Disorders of the Anterior Horn Cells (ALS)

Question 1

A motor neuron disease in which degeneration of CN IX and XII occurs:

Answer 1

Progressive Bulbar Palsy

Question 2

A group of 4 inhereted and sporadic motor neuron diseases of UMN’s, LMS’s or both:

Answer 2

1. ALS
2. Primary Lateral Sclerosis (degeneration of UMN)
3. Progressive bulbar palsy (degeneration of CN IX and XII)
4. Progressive muscular atrophy (loss of LMN)

Question 3

ALS clinical manifestations:

Answer 3

• 80% with UMN signs
• Normal cognition (35% with cognitive impairments, FTD)
• LMN S & S: weakness, hyporeflexia, hypotonicity, fasciculations (especially of tongue), atrophy
• UMN S & S: spasticity, pathological reflexes, hyperreflexia, muscle weakness
• Bulbar S & S: dysphagia, Dysarthria, sialorrhea, Pseudobulbar affect: uncontrollable crying ot laughing
• Respiratory: Exertional dyspnea, Nocturnal respiratory difficulty, Orthopnea, Hypoventilation, Secretion retention, Ineffective coug.
• Cognitive: mild to severe FTD, difficulty with verbal fluency, language comprehension, memory, abstract reasoning, intellectual function.
• Rare impairments: sensory, bowel and bladder dysfunction, ocular palsy

Question 4

ALS Diagnosis:

Answer 4

No gold standart for ALS Dx:

• Based on pattern of S & S along with ruling out everyhting else.
• Absence of sensory involvement* (Recent research shows some sensory involvements occurs)
• Progression of S & S is essential for confirmed Dx of ALS
• 70% have increase Creatine Phosphate Kinase
• Genteic testing for pt with family Hx of ALS
• EMG: signs of active denertvation
• NVC: usually normal
• MRI: to exclude other causes; MS, DDD

Question 5

ALS Etiology:

Answer 5

• Unknown cause
• 90% -95% sporadic
• 5% - 10% familial

Question 6

ALS Pathology:

Answer 6

Affects UMN’s and LMN’s:

1. Massive loss of Anterior Horn Cells of spinal cord (LMN) – Results in muscle atrophy & weakness (amyotrophy)
2. Loss of Betz cells in motor cortex (UMN) leads to demyelination & gliosis of corticospinal & corticobulbar tracts (lateral sclerosis) – Results in UMN symptoms

Question 7

True or false:

EMG/NCV diagnostic test for ALS shows that ALS is not consistent with peripheral neuropathy neither with polyradiculopathy, but with other type of nerve disorder.

Answer 7

True

Question 8

True or false:

Environmental toxins such as lead, aluminum, agricultural chemicals, selenium in drinking water, and exposure to electrical shocks are associated with causes of ALS.

Answer 8

True

Question 9

Hyper-reflexia and spasticity are _ _ _ signs

Answer 9

UMN

Question 10

In ALS, loss of Betz cells leads to what?

Answer 10

demyelination & gliosis of corticospinal & corticobulbar tracts (lateral sclerosis).

– Results in UMN symptoms

Gliosis: A process leading to scars in the central nervous system that involves the production of a dense fibrous network of neuroglia (supporting cells) in areas of damage

Question 11

In ALS, massive loss of Anterior Horn Cells of spinal cord results in what?

Answer 11

• LMN signs:
• Results in muscle atrophy & weakness (amyotrophy)

Question 12

In ALS, what is protein aggregates?

Answer 12

Abnormal clumps of protein in motor neurons found in persons with ALS

Question 13

Autoimmune-Induced Calcium Influx theory of ALS:

Answer 13

Calcium channel antibodies have been isolated which may lead to prolonged influx of calcium into neurons, resulting in cell death

Question 14

Name of disease in which degeneration of UMN’s occurs and belongs to a group of disorders known as motor neuron diseases:

Answer 14

Primary Lateral Sclerosis

Question 15

Name of disease in which loss of LMN’s occurs and belogns to a group of motor neuron diseases:

Answer 15

Progressive Muscular Attrophy

Question 16

In ALS, what can an Oxidative injury cause?

Answer 16

Accumulation of free radicals leads to cell death by oxidizing cell membranes, proteins or genetic material

Question 17

Primary role of imaging in ALS is to

Answer 17

• exclude other causes:
  
  • MS & Cervical degenerative disc disease

Question 18

The most common genetic casue of ALS is a mutation in which gene?

Answer 18

gene C9ORF72

Also linked to Frontotemporal dementia (FTD)

Question 19

Theories of what causes ALS:

Answer 19

1. Glutamate excitotoxicity
2. Oxydative injury: cell death by free radicals
3. Protein aggregates: in motor neurons
4. Axonal strangulation: nutrients can not reach the cell body
5. Autoimmune-Induced Calcium influx: resulting in cell death
6. Viral infections
7. Deficiency of Nerve Growth Factor
8. Apoptosis: preprogramed cell death
9. Trauma
10. Environmental factors: Lead, Aluminum, Agricultural chemicals, Selenium in drinking water, Exposure to electrical shocks.

Question 20

This disease is a progressive degeneration of motor neurons in spinal cord (Massive loss of Anterior Horn Cells), brainstem & motor cortex (loss of Betz cells) and affects UMN’s & LMN’s:

Answer 20

AMYOTROPHIC LATERAL SCLEROSIS (ALS)

Question 21

Weakness and atrophy are _ _ _ signs

Answer 21

LMN

Question 22

What ALS theory states that when neurofilaments of axons become tangled, nutrients cannot reach cell bodies resulting in cell death

Answer 22

Axonal Strangulation

Question 23

What are the later clinical manifestation of ALS?

