Myopathy and muscle disease in adults

• A myopathy is disease of the muscle fibres or their energy supply, most often presenting as symmetrical weakness of the girdles, neck flexors or distal muscles, rather than as pain or fatigue alone. ^[1]
• Creatine kinase (CK) is the cheapest and most useful first blood test, but a mildly raised CK is common and does not on its own diagnose muscle disease; a small rise (about threefold or less) with no weakness or pain is rarely myopathy. ^[3][1]
• Electromyography (EMG) can confirm that weakness arises in muscle rather than nerve or neuromuscular junction, yet a normal EMG never excludes a myopathy. ^[3][1]
• Inflammatory myopathies are treatable: high-dose glucocorticoids with a steroid-sparing agent such as methotrexate or azathioprine is first-line for most adults. ^[8]
• Long-standing proximal weakness in an adult is just as likely to be an inherited dystrophy (limb-girdle, facioscapulohumeral or myotonic) as an inflammatory one, and muscle biopsy or genetic testing settles the difference. ^[6][5]

By the end of this page you should be able to:

1. Decide when an elevated CK is worrisome and when it can be observed. ^[3]
2. Recognise the clinical patterns that separate inflammatory, statin-related, dystrophic and channelopathic myopathies. ^[1]
3. Explain what EMG and muscle biopsy add to the diagnosis, and their limits. ^[1][3]
4. Manage a patient with suspected inflammatory myopathy, including first-line drugs and when to refer. ^[8]
5. Outline the presentation, investigations and management of an adult with myotonic dystrophy or periodic paralysis. ^[7][2]
6. State the screening and safety steps (cardiac, respiratory, malignant hyperthermia) attached to common neuromuscular disease in adults. ^[7]

A myopathy is a disorder of skeletal muscle itself: its membrane channels, contractile proteins, or energy metabolism. Myopathies sit among the other lesions of the motor unit (motor neuron, peripheral nerve, neuromuscular junction), and the first diagnostic step is to decide which link is weak. ^[1]

For bedside use, the most useful division is between acquired and hereditary disease. Acquired myopathies include the idiopathic inflammatory myopathies (dermatomyositis, polymyositis, immune-mediated necrotising myopathy, inclusion body myositis, anti-synthetase syndrome and overlap myositis), statin-induced muscle symptoms, endocrine and toxic myopathies, and metabolic or mitochondrial disease in adults. Hereditary causes include the muscular dystrophies (limb-girdle and distal dystrophies, facioscapulohumeral dystrophy, myotonic dystrophy and Becker dystrophy) and the channelopathies (nondystrophic myotonia and periodic paralysis). ^[1][8][2][6]

Myositis as a whole is rare: incidence roughly 0.2-2 cases per 100,000 person-years and prevalence about 2-25 per 100,000. ^[8] Adults aged 45-60 years are most often affected, and every subtype except inclusion body myositis (IBM) is more common in women. ^[8] IBM is the commonest acquired myopathy in people over 50 years and is usually asymmetric. ^[8] Dermatomyositis can occur in children or adults, polymyositis rarely in childhood, and IBM most commonly over the age of 50. ^[1]

Muscular dystrophy is also an uncommon cause of adult presentation. The limb-girdle dystrophies overall are rare, with individual subtypes estimated at 0.07-0.43 per 100,000, while Becker muscular dystrophy runs at roughly 2.38-7.29 per 100,000. ^[6] Facioscapulohumeral dystrophy (FSHD) occurs in about 1 in 15,000 to 1 in 20,000 and is the third most common muscular dystrophy overall. ^[5] Myotonic dystrophy type 1 occurs in about 1 in 3,000 to 8,000 people worldwide. ^[7]

