Neurology: Neuromuscular disease

• Motor neurone: Approach to Neuromuscular Disease | Motor Neurone Disease | Caring for People with MND | Other Anterior Horn Cell Diseases
• Nerves: Approach to Peripheral Neuropathy | Diabetic and Painful Neuropathy | CIDP and Other Immune Neuropathies | Hereditary Neuropathies | Mononeuritis Multiplex | Common Mononeuropathies | Bell's Palsy and Facial Weakness | Radiculopathy and Plexopathy
• Neuromuscular junction: Myasthenia Gravis | Lambert–Eaton Myasthenic Syndrome
• Muscle: Approach to Myopathy | Inflammatory Myopathies | Statins and Muscle | Muscular Dystrophies | Other Muscle Disorders
• Revision: Drug Reference Table | Spot the Diagnosis | Exam-style Scenarios | Key Points | Guidelines and Further Reading

💪 Neuromuscular disease covers everything from the anterior horn cell in the spinal cord, through the nerve roots and peripheral nerves, to the neuromuscular junction and muscle. The pattern of weakness, sensory loss and reflexes usually points to the level. Guillain–Barré syndrome and myasthenic crisis are covered in the Neurological Emergencies chapter.
Your four questions for every patient: Which level is affected (anterior horn, root, nerve, junction or muscle)? Is it acute, subacute or chronic? Is there a treatable cause (diabetes, B12, drugs, inflammation, compression, cancer)? Is breathing or swallowing at risk?

Approach to Neuromuscular Disease

Key tests:

• Nerve conduction studies and EMG - the most useful test.
• CK.
• Antibodies (AChR, MuSK, VGCC, myositis antibodies).
• Bloods for causes of neuropathy.
• Muscle MRI and biopsy.
• Genetic tests.
• Forced vital capacity (lying and sitting) to monitor breathing.

⚠️ Safety Pearl: In neuromuscular weakness, oxygen saturations stay normal until late. Monitor FVC - falling below about 20 mL/kg, or a weak cough, means a high risk of respiratory failure.

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Motor Neurone Disease

What it is: A progressive degeneration of upper and lower motor neurones. About 5,000 people in the UK have it at any time. Median survival is about 2–3 years from symptom onset. Peak onset is 55–75, and it is slightly commoner in men.

Types:

• Amyotrophic lateral sclerosis (ALS) - mixed UMN and LMN signs (the commonest, about 80%).
• Progressive bulbar palsy - speech and swallowing first (worse prognosis).
• Progressive muscular atrophy - LMN only (better prognosis).
• Primary lateral sclerosis - UMN only (slow).

Features:

• Asymmetric, painless weakness - e.g. a weak hand or foot drop.
• Wasting and fasciculations, together with brisk reflexes and extensor plantars.
• "Split hand" - thumb-side hand muscles waste more than the little finger side.
• Bulbar features - slurred speech, dysphagia, tongue wasting and fasciculation.
• Respiratory weakness - breathlessness lying flat, morning headaches, poor sleep.
• Muscle cramps; weight loss.
• Emotional lability (pseudobulbar affect).
• Cognitive and behavioural change - frontotemporal dementia in about 15%; milder changes in up to half.
• Usually spared: Sensation, eye movements and sphincters.

Genetics: About 10% are familial. The commonest genes are C9orf72 (also linked to FTD) and SOD1. Genetic testing is increasingly offered.

Diagnosis:

• Clinical, supported by EMG (widespread denervation) and normal sensory nerve conduction.
• Exclude mimics:
  • Cervical myelopathy (MRI).
  • Multifocal motor neuropathy (treatable).
  • Myasthenia (bulbar onset).
  • Inclusion body myositis.
  • Kennedy's disease.
  • B12 and copper deficiency; thyrotoxicosis.
• NICE NG42: refer urgently to neurology if MND is suspected - don't wait for tests.

