Flashcards in OHCM - Motor Neuron Disease (MND) Deck (48):
MND vs MS or polyneuropathies?
UMN + LMN signs BUT no sensory loss or sphincter disturbance, thus distinguishing it from myasthenia.
ALS-FTD locus explains ...?
87% of familial ALS (eg AD D90A SOD1 mutation).
MND - 4 clinical patters:
1. ALS (archetypal; 50%).
2. Progressive bulbar palsy (10%).
3. Progressive muscular atrophy (10%).
4. Primary lateral sclerosis.
ALS - Main features:
Loss of motor neurons in motor cortex + the anterior horn of the cord, so weakness + UMN signs (eg upgoing plantars) + LMN wasting/fasciculations.
ALS - Worse prognosis if:
1. Bulbar onset.
2. Incr. age.
3. Decr. FVC.
ALS - The split hand sign:
The thumb's side of the hand seems cast adrift owing to excessive wasting around it - there is much less hypothenar wasting.
Progressive bulbar palsy:
Only affects cranial nerves IX-XII.
Progressive muscular atrophy:
Anterior horn cell lesion only, thus NO UMN signs - Affects DISTAL muscle groups before proximal.
ALS or progressive muscular atrophy better prognosis?
Progressive muscular atrophy better than ALS.
Primary lateral sclerosis:
Loss of Betz cells in motor cortex, thus mainly UMN signs + marked spastic leg weakness and pseudobulbar palsy.
--> No cognitive decline.
When to think of MND?
In those >40yrs with stumbling spastic gait, foot-drop +/- proximal myopathy, weak grip (door-handles don't turn) and shoulder abduction (hair-washing is hard), OR ASPIRATION PNEUMONIA.
FTD occurs together with MND in ...%.
MND - Diagnostic criteria:
1. Definite = LMN + UMN signs in 3 regions.
2. Probable = LMN + UMN signs in 2 regions.
3. Probable with lab support = LMN + UMN signs in 1 region, or UMN signs in >1region + EMG shows acute denervation in >2limbs.
4. Possible = LMN + UMN signs in 1 region.
5. Suspected = LMN OR UMN signs only - in 1 or more regions.
MND - Is there a diagnostic test?
Diagnosis - Brain/cord MRI helps ...?
EXCLUDE structural causes.
Diagnosis - LP helps?
EXCLUDE inflammatory causes.
Diagnosis - Neurophysiology:
Can detect subclinical denervation and help EXCLUDE mimicking motor neuropathies.
MND - Prevalence:
MND - Male:Female = ...?
MND - Median UK age at onset?
MND - Prognosis:
Often FATAL in 2-4yrs.
Due to MND's implacable course, its rarity, and its frightening nature, a multidisciplinary approach is best: neurologist, palliative nurse, hospice, physio, OT (occupational therapist), speech therapist, dietician, social services - all orchestrated by the GP.
MND - Death by choking?
Death by choking is RARE, so warmly reassure that a dignified end is the rule.
Treatment - Antiglutaminergic drugs:
Riluzole prolongs life by 3 months - it is costly.
--> Increased LFTs (do 3-monthly).
Riluzole - SE:
2. Incr. pulse.
6. LFT UP.
Treatment - Drooling:
1. Propantheline 15-30mg/8h.
2. Amitriptyline 25-50mg/8h.
(Doctors think this is quite effective, but patients disagree: and example of our wishful thinking.
Treatment - Dysphagia:
1. Blend food.
2. Would he or she like a NGT, or percutaneous catheter gastrostomy? - or would this prolong death?
Treatment - Joint pain and distress?
Analgesic ladder - NSAIDs, etc, then opioids.
Treatment - Respiratory failure (+/- aspiration pneumonia and sleep apnea):
Non-invasive ventilation (NIV) at home in selected patients may give valuable palliation.
If NO UMN signs + distal arm muscles are affected in the distribution of individual nerves - suspect?
Multifocal motor neuropathy with conduction block (diagnose on nerve conduction studies; Rx: IV Ig).
--> Gynecomastia, atrophic testes +/- infertility = Kennedy syndrome (bulbospinal muscular atrophy).
Bulbar palsy denotes ...?
Diseases of the nuclei of cranial nerves IX-XII in the medulla.
Bulbar palsy - Signs:
1. Of an LMN lesion of the tongue and muscles of talking and shallowing: flaccid, fasciculating tongue (like a sack of worms).
2. Jaw jerk is normal or absent.
3. Speech is quiet, hoarse, or nasal.
Bulbar palsy - Causes:
6. Brainstem tumors.
7. Central pontine myelinolysis.
UMN lesion of muscles of shallowing and talking due to bilateral lesions above the mid-pons, eg corticobulbar tracts.
Corticobulbar palsy - Etiology:
4. Central pontine myelinolysis.
Corticobulbar palsy or bulbar palsy is more common?
Corticobulbar palsy - Signs:
1. Slow tongue movements with slow deliberate speech.
2. Incr. jaw jerk.
3. Incr. pharyngeal and palatal reflexes.
4. Pseudobulbar affect (PBA) - Weeping unprovoked by sorrow or mood-incongruent giggling!
Emotional incontinence WITHOUT mood change is also seen in ...?
5. NO use.
6. Head injury.
In some countries, what is licensed for pseudobulbar affect (PBA)?
Following in the footprints of free radicals - Autopsies show that ...?
1. Changes to proteins and DNA that are signs or "footprints" of free-radical damage are more pronounced in MND brains than in controls.
2. Cultured fibroblasts from MND brains show increased sensitivity to oxidative insults (pesticides may have a role).
These 2 findings DO NOT explain 2 key phenomena:
1. Why is there a predilection for motor neurons?
2. Why do some MND brains have excess levels of glutamate?
Why is there a predilection for motor neurons?
One answer may be the sheer length + complex cytoarchitecture of motor cells, with their 1m axons and high levels of neurofilament proteins, and low levels of Ca-buffering proteins (thought to be protective).
Why is there a predilection for motor neurons? We note that ...?
Motor cells with the shortest axons (to the extraocular muscles) are unaffected in MND; this is not true of the tongue, which only requires slightly longer axons.
Why is there a predilection for motor neurons? Also, it isn't ONLY motor neurons that are affected:
Specific aphasias and dementias are part of the MND picture too.
Why do some MND brains have excess levels of glutamate? (glutamate is the chief excitatory neurotransmitter in the CNS)
This is thought to be from DECREASED activity of the excitatory amino acid transporter (EAAT2) which mops up glutamate - hence the notion that MND is an "excitotoxic" phenomenon.
Why do some MND brains have excess levels of glutamate? Motor cells have ...?
High levels of Cu/Zn SOD (thought to protect normal motor cells from glutamate toxicity/oxidative stress).
--> But a high level may itself be damaging, given certain genetic or acquired vulnerabilities.
--> Transgenic mice exhibiting high levels of SOD do indeed develop an MND phenotype.