Statin-associated muscle symptoms (SAMS) are the commonest practical myopathy problem encountered in clinic because statins are prescribed so widely. A large meta-analysis (over 4 million patients) gives an overall prevalence of statin intolerance of about 9.1% (8.0-10%). By the published definitions this was 7.0% with National Lipid Association (NLA) criteria, 6.7% with International Lipid Expert Panel (ILEP) criteria and 5.9% with European Atherosclerosis Society (EAS) criteria. ^[4] Statin intolerance was reported in roughly 4.9% of patients in randomised trials versus 17% in cohort studies, and older age, female sex, Asian and Black race, obesity, diabetes, hypothyroidism, chronic liver or renal disease, higher doses and concomitant antiarrhythmics or calcium-channel blockers were all associated with a higher risk. ^[4]

Most hereditary myopathies are genetic: autosomal dominant, autosomal recessive or X-linked. Patterns of inheritance matter for counselling as much as for diagnosis. ^[1][6]

Inflammatory myopathies are autoimmune. Drug triggers include statins (anti-HMGCR (3-hydroxy-3-methylglutaryl-CoA reductase) myopathy) and immune checkpoint inhibitors. ^[8] Statins, fibrates and many other drugs (including immune checkpoint inhibitors, beta-blockers, hydroxychloroquine, colchicine, alcohol and cocaine) sit among the non-neuromuscular causes of a high CK, so that a raised CK on a single test is not automatically myositis. ^[3]

Endocrine, metabolic and toxic causes (hypothyroidism, hyperthyroidism, hypoparathyroidism, alcohol, convulsions, exertion, infections, celiac disease, malignancy, trauma, intramuscular injections) can all raise CK modestly. ^[3]

The mechanism of weakness is different in each family of myopathy.

In inflammatory myopathy, immune attack produces inflammation, necrosis and regeneration in muscle; proximal hip and shoulder girdle weakness, objective weakness and a raised CK reflect the damage. ^[8][1]

In the channelopathies, a gain or loss of function in sodium, chloride, potassium or calcium channels changes sarcolemmal excitability. Increased excitability produces myotonia (delayed relaxation), and decreased excitability produces episodic flaccid paralysis when the membrane stays depolarised and sodium channels inactivate. ^[2]

In the muscular dystrophies, mutations in structural proteins (dystrophin, sarcoglycans, calpain, dysferlin, lamin A/C, D4Z4 repeat contraction in chromosome 4q35) weaken the membrane and make it leaky; CK may be very high (normal to more than 10 times normal, occasionally up to 100 times) because of membrane leakage. ^[6][5]

Myotonic dystrophy type 1 is an autosomal dominant triplet (CTG) repeat expansion disorder. A repeat expansion above 35 repeats is usually unstable and expanding, and 50 repeats or more is consistent with a diagnosis. The expanded RNA is toxic and affects many tissues, which is why the disease is multisystem. ^[7]

Myopathies are best recognised by pattern of weakness rather than by any single symptom. Patients usually say they cannot climb stairs, rise from a chair or a toilet, comb their hair or lift objects overhead. Proximal limb-girdle weakness is the commonest pattern. ^[1]

Worth asking:

• Which activities are difficult, and whether weakness is proximal, distal or axial. ^[1]
• Duration: acute/subacute (weeks) suggests an inflammatory myopathy; chronic slowly progressive (years) suggests dystrophy; episodic attacks with normal strength between episodes suggests channelopathy or metabolic myopathy. ^[1][2]
• Family history and inheritance pattern. ^[1][6]
• Precipitating factors: exercise, cold, fasting, high-carbohydrate or potassium-rich meals, fever, heat or a recent statin dose. ^[1][2]
• Associated systemic symptoms: rashes (dermatomyositis), breathlessness, swallowing difficulty, cognitive or frontal balding (myotonic dystrophy), cataracts, cardiac symptoms, joint or lung disease. ^[1][7]
• Drugs, alcohol, exercise in the days before the test. ^[3]