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Caring for People with MND

• Specialist MDT care - neurologist, MND nurse, physiotherapy, occupational therapy, speech and language therapy, dietitian, respiratory and palliative care.
• Disease-modifying drugs:
  • Riluzole 50 mg twice daily - extends survival by about 2–3 months. Check LFTs and FBC (neutropenia).
  • Tofersen - an intrathecal antisense drug for SOD1-related MND; licensed by the MHRA, with NICE assessment under way.
• Breathing:
  • Monitor FVC, sniff nasal pressure and symptoms every 2–3 months.
  • Non-invasive ventilation (NICE NG42) improves survival and quality of life - offer when respiratory weakness develops.
  • Cough assist devices.
• Nutrition:
  • Weight loss predicts shorter survival.
  • Discuss gastrostomy early - ideally before breathing is badly affected (placement risk rises as FVC falls).
• Communication: Speech and language therapy; communication aids; voice banking early.
• Symptoms:
  • Drooling - glycopyrronium, amitriptyline, hyoscine patches, botulinum toxin.
  • Thick secretions - carbocisteine, hydration.
  • Cramps - quinine (consider), baclofen.
  • Spasticity - baclofen, tizanidine.
  • Emotional lability - amitriptyline, SSRIs.
  • Pain; constipation; low mood.
• Advance care planning:
  • Discuss early and revisit - NIV, gastrostomy, place of death, ventilation withdrawal.
  • Advance decisions to refuse treatment, lasting power of attorney.
  • "Just in case" medications.
• Driving: Tell the DVLA.

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Other Anterior Horn Cell Diseases

• Spinal muscular atrophy (SMA):
  • Autosomal recessive (SMN1 gene).
  • Proximal LMN weakness. Type 1 presents in infancy (floppy baby, death by 2 without treatment); milder types later.
  • Transformed by nusinersen (intrathecal), risdiplam (oral) and onasemnogene abeparvovec (gene therapy) - best when given before symptoms.
  • Newborn screening is being introduced in the UK.
• Kennedy's disease (spinal and bulbar muscular atrophy):
  • X-linked (androgen receptor CAG repeat) - men.
  • Slowly progressive bulbar and limb weakness, fasciculations around the chin, gynaecomastia, reduced fertility, sensory neuropathy.
  • A slow MND mimic.
• Post-polio syndrome: New weakness and fatigue decades after polio, in previously affected muscles.
• Monomelic amyotrophy (Hirayama disease) - young men; wasting of one forearm and hand; self-limiting.

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Approach to Peripheral Neuropathy

Patterns:

• Length-dependent polyneuropathy (the commonest) - numbness and tingling starting in the toes, rising to the knees before affecting the fingers; loss of ankle reflexes.
• Mononeuropathy - one nerve (often entrapment).
• Mononeuritis multiplex - several separate nerves (vasculitis).
• Polyradiculoneuropathy - proximal and distal weakness (GBS, CIDP).
• Small fibre neuropathy - burning pain and temperature loss, with normal reflexes and normal nerve conduction.
• Sensory neuronopathy (ganglionopathy) - non-length-dependent, ataxic. Sjögren's, paraneoplastic (anti-Hu), cisplatin.

Causes:

• Common:
  • Diabetes (and prediabetes).
  • Alcohol.
  • B12 deficiency.
  • Hypothyroidism.
  • CKD.
• Drugs:
  • Chemotherapy - vincristine, platinum drugs, taxanes, bortezomib, thalidomide.
  • Isoniazid (give pyridoxine).
  • Metronidazole (long courses), nitrofurantoin, amiodarone, phenytoin, colchicine.
  • Nitrous oxide misuse (B12 inactivation - a rising cause in young people).
• Paraproteins: MGUS, myeloma, Waldenström's, AL amyloidosis, POEMS syndrome.
• Inflammatory: GBS, CIDP, vasculitis, Sjögren's, sarcoid, coeliac disease.
• Infection: HIV, hepatitis C (cryoglobulinaemia), Lyme, leprosy (worldwide).
• Hereditary: CMT, hereditary ATTR amyloidosis.
• Others: Paraneoplastic; critical illness.
• In about 1 in 4, no cause is found (chronic idiopathic axonal neuropathy - usually older people, slowly progressive).

First tests:

• FBC, U&E, LFTs, HbA1c or glucose, B12 and folate, TFTs, ESR and CRP.
• Serum protein electrophoresis and immunofixation.
• Consider HIV, coeliac serology, ANA/ENA, ANCA.
• Nerve conduction studies (axonal or demyelinating) - if the cause isn't clear, it is progressing, motor-predominant, asymmetric or painful.

