ALS

Question 1

what does the Amyotrophic Lateral Sclerosis mean?

Answer 1

• A - no/without
• Myo - muscle
• Trophic - nourishmen
• lateral - defines the areas in a person’s spinal cord where portions of the nerve cells that signal and control the muscles are located
• as this area degenerates, it leads to scarring or hardening (sclerosis) in the region

Question 2

Epidemiology of ALS

Answer 2

1. most common and devastating fatal of all motor neuron diseases
2. mortality typically in 2-5 years; highly variable symptoms
3. onset is often >50 years old but can occur in younger people
4. men are slightly more affected than women (1.5:1)

Question 3

what is ALS characterized by?

Answer 3

1. progressive degeneration and loss of motor neurons in the spinal cord, brain stem, and motor cortex
   
   • destruction of upper and lower motor neurons
   • degeneration of anterior horn cells and descending corticobulbar and corticospinal tract

Question 4

pathophysiology of ALS

Answer 4

1. demyelination and gliosis of the motor cortex, corticospinal and corticobulbar tracts resulting from degeneration of UMN cell bodies in the motor cortex

Question 5

describe the etiology of ALS

Answer 5

1. unknown
   
   • viral/autoimmune/toxic?
2. glutamate excitotoxicity
   
   • increased levels in CSF, plasma, post-mortem tissue
3. 5-10% genetic (autosomal dominant)

Question 6

Risk factors for ALS

Answer 6

1. Male > Female
2. Caucasian, non-Hispanic minorities
3. Geographical clusters
4. Family History
5. Age (55-75)
6. Prior trauma or TBI

Question 7

ALS Diagnosis

Answer 7

1. Diagnosis is very difficult
   
   • misdiagnosis is not uncomon
2. Largely diagnosis by exclusion
3. Clinical examination
4. EMG/NCV
5. MRI
6. CSF, blood and urine tests
   
   • creatine phosphokinase levels higher in ~70% cases
   • ID of biomarkers to rule out other neurological diseases

Question 8

clinical diagnosis of ALS requires what criteria?

Answer 8

1. a pattern of observed and reported symptoms of both UMN and LMN as well as persistent decline in physical function that cannot be attributed to other disorders
2. El Escorial criteria

Question 9

what is included in the El Escorial criteria for diagnosis of ALS?

Answer 9

1. exclusion of all other Dx + Progressive Functional Decline +
   
   • progressive UMN and LMN deficits in at least one limb or region of the human body or
   • LMN deficits in at least one region by clinical exam and/or by EMG in two body regions (defined as bulbar, cervical, thoracic, lumbosacral)
     
     • the EMG findings consist of neurogenic potentials and fibrillation potentials and/or sharp waves

Question 10

General Clinical Presentations of ALS

Answer 10

1. cardinal sign → progressive muscle weakness
2. UMN impairments
3. LMN impairments
4. Bulbar impairments
5. Respiratory impairments
6. Cognitive impairments
7. Additional impairments

Question 11

ALS S/S: Progressive Muscle Weakness

Answer 11

1. most common impairment focal, asymmetrical muscle weakness beginning in LE or UE or Bulbar weakness
2. Can be due to UMN and/or LMN involvement
   
   • LMN weakness >> UMN weakness
   • Eye, bowel and bladder muscle normally spared until terminal stages
3. Progresses to entire body involvement

Question 12

ALS UMN Impairments

Answer 12

1. spasticity
2. hyperreflexia
3. clonus
4. pathological reflexes
5. weakness

Question 13

ALS LMN Impairments

Answer 13

1. hyporeflexia
2. hypotonicity
3. atrophy
4. fasciculations
5. weakness

Question 14

ALS Bulbar Impairments

Answer 14

1. spastic bulbar palsy or flaccid bulbar palsy
2. dysarthria
3. sialorrhea

Question 15

ALS Respiratory Impairments

Answer 15

1. decreased respiratory muscle strength
2. reduction of VC up to 50% typically when symptoms arise

Question 16

ALS Cognitive Impairments

Answer 16

1. variable evidence on prevalence
   
   • verbal fluency
   • language comprehensive
   • memory
   • abstract reasoning

Question 17

ALS Additional impairments

Answer 17

1. pain
2. fatigue
3. ANS symptoms (1/3 cases)

Question 18

Clinical subtypes of ALS

Answer 18

1. Classic ALS
   
   • limb-onset
   • bulbar-onset
2. Primary Lateral Sclerosis (PLS)
3. Progressive Spinal Muscular Atrophy (SMA)
4. ALS with Frontotemporal Dementia (FTD)
5. Familial ALS

Question 19

early signs of classic ALS

Answer 19

1. progressive limb weakness
2. reduced dexterity
3. wasting of hands
4. muscle fasciculations
5. with additional bulbar involvement, there is wasting of the tongue, and muscles for speech and swallowing

Question 20

describe Limb-Onset Classic ALS

Answer 20

1. ~70-80% of cases (most common presentation of ALS)
2. first symptoms are a result from damage to motor neurons in motor cortex, specifically corticospinal tracts
3. distal → proximal
   
