7.4 Neuromuscular Disorders & Movement Disorders
Key Takeaways
Peripheral neuropathies present with symmetrical distal 'glove-and-stocking' sensory loss; vitamin B12 deficiency produces subacute combined degeneration of the cord combining dorsal column sensory ataxia with lateral corticospinal tract upper motor neuron weakness and absent ankle reflexes.
Guillain-Barré syndrome is an acute post-infectious demyelinating polyneuropathy (commonly post-Campylobacter jejuni) presenting with ascending flaccid weakness, areflexia, and autonomic instability; serial forced vital capacity (FVC) monitoring is critical, and treatment is IVIG or plasma exchange (corticosteroids are ineffective).
Myasthenia gravis is an autoimmune postsynaptic NMJ disorder with anti-AChR or anti-MuSK antibodies causing fatigable ocular, bulbar, and proximal weakness with preserved reflexes; patients require CT chest to screen for thymoma, treatment with pyridostigmine, and strict avoidance of aminoglycosides, beta-blockers, and macrolides.
Parkinson's disease presents with an asymmetrical resting tremor (4–6 Hz), lead-pipe/cogwheel rigidity, and bradykinesia; levodopa is first-line when quality of life is impaired, while dopamine agonists carry a high risk of impulse control disorders (gambling, hypersexuality).
Multiple sclerosis relapses are treated acutely with high-dose methylprednisolone (oral 500 mg daily for 5 days or IV 1 g daily for 3–5 days); clinical markers include optic neuritis with relative afferent pupillary defect, Uhthoff's phenomenon, and CSF oligoclonal bands.
Neuromuscular Disorders & Movement Disorders
Neuromuscular disorders encompass pathological lesions extending from the anterior horn cell and peripheral nerve to the neuromuscular junction and muscle fibre. Recognizing anatomical localization and identifying early signs of respiratory muscle compromise are paramount in emergency neurological care.
Peripheral Neuropathies & Subacute Combined Degeneration
1. Symmetrical Distal Polyneuropathy
- Clinical Presentation: Length-dependent axonal loss or demyelination producing symmetrical 'glove-and-stocking' sensory impairment (loss of vibration, proprioception, pinprick, and temperature starting in toes and feet, ascending to mid-shin before involving fingertips), distal lower limb muscle wasting, and loss of the ankle jerk reflexes.
- Common Aetiologies: Diabetic polyneuropathy (most common overall), chronic alcohol excess, chronic kidney disease (uraemic neuropathy), chemotherapy agents (vincristine, cisplatin, taxanes), and paraproteinaemias.
- Diabetic Neuropathy Management: Strict glycaemic optimization, annual podiatric diabetic foot screening, and first-line pharmacological treatment for neuropathic pain using Duloxetine (60 mg daily), Amitriptyline (10–75 mg nocte), Gabapentin, or Pregabalin.
2. Subacute Combined Degeneration of the Spinal Cord (SCDSC)
- Pathophysiology: Caused by severe Vitamin B12 (Cobalamin) deficiency (commonly pernicious anaemia or ileal resection), leading to defective myelin synthesis affecting both the central and peripheral nervous systems.
- Anatomical Pathways Affected:
- Dorsal Columns: Bilateral loss of vibration and joint position sense, sensory ataxia, positive Romberg's sign, and pseudoathetosis.
- Lateral Corticospinal Tracts: Upper motor neuron signs: spastic paraparesis, hypertonia, and bilateral extensor plantar responses (positive Babinski sign).
- Peripheral Nerves: Symmetrical distal sensory loss and hyporeflexia.
- Classic Exam Paradox: Bilateral extensor plantars (UMN) combined with absent ankle jerks (LMN).
- Investigations: Low serum B12 (<150 ng/L), macrocytic anaemia with elevated mean corpuscular volume (MCV > 100 fL), hypersegmented neutrophils on blood film, anti-intrinsic factor antibodies.
- Critical Prescribing Rule: Always replace Vitamin B12 (intramuscular Hydroxocobalamin) before or concurrently with Folic acid. Treating B12 deficiency with folic acid alone corrects megaloblastic anaemia while catastrophically accelerating irreversible subacute combined degeneration of the spinal cord.
