Lecture 1: Motor neuron diseases

Question 1

Myelopathy

Answer 1

• Cervical spondolysis
• Spinal cord tumor
• Trauma

Question 2

Anterior Horn cell disorders

Answer 2

• ALS
• Polio
• Progressive nuclear palsy
• GB

Question 3

Nerve root lesions

Answer 3

• Cervical rib syndrome
• Acute intervertebral prolapse

Question 4

Peripheral nerve lesions

Answer 4

• Poly & mono neuropathy

Question 5

Neuromuscular junction lesions

Answer 5

• Myasthenia gravis

Question 6

Characteristics of MND caused by anterior horn lesions

Answer 6

• Affect anterior horn alpha-motor neurons
• 30-60 y/o
• Men
• 95% = sporadic onset (may be genetic in subsequent generations)
• 5-10% = familial

Question 7

5 subclasses of adult anterior horn cell-MND

Answer 7

• progressive nuclear palsy
• pseudobulbar palsy
• progressive spinal muscular atrophy (PMA)
• primary lateral sclerosis (PLS)
• amyotrophic lateral scelrosis (ALS)

Question 8

ALS stands for:

Answer 8

Amytrophic: atrophy of muscle

Lateral Sclerosis: hardening of the lateral corticalspinal tracts

Question 9

Population Affected by ALS

Answer 9

• 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%

Question 10

2 things that stay in tact (symptom wise with ALS)

Answer 10

• No changes in sensation
• No extraocular or sphincter muscle involvement

Question 11

Signs and Symptoms of ALS

Answer 11

• Weakness (reduced power or force)
  
  • clumsiness, fatigue, heaviness
• Atrophy/muscle wasting
• Progressice
• Fasiculations
• Areflexia
• Hypotonia

Question 12

Cognitive function of ALS

Answer 12

• Extent and level is highly variable
  
  • 50-60% develop frontotemporal function defecit
  • Range from full frontotemporal dimentia, neuropsychological, speech/language defecits

Question 13

Risk factors for ALS

Answer 13

• Older age
• Male
• Caucasian
• Guamanian origin

Question 14

Only ___ were linked to ALS risk

Answer 14

blood-lipids

Question 15

Etiology of ALS

Answer 15

• 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
• Mutations in SOD-1 (involved in free radical control)

Question 16

Autophagy is up/down regulated in response to:

Answer 16

growth signals & environmental ques

Question 17

Autophagy roll in cancer

Answer 17

• Protects against cancer by controlling growth
  
  • Down-regulation confers a survival advantage in some caners

Question 18

Autophagy in neurodegenerative diseases (NDDs):

Many NDDs are characterized by age-dependent:

Answer 18

• Neuronal death
  
  • due to accumulation of normal proteo-metabolsim products
• Autophagy tags and clears these proteins – body’s only mechanism for disposal

Question 19

Defect is autophagy pathway ___ , contribute to ___ accumulation and neurotoxicity

Answer 19

SOD-1 pathway

TDP43 build up

Question 20

Most common form of ALS

Answer 20

Sporadic (90%)

Question 21

Familal cases accout for ___% of ALS cases

Answer 21

• 10% = familial cases
• Autosomal dominence inheritance pattern
• 50% change of passing it on
• 20% have SOD mutation

Question 22

ALS and Retrovirus association

Answer 22

• Human endogenous retrovirus (HERV) is + in many ALS pt’s

Question 23

other environmental stimuli for ALS

Answer 23

• Cyanobacteria
• Heavy metals
• Pesticides
• Intense PA
• Head injury
• Smoking
• Electomagnetic field / electric shock

Question 24

20% of ALS patients present with ___ involvement

Answer 24

Bulbar

Question 25

Bulbar involvement (ALS) signs

Answer 25

* Difficulty chewing/swallowing * Coughing * Dysarthia & dysphagia * Fasciulations * Decreased resp. strength: often primary cause of death * Still no sensory loss or extraoccular/sphincter loss

Question 26

80% of ALS cases are ____ involvement

Answer 26

spinal

Question 27

Spinal involvement (ALS) signs

Answer 27

* 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

Question 28

Primarly lateral sclerosis is primarily ___ involvement

Answer 28

upper-motor neuron -better outcomes than PMA

Question 29

Primary muscular atrophy is primarily in ___ involvement

Answer 29

lower-motor neuron

Question 30

which has worst outcomes: bulbar or spinal involvement?

Answer 30

Bulbar

Question 31

Treatment for ALS (PT)

Answer 31

* **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

Question 32

3 classes of disorders at the neuromuscular junction

Answer 32

1. blockage of Ca+ channels: Lambert-eaton syndrome 2. Impaired Ca+ mediated release of Ach: Botulism 3. Antibody induced down regulation of Ach receptors: Myasthenia Gravis

Question 33

Lambert-Eaton Syndrome

Answer 33

* 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

Question 34

Myasthenia Gravis

Answer 34

* 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.**

Question 35

Myasthenia Gravs Presentation

Answer 35

* 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

Question 36

Myasthenia Gravis ***Classic Presentation***

Answer 36

***sustained*** muscular effort impaired ***Brief effort is normal***

Question 37

Diagnosis of Myasthenia Gravis

Answer 37

* Administer a cholinesterase inhibitor * Tensilon test: have pt do repeated voluntary contractues: if symptoms improve, then test is (+)

Question 38

Etiology of Myasthenia Gravis

Answer 38

* 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

Question 39

Critical illness polyneuropathy

Answer 39

* Severe * Systemic weakness associated with critical illness, sepsis and multi-organ failure

Question 40

Critical illness myopathy

Answer 40

* 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

Question 41

Characteristics of Myasthenia Gravis

Answer 41

* 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

Question 42

Treatment for Myasthennia Gravis

Answer 42

Immunotherapy

Question 43

Exercise with Myasthenia Gravis

Answer 43

Active exercise must be administered carefully and in small doses secondary to easily fatigued and may lead to exhuastion