Motor Neuron Disease — Written Clinical Reasoning

SAQ 1 — Integrated Management of Bulbar-Onset ALS with Respiratory Failure (15 marks, 20 minutes)

Prompt: Outline your integrated management of this patient, addressing the diagnosis, respiratory support, nutritional support, symptom management, multidisciplinary care and advance care planning. Justify each step with reference to physiological thresholds and guideline recommendations. [1]

Model Answer

Confirm the diagnosis and its certainty (2 marks): [1]

This patient has clinically definite amyotrophic lateral sclerosis (ALS) by the revised El Escorial criteria — combined upper motor neuron (UMN) and lower motor neuron (LMN) signs in bulbar, cervical and lumbar regions (tongue wasting and fasciculation with a brisk jaw jerk; wasted right arm with brisk reflexes; spastic hyperreflexic legs with extensor plantar responses), with sensation spared [4]. The diagnosis should be confirmed by EMG demonstrating active denervation and chronic reinnervation in at least two body regions, MRI of the cervical spine to exclude cervical myelopathy, and a blood screen (including vitamin B12 and creatine kinase) to exclude mimics. Anti-GM1 antibodies and motor nerve conduction studies are warranted if any doubt about multifocal motor neuropathy exists, though the bulbar and UMN signs here make ALS far more likely.

Respiratory support — non-invasive ventilation (4 marks): [1]

This patient has symptomatic respiratory muscle weakness crossing guideline thresholds for offering non-invasive ventilation (NIV) [1][3]. Specifically: she has symptoms (orthopnoea, morning headache from nocturnal hypoventilation); her sniff nasal inspiratory pressure is 36 cmH2O (below the 40 cmH2O threshold); her supine forced vital capacity is 35 per cent predicted (below 50 per cent); and she has established daytime hypercapnia (pCO2 48 mmHg) with a compensatory respiratory acidosis-buffering bicarbonate of 28 mmol/L. The hypercapnia is a late, ominous sign — she is on the cusp of decompensation.

NIV is the single intervention with the largest survival benefit in ALS, extending median survival by 7 to 13 months in the Bourke randomised trial, with parallel improvement in sleep quality, daytime symptoms and quality of life [1]. She should be commenced on bilevel positive airway pressure (BiPAP), titrated to symptoms and nocturnal oxygenation/capnography, beginning overnight and extending to daytime use as the disease progresses. Patient and family education on mask fitting and anticipatory troubleshooting is essential, because tolerance and carer capacity — not physiology — usually determine NIV success. She must NOT be allowed to decompensate further before NIV is established.

Nutritional support — PEG timing (3 marks): [1]

She has bulbar disease, dysphagia and significant weight loss (BMI 19, 10 kg lost), all of which independently shorten survival and indicate percutaneous endoscopic gastrostomy (PEG) [3]. The critical principle is timing: PEG is safest and most effective before respiratory function falls below an FVC of 50 per cent predicted. Her erect FVC is 52 per cent but her supine FVC is already 35 per cent and she is hypercapnic, so the procedural risk of sedation is now substantial. PEG should therefore be performed urgently, coordinated with the respiratory team for periprocedural NIV, and a radiologically inserted gastrostomy (RIG) should be considered as the safer alternative given her respiratory compromise. The principle is that PEG timing is determined by respiratory surveillance, not by appetite.

Symptom management (2 marks): [1]

• Sialorrhoea (likely from impaired swallowing of saliva): hyoscine hydrobromide 1 mg patch every 72 hours, or glycopyrrolate; botulinum toxin into the salivary glands if refractory.
• Spasticity: baclofen, titrated from 5 mg three times daily.
• Pseudobulbar affect: screen for it; treat with dextromethorphan-quinidine (check QT interval first) or an SSRI if contraindicated.
• Pain, constipation, dysarthria (speech therapy and augmentative communication): address proactively. [1]

Multidisciplinary care and advance care planning (4 marks): [1]

Refer to a specialist multidisciplinary ALS clinic, which independently prolongs survival [5]. The team — neurologist, respiratory physician, speech and language therapist, dietitian, occupational therapist, physiotherapist, specialist nurse, palliative care and clinical psychology — coordinates the interventions above.

