ALS

Question 1

Degenerative disease of the CNS

Answer 1

• can affect grey matter, white matter or both
• the pattern of neuronal loss is selective, affecting one r more groups of neurons while leaving the others intact
• changes can arise w/o any initiating factors
• present as slow deterioration of body functions

Question 2

ALS

Answer 2

• degenerative, adult onset terminal disease of unknown cause
• combination of both UMN and LMN clinical S/S resulting in profound limitation of movement
• men more than women

Question 3

ALS characterized by degeneration of neurons in…

Answer 3

• SC ( anterior horn cells)
• BS ( corticobulbar and corticospinal tracts)
• brain (betz cells in motor cortex

Question 4

ALS epidemiology/incidence

Answer 4

• the avg of onset is in the mid to late 50s

- men affected more than women

Question 5

ALS etiology

Answer 5

• unknown, may be the result of multiple mechnanisms that leads to neurodegeneration
• glutamate triggers events that lead to cell death when present in excess. increased levels in the CSF and plasma have been found in individuals with ALS
• clumping of neurofilament proteins into spheres in the cell body and axon in ALS people
• lymphocytes are present which indocate immunoreactions

Question 6

Superoxide dismutases (SODs)

Answer 6

• a group of enzymes that eliminate oxygen free radicals have been implicated in neurodegeneration
• three formsCuZnSOD, MnSOD, ECSOD

Question 7

SOD1

Answer 7

-is a gene on chromosome 1 that encodes CuZnSOD. 20% of people with ALS have a mutation of this gene. the mutant SOD 1 protein may have toxic properties that leads to an increase in free radicals that accumulate causing cell damage

Question 8

Toxic theories in ALS

Answer 8

• related to lead or aluminum and abnormalities in magnesium and calcium levels
• exogenous or environmental triggers for apoptosis

Question 9

Summary of possible causes of ALS

Answer 9

• Gene mutation SOD1- increase in free radicals
  -Glutamate
  -Clumping of neurofilaments proteins
  -lymphocytes
  -toxic theories
  environmental triggers

Question 10

ALS pathophysiology

Answer 10

• massive loss of anteiror horn cells of the SC and motor cranial nerve nuclei in th elower brain stem results in muscle weakness
• the greatest loss occurs in the cervical and lumbar regions of the cord and between the internal capsule and bulbar pyramids
• demyelination and gliosis of the corticospinal and corticobulbar tracts
• death of the peripheral nerves leads to denervation. some reinervation may occur from sprouting nearby distal axon terminals but it is not adequate to restore function

Question 11

ALS dementia

Answer 11

• may occur due to changes n the frontotemporal cortices and or in the basal ganglia
• unique to ALS the RNS content is reduced in the damaged and normal neurons in the area

Question 12

ALS impact on BS nuclei for visions

Answer 12

• brainstem nuclei for the cranial nerves controlling the external ocular muscles III, IV, VI are usually spared

Question 13

ALS and pelvic floor

Answer 13

• motor neurons in the ventral margin of the anterior horn cell in the sacral spinal levels are usually spared which control the muscles of the pelvic floor

Question 14

What is spared in ALS

Answer 14

• external ocular muscles III,IV, VI are usually spared
• control the muscles of the pelvic floor
• sensory systems and the spinocerebellar tracts are also generally spared

Question 15

ALS diagnosis

Answer 15

• largely clinical
• neurological exam and EMG studies
• spontaneous fibrillations and fasciculations in at least 3 limbs and the paraspinal muscles
• these changes occur with out any change in sensory response
• no single laboratory test- creatine phosphate levels elevated

Question 16

Diagnostic findings of suspected ALS

Answer 16

• LMN signs in more than 2 regions

- UMN signs in more than one region

Question 17

Diagnostic findings of possible ALS

Answer 17

• UMN + LMN sign in one region

- UMN+ LMN signs in more than two regions

Question 18

Diagnostic findings of probable ALS

Answer 18

• UMN + LMN signs in two regions

- UMN + LMN signs in more than two regions

Question 19

Diagnostic findings of definite ALS

Answer 19

• UMN +LMN in three regions

- UMN +LMN signs in more than three regions

Question 20

earliest clinical markers of ALS

Answer 20

• fasciculations, especially of the tongue, muscle cramps, complaints of stiffness, fatigue, weakness and atrophy

Question 21

ALS clinical manifestations

Answer 21

• neck stiffness and heaviness
• lumbar lordosis
  -difficulty stabilizing
  weakness and atrophy as well as hyper-reflexian, spasticity, positibe Hoffman and Babinski
• asymmetrical weakness of the UE or LE or weakness in the bulbar muscles
  -cognitive impairments
  -chewing, swallowing

Question 22

pseudobulbar palsy

Answer 22

• reflects damage in the corticospinal tract

Question 23

progressive bulbar palsy

Answer 23

• cranial nerve nuclei involvement
• weakness in the muscles that control chewing swallowing and facial gestures
• dysarthria

Question 24

primary lateral sclerosis

Answer 24

• result of neuronal loss in the cortex

- corticospinaal trcat involvement including hyperactive reflexes, weakness, spasticity

Question 25

progressive spinal muscular atrophy

Answer 25

• loss of motor neurons in the anterior horn cells of the SC
• weakness and wasting in the muscles of the cervical spine, hands with progression to other area of the body including facila symptoms and repsiratoryfailure

Question 26

TX : Riluzole

Answer 26

• remains the only food and drug administration approved drug for ALS
• inhibits glutamate release, post synaptic glutamate receptor activation and sodium channel activation
• appears to be neuroprotective to slow the disease by 10% to 15%, but it is not curative

Question 27

TX: controlling inflammation

Answer 27

• may be helpful because of the neuroinflammaion that occurs in the SC an dthe BS

Question 28

TX: celastrol

Answer 28

• is a strong anti-inflammatory and antioxidant that suppresses nitric oxide production

Question 29

TX: tamoxafin

Answer 29

• may also be helpful because of its ability to inhibit protein kinase C which mediates inflammation

Question 30

TX: talampanel

Answer 30

• modulator of ionotripic flutmate reeptors that may be helpful but is used primarily as an antilepti agent

Question 31

TX: minocycline

Answer 31

-second generation tetracycline antibiotic that prevent microglial activation

Question 32

TX: memantine

Answer 32

• is used as an alzheimers diseasd

Question 33

TX: myotrophin

Answer 33

-appears to affect motor by promoting survival of motor neurons and regeneration of motor nerves

Question 34

TX: coenzyme Q10

Answer 34

-helps mitochondrial function and I used in diseases mitochondria dysfunction is implicated

Question 35

TX: ketogenic diet

Answer 35

• similar to the one to control epilepsy can later mitochondrial function and can be helpful in ALS

Question 36

ALS disease course

Answer 36

• relenteless progressive deterioration and death
• death occurs within 2-5 years of DX ususally from pneumonia or respiratory failure
• bulbar involvement have a mor erapid course than those with lateral sclerosis