Look for objective weakness, not just fatigue. Use the Medical Research Council (MRC) 0-5 scale, testing bilaterally and against gravity. ^[1] Cranial muscles, neck flexors and extensors, shoulder and pelvic girdles, and distal muscles should all be tested; neck extensor weakness is characteristic of some dystrophies and myasthenia. ^[1][6]

Signs that steer the diagnosis:

• Heliotrope rash and Gottron papules over the knuckles: dermatomyositis. ^[8]
• Asymmetric distal arm/proximal leg weakness with finger flexor wasting: inclusion body myositis. ^[1]
• Periscapular weakness and scapular winging with often asymmetric weakness: facioscapulohumeral dystrophy. ^[5]
• Ptosis, facial weakness, myotonia and distal wasting: myotonic dystrophy. ^[1][7]
• Muscle stiffness that improves with repeated contractions (warm-up) or worsens with cold: nondystrophic myotonia. ^[2]
• Myotonic lid lag or grip myotonia on percussion: nondystrophic myotonia or myotonic dystrophy. ^[1][2]
• Episodic flaccid weakness with areflexia, normal sensation, normal strength between attacks: periodic paralysis. ^[2]

For inflammatory myositis, extramuscular findings (rash, arthritis, interstitial lung disease, dysphagia) are common and should be looked for. ^[8]

The main question is whether weakness is myopathic. Causes to separate include motor neuron disease (fasciculations, wasting, upper motor neuron signs), peripheral neuropathy (distal sensory loss, diminished reflexes), neuromuscular junction disease (fluctuating fatigable weakness, diplopia), and central causes. ^[1]

Among myopathic causes, age of onset and pattern help: dermatomyositis and polymyositis can begin at any adult age; IBM is usually over 50; FSHD often starts in the second decade but can begin at any age; myotonic dystrophy presents as an adult; periodic paralysis usually starts before 20 years but may present late. ^{[1][5][7] [2]}

The table compares the common acquired and hereditary myopathies of adults.

CK is released when the muscle fibre membrane is damaged. It is cheap and should be measured in any suspected myopathy, but several rules make it interpretable. ^[1][3]

• CK varies by sex and ethnicity; common reference ranges often underestimate normal values in Black and Asian individuals. ^[3]
• Strenuous exercise, trauma, intramuscular injection, EMG, seizures, recent surgery, hypothyroidism, and many drugs can raise CK modestly. ^[3][1]
• Inflammatory and necrotising myopathies raise CK often many times the upper limit of normal; dystrophies can give anything from normal to over 100 times normal; a small rise (about threefold or less) without pain or weakness is rarely myopathic. ^[1][6]
• Neurogenic disorders such as amyotrophic lateral sclerosis or Kennedy disease (bulbar and spinal muscular atrophy type 1) may also raise CK, usually to less than 5 times normal, occasionally up to 10 times. ^[3]
• A raised ALT or AST without another cause can come from muscle; check CK and gamma-glutamyl transferase (GGT) before sending the patient for a liver work-up. ^[1]

For persistent asymptomatic (oligo/asymptomatic) hyperCKemia, the European Academy of Neurology (EAN) 2024 guideline sets out a staged approach: repeat CK after at least 72 hours (preferably a week) off strenuous exercise and off provoking drugs; repeat it twice more at least a month apart before deciding it is persistent; investigate when it is persistently above 1.5 times the upper limit of normal (ULN); and ideally use sex-, age- and ethnicity-specific reference values rather than a single cut-off. ^[3] European (NORIP) Caucasian 97.5th centile values quoted by the guideline are about 210 units per litre for women aged 18 or over, 400 for men aged 18-50, and 280 for men 50 or over; for non-Caucasian adults the Brewster values are higher: South Asian women 313, South Asian men 641, Black women 414 and Black men 801 units per litre. ^[3] EMG (sensitivity 0.53, specificity 0.67 against biopsy in this setting) separates myopathic from neurogenic causes, and muscle biopsy (sensitivity 0.39, specificity 0.55) is now reserved for cases with uninformative genetics. ^{[3] [2][8]}

