Motor Neuron Disease (Kalra) Flashcards
Classify weakness, bulk, fasciculations, tone, and reflexes in UMN vs LMN degeneration
- weakness: UMN +, LMN +++
- bulk: UMN normal, LMN atrophy
- fasciculations: UMN absent, LMN present
- tone: UMN increased, LMN decreased
- reflexes: UMN increased, LMN decreased
TRUE or FALSE: primary lateral sclerosis is purely LMN signs, and progressive muscular atrophy is purely UMN signs
FALSE: primary lateral sclerosis = UMN; progressive muscular atrophy = LMN
Does ALS have UMN or LMN signs?
both
What does amyotrophy result from?
loss of anterior horn cells
What is the most common idiopathic motor neuron disorder?
ALS
Who was the first person to describe concurrent upper and lower motor neuron pathology?
Charcot
When does onset of ALS occur? What is the male to female ratio?
- anytime in adulthood (around 55 years)
- male:female, 1.5:1
What are the risk factors for ALS?
- age
- smoking
- service in armed forces
What are the clinical features of ALS (i.e. bulbar, limb, respiratory) in general?
BULBAR:
- dysarthria
- dysphagia
- dysphonia
- labile affect
LIMB:
- weakness
- cramps
- stiffness
RESPIRATORY:
- resp muscles weaken…major cause of death from ALS
What functions are spared in ALS?
- sensation
- sphincter
- (cognitive)
What are the clinical features of upper and lower extremities in ALS?
UPPER EXTREMITY:
- hand - fine motor activities
- shoulder - proximal arm weakness; “frozen shoulder”
- axial - stooped posture
LOWER EXTREMITY:
- foot drop
- difficulty with chairs, stairs
What are the respiratory features of ALS?
- dyspnea (shortness of breath)
- orthopnea (difficulty breathing when lying down)
- sleep disordered breathing
What are the frontotemporal features of ALS?
- cognitive impairments - executive, language, social cognition
- behavioural impairments - apathy
In what ways does cognitive impairment affect individuals with ALS?
- impact decision making capacity
- reduce survival
Is there decreased grey matter or white matter in ALS? In which areas do you see these decreases?
- decreased grey matter
- bilateral motor cortex
- left frontal/temporal cortex
- ACC
- left lenticular cortex
What gene expansion is associated with ALS?
C9ORF72
Degeneration of which part of the brain is associated with the extra-motor pathology of ALS?
- frontotemporal lobar degeneration (FTLD)
- neuronal loss, gliosis
- superficial spongiform degeneration in layers II/III
What is the molecular link between ALS and FTD?
TDP-43 protein
What is the genetic link between ALS and FTD?
C9ORF72
What is a marker of neurointegrity that can be quantified in vivo? What does a decrease in this marker indicate?
- NAA
- decrease NAA = increase disease progression
What are the 4 neuropathological stages of pathological TDP-43 distribution in ALS?
- stage 1: motor cortex, bulbar and spinal somatomotor neurons
- stage 2: reticular formation, precerebellar nuclei, thalamus
- stage 3: prefrontal neocortex, basal ganglia
- stage 4: anteromedial temporal lobe, hippocampal formation
Describe the ALS-FTD spectrum and the PMA-ALS-PLS spectrum.
see slide 24
What is the ALS Functional Rating Scale used for? What is the average decline? What percent change in slope is considered clinically meaningful?
- important endpoint in contemporary clinical trials
- measure of disability; monitor disease progression
- average decline of 1.02 points/month
- 20-25%
What are challenges resulting from extreme heterogeneity?
- delayed diagnosis
- delayed treatment
- unable to predict prognosis
- unable to predict treatment response
- clinical trial failures
How is ALS largely diagnosed? Describe the work up.
- largely diagnoised by ruling out other diseases
- NCS/EMG –> rule out neuropathy, subclinical denervation, staging
- MRI brain or cervical spine
- blood tests
- pulmonary function tests
What condition mimics ALS?
cervical spondylosis
What is the WHO definition of palliative care?
the active total care of the patient whose disease is not responsive to curative therapy
What are the principles of management of ALS?
- patient autonomy
- holistic and team approach
- patient participation in clinical trials
- effective use of home and hospice care
- close communication between all parties involved
- PALLIATIVE CARE
What are the goals of ALS management?
maximize quality of life and quality of death
What are some disease modifying treatments for ALS? Describe each.
RILUZOLE
- anti-glutamatergic
- prolong survival 3-6 months
EDARAVONE
- anti-oxidant
- slow disability 33%
AMX0035
- phenylbutyrate + taurursodiol
- reduces ER stress and mitochondrial dysfuntion
- slow disability, prolong survival
TOFERSON (miracle drug)
- ASO
- SOD1
How do you manage sialorrhea/salivation in ALS?
anticholinergics
Which drug can be used to manage pseudobulbar symtpoms, anxiety, and insomnia in ALS?
amitryptyline
What can BiPAP be used for in ALS?
- best intervention for respiratory support
- provide + pressure
What is PEG used for in ALS?
feeding tube