Guillain-Barré Syndrome vs. Myasthenia Gravis
Rapid differentiation between Guillain-Barré syndrome (GBS) and Myasthenia Gravis (MG) is a high-yield clinical competence, as both can cause acute neuromuscular respiratory failure.
| Clinical Feature | Guillain-Barré Syndrome (GBS / AIDP) | Myasthenia Gravis (MG) |
|---|---|---|
| Primary Pathophysiology | Acute post-infectious demyelination of peripheral nerves and roots driven by molecular mimicry | Autoimmune destruction of post-synaptic nicotinic acetylcholine receptors (AChR) or MuSK at the NMJ |
| Precipitating Triggers | Preceding gastroenteritis (Campylobacter jejuni #1) or upper respiratory infection (CMV, EBV, Zika) 1–3 weeks prior | Pregnancy, systemic infection, emotional stress, surgery, or culprit medications (aminoglycosides, beta-blockers) |
| Pattern of Weakness | Symmetrical, rapidly progressive ascending flaccid paralysis (starts in legs, ascends to arms, trunk, and cranial nerves) | Fatigable muscle weakness (worsens with repetitive exertion and towards evening; improves with rest); extraocular and bulbar predilection |
| Deep Tendon Reflexes | Generalised Areflexia / Hyporeflexia (early, universal finding) | Preserved / Normal reflexes (never depressed by the disease) |
| Cranial Nerve Involvement | Bilateral Lower Motor Neuron Facial Nerve (CN VII) palsy in ~50% of cases | Extraocular muscles (asymmetric ptosis, diplopia with pupillary sparing); bulbar weakness (dysphagia, nasal dysarthria) |
| Sensory Findings | Distal mild paresthesias or sensory loss common; severe back/radicular pain | Completely absent (pure motor disorder; sensation is always intact) |
| Autonomic Dysfunction | Frequent and life-threatening: labile blood pressure, cardiac arrhythmias, sinus tachycardia, urinary retention | Absent / rare |
| CSF Findings | Albuminocytological Dissociation: Markedly elevated protein (>0.55–2.0 g/L) with normal white cell count (<5/µL) | Completely normal CSF composition |
| Bedside & Confirmatory Tests | Serial Forced Vital Capacity (FVC) every 4–6h; demyelinating conduction block on nerve conduction studies | Ice pack test (>2 mm ptosis improvement after 2–5 min); serum anti-AChR / anti-MuSK antibodies; single-fibre EMG (increased jitter) |
| Thymic Association | None | Thymoma present in 10–15%; thymic lymphoid hyperplasia in 65%; mandatory CT thorax screening in all patients |
| Definitive Treatment | IV Immunoglobulin (IVIG 0.4 g/kg/day for 5 days) OR Plasma Exchange (Plasmapheresis) | First-line symptomatic: Oral Pyridostigmine (acetylcholinesterase inhibitor); Immunosuppression: Prednisolone + Azathioprine |
| Role of Corticosteroids | Corticosteroids are INEFFECTIVE and NOT recommended (clinical trials show no benefit and potential harm) | Standard second-line disease-modifying therapy (titrated carefully to avoid initial steroid-induced flare) |
Acute Respiratory Failure & Crisis Management
- Forced Vital Capacity (FVC) Monitoring: The gold standard bedside assessment in both GBS and Myasthenic Crisis. Peak expiratory flow rate (PEFR) is unreliable because it reflects airway caliber rather than diaphragmatic neuromuscular strength. FVC must be checked every 4–6 hours.
- Indications for Urgent ICU Admission & Elective Endotracheal Intubation:
- FVC falling below 15–20 mL/kg (or <1.0 L in an average adult)
- Maximum inspiratory pressure < 30 cm H₂O
- Paradoxical abdominal breathing (inward movement of abdomen on inspiration indicating diaphragmatic exhaustion)
- Single-breath counting < 15
- Arterial blood gas showing hypercapnic respiratory acidosis (late, catastrophic sign)
- Drugs to Strictly Avoid in Myasthenia Gravis:
- Antibiotics: Aminoglycosides (gentamicin, amikacin), Macrolides (clarithromycin, erythromycin), Fluoroquinolones (ciprofloxacin)
- Cardiovascular: Beta-blockers (propranolol, atenolol), Calcium channel blockers
- Other: Magnesium sulphate, D-penicillamine, neuromuscular blocking drugs (vecuronium, rocuronium)
Parkinson's Disease & Movement Disorders
Parkinson's disease is a progressive neurodegenerative disorder caused by degeneration of dopaminergic neurons within the substantia nigra pars compacta, resulting in striatal dopamine depletion. Histopathology reveals intracytoplasmic Lewy bodies composed of aggregated alpha-synuclein.
The Cardinal Motor Triad (Characteristically Asymmetric Onset)
- Resting Tremor: 4–6 Hz coarse tremor, classically 'pill-rolling' (thumb rubbing against index finger). Present at rest, dampened during voluntary purposeful movement, and exaggerated by distraction or mental stress.
