Motor Neurone Disease

Question 1

What is MND?

Answer 1

• Progressive Weakness and Death typically secondary to Respiratory Failure or Aspiration; 2 per 100,000; Presents 50 – 75yrs
• Upper and Lower Motor Neurones of the Spinal Cord, CN Motor Nuclei and Cortex; Also, Frontotemporal Dementia (5%), Up to 40% Frontal Cognitive Impairment
• Sporadic; Unknown Aetiology and no know environmental risk factors

Question 2

Pathophysiology of MND

Answer 2

Ubiquinated Cytoplasmic Inclusions (containing RNA Processing Proteins TDP43 and FUS) are pathological hallmarks found in axons
o Indicates Protein Aggregation might be involved in Pathogenesis

Question 3

Genetics of MND

Answer 3

5 – 10% Familial, Mutations in Free-radical Scavenging Enzyme SOD-1 and others, including in TDP43 and FUS have been identified; Repeat Expansion on Chromosome 9 also accounts for familial cases of MND-FTD overlap

Question 4

ALS: Clinical Pattern

Answer 4

Classic, Simultaneous involvement of UMN and LMN usually in one limb, spreading to other limbs and trunk muscles
o Progressive Focal Muscle Weakness/Wasting with Fasciculations due to Spontaneous Firing of abnormally large Motor Units (Formed by surviving axons branching to innervate fibres which have lost their nerve supply); Cramps common
o UMN Signs – Hyperreflexia (Brisk reflex in a Wasted Muscle is classic), Upgoing
Plantars (Babinski’s) and Spasticity
▪ Asymmetric Spastic Paraparesis with LMN features developing months later
o Relentless progression over months allows diagnosis to be confirmed

Question 5

Progressive Muscular Atrophy

Answer 5

Pure LMN Presentation with Weakness, Muscle
Wasting and Fasciculations usually starting in one limb, and gradually spreading to involve other adjacent spinal segments

Question 6

Progressive Bulbar and Pseudobulbar Palsy

Answer 6

Lower Cranial Nerve Nuclei and Supranuclear connections involved, leading to Dysarthria, Dysphagia, Nasal Regurgitation and Choking
o Tongue Fasciculation with Slow, Stiff movements are a classic finding
o Emotional Incontinence – Pathological laughing and crying in Pseudobulbar

Question 7

Primary Lateral Sclerosis

Answer 7

Rare (1-2% of MND); Confined to UMN, causing Slowly Progressive Tetraparesis and Pseudobulbar Palsy

Question 8

Management of MND

Answer 8

• Largely clinical diagnosis; Denervation of muscles due to LMN Degeneration confirmed by EMG; Need to clinically distinguish from Radiculopathy/Myelopathy, or Motor Neuropathies
• Survival >3yrs is uncommon; No treatment has been shown to influence outcome substantially; Riluzole (Na Channel Blocker which reduces Glutamate release) slows progression slightly, increasing Life Expectancy by 3 – 4/12 on average
• NIV Support and Gastrostomy Feeding help prolong survival
• Specialist MDT and access to Palliative Care team