Next-generation sequencing is recommended over muscle biopsy for possible myopathic hyperCKemia once acquired and neurogenic causes are excluded; biopsy is still offered when there is a variant of unknown significance, suspected metabolic or inflammatory myopathy, abnormal muscle MRI, CK at or above 3 times ULN, a family history of muscle disease, or age under 25. ^[3]

Nerve conduction studies (NCS) and needle EMG confirm whether weakness is myopathic, neurogenic or junctional, and sample many muscles at once. ^[1][3]

A myopathic pattern on EMG is brief-duration, small-amplitude motor units with increased recruitment; fibrillations and positive sharp waves may appear. ^[1] EMG can also show a myotonic pattern (a dive-bomber waxing-and-waning sound) that points to a channelopathy or myotonic dystrophy. ^[2][7]

Limits: EMG may be normal in a myopathy, especially early or in distal dystrophies, and a normal EMG never excludes muscle disease. ^[1][3] Needle EMG also makes the needled muscle unsuitable for biopsy. ^[1]

Muscle biopsy shows the nature of the damage: necrosis and regeneration with inflammation in inflammatory myopathy, vacuoles in inclusion body myositis, dystrophic changes in the dystrophies, and specific protein loss on immunostaining (for example dystrophin) or Western blot. ^[1][8]

Genetic testing now often replaces biopsy in hereditary disease. In inflammatory myopathy, autoantibody testing is the most useful serological step: myositis-specific antibodies such as anti-Jo-1, anti-Mi-2, anti-SRP (signal recognition particle) and anti-HMGCR are fairly specific and help classify the subtype; they are detectable in only about half of patients. ^[8] Where myositis is clinically suspected and autoantibodies are absent, biopsy (and sometimes MRI) confirms it. ^[8]

The flow below is a teaching outline for adults, not a protocol; follow local guidance and involve the neuromuscular team.

Inflammatory myopathies are acquired, autoimmune and, apart from IBM, usually treatable. The subtypes are dermatomyositis, polymyositis, immune-mediated necrotising myopathy (IMNM), IBM, anti-synthetase syndrome, overlap myositis and clinically amyopathic dermatomyositis. ^[8]

• Dermatomyositis gives proximal weakness plus characteristic skin disease (heliotrope rash, Gottron papules) and periorbital oedema. ^[8][1]
• Polymyositis gives proximal weakness without rash. ^[8]
• IMNM is marked by severe proximal weakness and fibre necrosis with little inflammation; anti-SRP and anti-HMGCR are the common autoantibodies. ^[8]
• Anti-synthetase syndrome adds interstitial lung disease, arthritis, Raynaud phenomenon and mechanic's hands to myositis. ^[8]
• IBM affects people over 50 with asymmetric distal-arm and proximal-leg weakness (finger flexors and quadriceps) and is usually treatment-resistant. ^[8][1]
• Clinically amyopathic dermatomyositis has skin disease without measurable weakness. ^[8]

Screening at diagnosis: many of these disorders associate with underlying malignancy (ovarian, breast, lung, gastrointestinal, pancreatic, cervical and colorectal cancers and Hodgkin lymphoma), and with interstitial lung disease, so a directed cancer and lung screen is part of normal care. ^[8]

Statin therapy can cause myalgia, mild CK rise and, rarely, a true autoimmune anti-HMGCR myopathy. ^[8][4] Most statin muscle symptoms are mild and reversible.