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Diabetic and Painful Neuropathy

Forms of diabetic neuropathy:

• Distal symmetrical polyneuropathy (the commonest) - numb feet, loss of protective sensation; foot ulcers and Charcot joints.
• Painful diabetic neuropathy - burning, shooting pains, worse at night.
• Autonomic neuropathy:
  • Postural hypotension.
  • Resting tachycardia.
  • Gastroparesis.
  • Diarrhoea.
  • Bladder dysfunction.
  • Erectile dysfunction.
  • Sweating problems.
  • Hypoglycaemia unawareness.
• Mononeuropathies - carpal tunnel, third nerve palsy (pupil-sparing).
• Diabetic amyotrophy (lumbosacral radiculoplexus neuropathy) - severe thigh pain, then weakness and wasting of the thigh, with weight loss; usually type 2. Gradual partial recovery.
• Treatment-induced neuropathy - after rapid improvement in glucose control.

Management:

• Glucose control, plus BP and lipid control.
• Annual foot checks (monofilament); foot protection service; education.

Treating neuropathic pain (NICE CG173 - any cause):

• First line: Amitriptyline, duloxetine, gabapentin or pregabalin. If one fails, switch to another.
• Topical capsaicin cream or lidocaine plasters for localised pain (e.g. post-herpetic neuralgia).
• Tramadol only as short-term rescue.
• Avoid long-term strong opioids.
• Gabapentinoids are controlled drugs - risk of dependence, misuse and breathing depression (especially with opioids). Reduce the dose in kidney impairment.
• Carbamazepine for trigeminal neuralgia.

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CIDP and Other Immune Neuropathies

• Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP):
  • Like a slow GBS - weakness progresses over more than 8 weeks (or relapses).
  • Proximal and distal symmetrical weakness, sensory loss, absent reflexes.
  • Tests:
    • Demyelinating nerve conduction studies.
    • Raised CSF protein with normal cells.
    • MRI may show thickened nerve roots.
    • Check for paraproteins.
  • Treatment:
    • IVIg, steroids or plasma exchange.
    • Maintenance IVIg or subcutaneous immunoglobulin.
    • Efgartigimod (FcRn blocker) is a newer option.
• Multifocal motor neuropathy:
  • Asymmetric pure motor weakness, usually in the hands and forearms, often with fasciculations - mimics MND.
  • Conduction block on nerve studies; anti-GM1 antibodies.
  • IVIg works. Steroids can make it worse.
• Paraprotein-associated neuropathies:
  • Anti-MAG (IgM paraprotein) - slowly progressive distal sensory ataxic neuropathy and tremor in older men. Rituximab.
  • POEMS syndrome - Polyneuropathy, Organomegaly, Endocrinopathy, M-protein (lambda), Skin changes; high VEGF; sclerotic bone lesions. Haematology treatment.
  • AL amyloidosis - painful small fibre neuropathy, autonomic failure, carpal tunnel syndrome, heart and kidney involvement.
• Hereditary ATTR amyloidosis: Progressive neuropathy with autonomic and cardiac involvement (e.g. V122I variant in people of African descent). Patisiran, vutrisiran, inotersen and tafamidis are treatment options.

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Hereditary Neuropathies

• Charcot–Marie–Tooth disease (CMT) - the commonest inherited neurological disorder (about 1 in 2,500):
  • CMT1A (PMP22 duplication, autosomal dominant, demyelinating) is the commonest type.
  • Features:
    • Slowly progressive distal weakness and wasting from childhood or adolescence - "inverted champagne bottle" legs.
    • Pes cavus (high arches) and hammer toes.
    • Foot drop; tripping; sprained ankles.
    • Absent reflexes; mild sensory loss.
    • Family history.
  • Management:
    • Physiotherapy; ankle–foot orthoses; orthopaedic foot surgery.
    • Genetic counselling.
    • Avoid neurotoxic drugs, especially vincristine (can cause severe weakness).
• Hereditary neuropathy with liability to pressure palsies (HNPP): PMP22 deletion - recurrent painless nerve palsies after minor pressure (e.g. peroneal palsy from crossing legs).
• Hereditary sensory and autonomic neuropathies - painless injuries and ulcers.
• Neuropathy also features in Friedreich's ataxia, Refsum disease, Fabry disease (painful hands and feet, angiokeratomas, kidney and heart disease - enzyme replacement) and porphyria (acute motor neuropathy).

