motor neurone disease

Question 1

definition of MND

Answer 1

• Cluster of degenerative disease characterised by axonal degeneration of neurones in the motor cortex, CN somatic motor nuclei (UMNs) and anterior horn cells (LMNs)
• Upper and lower motor neurons are affected
• There is NO sensory loss or sphincter disturbance – this distinguishes MND from MS and polyneuropathies.
• MND NEVER affects eye movements – distinguishing it from myasthenia
• There is usually relentless progression of disease to death within 1- 5 years

.

Question 2

aetiology

Answer 2

• Unknown

~10% familial: SOD1 mutation in 20% of those – chrom 21 = autosomal dominant ALS

Question 3

4 clinical patterns of MND

Answer 3

• Amyotrophic Lateral Sclerosis (ALS): 50%
• (50% of patients)

typically LMN signs in arms and UMN signs in legs

• Lower limbs:

>>>>>lower motor neurone lesions develop at a late stage so that for much of the time, the presentation is that of an uncomplicated picture of corticospinal tract degeneration. Weakness and spasticity are the major features but they are rarely severe.

Upper limbs:

>>>upper and lower motor neurone signs are evident causing weakness much greater than suggested by the degree of wasting.

>>>>reflexes may be impaired or exaggerated depending upon whether the LMN or UMN degeneration is greatest.

>>>>consequently, exaggerated reflexes may occur in the presence of severe wasting - a unique picture

• Specific clinical features: Split hand sign – excessive wasting
• in familial cases the gene responsible lies on chromosome 21 and codes for superoxide dismutase
• Progressive Bulbar Palsy: 10%
• Only affects CN 9-12 → bulbar palsy
• palsy of the tongue, muscles of chewing/swallowing and facial muscles due to loss of function of brainstem motor nuclei

carries worst prognosis

• Progressive Muscular Atrophy: 10%
• Anterior horn cell lesion → LMN signs only
• affects distal muscles before proximal
• carries best prognosis
• Primary Lateral Sclerosis
• Loss of Betz cells in motor cortex → only UMN signs
• Marked spastic leg weakness and pseudobulbar palsy
• no cognitive decline

Question 4

bulbar palsy- define, signs, causes

Answer 4

Bulbar Palsy

• Diseases of nuclei of CN 9-12 in the medulla
• LMN lesions of tongue, muscles of talking and swallowing
• Signs
• Flaccid, fasciculating tongue
• Speech: quiet or nasal (“Donald Duck” speech)
• Normal / absent jaw jerk
• ± Jaw jerk
• Causes
• MND
• GBS
• MG
• syringiobulbia
• Central pontine myelinolysis (CPM)

Question 5

pseudobulbar/corticobulbar palsy- define, signs, causes

Answer 5

Pseudobulbar / Corticobulbar Palsy

• Commoner than bulbar palsy
• Bilateral lesions above mid-pons (e.g. corticobulbartracts) → UMN lesions of muscles swallowing and talking
• CN motor nuclei have bilateral cortical

representation except lower half of CN7

• Signs
• Spastic tongue
• Slow tongue movements w/ slow deliberate speech: “hot-potato” speech
• Brisk jaw jerk
• Emotional incontinence
• Causes
• MS
• MND
• Stroke
• CPM- Central pontine myelinolysis

Question 6

epidemiology

Answer 6

• Prevalence: 6/100,000
• Sex: M>F=3:2

Median age @ onset: 60yrs, Often fatal in 2-4yrs

Question 7

which clinical presentation [PC, s/s] would make you consider MND?

Answer 7

• Consider MND:
• Age: >40yr
• PC: stumbling spastic gait, foot drop ± proximal myopathy, difficulty opening doors (weak grip), difficulty washing/brushing hair (shoulder abduction) or aspiration pneumonia
• Signs/symptoms:
• UMN: spasticity, brisk reflexes, ↑ plantars
• LMN: wasting, fasciculation of tongue / abdo / thigh, weakness
• Speech or swallowing impairment (bulbar signs)

Fronto-temporal dementia: ~25%

Question 8

features of UMN + LMN lesions

Answer 8

Features of upper and lower motor neuron lesions

• Lower MN = everything lowered (less muscle mass, ↓ muscle tone, ↓ reflexes, down-going toes)
• Upper MN = everything up (tone, DTRs, toes)

Upper motor neuron

Lower motor neuron

Spastic paralysis

Flaccid paralysis

Clasp knife spasticity

No Clasp knife spasticity

No wasting

Muscle wasting

No fasciculations

Fasciculations present

↑ tone

↓ tone

Brisk reflexes

↓ or absent reflexes

Clonus

No clonus

Extensor plantar response

(Babinski)

Plantar response flexor

or absent

Question 9

ix- nb theres no diagnostic test

Answer 9

• Brain/cord MRI: exclude structural cause
• Cervical cord compression → myelopathy
• Brainstem lesions
• LP: exclude inflammatory cause
• EMG: shows denervation

- Nerve conductionstudies: ↓ motor nerve conduction amplitudes

Question 10

diagnosis: revised el escordial diagnostic criteria for ALS

Answer 10

• Definite: Lower + upper motor neuron signs in 3 regions
• Probable: Lower + upper motor neuron signs in 2 regions
• Probably with lab support: Lower + upper motor neuron signs in 1 region, or upper motor neuron signs in ≥1 region + EMG shows acute denervation in ≥2 limbs
• Possible: Lower + upper motor neuron signs in 1 region

- Suspected: Upper or lower motor neuron signs only—in 1 or more regions

Question 11

mx:

Answer 11

• MDT: neurologist, physio, OT, dietician, palliative nurse, GP, family
• Discussion of end-of-life decisions
• E.g. Advanced directive, DNAR
• Specific
• Antiglutamatergic: Riluzole - that prolongs life by ~3mo
• Supportive
• Drooling: propantheline or amitriptyline
• Dysphagia: blend food, NG or PEG feeding
• Respiratory failure (±aspiration pneumonia and sleep apnoea): NIV
• Joint Pain: analgesic ladder
• Spasticity: baclofen, botulinum

~~~~~~~~~~~~

Riluzole

prevents stimulation of glutamate receptors

used mainly in amyotrophic lateral sclerosis

prolongs life by about 3 months

Respiratory care

non-invasive ventilation (usually BIPAP) is used at night

studies have shown a survival benefit of around 7 months

Question 12

prognosis

Answer 12

• Most die w/i 3yrs
• Bronchopneumonia and respiratory failure
• Worse prog: elderly, female, bulbar involvement

Question 13

ddx

Answer 13

Other diseases which lead to muscular wasting, especially of the upper limbs, must be considered:

• syringomyelia - fasciculations are rare; dissociated sensory loss from an early age
• intramedullary tumour - sensory loss usually prominent
• cervical spondylosis - sensory loss is usually present but the upper limb weakness and lower limb spasticity may be remarkably similar to MND. MND has a more rapid myelopathy and cervical disc protrusion will be absent on X-ray. Occasionally, MND may co-exist with cervical spondylosis.
• cervical rib - fasciculation absent, pain prominent, sensory loss usually present, characteristic radiology
• peripheral nerve lesions - localised wasting, usually accompanied by sensory loss.
• peroneal muscular atrophy - sensory loss
• chronic polymyositis - differentiate by electromyography and muscle biopsy
• myasthenia gravis - bulbar signs but rarely muscular wasting; responds rapidly to anticholinesterase