When the CK is raised on a statin:

• Mild rise (up to about 10 times normal) without symptoms is usually observed rather than treated. The EAN 2024 guideline advises that statins need not be withheld in asymptomatic people with CK up to about 10 times ULN, if a statin is otherwise indicated, with close follow-up. ^[3]
• Symptomatic pain or weakness usually responds to stopping the statin and reintroducing a lower dose or a different statin; complete intolerance (true statin intolerance) affects roughly 9.1% of patients overall, although the figure is lower in trials than in cohort data, and risk factors include age, female sex, higher dose and several metabolic conditions. ^[4]
• Progressive proximal weakness with a very high CK that continues after the statin is stopped is a red flag for autoimmune anti-HMGCR IMNM; measure anti-HMGCR and refer to a neuromuscular specialist, because this may need immunosuppressive treatment. ^[8]
• Do not delay investigations: a "statin myopathy" label can hide an underlying muscular dystrophy, especially in an adult with long-standing weakness. ^[3][6]

In an adult with slowly progressive weakness, hereditary dystrophy is as likely as inflammation. CK may be mildly to massively raised, EMG is myopathic, and biopsy often shows dystrophic change; the diagnosis is settled by genetic testing. ^[1][6]

Limb-girdle muscular dystrophy (LGMD) presents with proximal symmetrical weakness and normal sensation, with an autosomal dominant (LGMD1) or recessive (LGMD2) pattern. ^[6] Distal dystrophies add asymmetric or compartment-selective weakness. ^[6]

Key points from the AAN (2014) evidence-based guideline:

• Prevalences are low (about 0.07-0.43 per 100,000 for the rarer subtypes; Becker dystrophy is more common, roughly 2.38-7.29 per 100,000). ^[6]
• Many subtypes carry cardiac or respiratory disease even before symptoms appear; newly diagnosed patients at known high cardiac risk should have ECG, echocardiography or cardiac MRI, and high-respiratory-risk subtypes need periodic pulmonary function testing. ^[6]
• Gene therapy, myoblast transplantation, myostatin antibody and growth hormone are not recommended outside trials. ^[6]
• Aerobic exercise, submaximal strength training, bracing and assistive devices are safe and are recommended; patients should be counselled to hydrate and avoid supramaximal, exhaustive exercise. ^[6]

Patients should be referred to a centre with multidisciplinary neuromuscular care (physiotherapy, occupational and speech therapy, respiratory and cardiac services, genetics). ^[6]

FSHD is an autosomal dominant disorder caused by contraction of D4Z4 repeats on chromosome 4q (FSHD1, about 95% of cases), with FSHD2 accounting for the rest. ^[5] Weakness starts in the face, scapular fixators and humeral muscles and is often asymmetric; about 20% of patients need a wheelchair after age 50. ^[5]

Management points from the AAN (2015) evidence-based guideline:

• Respiratory insufficiency occurs in a minority; obtain baseline pulmonary function tests, and monitor if baseline or risk factors are abnormal. ^[5]
• Routine cardiac screening is not needed without cardiac symptoms, but cardiac evaluation is recommended when these occur. ^[5]
• Symptomatic retinal vascular disease is rare (about 0.6%), but patients with large deletions need an experienced ophthalmologist for dilated indirect ophthalmoscopy. ^[5]
• Hearing loss is concentrated in childhood-onset disease with large deletions, so audiometry is recommended from diagnosis. ^[5]
• Pain is common (up to 79% in series), so ask about it and offer analgesia and physiotherapy; nonsteroidal anti-inflammatory drugs for acute pain, antidepressants or antiepileptics for chronic pain. ^[5]
• Albuterol is ineffective for strength; scapular fixation may cautiously be offered to selected patients; low-intensity aerobic exercise is encouraged. ^[5]

Myotonic dystrophy type 1 is the commonest adult muscular dystrophy in many populations and is autosomal dominant; it causes distal weakness, facial and neck weakness, and myotonia, plus systemic disease (heart, brain, gut, endocrine, respiratory). ^[7] Severity increases with repeat size and anticipation can produce congenital disease in offspring. ^[7]