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Mononeuritis Multiplex

• What it is: Damage to two or more separate nerves, often painful, developing over days to weeks (e.g. a foot drop then a wrist drop). It can merge into an asymmetric polyneuropathy.
• Causes ("WARDS PLC" is one memory aid):
  • Vasculitis - polyarteritis nodosa, EGPA (asthma, eosinophilia), GPA, microscopic polyangiitis, rheumatoid arthritis, SLE, Sjögren's syndrome, cryoglobulinaemia (hepatitis C).
  • Diabetes.
  • Sarcoidosis.
  • Leprosy (the commonest worldwide).
  • HIV; Lyme disease.
  • Cancer infiltration (lymphoma).
  • HNPP.
• Tests:
  • ESR and CRP, ANCA, ANA, ENA, rheumatoid factor, complement, cryoglobulins, hepatitis B and C, HIV.
  • Eosinophil count; urinalysis (kidney involvement); chest X-ray.
  • Nerve conduction studies.
  • Nerve (and muscle) biopsy to confirm vasculitis.
• Treatment: Vasculitic neuropathy is urgent - high-dose steroids with cyclophosphamide or rituximab. Treat the underlying disease; neuropathic pain relief.

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Common Mononeuropathies

Carpal tunnel treatment:

• Wrist splints at night.
• Steroid injection.
• Surgical decompression if severe (wasting, constant numbness) or symptoms persist.
• Treat the cause (e.g. hypothyroidism).

Other entrapments: Avoid pressure; splints; surgery if severe or persistent.

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Bell's Palsy and Facial Weakness

Bell's palsy: Sudden (within 72 hours) LMN facial weakness of unknown cause (probably viral).

• Features:
  • The whole of one side of the face is weak, including the forehead.
  • Can't close the eye fully.
  • Pain behind the ear.
  • Altered taste.
  • Sensitivity to loud noise (hyperacusis).
• Commoner in pregnancy and diabetes.
• Treatment (within 72 hours of onset):
  • Prednisolone - 50 mg daily for 10 days, or 60 mg daily for 5 days then reduced by 10 mg a day.
  • Antivirals alone don't work; they are sometimes added in severe palsy.
  • Eye protection - lubricating drops by day, ointment at night, tape the eye shut for sleep, sunglasses. Urgent eye review if the eye is painful or red.
• Outlook: Most recover fully over 3–6 months; about 1 in 5 have some lasting weakness or "synkinesis" (abnormal linked movements, "crocodile tears").
• Refer if:
  • No improvement after 3 weeks.
  • Other cranial nerves are involved.
  • A parotid mass or ear disease is present.
  • The palsy is recurrent or bilateral.
  • Onset is slow (tumour).

Other causes of facial weakness:

• UMN (forehead spared) - stroke, tumour, MS.
• Ramsay Hunt syndrome (herpes zoster of the geniculate ganglion):
  • Facial palsy with a vesicular rash in the ear canal or palate.
  • Ear pain; hearing loss and vertigo.
  • Worse prognosis.
  • Aciclovir or valaciclovir plus prednisolone.
• Bilateral facial palsy:
  • Guillain–Barré syndrome.
  • Lyme disease.
  • Sarcoidosis.
  • HIV.
  • Leukaemia or lymphoma.
  • Myasthenia (mimic).
• Ear and parotid disease - otitis media, cholesteatoma, parotid tumours, skull base fractures.

