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

1
Q

What is ALS?

A

ALS is a wasting disease of skeletal muscle

  • prgressive
  • generalized (limb, respiratory, vocal, swallowing muscles)
  • fatal
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2
Q

ALS pathology:

A

Selective degeneration of motor cells:

  • Upper motor neurons (UMN) (motor cortex Betz cells)
  • Lower motor neurons (LMN) (brainstem, anterior horns)
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3
Q

Signs and symptoms of ALS:

A
  • weakness
  • atrophy
  • fasciculations (involuntary muscle twitching)
  • spasticity
    • increased muscle tone
    • exaggerated tendon reflexes
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4
Q

What does ALS spare?

A
  • sensory system
  • bowel and bladder control system
  • oculomotor system
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5
Q

ALS - most common initial symptoms:

A
  • 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
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6
Q

ALS - Clinical examination - LMN signs:

A

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
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7
Q

ALS - Clinical examination - UMN signs:

A

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
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8
Q

What are the clinical forms of ALS?

A
  • classical ALS
  • progressive bulbar palsy
  • progressive msucular atrophy (PMA)
  • primary lateral sclerosis (PLS)
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9
Q

Classical ALS:

A
  • 2/3 of all cases

- upper and lower motor neuron involvement

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10
Q

Progressive bulbar palsy:

A
  • initially affects bulbar region

- extremely poor prognosis

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11
Q

Progressive msucular atrophy (PMA):

A
  • initially presents with lower motor neuron symptoms
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12
Q

Primary lateral sclerosis (PLS):

A
  • initially presents with upper motor neuron symptoms

- extremely rare

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13
Q

ALS epidemiology - incidence:

A

incidence 0.4-2.4 per 100 000 populations annually

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14
Q

ALS epidemiology - average age of onset:

A

mid 50s

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15
Q

ALS epidemiology - M:F:

A

1,5:1

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16
Q

ALS epidemiology - causes:

A
  • about 90% cases: sporadic ALS - cause unknown

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

17
Q

ALS pathogenesis:

A
  • unknown
  • current hypothesis:
    • altered glutamate metabolism
    • autoimmune mechanism
    • oxidative stress
    • exogenous excitotoxins
    • cytoskeletal abnormalities
    • prions?
18
Q

ALS - genetic factors:

A

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

19
Q

Mutated SOD1:

A

toxic gain of function

20
Q

ALS - diagnosis:

A
  • 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
21
Q

ALS differential diagnosis

A

SEE THE SLIDE

22
Q

ALS diagnostic studies:

A
  • 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
23
Q

ALS prognosis:

A
  • 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
24
Q

What are the primary causes of death in ALS?

A
  • respiratory failure

- sometimes aspiration

25
Q

ALS pharmacotherapy:

A

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
26
Q

ALS non-pharmacological interventions:

A
  • 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)
27
Q

Spinal muscular atrophy (SMA) - signs:

A

only lower motor neuron, rarely bulbar signs

28
Q

Spinal muscular atrophy (SMA) - cause:

A

autosmal recessive inheritance

29
Q

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

A

1:35

30
Q

SMA genes

A
  • SMN1 (survival motor neuron) gene mutation
  • SMN2 gene - “surrogate” protein; copy number determinates clinical types
  • Types: infantile, early childhood, adolescent (I, II, III)
31
Q

Spinobulbar muscular atrophy (SBMA, Kennedy disease):

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