Chronic & Progressive lecture: ALS (part 1)

Who coined the name ALS ?

Charcot

Relentless, rapid progression without remission and fatal

ALS

True or false: ALS is a uniquely human disorder

true

What is the first sign in 90% of individuals with ALS?

Muscle Weakness

True or false: ALS affects LMN

false - ALS affects UMN and LMN

Where are UMN located that are affected in ALS ?

corticospinal tract

Where are the LMN located that are affected in MS ?

anterior horn cells

UMN signs and symptoms

hyperreflexia, clonus, spasticity, pathologic reflexes, weakness

LMN signs and symptoms :

muscle atrophy, fasciculations, cramping, weakness, hyporeflexia

Adult onset, progressive neurodegenerative disease of the voluntary motor system

ALS

What is the most common of the motor neuron diseases?

ALS

Age of diagnosis of ALS

average age = 55 (between 40-70)

In what gender and race is ALS most common?

white men

True or false: MS is the most common form of motor neuron disease ?

False - ALS

What are the two etiologies of ALS ?

Familial or sporadic

What etiology of ALS do most people have?

sporadic

What are environmental factors that could contribute to sporadic ALS?

heavy metal/pesticide exposure, exposure to tobacco smoke, viral infection

What are the only definitive non-genetic risks for ALS?

aging & male sex

True or false: Physical activity is a risk for Sporadic ALS

true

Explain the pathogenesis of ALS

Mitochondrial dysfunction - protein aggregation - free radical formation - excitotoxicity - neuronal transport defects - inflammation - impaired muscle function

What leads to impaired muscle function in those with ALS ?

increased Nogo-A protein concentration in muscle cells

Aggregation of what protein leads to clogging of the neural system ?

Extra nuclear aggregation of TDP-43

How is maternal age correlated to ALS?

increased maternal age

If you have a genetic pre-dispostion for ALS then what are you more susceptible for?

neuro inflammation, excitotoxity, mitochondrial dysfunction, oxidative stress, environmental risk factors

Describe Classic motor involvement of ALS

UE/LE involvement, widespread UMN/LMN distribution

Describe Bulbar motor involvement in ALS

predominant cranial nerve signs first 6 months

Describe flail arm/leg

flaccid LE or UE involvement for first 12 months

Describe respiratory motor involvement

Dyspnea, spinal or bulbar symptoms for first 6 months

True or false: 30-50% of patients with ALS may have cognitive involvement (frontotemporal dementia) but not all will have cognitive deficits

true

What are additional / non motor symptoms involved in the clinical presentation of ALS

sensation deficits, autonomic dysfunction, Executive dysfunction, frontotemporal dementia

Describe autonomic dysfunction in those with ALS

cardiovascular, GI, salvia and lacrimal dysfunction

Describe executive dysfunction issues in those with ALS

deficits in working memory, disinhibiting, motivation

what are symptoms of frontotemporal dementia ?

changes in personality & behavior, language impairment

what criteria is used to diagnosis ALS?

Gold Coast criteria

What would an EMG show when diagnosing ALS?

consisted with muscle fiber denervation and reinnervation

Describe sensory nerve conduction in ALS

normal

Describe the trend of motor nerve conduction in a patient with ALS

motor nerve conduction is normal in early stages but will become atypical in later stages

What is DTI used for in diagnosing ALS?

assess integrity of descending corticospinal tract

What are 3 types of testing used in the diagnosis process for ALS ?

Electrophysiology, imaging, lumbar puncture

Purpose of a lumbar puncture for diagnosis of ALS

examine CSF fluid

True or false: ALS is a diagnosis of exclusion

true

What does a person with bulbar symptoms with ALS have a higher mortality rate ?

swallowing muscles are affected and respiratory compromise

What is the progression of ALS influenced by ?

age, site of onset, type, genetic factors, psychosocial factors, smoking, treatment, weight

Length of survival <5 years

60%

Length of survival with ALS >5 years

25%

length of survival with ALS >10 years

10%

Length of survival with ALS >20 years

5%

based on objective clinical milestones corresponding to disease progression

king's clinical staging system

Based on loss of independence in 4 key domains of the ALS functional rating scale

MiToS functional staging system

What are the 4 key domains of the ALS functional rating scale?

swallowing, walking/self-care, communicating, breathing

Stage 1 clinical classification of ALS

mild weakness in specific muscle groups; functional independence and mobility are still preserved

Stage 2 clinical classification of ALS

moderate muscle weakness & more muscle groups involved; functional independence with adaptations/equipment

Stage III Clinical classification

Severe muscle weakness in specific muscle groups; mild to moderate limitations in functional ability, greater susceptibility to fatigue

Stage 4 Clinical Classification of ALS

greater distribution of severe weakness; may or may not complete ADLs

Stage 5 clinical classification of ALS

increasing dependence with increased difficulty with transfers

Stage 6 clinical classification of ALS

Patient requires total care