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Radiculopathy and Plexopathy

• Cervical radiculopathy (usually C6 or C7 - disc or spondylosis):
  • Neck and arm pain in a root distribution, tingling, weakness and reflex loss.
  • Most improve with analgesia and physiotherapy.
  • MRI and surgical referral for progressive weakness or persistent pain.
• Lumbar radiculopathy (sciatica) - usually L5 or S1 (disc prolapse):
  • Leg pain below the knee, worse than back pain.
  • Most settle within 6–12 weeks.
  • NICE NG59: NSAIDs, staying active, exercise.
  • Gabapentinoids, antiepileptics and oral steroids are not recommended for sciatica.
  • Epidural injection or surgery for persistent severe pain.
• Red flags:
  • Cauda equina symptoms (saddle numbness, bladder or bowel change, bilateral sciatica) - emergency MRI.
  • Progressive weakness.
  • Cancer history.
  • Fever or immunosuppression.
• Neuralgic amyotrophy (Parsonage–Turner syndrome):
  • Sudden severe shoulder and arm pain lasting days to weeks, followed by patchy weakness and wasting (e.g. serratus anterior - winged scapula, deltoid, spinati, anterior interosseous nerve).
  • Often after infection, surgery or vaccination; hepatitis E is a recognised trigger.
  • Slow recovery over months to years. Pain relief, physiotherapy.
• Brachial plexopathy:
  • Pancoast tumour (lower plexus - hand weakness, Horner's).
  • Radiation (breast cancer - painless, years later).
  • Trauma (motorcycle injuries).
  • Thoracic outlet syndrome (cervical rib - wasting of the hand).
• Lumbosacral plexopathy: Diabetic amyotrophy, pelvic tumours, retroperitoneal haematoma (anticoagulants), radiation.

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Myasthenia Gravis

What it is: An autoimmune disease in which antibodies block or destroy acetylcholine receptors at the neuromuscular junction, causing fatigable weakness.

Who gets it:

• Two peaks - young women (20–40) and older men (over 60).
• Thymoma in about 10–15%; thymic hyperplasia in younger patients.

Features:

• Fatigable weakness - worse with repeated use and later in the day; better after rest.
• Ocular - ptosis (often asymmetric, variable) and diplopia. About 15% stay purely ocular.
• Bulbar - nasal speech, difficulty chewing and swallowing, weak neck.
• Limb - proximal weakness.
• Respiratory weakness (crisis - see the Neurological Emergencies chapter).
• Normal pupils, sensation and reflexes.

Antibodies:

• AChR antibodies - about 85% of generalised MG (about 50% of ocular).
• MuSK antibodies - bulbar, facial and neck weakness; respond poorly to pyridostigmine; respond well to rituximab.
• LRP4; seronegative MG.

Diagnosis:

• Antibodies.
• Neurophysiology - decrement on repetitive nerve stimulation; jitter on single-fibre EMG.
• Ice pack test for ptosis (improves with cooling).
• CT chest for thymoma.
• TFTs (associated thyroid disease).

Drugs that can worsen MG - avoid or use with care:

• Antibiotics - aminoglycosides, fluoroquinolones, macrolides, IV magnesium.
• Beta-blockers.
• Calcium channel blockers.
• Lithium.
• Chloroquine and hydroxychloroquine.
• Muscle relaxants in anaesthesia.
• Checkpoint inhibitors and penicillamine can cause MG.
• Statins can worsen it.

Treatment:

• Symptomatic: Pyridostigmine 30–60 mg 4–6 times daily. Side effects: diarrhoea, cramps, sweating, salivation (glycopyrronium or propantheline help). Too much causes a cholinergic crisis (weakness, secretions).
• Immunosuppression:
  • Prednisolone - start low and increase slowly. High starting doses can cause a temporary worsening in the first 1–2 weeks. Bone protection.
  • Steroid-sparing: Azathioprine (check TPMT; takes 12–18 months), mycophenolate, methotrexate.
• Thymectomy:
  • Essential if there is a thymoma.
  • Also benefits AChR-positive generalised MG in people under about 65 (MGTX trial), even without thymoma.
• Refractory disease: Rituximab (especially MuSK); newer treatments - complement inhibitors (eculizumab, ravulizumab, zilucoplan - meningococcal vaccination needed) and FcRn blockers (efgartigimod, rozanolixizumab). Access through specialist centres varies.
• Rapid short-term treatment (crisis, before surgery): IVIg or plasma exchange.
• Pregnancy: MG can worsen, especially postpartum. Babies can have temporary neonatal myasthenia (feeding and breathing problems). Avoid magnesium sulfate for pre-eclampsia.