Because she already has respiratory failure, advance care planning must begin now, while she retains capacity. Cover: goals and fears; the disease trajectory; advance directive and substitute decision-maker appointment; the role and limits of NIV, PEG and tracheostomy ventilation; and the transition to palliative care. Palliative care involvement from diagnosis is increasingly standard. The principle is that withholding unwanted life-prolonging treatment is good palliative care, not euthanasia. Screen for cognitive impairment (ECAS) because frontotemporal dementia coexists with ALS in 15 per cent and predicts poor NIV adherence and shorter survival. [1]

SAQ 2 — The Treatable Mimic: Multifocal Motor Neuropathy (10 marks, 15 minutes)

Prompt: A 52-year-old man presents with a 14-month history of slowly progressive weakness and wasting confined to the left hand and forearm, with fasciculations but no sensory loss and no upper motor neuron signs. Contrast his presentation, investigation and management with the patient in SAQ 1, and explain why the distinction matters. [1]

Model Answer

Clinical contrast (3 marks): [1]

This second patient has a pattern that is the mirror image of SAQ 1 in the features that matter most for the differential [4]:

• Distribution: asymmetric, predominantly distal, upper-limb weakness — unlike ALS, which is usually more widespread and involves multiple regions including bulbar.
• UMN signs: absent — no spasticity, hyperreflexia, clonus or extensor plantar responses. ALS requires UMN signs; their absence here is pivotal.
• Bulbar involvement: absent — no tongue wasting or jaw-jerk abnormality.
• Sensation: clinically intact (and, critically, normal on nerve conduction studies), ruling out a sensory neuropathy and arguing against Kennedy disease.
• Course: slowly progressive over more than a year without spreading beyond one limb — atypical for ALS, which usually generalises faster. [1]

This phenotype — asymmetric distal upper-limb LMN weakness, no UMN signs, normal sensation, slow course — is the classic presentation of multifocal motor neuropathy (MMN) with conduction block, a treatable mimic of ALS. [1]

Confirmatory investigation (3 marks): [1]

• Motor nerve conduction studies are the diagnostic test: they show focal conduction block across non-entrapment sites (e.g. in the ulnar or median nerve in the forearm) with otherwise preserved conduction velocity, and normal sensory studies. Conduction block is the electrophysiological signature of MMN and is NOT a feature of ALS.
• Anti-GM1 antibodies (IgM) are positive in about 30 to 80 per cent of MMN cases and support the diagnosis, but a negative result does not exclude it; conduction block is more important.
• MRI of the cervical spine excludes cervical radiculopathy or myelopathy as an alternative.
• Cerebrospinal fluid protein may be mildly elevated; a markedly raised protein should raise CIDP, which differs from MMN in having sensory involvement. [1]

Management and why the distinction matters (4 marks): [1]

MMN responds to intravenous immunoglobulin (IVIG), which can improve strength and function for years and is first-line therapy [4]. Maintenance therapy is usually required. Corticosteroids and plasma exchange are ineffective and may worsen MMN, and must be avoided.

The distinction from ALS is one of the most important in clinical neurology because the consequences of error are profound: misdiagnosing MMN as ALS denies a patient years of treatable function and exposes them to the psychological burden of a fatal diagnosis they do not have, while misdiagnosing ALS as MMN subjects a patient to futile and expensive immunotherapy. The differentiating features to commit to memory are: ALS has UMN signs, bulbar involvement, EMG denervation with reinnervation across multiple regions, and normal motor conduction (no block); MMN has no UMN signs, no bulbar involvement, motor conduction block, anti-GM1 antibodies, and a response to IVIG. The single most discriminating test is the motor nerve conduction study looking for conduction block. [1]

Examiner takeaway: In any patient with progressive, painless weakness, ask three questions at the bedside — are there UMN signs, is sensation spared, and is the process asymmetric and distal in one arm? The answers determine whether you are chasing ALS (combined UMN/LMN, multisystem) or MMN (pure LMN, asymmetric, IVIG-responsive) — and getting it right changes everything. [1]