Motor neurone disease Flashcards
Define motor neuron disease.
Neurodegenerative disorder, characterised by progressive degeneration of motor neurons causing weakness that can start in limb, axial, bulbar, or respiratory muscles and then generalises relentlessly, causing progressive disability and ultimately death, usually from respiratory failure.
What are the other names for MND?
Also called: Amyotrophic Lateral Sclerosis (ALS), Lou Gehrig’s disease, Charcot’s disease.
MND makes sense as it affects motor neurons but ALS is most descriptive as there is lack of feeding to the muscles and hardening/death of the lateral corticospinal tracts.
How common is MND? Who is usually affected?
- Rare with annual incidence 2 per 100,000
- Mean age of onset is 57 years
- In elderly slightly more common in females
- Only 5-10% have FH with AD inheritance
What is the aetiology of MND?
Mechanisms proposed:
- Glutamate toxicity - excess neurotransmitter allowing cell death by oxidative stress from Ca entry. Its antagonist drug Riluzole improved survival.
- Protein misfolding - interference with anti-apoptosis causing programmed cell death
- Oxidative stress - e.g. mutant SOD1 aggregation
- Microglial activation
- Mitochondrial dysfunction
- Disrupted axonal transport
- RNA metabolism
What are the risk factors for MND?
- Genetic predisposition/FH
- Age >40yrs
Weak:
- Military service
- Athletic activity
- Cigarette smoking
- Agricultural chemical exposure
- Lead exposure
What is the pathophysiology of MND?
There is neurodegeneration with progressive loss of motor neurons in:
- Cortical (frontotemporal)
- Bulbar (pons, medulla)
- Ventral cord
What are the different types of MND?
ALS/Lou Gehrig’s disease (70%) - combined degeneration of upper and lower motor neurones producing UMN and LMN mix
Progressive muscular atrophy variant - only LMN e.g. flail arm/foot. Better prognosis.
Progressive bulbar palsy variant (20%)- dysarthria and dysphagia with wasted fasciculating tongue (LMN) and brisk jaw refelx (UMN)
Primary lateral sclerosis variant - UMN pattern of weakness, brisk reflexes, extensor plantar responses, without LMN signs
What are the symptoms of MND?
- Weakness of limbs (focal or asymmetrical) - limbs, trunk, tongue and respiratory/intercostal muscles
- Speech disturbance (slurring or reduction in volume)
- Swallowing disturbance (e.g. choking on food, nasal regurgitation) (NB: speech and swallowing = bulbar signs)
May be behavioural changes (e.g. disinhibition, emotional liability). Cognitive function may be affected in a minority of cases (~15%)
What are the signs of MND on physical examination?
Combination of UMN and LMN signs often affecting several regions asymmetrically:
LMN features -
- muscle wasting → falls
- fasciculations - painful cramps
- flaccid weakness - sialorrhoea and drooling
- depressed/absent reflexes
- extensor>flexor weakness → head drop, worsening posture
UMN features -
- spastic weakness
- brisk reflexes
- extensor plantars
- dysarthria → strained, slow speech
Sensory exam - NORMAL
Pseudobulbar affect → inappropriate bursts of crying or laughing
Coughing and choking on liquids and eventually food - due to UMN loss of coordination of tongue and pharyngeal constrictors and LMN muscle weakness.
What is spared in MND?
Oculomotor, sensory and autonomic function
Therefore no impairment of bladder, bowel or sexual function. This differentiates it from conditions like Parkinson’s. Also how Hawking was able to communicate – using eye movements.
What investigations would you do for MND?
CLINICAL DIAGNOSIS with UMN and LMN signs which are progressive and have no other explanation. Must exclude other causes.
Bloods:
- CK - may be elevated up to 1000
- Anti-GM1 ganglioside abs -should be negative to exclude multifocal mononeuropathy
- Voltage gated Ca channel abs - rule out Lamber Eaton syndrome
- AChR abs - rule out MG
- B12/folate/HIV
Imaging: MOST IMPORTANT
- EMG - diffuse chronic denervation but normal sensory nerve conduction
- Nerve conduction studies - show normal motor and sensory conduction in MND.
- MRI - exclude cord or root compression
- Spirometry - assess respiratory muscle weakness (FVC)
- Muscle biopsy - exclude myopathic conditions
- Repetitive nerve stimulation - no large decreases in motor action amplitude after repetitive stimuli excludes MG
What is the prognosis with MND?
- Relentless progression with mean survival 3years from diagnosis
- Blubar onset and young onset have worse prognosis
- Death is usually due to respiratory failure because of weakness of ventilatory muscles (usual cause of death)
What are LMN vs UMN signs?
What is “bulbar pasly”? How does it present?
Lesion affecting cranial nerves IX-XII at nuclear, nerve or muscle level
Presents with:
- nasal speech, nasal regurgitation of food, especially fluids (palatal weakness),
- reduced gag reflex,
- absent jaw reflex,
- wasted fasciculating tongue.
Bulbar = relating to the medula oblongata which is shaped like a bulb.
What is pseudobulbar palsy?
Any UMN (corticobulbar) lesion to the lower brainstem
Presenting with:
- monotonous or explosive speech
- dysphagia
- increased gag reflex
- brisk jaw reflex
- shrunken immobile tongue
- emotional lability
- UMN limb spasticity and weakness