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Lambert–Eaton Myasthenic Syndrome

• What it is: Antibodies against voltage-gated calcium channels reduce acetylcholine release.
• Cause: About half to two-thirds are paraneoplastic, mainly small cell lung cancer (smokers). The rest are autoimmune.
• Features:
  • Proximal leg weakness (difficulty with stairs and rising from chairs).
  • Weakness improves briefly with exercise.
  • Reduced or absent reflexes that increase after brief exercise ("facilitation").
  • Autonomic symptoms - dry mouth, constipation, erectile dysfunction.
  • Ptosis and bulbar weakness are mild compared with MG.
• Diagnosis:
  • VGCC antibodies.
  • Increment on repetitive nerve stimulation after exercise (over 100%).
  • Look for cancer - CT chest and PET-CT, repeated for at least 2 years if negative.
• Treatment:
  • Treat the cancer.
  • Amifampridine (3,4-diaminopyridine) - increases acetylcholine release.
  • Pyridostigmine (modest benefit).
  • Immunosuppression (steroids, azathioprine), IVIg.

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Approach to Myopathy

Clues:

• Symmetrical proximal weakness - trouble climbing stairs, standing from low chairs, combing hair.
• Normal sensation.
• Muscle pain (inflammatory, metabolic, drug-induced).
• Family history.
• Rash (dermatomyositis); breathlessness (ILD, respiratory muscle or cardiac involvement).

Causes:

• Inflammatory - dermatomyositis, immune-mediated necrotising myopathy, antisynthetase syndrome, inclusion body myositis, overlap myositis.
• Endocrine:
  • Hypothyroidism (raised CK) and hyperthyroidism.
  • Cushing's and steroid myopathy (normal CK).
  • Osteomalacia (vitamin D) and hyperparathyroidism.
  • Acromegaly.
• Drugs and toxins - statins, steroids, alcohol, colchicine, hydroxychloroquine, zidovudine, checkpoint inhibitors.
• Metabolic:
  • McArdle disease (glycogen storage disease type V) - cramps and exercise intolerance early in exercise, with a "second wind"; rhabdomyolysis.
  • CPT2 deficiency - rhabdomyolysis after prolonged exercise or fasting.
  • Pompe disease.
• Mitochondrial.
• Inherited - muscular dystrophies, myotonic dystrophy.
• Electrolytes - low potassium, phosphate, calcium or magnesium.
• Critical illness myopathy.

Tests:

• CK, TFTs, U&E, calcium, phosphate, vitamin D, magnesium, potassium.
• Myositis antibodies.
• EMG.
• Muscle MRI (pattern and biopsy site).
• Muscle biopsy.
• Genetic testing.
• ECG and echo; lung function and HRCT where relevant.

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Inflammatory Myopathies

• Dermatomyositis:
  • Proximal weakness with a characteristic rash:
    • Heliotrope (purple) rash on the eyelids, often with swelling.
    • Gottron's papules over the knuckles.
    • "Shawl sign" and "V-sign" on sun-exposed areas.
    • Nailfold changes.
    • Calcinosis (children).
  • Associated cancer in about 15–25% of adults (ovary, lung, stomach, bowel, breast, nasopharynx) - screen for cancer at diagnosis and for 3–5 years. Anti-TIF1γ and anti-NXP2 antibodies carry the highest cancer risk.
  • Anti-MDA5 - little muscle weakness but rapidly progressive ILD and skin ulcers.
• Antisynthetase syndrome (anti-Jo-1 and others):
  • Myositis.
  • Interstitial lung disease.
  • Arthritis.
  • Raynaud's phenomenon.
  • "Mechanic's hands" (cracked rough skin on the fingers).
  • Fever.
• Immune-mediated necrotising myopathy:
  • Severe proximal weakness with a very high CK (often over 10,000 IU/L).
  • Anti-HMGCR (linked to statins - it continues after the statin is stopped) or anti-SRP.
• Polymyositis - now a rare diagnosis; many cases turn out to be another type.
• Treatment (except inclusion body myositis):
  • High-dose steroids (prednisolone about 1 mg/kg, or IV methylprednisolone if severe).
  • Plus a steroid-sparing drug (methotrexate, azathioprine, mycophenolate).
  • IVIg (especially dermatomyositis, necrotising myopathy, dysphagia).
  • Rituximab or cyclophosphamide for severe disease or ILD.
  • Physiotherapy; swallow assessment.
• Inclusion body myositis:
  • The commonest acquired myopathy over 50 (men more than women).
  • Slowly progressive, often asymmetric weakness of the quadriceps (falls, knee giving way) and finger flexors (weak grip).
  • Dysphagia.
  • CK normal or mildly raised; anti-cN1A antibodies.
  • Doesn't respond to immunosuppression - supportive care and physiotherapy.