- Rigidity: Increased tone sustained throughout the entire passive range of motion. Appears as lead-pipe rigidity (smooth uniform resistance) or cogwheel rigidity (ratchet-like resistance produced by underlying resting tremor superimposed on lead-pipe rigidity).
- Bradykinesia: Slowness of movement initiation and progressive decrement in amplitude and speed during repetitive movements (tested via finger tapping or foot tapping). Manifests clinically as hypomimia ('masked' facial expression), reduced blink rate, micrographia (handwriting becoming progressively smaller and cramped), quiet/monotone hypophonic speech, and a slow, shuffling festinant gait with reduced unilateral arm swing and difficulty turning ('en bloc').
- Non-Motor Features: Often predate motor signs by years: anosmia (loss of smell), REM sleep behaviour disorder (vocalizing or acting out dreams), chronic constipation, orthostatic hypotension, depression, and late-stage Lewy body dementia.
Pharmacotherapy of Parkinson's Disease (NICE Guidelines)
| Pharmacological Class | Representative Agents | Mechanism of Action | Clinical Role & Indications | Key Adverse Effects & Clinical Pearls |
|---|---|---|---|---|
| Dopamine Precursor + Peripheral DDC Inhibitor | Co-beneldopa (Levodopa + Benserazide); Co-careldopa (Levodopa + Carbidopa) | Levodopa crosses the blood-brain barrier and is converted to dopamine; DDC inhibitor prevents peripheral breakdown | Most effective symptomatic therapy. First-line when motor symptoms impair quality of life | Nausea, orthostatic hypotension, visual hallucinations. Long-term use (>5 years) leads to motor complications: 'wearing-off' (end-of-dose motor fluctuations) and peak-dose dyskinesias (chorea/dystonia) |
| Non-Ergot Dopamine Agonists | Pramipexole, Ropinirole, Rotigotine (transdermal patch) | Direct stimulation of post-synaptic striatal D₂ and D₃ dopamine receptors | Initial monotherapy in younger patients (<60–65y) to delay levodopa-associated motor complications | Impulse Control Disorders (ICDs) in up to 15% (pathological gambling, hypersexuality, binge eating, compulsive spending); excessive daytime somnolence and sudden-onset sleep attacks |
| MAO-B Inhibitors | Rasagiline, Selegiline | Irreversibly inhibit monoamine oxidase B, preventing central dopamine catabolism | Initial monotherapy for mild motor symptoms or adjunct to reduce levodopa motor fluctuations | Insomnia, headache; do not provoke the 'cheese reaction' at clinical doses due to MAO-B selectivity |
| COMT Inhibitors | Entacapone, Tolcapone | Inhibit catechol-O-methyltransferase, preventing peripheral metabolism of levodopa | Strictly adjunctive therapy with levodopa to extend its half-life and reduce 'wearing-off' | Exacerbates levodopa dyskinesias; harmless reddish-brown/orange discoloration of urine (entacapone); hepatotoxicity requiring regular LFTs (tolcapone) |
| Ergot Dopamine Agonists | Bromocriptine, Cabergoline | Direct dopamine receptor stimulation | Rarely used; strictly restricted due to fibrotic complications | Cardiac valvular fibrosis, pulmonary fibrosis, retroperitoneal fibrosis; requires baseline echocardiogram, CXR, and ESR |
Atypical Parkinsonian Syndromes (Parkinson-Plus)
- Progressive Supranuclear Palsy (PSP): Characterised by symmetrical onset, early unexplained postural instability and falls within the first 12 months, supranuclear vertical gaze palsy (marked limitation of downward voluntary saccades), axial rigidity greater than limb rigidity, retrocollis, and poor response to levodopa.
- Multiple System Atrophy (MSA): Characterised by parkinsonian features combined with severe, early autonomic failure (profound orthostatic hypotension, urinary incontinence, erectile dysfunction) and/or cerebellar ataxia (MSA-C). MRI may show the 'hot cross bun' sign in the pons.
Multiple Sclerosis (MS)
Multiple Sclerosis is a chronic autoimmune inflammatory demyelinating disease of the central nervous system disseminated in space (multiple anatomical CNS lesions) and time (multiple episodes separated by time).
- Subtypes: Relapsing-Remitting MS (RRMS; ~85% of initial presentations), Secondary Progressive MS (SPMS), and Primary Progressive MS (PPMS; progressive from onset).
- Characteristic Manifestations:
- Optic Neuritis: Subacute painful unilateral visual loss, central scotoma, marked colour desaturation (especially red desaturation), and a Relative Afferent Pupillary Defect (RAPD / Marcus Gunn pupil).