Cardiac and respiratory disease dominate prognosis: pulmonary complications are the leading cause of death and cardiac complications the second. ^[7] An adult with DM1 should have baseline and annual ECG, echocardiography every 3-5 years, periodic pulmonary function (forced vital capacity, peak cough flow and maximal inspiratory pressure), swallow and nutrition assessment, cataract screening, thyroid and glucose testing (thyroid at baseline and every 3 years; glucose control annually), and lipids every 3 years. ^[7]

Cardiac investigation is triggered by palpitations, chest pain, dyspnoea, orthopnoea or syncope, or by impulse-conduction abnormalities on ECG: sinus rate under 50, PR interval above 200 ms, QRS above 100 ms, fascicular block, atrial tachycardia, fibrillation or flutter, or ventricular arrhythmias. ^[7] Respiratory referral thresholds include ineffective cough (peak expiratory flow under about 270 L/min), maximal inspiratory pressure under 60 cm H2O, or FVC below about 50% of predicted; patients may need nocturnal non-invasive ventilation. ^[7]

Myotonia can be treated with mexiletine, but it is contraindicated in cardiac involvement; other agents include phenytoin, carbamazepine and propafenone. ^[7][2] General anaesthesia and opioids are hazardous: post-anaesthetic complications are common, so anaesthesia should only be given by teams experienced in DM1, with preoperative respiratory assessment. ^[7] Cognitive behavioural therapy added to standard care improved activity and participation in a large randomised trial of DM1 patients with severe fatigue. ^[7]

Periodic paralysis is a group of channelopathies in which ion-channel mutations (sodium SCN4A, calcium CACNA1S, potassium KCNJ2) produce episodic attacks of flaccid weakness with abnormal extracellular potassium during attacks and normal potassium between. ^[2] Secondary causes (thyrotoxic, renal, adrenal and others) must be excluded. ^[2]

• Hypokalemic: prevalence about 1 in 100,000, onset before age 20, attacks hours to days, about 7-9 per month, triggered by carbohydrate-rich meals, stress, alcohol or rest after exercise; serum potassium falls below 3.0 mmol/L during an attack; CK rises transiently. ^[2]
• Hyperkalemic: prevalence under 1 in 100,000, onset in the first decade, shorter attacks (minutes to hours, about 16 per month), triggered by fasting, rest after exercise and potassium-rich or carbohydrate loads; potassium above 5 mmol/L or rising by over 1.5 mmol/L during an attack; some families also have myotonia. ^[2]
• Andersen-Tawil syndrome: episodic paralysis with dysmorphic features (short stature, low-set ears, hypertelorism, small mandible, clinodactyly) and cardiac arrhythmias; a potassium inward-rectifier (KCNJ2) mutation in about 60% of patients. ^[2]
• Thyrotoxic periodic paralysis: the most common form, affecting about 0.1% of thyrotoxic patients in White populations and up to 10% in Asian or Hispanic populations. ^[2]

Diagnosis is supported by exercise testing (long exercise test shows greater than 40% drop in compound muscle action potential amplitude at 25-30 minutes, positive in about 80% of cases) and confirmed by genetics. ^[2]

Treatment:

• Acute hypokalemic attack: potassium 10-20 mEq orally every 15-30 minutes over 1-3 hours, not to exceed 200 mEq in 24 hours; if the patient cannot take oral potassium, give 35 mEq in 1 L of 5% mannitol at 250 mL/h (max 200 mEq/24 h). ^[2]
• Chronic hypokalemic: low-carbohydrate, low-sodium diet with potassium salt supplementation (10-20 mEq up to 3 times daily, maintaining serum potassium near 4 mEq/L), plus carbonic anhydrase inhibitors or potassium-sparing diuretics. ^[2]
• Hyperkalemic: acute attacks may respond to oral carbohydrate or glucose; prevention with low potassium, high carbohydrate diet, avoidance of fasting, strenuous activity and cold, plus carbonic anhydrase inhibitors, thiazide diuretics. ^[2]
• Andersen-Tawil patients need yearly ECG and Holter monitoring and avoidance of QT-prolonging drugs; implantable defibrillator for unexplained syncope due to arrhythmia. ^[2]
• Carbonic anhydrase inhibitors reduce attack frequency or severity in all periodic paralyses. ^[2]
• All channelopathies need caution with general anaesthesia because of risk of malignant hyperthermia and severe paralysis. ^[2]

