Motor Neuron Disease (MND-ALS)

Related Subjects: |Neurological History taking |Motor Neuron Disease (MND-ALS) |Miller-Fisher syndrome |Guillain Barre Syndrome |Multifocal Motor Neuropathy with Conduction block |Multiple Sclerosis (MS) Demyelination |Inclusion Body Myositis |Cervical spondylosis |Anterior Spinal Cord syndrome |Central Spinal Cord syndrome |Brown-Sequard Spinal Cord syndrome |Spinal Cord Compression |Spinal Cord Haematoma |Spinal Cord Infarction

🧠 Motor Neurone Disease (MND) presents with generalized and bulbar weakness, muscle wasting, brisk reflexes, and no sensory loss. Eye and bladder function are typically spared. ⚡ There is no definitive diagnostic test - diagnosis relies on clinical signs involving both the brain and spinal cord.

ℹ️ About

• Also known as Amyotrophic Lateral Sclerosis (ALS), Charcot's disease, and Lou Gehrig's disease.
• ⏳ Diagnosis is often delayed, sometimes taking >16 months from symptom onset.
• Initial symptoms may be vague, e.g., fatigue or weakness.

How Common Is It? 📊

• Incidence: 1.8–2.2 per 100,000 population.
• Prevalence: 4.0–4.7 per 100,000 population in the UK.
• At any given time, ~2,000 individuals in England and Wales are affected.

Pathology 🔬

• Degeneration of motor giant pyramidal Betz cells (layer V, primary motor cortex).
• Loss of anterior horn cells in the spinal cord.
• Degeneration of cranial motor nuclei in the brainstem.

Aetiology / Genetics 🧬

• 🌍 Guam variant: linked with dementia & parkinsonism in the Chamorro people.
• SOD1 mutations implicated in familial ALS.
• Other mutations: RNA processing, axonal transport, cytoskeletal proteins.
• Familial ALS = ~10% of cases, usually autosomal dominant.

Forms of MND 🧾

• Progressive Muscular Atrophy: LMN predominant. ⏳ Survival 5–10 yrs.
• Progressive Bulbar Palsy: Tongue wasting, fasciculations, spastic palate. ⏳ Survival 2–3 yrs.
• Primary Lateral Sclerosis: UMN predominant, symmetrical. 👍 Good prognosis.
• ALS: UMN + LMN features. ⏳ Survival 3–4 yrs.
• MND-Dementia: Associated with FTD (frontotemporal dementia).

Clinical Features ⚠️

• 💪 Subtle weakness → progresses to wasting & fasciculations (esp. hands).
• 🌙 Painful nocturnal cramps (thighs common).
• Mixed UMN + LMN signs: weakness + brisk reflexes + extensor plantar.
• 🙅‍♂️ No significant sensory loss; eye movements & sphincters spared.
• 👅 Bulbar involvement: wasted fibrillating tongue, dysarthria, dysphagia.
• ⚖️ Weight loss due to dysphagia & wasting.
• “Dropped head” & wasted hands appearance.

El Escorial Criteria 📋

• Clinically Definite ALS: UMN + LMN signs in ≥3 regions (bulbar, cervical, thoracic, lumbar).
• Clinically Probable ALS: UMN + LMN in 2 regions, UMN above LMN.
• Clinically Possible ALS: UMN + LMN in 1 region only.

Differential Diagnosis 🔍

• MMN with conduction block (check GM-1 antibodies).
• Cervical spondylotic myelopathy, foramen magnum lesions (MRI).
• CIDP, Inclusion Body Myositis.
• Myasthenia Gravis (Tensilon, antibodies, EMG).
• Kennedy’s syndrome (X-linked).
• B12 deficiency, Lyme disease, malignancy.

Investigations 🧪

• FBC, U&E, TFT, CK, syphilis serology.
• CSF: may show mild ↑ protein.
• Autoantibody panel (exclude mimics).
• MRI brain/cervical spine → rule out mimics (syrinx, compression, vascular).
• EMG: fasciculations + fibrillation (LMN loss).
• Nerve conduction: often normal until late.

Management 🩺

• 👩‍⚕️ Multidisciplinary Support: Physio, OT, SALT, dietician, palliative input.
• 💊 Riluzole 50mg bd: Glutamate antagonist → extends survival by ~2–3 months.
• 💧 Anticholinergics: Glycopyrrolate, amitriptyline, or hyoscine for drooling.
• 🦵 Baclofen / Diazepam: Spasticity control.
• 🥤 Feeding support: NG, PEG, or RIG feeding when bulbar involvement advances.
• 😴 NIV (BiPAP): Improves sleep, reduces fatigue, ↑ survival by ~6 months.
• 🗣️ Speech synthesizers: Assist communication.
• 💊 Quinine, Carbamazepine, Gabapentin → muscle cramps.
• 🙂 SSRIs or mood stabilisers for depression & emotional lability.

Prognosis 📉

• Median survival: 2–3 yrs from diagnosis.
• ~25% survive ≥5 yrs.

References 📚

• NICE Guidance on Riluzole

Cases - Motor Neurone Disease (MND)

• Case 1 - Amyotrophic Lateral Sclerosis (ALS, Mixed UMN & LMN) ⚡: A 58-year-old man presents with progressive weakness in his right hand, muscle fasciculations, and stiffness in his legs. Exam: wasting of hand intrinsic muscles, brisk reflexes, extensor plantar responses. No sensory loss. Diagnosis: ALS (most common form of MND). Management: Riluzole to modestly extend survival; physiotherapy; MDT input; NIV (non-invasive ventilation) for respiratory support.
• Case 2 - Progressive Bulbar Palsy 🗣️: A 62-year-old woman presents with slurred speech, difficulty swallowing, and choking on liquids. Exam: tongue wasting with fasciculations, brisk jaw jerk, nasal dysarthria. Diagnosis: Bulbar-onset MND (progressive bulbar palsy). Management: MDT care; speech and language therapy; gastrostomy for nutrition; NIV; symptomatic treatment of sialorrhoea.
• Case 3 - Primary Lateral Sclerosis (PLS, UMN-Predominant) 🧠: A 50-year-old man presents with progressive leg stiffness and spastic gait over 3 years. Exam: pyramidal weakness, brisk reflexes, extensor plantar responses, but no fasciculations or wasting. Sensation intact. Diagnosis: Primary lateral sclerosis (UMN-predominant MND variant). Management: Supportive - physiotherapy, spasticity control (baclofen, tizanidine), MDT monitoring.

Teaching Commentary 🧠

MND is a group of progressive neurodegenerative disorders of upper and lower motor neurones. - ALS: UMN + LMN signs, most common. - Bulbar Palsy: speech and swallowing first; poorer prognosis. - PLS: UMN-predominant; slower progression. - PMA (progressive muscular atrophy): LMN-predominant. Clues: weakness with fasciculations, mixed UMN/LMN signs, no sensory loss, progressive. Dx: clinical + EMG (denervation); MRI excludes mimics. Mx: Riluzole, multidisciplinary care, NIV, gastrostomy, palliative support. Prognosis: average survival 2–5 years (longer in PLS).