Answer 23

Weakness spreads:

• Distal to proximal, then bulbar symptoms
• Flex. weaker that ext.
• Asymmetrical weakness
• Dysphagia
• Dysarthria
• Respiratory dysfunction

Question 24

What are the typical MRI findings in ALS that have been described in literature?

Answer 24

High signal intensity of corticospinal tract, extending from corona radiata through posterior limb of internal capsule, ventral brain-stem and into spinal cord

Question 25

What does the World Federation of Neurology consider a **Clinically Definite** diagnosis of ALS?

Answer 25

1. Concomitant UMN & LMN signs in 3 spinal regions (cervical, thoracic, lumbar) **OR** 2. UMN & LMN signs in bulbar region and at least 2 spinal regions

Question 26

What is **essential** to confirm Dx of ALS?

Answer 26

* Progression of S & S during the entire lifespan. * Pattern of S & S along with inclusionary & exclusionary diagnostic tests suchs as MRI

Question 27

What is spared in ALS?

Answer 27

* Bowel and bladder function is normal * Oculomotor nuclei is spared * Sensory

Question 28

What is the gold standart lab test for the diagnosis of ALS?

Answer 28

* No single lab test can confirm Dx of ALS * 70% of patients have increased CPK * Genetic testing for patients with family Hx of ALS ## Footnote *CPK: Creatine Phosphate Kinase*

Question 29

What is the primary role of MRI **imaging** in ALS?

Answer 29

* **to exclude other causes:** * MS * Cervical degenerative disc disease

Question 30

What are the **earlier** clinical manifestation of ALS?

Answer 30

Muscle weakness: * Focal, asymmetrical * Hands, feet, arms legs and/or muscles of speech, swallowing or breathing * In 60% of patients * By the time weakness is noticeable, most pt have lost 80% of motor neurons.

Question 31

Which is the most common form of **motor neuron** disease?

Answer 31

**Amyotrophic Lateral Sclerosis (ALS)**

Question 32

**World Federation of Neurology** suggested which diagnostic criteria for patients with ALS in clinical practice, clinical trials and research?

Answer 32

looks at UMN/LMN findings in 4 regions of body

Question 33

Secondary & Composite impairments in ALS:

Answer 33

* Fatigue/ deconditioning * Weight loss * Cachexia *(or wasting syndrome is loss of weight, muscle atrophy, fatigue, weakness, and significant loss of appetite in someone who is not actively trying to lose weight)* * ROM * Tendon shortening, * Joint contracture or subluxation * Pain * Balance/postural control * Gait disturbances

Question 34

ALS - Disease **course**:

Answer 34

* Onset of LE weakness more common than UE * Onset with bulbar symptoms less common. * Unremitting spread of weakness: total paralysis of spinally innervated muscles and muscles innervated by CNs. * More rapid loss of strength in UE than LE * **Death 3-5 years after Dx** due to respiratory failure

Question 35

**Prognosis** of ALS:

Answer 35

* More rapid progression to death if onset with bulbar S & S vs limb onset * Median survival 4.08 years after onset: * 50% die within 18 months of DX * 9% to 40% survive 5 years * 8% to 16% survive 10 years (usually on ventilator) * 5% survive \> 20 years (not true ALS)

Question 36

Factors related to a better prognosis in ALS:

Answer 36

* Age \<35-40 better 5 yr survival rate * Less severe at time of Dx * No dyspnea at onset * Psychological well being

Question 37

True or false: Small number of patients with ALS exhibit halting of progression of disease or remittance of symptoms.

Answer 37

**True**, casue is unknown

Question 38

True or false: Small number of patients with ALS exhibit halting of progression of disease or remittance of symptoms

Answer 38

true

Question 39

What is the only drug aproved by the FDA to treat ALS?

Answer 39

**Riluzole (Rilutek)**, prolongs survival of patients with ALS by slowing progression of disease

Question 40

Which ALS drug treat pseudobulbar affects symptoms?

Answer 40

Nuedexta

Question 41

Pharmacological treatments of ALS under research:

Answer 41

– Gabapentin – Tocopheral (vitamin E) – Insulin-like growth factors (rhIGF-1) – Mexiletin – GM604

Question 42

Stem cell treatments of ALS:

Answer 42

* Brainstorm study: use patient’s own stem cells from bone marrow * Fetal-derived neural cells introduced into patient’s spinal cord

Question 43

Rehabilitation considerations of ALS:

Answer 43

* Rate of disease progression * Stages of disease * Extent and areas of involvement * Need to re-examine at regular intervals * Pt, family, caregiver education * Psychological support * Referrals

Question 44

Goals of rehabilitation in ALS:

Answer 44

* Difficult due to progression * Maintain maximal idependence and QOL as long as possible

Question 45

therapeutic **preventions** during ALS:

Answer 45

* **Prevention of disuse atrophy:** * Prevent further disuse beyond level caused by disease process itself * **Prevention of overuse injury** * “Do no harm” * Research: vigorous exercise damaged muscles with less than 1/3 of motor units functional * Amount of strengthening proportional to # of intact motor units * Avoid heavy eccentric exercise

Question 46

True or false: Studies show that weakened, denervated muscle may not be able to tolerate amount of exercise needed for training effect to occur in normal muscle and that strength training of muscles with less than 10% of normal strength is ineffective.

Answer 46

True

Question 47

Respiratory Management of ALS:

Answer 47

* **Respiratory therapy:** * **Pulmonary PT:** chest PT, breathing exercises, energy conservation * **Non-invasive ventilation:** * Extends survival by several months * Improves QOL * **Progress to ventilation via tracheostomy** OR * **Palliative care**