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Statins and Muscle

• Muscle aches with a normal CK are common but often not caused by the statin (in blinded trials, symptoms are similar with placebo).
• Spectrum:
  • Myalgia with normal CK.
  • Myositis (CK raised).
  • Rhabdomyolysis (CK over 10 times the upper limit, AKI, dark urine) - rare.
  • Anti-HMGCR necrotising myopathy - persists or progresses after stopping.
• Risk factors:
  • High doses (especially simvastatin 80 mg).
  • Interacting drugs - clarithromycin, erythromycin, itraconazole, ciclosporin, gemfibrozil, amiodarone, diltiazem, verapamil, HIV protease inhibitors, grapefruit juice.
  • Hypothyroidism.
  • Older age; low body weight.
  • Kidney or liver impairment.
  • Alcohol.
  • Vitamin D deficiency.
• Management (NICE NG238):
  • Check CK and TFTs.
  • CK over 5 times the upper limit - stop the statin and recheck.
  • Normal or mildly raised CK - consider a break and re-challenge, a lower dose, or a different statin. Don't abandon lipid lowering - consider ezetimibe, bempedoic acid or inclisiran.
  • Persistent weakness and very high CK after stopping - test anti-HMGCR and refer.

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Muscular Dystrophies

• Duchenne muscular dystrophy:
  • X-linked recessive - boys; absent dystrophin.
  • Features:
    • Delayed walking.
    • Frequent falls by 3–5 years.
    • Gowers' sign (uses hands to "climb up" the legs to stand).
    • Calf pseudohypertrophy.
    • Waddling gait; toe walking.
  • CK very high (often over 10,000 IU/L).
  • Loss of walking by about 12; scoliosis.
  • Cardiomyopathy and respiratory failure in the late teens to twenties.
  • Management:
    • Corticosteroids (deflazacort, prednisolone, or vamorolone).
    • Physiotherapy; spinal surgery.
    • Heart treatment (ACE inhibitors) and NIV.
    • Gene-targeted therapies are emerging.
    • Survival is now into the 30s and beyond.
  • Female carriers can develop cardiomyopathy - offer cardiac screening.
• Becker muscular dystrophy: Reduced or abnormal dystrophin - milder and later (walking into adulthood); cardiomyopathy can be severe.
• Myotonic dystrophy type 1 - the commonest adult muscular dystrophy:
  • Genetics: Autosomal dominant CTG repeat (DMPK) with anticipation. Congenital forms (floppy baby, learning disability) come from the mother.
  • Muscle features:
    • Distal weakness (hands, foot drop).
    • Myotonia - slow relaxation after gripping (can't let go of a handshake).
    • Ptosis, facial weakness and temporal wasting ("hatchet face").
    • Neck flexor weakness.
  • Other features:
    • Frontal balding.
    • Cataracts (early).
    • Cardiac conduction disease - heart block and sudden death (yearly ECG; pacing or ICD).
    • Diabetes; hypogonadism.
    • Excessive daytime sleepiness; respiratory weakness.
    • Dysphagia; gallstones.
    • Cognitive and personality change.
    • High anaesthetic risk.
  • Treatment: Mexiletine for troublesome myotonia (cardiology input).
• Facioscapulohumeral dystrophy:
  • Autosomal dominant.
  • Facial weakness (can't whistle or close the eyes tightly).
  • Scapular winging.
  • Upper arm weakness - often asymmetric.
  • Foot drop; hearing loss and retinal vessel changes in some.
• Limb-girdle dystrophies - many genetic types with shoulder and hip girdle weakness; some have cardiac involvement.
• Oculopharyngeal dystrophy - late-onset ptosis and dysphagia.