   • fasciculations
   • atrophy
   • weakness
   • spasticity

Question 21

describe bulbar-onset classic ALS

Answer 21

1. ~20-30% of cases. Progresses faster than limb-onset
2. first symptoms are a result of damage to motor neurons in brainstem, specifically corticobulbar tracts (face, head, neck, muscles)
   
   • affects CN IX and XII causing dysarthria and dysphagia
   • tongue atrophy, tongue fasciculations
   • vocal cord spasms
3. more common in older female with male:female (2:3)

Question 22

describe Primary Lateral Sclerosis

Answer 22

1. rare condition (5% of those with ALS)
2. Upper motor neuron signs and symptoms ONLY
   
   • can progress to classical ALS
   • key exam findings can include spasticity, upper motor neuron pattern weakness, and pseudobulbar findings
3. VERY different prognostic story → relatively good with life expectancy comparable to normal!

Question 23

describe Progressive SMA

Answer 23

1. 5-10% of cases
2. LMN involvement ONLY
   
   • flaccid weakness
   • atrophy
   • fasciculation
   • hyporeflexia or areflexia
3. Mainly limb involvement
   
   • bulbar palsy can develop later
4. Mainly affects men (male > female, 2:1)
5. May be limited to one region
6. Progression highly variable, can be slow or very rapid

Question 24

what regions may AMS be limited to?

Answer 24

1. Flail arm syndrome (cervical) → Man-in barrel syndrome
2. Flail leg syndrome (lumbosacral)

Question 25

describe ALS with FTD

Answer 25

1. cognitive symptoms and dementia once thought to be uncommon ALS symptom. Recent studies suggest that: * roughly 30% of pts with ALS demonstrate mild to moderate cog and/or behavioral impairments w/o dementia * 20% of individuals with ALS with develop FTD 2. Common deficits invovle executive function, either language or personality. Causes problems with judgement, impulsivity, decreased ability to handle routine tasks

Question 26

describe Familial ALS

Answer 26

1. Affects 5-10% of pts with ALS 2. Genetic risk for ALS prob represents combined effects of multiple genes that establish a person's overall genetic susceptibility, acting with environmental and random effects leading to disease onset 3. pattern of inheritance varies depending on gene involved; most cases are inherited in an autosomal dominant pattern 4. Onset: late 40s or early 50s 5. No difference between familial and sporadic ALS on neuro exam

Question 27

stage 1 of ALS

Answer 27

1. early disease 2. mild focal weakness 3. asymmetrical distribution 4. symptoms of hand cramping and fasciculations

Question 28

stage 2 of ALS

Answer 28

1. moderate weakness in groups of muscles 2. some wasting (atrophy) of muscles 3. modified independence with AD

Question 29

stage 3 of ALS

Answer 29

1. severe weakness of specific muscles 2. increasing fatigue 3. mild to moderate functional limitations 4. ambulatory

Question 30

stage 4 of ALS

Answer 30

1. severe weakness and wasting of LEs 2. mild weakness of UEs 3. moderate assistive and AD 4. wheelchair user

Question 31

stage 5 of ALS

Answer 31

1. progressive weakness with deterioriation of mobility and endurance 2. increased fatigue 3. moderate to severe weakness of whole limbs and trunk 4. spasiticty 5. hyperreflexia 6. loss of head control 7. maximal assist

Question 32

stage 6 of ALS

Answer 32

1. bedridden 2. dependent ADLs 3. FMS 4. progressive respiratory distress

Question 33

medical management of ALS

Answer 33

1. no effective treatment for disease 2. disease-modifying * riluzole → glutamate antagonist 3. symptomatic treatment * cramps * spasticity * sialorrhea * depression * excessive laughing and crying

Question 34

Outcome measure for ALS

Answer 34

ALS Functional Rating Scale (ALSFRS-R)

Question 35

describe the ALSFRS-R

Answer 35

1. measures ADL and global function across 12 functional categories 2. used to assess response to treatment or disease progression 3. total possible score 48 with higher scores reflecting worse performance

Question 36

ALSFRS-R items

Answer 36

1. speech 2. salivation 3. swallowing 4. handwriting 5. cutting food 6. dressing and hygiene 7. turning in bed 8. walking 9. climbing stairs 10. dyspnea 11. orthopnea 12. respiratory insufficiency

Question 37

ALS prognosis

Answer 37

1. terminal diagnosis * average mortality rate 2-5 years * small % live 15-20 years * EXCEPTION → Stephen Hawking * ultimately progresses to respiratory failure

Question 38

ALS Negative Prognostic factors

Answer 38

1. Bulbar onset 2. Early respiratory signs

Question 39

ALS Positive Prognostic factors

Answer 39

1. according to the American Academy of Neurology, pts who participate in multidisciplinary clinics live longer and have an improved QOL

Question 40

How can mortality be delayed in ALS pts?

Answer 40

by initating home-based mechanical ventilation as opposed to palliative or comfort care only