- Uhthoff's Phenomenon: Transient worsening of existing neurological symptoms triggered by elevated body temperature (hot bath, intense physical exercise, or fever).
- Lhermitte's Sign: Electric shock-like sensation shooting down the spine into the limbs provoked by forward neck flexion (indicating cervical cord demyelinating plaques).
- Internuclear Ophthalmoplegia (INO): Demyelination of the medial longitudinal fasciculus (MLF); failure of adduction in the ipsilateral eye with horizontal nystagmus of the contralateral abducting eye on lateral conjugate gaze.
- Diagnostic Investigations:
- MRI Brain and Spine with Gadolinium: Demonstrates periventricular demyelinating plaques oriented perpendicular to the lateral ventricles ('Dawson's fingers'), infratentorial, and spinal lesions.
- Lumbar Puncture: Demonstrates oligoclonal IgG bands present in the CSF that are absent in matched serum (reflecting intrathecal clonal B-cell immunoglobulin synthesis).
- Relapse Management: Treat acute, disabling relapses with high-dose corticosteroid therapy to hasten clinical recovery: Oral Methylprednisolone 500 mg daily for 5 days OR Intravenous Methylprednisolone 1 g daily for 3–5 days. (Note: Steroids accelerate relapse recovery but do not alter long-term disease progression).
Essential Tremor
The commonest movement disorder: a bilateral postural and action tremor of the hands (and sometimes head or voice), often with a family history (autosomal dominant) and temporary improvement with alcohol. Unlike Parkinson's disease there is no rigidity or bradykinesia and the tremor is absent at rest. Treatment, if it interferes with function, is propranolol or primidone.
A 32-year-old man presents to the acute medical unit with progressive weakness in both legs over the past 3 days. Today, he has severe difficulty climbing stairs and notices tingling in his toes. Ten days ago, he had an episode of severe abdominal cramping and bloody diarrhoea that resolved spontaneously without antibiotics. On physical examination, power is 3/5 in bilateral lower limbs and 4/5 in both upper limbs. Deep tendon knee and ankle reflexes are completely absent bilaterally, and plantar responses are flexor. Sensation to light touch and vibration is slightly diminished at the toes. Forced vital capacity (FVC) is measured at 2.8 L (predicted 4.2 L). Which of the following represents the single most appropriate initial diagnostic investigation and definitive medical therapy for this patient?
Tensilon test and oral pyridostigmine therapy
Lumbar puncture (evaluating for albuminocytological dissociation) and intravenous immunoglobulin (IVIG)
MRI of the whole spine with gadolinium and intravenous high-dose methylprednisolone
CT head and therapeutic anticoagulation with subcutaneous low-molecular-weight heparin
A 26-year-old woman presents with a 4-month history of intermittent double vision and drooping of her left eyelid that worsens noticeably toward the evening and improves after sleeping. Recently, her voice becomes quiet and nasal when talking for prolonged periods on the phone. On examination, sustained upward gaze for 60 seconds produces worsening bilateral ptosis. Sensation and deep tendon reflexes are completely normal throughout all four limbs. An ice pack applied to the left eye for 3 minutes results in complete resolution of her left ptosis. Which of the following investigations is mandatory in this patient's diagnostic workup, and which class of medications must be strictly avoided due to the risk of precipitating a myasthenic crisis?
24-hour ambulatory blood pressure monitoring; avoid selective serotonin reuptake inhibitors
Brain magnetic resonance angiography (MRA); avoid calcium channel blockers only
Genetic testing for trinucleotide repeats; avoid all non-steroidal anti-inflammatory drugs
Contrast-enhanced CT scan of the thorax to evaluate for thymoma; avoid aminoglycoside antibiotics
A 58-year-old accountant with Parkinson's disease attends the movement disorder clinic with his wife. He was started on a new anti-parkinsonian medication 6 months ago, which has significantly improved his bradykinesia and resting tremor. However, his wife expresses grave concern because over the last 3 months, he has secretly spent over £25,000 on online sports gambling, opened four new credit cards, and exhibited uncharacteristic hypersexual behaviour. He admits to uncontrollable urges to gamble. Which class of anti-parkinsonian medication was most likely prescribed, and what is the underlying mechanism responsible for this complication?
A dopamine agonist such as ropinirole, overstimulating mesolimbic D3 receptors
Levodopa/carbidopa due to peripheral conversion of levodopa into norepinephrine
Selegiline due to irreversible monoamine oxidase B inhibition causing cheese-reaction hypertensive crisis
Entacapone due to central inhibition of catechol-O-methyltransferase in the prefrontal cortex
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