Lecture 1: Motor neuron diseases Flashcards
Myelopathy
- Cervical spondolysis
- Spinal cord tumor
- Trauma
Anterior Horn cell disorders
- ALS
- Polio
- Progressive nuclear palsy
- GB
Nerve root lesions
- Cervical rib syndrome
- Acute intervertebral prolapse
Peripheral nerve lesions
- Poly & mono neuropathy
Neuromuscular junction lesions
- Myasthenia gravis
Characteristics of MND caused by anterior horn lesions
- Affect anterior horn alpha-motor neurons
- 30-60 y/o
- Men
- 95% = sporadic onset (may be genetic in subsequent generations)
- 5-10% = familial
5 subclasses of adult anterior horn cell-MND
- progressive nuclear palsy
- pseudobulbar palsy
- progressive spinal muscular atrophy (PMA)
- primary lateral sclerosis (PLS)
- amyotrophic lateral scelrosis (ALS)
ALS stands for:
Amytrophic: atrophy of muscle
Lateral Sclerosis: hardening of the lateral corticalspinal tracts
Population Affected by ALS
- 60% of male
- 20% more common in males
- With increasing age, incidence in females approaches that of males
- 93% caucasion
- Majority diagnosed between 40-70
- Diagnosis age = 55
- Cases can occur in 20s-30s
- Life expectancy:
- 5yrs: 20%
- 10yrs: 10%
- 20yrs: 5%
2 things that stay in tact (symptom wise with ALS)
- No changes in sensation
- No extraocular or sphincter muscle involvement
Signs and Symptoms of ALS
- Weakness (reduced power or force)
- clumsiness, fatigue, heaviness
- Atrophy/muscle wasting
- Progressice
- Fasiculations
- Areflexia
- Hypotonia
Cognitive function of ALS
- Extent and level is highly variable
- 50-60% develop frontotemporal function defecit
- Range from full frontotemporal dimentia, neuropsychological, speech/language defecits
Risk factors for ALS
- Older age
- Male
- Caucasian
- Guamanian origin
Only ___ were linked to ALS risk
blood-lipids
Etiology of ALS
- Complex genetic and environmental
- Contiuum that includes frontotemporal dementia
- Mutations in DNA/RNA regulating protein C9ORF72 → dysregulation in RNA processing & toxic cellular accumulations
- 40% of famial and 20% of sporadic
- Leads to accumulation of cellular RNA and/or proteins that are toxic:
- TDP-43 = PRIMARY PRODUCT THAT ACCUMULATES
- Leads to accumulation of cellular RNA and/or proteins that are toxic:
- 40% of famial and 20% of sporadic
- Mutations in SOD-1 (involved in free radical control)
Autophagy is up/down regulated in response to:
growth signals & environmental ques
Autophagy roll in cancer
- Protects against cancer by controlling growth
- Down-regulation confers a survival advantage in some caners
Autophagy in neurodegenerative diseases (NDDs):
Many NDDs are characterized by age-dependent:
- Neuronal death
- due to accumulation of normal proteo-metabolsim products
- Autophagy tags and clears these proteins – body’s only mechanism for disposal
Defect is autophagy pathway ___ , contribute to ___ accumulation and neurotoxicity
SOD-1 pathway
TDP43 build up
Most common form of ALS
Sporadic (90%)
Familal cases accout for ___% of ALS cases
- 10% = familial cases
- Autosomal dominence inheritance pattern
- 50% change of passing it on
- 20% have SOD mutation
ALS and Retrovirus association
- Human endogenous retrovirus (HERV) is + in many ALS pt’s
other environmental stimuli for ALS
- Cyanobacteria
- Heavy metals
- Pesticides
- Intense PA
- Head injury
- Smoking
- Electomagnetic field / electric shock
20% of ALS patients present with ___ involvement
Bulbar
Bulbar involvement (ALS) signs
- Difficulty chewing/swallowing
- Coughing
- Dysarthia & dysphagia
- Fasciulations
- Decreased resp. strength: often primary cause of death
- Still no sensory loss or extraoccular/sphincter loss
80% of ALS cases are ____ involvement
spinal
Spinal involvement (ALS) signs
- UE affected first - 50% of pts
- Fatigue
- Weakness
- Cramping
- Wasting
- Muscle twitching
- Stiffness
- Lesser extent of speech and swallowing
- Cognitive function not typically affected
- No senosry loss of extraocular or sphincter muscles
Primarly lateral sclerosis is primarily ___ involvement
upper-motor neuron
-better outcomes than PMA
Primary muscular atrophy is primarily in ___ involvement
lower-motor neuron
which has worst outcomes: bulbar or spinal involvement?
Bulbar
Treatment for ALS (PT)
- NOT TO OVERTAX pt
- Active ROM
- Active-assisted
- PROM
- Respiratory/Chest PT:
- Percussion, vibration, mechanical vibrators, precursors
- Postural drainage
- Cough assist
- Inspiratory muscle training
- Weights versus inspiratory trainer or spironmeter
3 classes of disorders at the neuromuscular junction
- blockage of Ca+ channels: Lambert-eaton syndrome
- Impaired Ca+ mediated release of Ach: Botulism
- Antibody induced down regulation of Ach receptors: Myasthenia Gravis
Lambert-Eaton Syndrome
- Autoimmune disease which presynaptic NMJ Ca+ channels are destroyed by antibodies
- Decreased Ach release
- Weakness and areflexia that improve with sustained contraction
- Treatment based on K+ channel blocker and Ca2+ channel agonist
Myasthenia Gravis
- Auto-immune down regulation of Ach receptors
- Fluctuating weakness and easy fatigue
- Thymus tumor, thyrotoxicosis, RA, lupus
- Females > males
-
Biases: external ocular and other cranial nerves:
- Muscles of mastication, swallowing, etc.
Myasthenia Gravs Presentation
- Diplopia (double vision) ~90%
- Ptosis (drooping eye-lid)
- Pupillary reflex not affected
- Dysarthria (difficulty speaking)
- LE weakness
- General weakness
- Dysphagia
- Reflexes may be normal / little atrophy
Myasthenia Gravis Classic Presentation
sustained muscular effort impaired
Brief effort is normal
Diagnosis of Myasthenia Gravis
- Administer a cholinesterase inhibitor
- Tensilon test: have pt do repeated voluntary contractues: if symptoms improve, then test is (+)
Etiology of Myasthenia Gravis
- Patients develop antibodies to Ach receptors (most common) or to muscle specific kinase or LDL-receptor related protein
- Leads to Ach receptor damage and loss, making it difficult to stimulate muscles
Critical illness polyneuropathy
- Severe
- Systemic weakness associated with critical illness, sepsis and multi-organ failure
Critical illness myopathy
- Acute onset of severe diffuse weakness including respiratory muscles and loss of DTR
- Associated with steroid use and/or neuromuscular blockade
- Elevated serum CK & MG levels
Characteristics of Myasthenia Gravis
- Insidious onset
- Avg age:
- Women: 28
- Males: 42
- Slowly progressive, fluctuating course
- Managed with medications, but difficult to cure
- May ultimately be fatal
- Respiratory infections or other complicaitons
Treatment for Myasthennia Gravis
Immunotherapy
Exercise with Myasthenia Gravis
Active exercise must be administered carefully and in small doses secondary to easily fatigued and may lead to exhuastion