There is no single severity score across all myopathies, but useful anchors:

• HyperCKemia is worth investigating when persistent and above 1.5 times ULN; biopsy (or NGS first) is triggered by CK at or above 3 times ULN, abnormal MRI, suspected inflammatory or metabolic disease, or young age. ^[3]
• The 2017 European League Against Rheumatism / American College of Rheumatology classification criteria (EULAR/ACR) are the current standard classification for adult and juvenile IIM subtypes; the European Neuromuscular Centre (ENMC) 2004 (Hoogendijk) criteria preceded them and ENMC workshops continue to refine subtype definitions (including a 2016 workshop published in 2018 on immune-mediated necrotising myopathy). ^[8]
• Immune-mediated necrotising myopathy has ENMC treatment recommendations (2018): high-dose glucocorticoid (oral 1 mg/kg per day or intravenous 0.5-1 g per day for 3-5 days) plus methotrexate (or rituximab for anti-SRP, IVIG for anti-HMGCR in severe disease). ^[8]
• First-line therapy for most inflammatory myopathies (other than IBM): high-dose glucocorticoids (prednisone/prednisolone 0.5-1 mg/kg per day, with intravenous methylprednisolone pulses for severe disease) plus a steroid-sparing agent such as methotrexate or azathioprine; IVIG and biologics (rituximab, abatacept) for refractory disease; IBM has no effective pharmacological treatment beyond supportive and rehabilitative care. ^[8]
• No disease-modifying therapy exists for DM1; management is supportive with screening as above. ^[7]
• No disease-modifying therapy exists for most dystrophies; some forms have specific rehabilitation and surgical options (for example scapular fixation in FSHD). ^[5][6]

Red flags needing rapid action: rapidly progressive weakness over hours to weeks, bulbar or swallowing involvement, breathlessness at rest or when lying flat, suspected acute rhabdomyolysis with dark urine, and acute weakness with hypokalaemia. ^[9][2] NICE (NG127) advises referring for neuromuscular assessment in slowly progressive adult weakness, urgently if swallowing is affected, and immediately if there is breathlessness at rest or when lying flat. ^[9]

For inflammatory myopathy: treat with immunosuppression as above, encourage supervised exercise, and screen for ILD and malignancy. ^[8]

For statin myopathy: stop the statin if symptomatic; reintroduce lower dose or alternative statin; test anti-HMGCR if weakness persists off the drug; treat autoimmune necrotising myopathy as IMNM. ^[8][4]

For dystrophy: multidisciplinary care; genetic counselling; cardiac and pulmonary surveillance; pain management; rehabilitation; and specific measures (non-invasive ventilation, cardiac devices, ophthalmology and audiology in FSHD). ^[5][6]

For myotonic dystrophy: supportive multisystem care with regular cardiac, respiratory, endocrine and ophthalmic screening; mexiletine for myotonia if no cardiac disease; caution with anaesthesia. ^[7]

For periodic paralysis: dietary and behavioural avoidance, potassium as directed above, carbonic anhydrase inhibitors; treat thyrotoxicosis for thyrotoxic periodic paralysis. ^[2]

• Limb weakness, falls and loss of independence; dysphagia and aspiration pneumonia. ^[1][8]
• Respiratory insufficiency, especially in DM1, some LGMD subtypes and FSHD; nocturnal hypoventilation develops before breathlessness. ^[7][6][5]
• Cardiac conduction disease and arrhythmia in DM1 (second commonest cause of death); cardiomyopathy in many LGMDs. ^[7][6]
• Cataracts and endocrine disease in DM1. ^[7]
• Fixed weakness and scapular problems in FSHD. ^[5]
• Renal failure from rhabdomyolysis in metabolic or periodic paralysis. ^[2][1]
• Malignancy and ILD in inflammatory myositis. ^[8]

