Motor Neuron Disease Flashcards
What is the epidemiology of MND?
Slight male predominance
Usually middle aged onset (ALS)
PBD tends to be later and slightly more prevalent in women
Prognosis is usually <3yrs, unremitting and death usually via bronchopneumonia as a result of aspiration
5yr survival from diagnosis is <10%
What is the aetiology of MND?
Essentially unknown but contributory factors:
Ageing:
Premature ageing of some motor cells → damage and destruction → puts pressure on surviving cells to perform original functions → increased metabolic processes → further damage to remaining cells
Biochemistry:
Chronic calcium deficiency may play a role → there is an association with hyperparathyroidism
Backed up by gastric surgery patients → incidence of MDN is increased and there is reduced uptake of calcium
Genetics:
One specific gene mutation (on ch21) has been identified in some individuals
Therefore may be many cases within one family
Toxicity:
Some metal toxicity – lead, selenium, mercury, manganese
Excitotoxicity – glutamate excess
What is the pathophysiology of MND?
Degeneration of motor neurons in motor cortex and spinal cord
Affecting UMN and LMN
Not affecting sensation
Through mechanisms similar to other neurodegenerative conditions:
Oxidative neuronal damage
Aggregation of abnormally large amounts of protein inside cells
Glutamate excitotoxicity
Prolonged caspase activity (protease) →
Apoptosis
How is MND classified?
ALS – Amyotropic lateral sclerosis:
75% of cases/most common form
Produces UMN/LMN signs
Typically – progressive weakness and wasting of limbs
PBP – progressive bulbar palsy:
25% of cases
Present with problems speaking and swallowing
PMA – progressive muscular atrophy:
Typically only affects the LMNs of upper limbs
SMA – spinal muscular atrophy:
Weakness and wasting of spinal muscles
In many patients, as the disease progresses, several of the subtypes will be present in a single individual
What are the differences between upper and lower motor neuron lesions?
Tone:
UMN - hypertonia
LMN - hypotonia
Muscle atrophy:
UMN - absent initially but will occur with time
LMN - present
Fasciculations:
UMN - absent
LMN - present (occurs as surviving axons branch out to motor units in attempts to innervate them → spontaneous discharge)
Reflexes:
UMN - increased (due to loss of corticospinal neurons)
LMN - diminished/absent
Babinski:
UMN - present
LMN - absent
What are some general features of MND presentation?
Usually no pain
Muscle cramps are common
Dementia – in the frontotemporal region – seen in 10-30% of cases; may initially present with language difficulties – in some cases can be very hard to diagnose, especially if there is well advanced dysphagia
Never occur:
Sensory loss
Loss of sphincter control - bladder and bowel
Helps to distinguish from MS + polyneuropathies
What are the two key features of ALS?
Lateral sclerosis = damage to lateral corticospinal tracts → spastic paraparesis (partial paralysis of lower limbs) +
Amytrophic = loss of muscle tone
These two features rarely co-occur together except in MND
Pyramidal weakness – in extensors in upper limbs, flexors in the lower
Also associated with frontotemporal dementia
What is the key feature of PMA?
Symmetrical weakness + wasting (75% of patients) – begins in hands and spreads; may be unilateral → bilateral
What are the key features of progressive bulbar palsy?
Range of different symptoms linked to impairment of CN9-12
LMN lesion in the medulla or from lesions of the lower cranial nerves outside the brainstem
Dysphagia, dysarthria, palate weakness, choking – swallowing solids may be difficult as tongue may be immobile/wasted/fasciculating; dribbling; normal/absent jaw jerk/gag reflexes
Eye movements usually spared – allows to distinguish from myasthenia gravis
What is pseudobulbar palsy?
UMN lesion of the muscles of swallowing and talking due to bilateral lesions above the mid-pons i.e. corticobulbar tracts
More common than bulbar palsy
Slow tongue movements with slow deliberate speech
Jaw jerk
Increased pharyngeal and palatal reflexes
Pseudobulbar affect – weeping or giggling not provoked by mood
Treatment:
Dextromethorphan + quinidine
How do you investigate MND?
EMG:
Denervation + fibrillation
Though denervation may not be present in PLS
Nerve conduction studies:
Will appear normal – to exclude multifocal neuropathy
MRI:
Will be normal – to exclude spinal cord compression
TFTs:
To exclude hyperthyroidism
Calcium studies:
To exclude calcium/parathyroid problems
Bloods:
Raised creatinine kinase due to increased muscle breakdown
What is necessary for a diagnosis of MND?
Usually clinical, requires:
UMN + LMN signs in 3 regions = definitive
No sensory signs
Progressive pattern
Other possible signs:
Fasciculations
Normal nerve conduction
How do you manage MND?
Riluzole:
Sodium channel blocker
Reduction in the efficacy of glutamate
May slow progression by 3-5 months - especially in bulbar features cases
Recommended asap even in patients with likely not definite diagnosis
What other treatments can be used in MND?
Drooling
i) Propantheline
ii) Amitriptyline
Dysphagia
i) Blending food? NG tube? Parentral feeding?
Spasticity
i) Baclofen (GABA agonist)
Ventilation support
PT + OT
What is important in palliative care for MND?
All people with MND should be placed onto local palliative care registers where possible - to ensure services are available as and when
Domains: Pain management Psychological support Social support Spiritual support
