at an increased risk of developing respiratory depression, but this does become a major concern as respiratory function decreases. Ventilated patients do not suffer in the same way from depression of respiratory drive, and noninvasive positive pressure ventilation does at least partially address the problem. During the final stage of life, the benzodiazepines are often very effective, especially when used together with opiates, in controlling terminal anxiety and air hunger. Earlier in the disease, a low-dose, short-acting benzodiazepine is often tolerated and can be used with careful monitoring for signs of carbon dioxide retention (eg, headache, somnolence, and confusion).
Pain
Pain is reported by about half of patients with ALS. Pain is not directly caused by ALS, but rather the symptom results from immobility and weakness. Physical therapy and optimal seating and bed arrangements can often prevent or limit pain, but pharmacologic intervention is often necessary. The first line of pharmacologic treatment is acetaminophen because it lacks major side effects; nonsteroidal anti-inflammatory drugs are also useful. For localized superficial pain, lidocaine in patches or cream can be used. Similar to the before-mentioned benzodiazepines, opiates act as respiratory depressants, and this complicates their use in the respiratory challenged ALS population in a similar way.
Spasticity
Spasticity is a significant problem for many patients with ALS with upper motor neuron dominant disease. Although physical therapy is the first line of therapy, medications are often useful. Baclofen and other muscle relaxants often provide adequate relief without problematic sedation or other side effects. Dosing before bedtime or divided up to 4 times per day can be tried depending on when the symptom is most troubling. All types of pharmacologic management for spasticity result in functional muscle weakness, so reduced spasticity will need to be balanced against the strength loss to achieve optimal function for the patient. When oral muscle relaxants cause too much sedation, then intrathecal baclofen delivered by an implantable pump can be very useful. Patients selected for the procedure should be robust enough to tolerate surgery without a protracted recovery and have a life expectancy in which they would have a chance of benefiting from the procedure. Botulinum toxin can be used with great effect providing targeted and fairly local effect on the muscles selected. Because botulinum toxin’s mechanism of action is to functionally denervate the target muscle, significant consideration has to be taken into the functional consequence of weakening the spastic muscle. There is the potential for the disease process to advance during the time the muscle is functionally denervated, which will limit the muscle’s ability to recover from the botulinum injections.
Muscle cramps
Muscle cramps are a common symptom in ALS, affecting 62% of patients. Nonpharmacologic measures, such as stretching, can often alleviate these symptoms. Quinine was previously the most used medication for treatment of muscle cramps. Quinine is deemed effective by both meta-analyses and by ALS clinicians, and it remains the favored agent outside of the United States. The FDA and Health Canada have advised against the use of quinine for muscle cramps because of very rare fatal hematological side effects attributed to quinine. Quinine is still marketed in the United States, making off-label use against muscle cramps possible, but this is contrary to the specific recommendation of the FDA. Other medications that can be used include mexiletine, baclofen, and gabapentin.
Fasciculations
Fasciculations are a very treatment-resistant symptom, which often spontaneously diminishes over time. No medications have been proven to reduce the symptom nor are any medications supported by anecdotal evidence.
Sialorrhea
Drooling and the experience of sialorrhea are the result of poor swallowing function in ALS. Saliva production is not increased because of ALS, but reducing saliva production is the most effective way of reducing these symptoms. Nonpharmacologic measures can include napkins, oral suction machines, and addressing any dental problems. Anticholinergic medications effectively reduce saliva production and glycopyrrolate can be very effective. Other anticholinergics commonly used are atropine drops and scopolamine patches. Anticholinergic medications can cause a dry mouth, constipation, confusion, and worsening of balance, but if one of these side effects limits use, then other options are available. Botulinum toxin directed at the salivary glands is often used, but radiation and even surgery can be used to reduce secretions.
Laryngospasms
Laryngospasm occurs owing to airway spasticity in ALS. It can be caused by dysphagia, but often the cause is gastroesophageal reflux from the stomach. The airway cramp is often brief, but the symptom can be terrifying. If a patient loses consciousness from laryngospasm obstructing the airway, the spasm is relieved. Informing patients that the spasm will not be fatal can offer some reassurance for the patient. Preventive treatment with proton pump inhibitors is normally effective and more practical than attempts of abortive treatment with nitroglycerin or benzodiazepines. The brief duration of attacks and potential choking hazard of oral administration of medications during an attack makes the abortive options less attractive.
Secretion management
Respiratory secretions can be troubling to patients with ALS with reduced pharyngeal function and weak cough. Nonpharmacologic interventions include in/exsufflators and chest percussion. It is important to determine whether the problem is the thickness of the secretions or if the secretions are excessive, because the treatments differ. Anticholinergic medications effectively reduce secretion production and glycopyrrolate can also be very effective. The problem with reducing secretions is that any remaining secretion will be thicker and this can be more troubling for some patients. To liquefy secretions, improved hydration is often a useful first step. Medications that can have an effect on thinning secretions are guaifenesin, acetylcysteine nebulization, and beta-blockers.
Urinary urgency
Urinary urgency is yet another common problem in ALS. Anticholinergics are again useful. Tolterodine has a more bladder-specific effect and thus may be the best choice, but other anticholinergic agents are also useful. Botulinum toxin injections into the bladder detrusor muscle are another option.
In summary, these medications can help alleviate many of the difficult symptoms of ALS, and pharmacologic management of ALS can significantly improve the quality of life for the person suffering from the disease. The role of symptom management in ALS can be expected to increase as we achieve longer survival until there is a treatment that can reverse the condition. A summary of pharmacologic management options for managing ALS is in Table 1 .
| Target | Medication | Typical Dose | Comment |
|---|---|---|---|
| ALS | Riluzole | 50 mg BID | Periodic liver function testing |
| PBA | Dextromethorphan/quinidine | 20/10 mg BID | |
| Fluoxetine (or other SSRI) a | 20–80 mg QD | ||
| Amitriptyline (or other TCA) a | 10–75 mg BID | ||
| Fatigue | Modafinil a | 100–200 mg QAM | |
| Fluoxetine (or other activating SSRI) a | 20–80 mg QD | ||
| Spasticity | Baclofen | 10–80 mg divided over 24 h | |
| Muscle cramps | Quinine a | 324 mg QHS | |
| Mexiletine a | 200 mg BID | ||
| Gabapentin a | 1200 mg TID | ||
| Sialorrhea | Glycopyrrolate a | 1–2 mg QD to QID | |
| Scopolamine patch a | 1.5 mg Q 3 d | ||
| Atropine 1% solution a | 1–4 gtt Q 2 h PRN | ||
| Laryngospasm | Omeprazole a | 20 mg QD | |
| Respiratory secretions | Glucopyrrolate a | 1–2 mg QD to QID | |
| Guaifenesin | 200–400 mg Q 4 h | ||
| Acetylcysteine 20% | 3–5 mL TID PRN |
Related posts:
Chronic Pain in Neuromuscular Disease
Bone Health and Associated Metabolic Complications in Neuromuscular Diseases
Novel Approaches to Corticosteroid Treatment in Duchenne Muscular Dystrophy
Mobility-Assistive Technology in Progressive Neuromuscular Disease
Cardiac Management in Neuromuscular Diseases
Treatment of Spine Deformity in Neuromuscular Diseases
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