Prognosis depends on subtype. Inflammatory myopathies other than IBM usually respond to immunosuppression, though relapse is common. IBM is progressive and treatment-resistant. ^[8] IBM and DM are associated with increased mortality compared with the general population; pulmonary and cardiac complications are the main causes in DM1. ^[7][8] Statin myopathy mostly resolves. Dystrophies are lifelong but compatible with decades of useful function with good care. ^[5][6]

Pregnancy: myotonic dystrophy in pregnancy carries risks of miscarriage, preterm delivery and respiratory insufficiency, and anaesthetic caution is needed; high-risk obstetric care and genetic counselling are advised. ^[7]

Children: childhood myositis and dystrophies are not the main scope of this page, but hereditary dystrophies presenting in childhood need genetic counselling and paediatric neuromuscular care; hearing loss in FSHD is sought in young children. ^[5]

Older adults: late-onset myopathy may reflect IBM, toxic or statin myopathy, or inherited disease presenting in mid-life; do not assume inflammation. ^[8][6]

• CK and a careful examination are the most useful tools where EMG and genetics are unavailable. ^[3][1]
• Pattern recognition (proximal girdle versus distal involvement, rash, myotonia, episodic attacks) allows a working diagnosis even without advanced testing. ^[1]
• Reserve immunosuppression for clear inflammatory disease, because muscle biopsy or autoantibody confirmation reduces harmful empiric treatment. ^[8]
• In rhabdomyolysis or severe periodic paralysis, rehydrate aggressively and check potassium; in acute hypokalemic paralysis, give oral potassium as above (or IV potassium in 5% mannitol) and avoid glucose-containing fluids. ^[2]
• Good nutrition, falls prevention, breathing support and contracture prevention matter more than rare drugs when specialist care is far away. ^[6]

• Muscle disease is a motor-unit problem localised to the muscle; weak, wasted and areflexic limbs from nerve or anterior horn cell disease are differentials to exclude first. ^[1]
• Symmetrical proximal weakness is the most common pattern across myopathies. ^[1]
• CK is useful and cheap but must be interpreted by sex, ethnicity and provoking factors; a rise of about threefold or less without pain or weakness is rarely myopathic. ^[1][3]
• EMG confirms a myopathic pattern but may be normal; needle EMG excludes simultaneous biopsy of that muscle. ^[1]
• Inflammatory myopathies except IBM are treatable with high-dose glucocorticoids plus a steroid-sparing agent. ^[8]
• IBM and most dystrophies have no effective drug treatment beyond rehabilitation and surveillance. ^[8][6]
• Statin myopathy is usually reversible; persisting weakness off the drug needs anti-HMGCR testing. ^[4][8]
• Adult "polymyositis" that does not respond to immunosuppression is often IBM. ^[1][8]
• DM1 is a multisystem disease in which pulmonary and cardiac complications dominate prognosis; screen regularly. ^[7]
• Periodic paralysis is diagnosed from the precipitating pattern and potassium, confirmed genetically; acute hypokalemic attacks respond to potassium, and CAIs prevent recurrence. ^[2]
• Hereditary dystrophies carry cardiac and respiratory surveillance needs and require multidisciplinary care. ^[5][6]
• Approach every adult with weak legs as an algorithm: pattern, history and inheritance, then CK, EMG, serology, biopsy and genetics as indicated. ^[1][3][6]

Muscular and neuromuscular junction disorders (myasthenia gravis; Lambert-Eaton syndrome); motor neuron disease; peripheral neuropathy; hypothyroidism; statin therapy and dyslipidaemia; dermatomyositis and rheumatological disease; pulmonary function and respiratory failure.