Motor neuron disease and other disease of the spinal cord - DONE

Question 1

What is ALS?

Answer 1

ALS is a wasting disease of skeletal muscle

• prgressive
• generalized (limb, respiratory, vocal, swallowing muscles)
• fatal

Question 2

ALS pathology:

Answer 2

Selective degeneration of motor cells:

• Upper motor neurons (UMN) (motor cortex Betz cells)
• Lower motor neurons (LMN) (brainstem, anterior horns)

Question 3

Signs and symptoms of ALS:

Answer 3

• weakness
• atrophy
• fasciculations (involuntary muscle twitching)
• spasticity
  
  • increased muscle tone
  • exaggerated tendon reflexes

Question 4

What does ALS spare?

Answer 4

• sensory system
• bowel and bladder control system
• oculomotor system

Question 5

ALS - most common initial symptoms:

Answer 5

• weakness
  
  • distal (hand - turning a key, buttoning a shirt; foot drop
  • proximal - difficulty raising from chair, drying hair
• speech impairment - slurred, slow speech
• eating difficulties - problems with swallowing, chewing

Question 6

ALS - Clinical examination - LMN signs:

Answer 6

Weakness, atrophy, fasciculations:

• brainstem (bulbar) level: jaw, face, palate, tongue, larynx
• cervical level: neck, arm, hand, diaphragm
• thoracic level: back, abdomen
• lumbosacral level: back, abdomen, leg, foot

Question 7

ALS - Clinical examination - UMN signs:

Answer 7

Exaggerated deep tendon reflexes (DTRs), pyramidal pathological sings, clonus etc:

• brainstem (bulbar level): clonic jaw jerk, exaggerated gag reflex, primitive reflexes eg palmomental, pseudobulbar affect (pathological, uncontrollable laughter or crying)
• cervical level: exaggerated exaggerated/clonic DTRs, Hoffman sign, spastic tone
• thoracic level: loss of superficial abdominal reflexes
• lumbosacral level: exaggerated/clonic DTRs, extensor plantar response, spastic tone

Question 8

What are the clinical forms of ALS?

Answer 8

• classical ALS
• progressive bulbar palsy
• progressive msucular atrophy (PMA)
• primary lateral sclerosis (PLS)

Question 9

Classical ALS:

Answer 9

• 2/3 of all cases

- upper and lower motor neuron involvement

Question 10

Progressive bulbar palsy:

Answer 10

• initially affects bulbar region

- extremely poor prognosis

Question 11

Progressive msucular atrophy (PMA):

Answer 11

• initially presents with lower motor neuron symptoms

Question 12

Primary lateral sclerosis (PLS):

Answer 12

• initially presents with upper motor neuron symptoms

- extremely rare

Question 13

ALS epidemiology - incidence:

Answer 13

incidence 0.4-2.4 per 100 000 populations annually

Question 14

ALS epidemiology - average age of onset:

Answer 14

mid 50s

Question 15

ALS epidemiology - M:F:

Answer 15

1,5:1

Question 16

ALS epidemiology - causes:

Answer 16

• about 90% cases: sporadic ALS - cause unknown

- 5-10% cases: familial ALS (FALS) - genetically linked

Question 17

ALS pathogenesis:

Answer 17

• unknown
• current hypothesis:
  
  • altered glutamate metabolism
  • autoimmune mechanism
  • oxidative stress
  • exogenous excitotoxins
  • cytoskeletal abnormalities
  • prions?

Question 18

ALS - genetic factors:

Answer 18

superoxide dismutase (SOD) gene mutation in about 20% of FALS cases

Question 19

Mutated SOD1:

Answer 19

toxic gain of function

Question 20

ALS - diagnosis:

Answer 20

• no definite bimarker
• El Escorial ALS criteria
  
  • Signs of lower motor neuron (LMN) degeneration by clinical, electrophysiological or neuropathologic examination
  • Signs of upper motor neuron (UMN) degeneration by clinical examination
  • Progressive spread of signs within a region or to other regions
  • together with the absence of exclusion criteria

Question 21

ALS differential diagnosis

Answer 21

SEE THE SLIDE

Question 22

ALS diagnostic studies:

Answer 22

• electromyogram - widespread denerviation and reinnervation
• nerve conduction: reduced compound action potential, normal or almost normal CV
• MRI: no characteristic features (to exclude other diseases)
• CSF: normal

Question 23

ALS prognosis:

Answer 23

• inevitably progressive course
• appr. 50% die within 3-4 yrs
• appr. 20% live >5 yrs
• appr. 10% live >10 yrs
• occationally, patients live 20 yrs

Question 24

What are the primary causes of death in ALS?

Answer 24

• respiratory failure

- sometimes aspiration

Question 25

ALS pharmacotherapy:

Answer 25

Riluzole:

• protects motor neurons from degenerative death
• the mode of action not fully elucidated (MORE ON THE SLIDE…not think it is important)
• dosage: 50 mg every 12 hrs (100mg/day)
• liver function test

Question 26

ALS non-pharmacological interventions:

Answer 26

• non-invasive mechanical ventilation
• tracheotomy, invasive mechanical ventilation
• gastrostomy (PEG)
• physiotherapy (gentle kinesiotherapy, logopedic therapy)
• electronic communication advices
• experimental therapies: stem cell transplantation, gene therapy (SOD silencing)

Question 27

Spinal muscular atrophy (SMA) - signs:

Answer 27

only lower motor neuron, rarely bulbar signs

Question 28

Spinal muscular atrophy (SMA) - cause:

Answer 28

autosmal recessive inheritance

Question 29

Spinal muscular atrophy (SMA) - carrier frequency in poland:

Answer 29

1:35

Question 30

SMA genes

Answer 30

• SMN1 (survival motor neuron) gene mutation
• SMN2 gene - “surrogate” protein; copy number determinates clinical types
• Types: infantile, early childhood, adolescent (I, II, III)

Question 31

Spinobulbar muscular atrophy (SBMA, Kennedy disease):

Answer 31

• x-linked inheritance
• prominent bulbar involvement (dysarthria, dysphagia)
• lower motor neuron
• fascial fasciculations
• gynecomastia (androgen receptor mutation)