AMYOTROPIC LATERAL SCLEROSIS

• Commonly known as Lou Gehrig’s disease

• Combination of Upper Motor Neuron and Lower Motor Neuron disorder

• Degeneration and loss of motor neurons in the SC, brainstem and brain, resulting into a variety of UMN and LMN signs and symptoms

• M.C. and most fatal Motor Neuron Disease among adults

EPIDEMIOLOGY• 4 – 10 cases per 100,000

• Average age of onset: mid to late 50s

• Men > Women with a ratio of 1.7:1

• 5 – 10% of cases were inherited as an autosomal dominant trait (Familial ALS/ FALS)

• Large majority have no family history (Sporadic ALS)

• 70-80%: Limb onset ALS

• 20-30% Bulbar onset ALS

ETIOLOGY1. Superoxide Dismutase

- Group of enzymes that eliminate oxygen free radicals- Mutations in gene SOD1 in Chromosome 21 that causes toxic

properties leading to death of neurons

2. Glutamate

- Excess glutamate causes cascade of events leading to cell death

- Increased levels of glutamate in CSF and plasma and postmortem tissues of Pt.’s with ALS

ETIOLOGY3. Clumping of neurofilament proteins into spheroids in cell bodies

4. Autoimmune reaction

ETIOLOGYKnown Risk Factors for ALS

- Disease causing mutations (SOD1)

- Clusters ( Western Pacific ALS/PDC)

- Family History

- Age

- Gender (male>female)

ETIOLOGYPossible Risk Factors for ALS

- Neurotoxicant exposures (lead, mercury, pesticide, solvent)

- Lifestyle factors (cig. Smoking, alcohol intake)

- Certain occupation characteristics (electrical workers, farmers, industrial occupants)

- Diet (High fat intake, high glutamate intake, low fiber intake, low antioxidant intake)

- Trauma (skeletal trauma, fractures, severe electrical shock)

- Vigorous physical activity ( heavy manual labor, athleticism)

PATHOPHYSIOLOGY- Progressive degeneration and loss of motor neurons in the SC,

brainstem, and motor cortex

- Brainstem nuclei for CN V, VII, IX, X, and XII and anterior horn cells in SC

- Brainstem nuclei for III,IV,VI (extraocular) usually spared

- Motor neurons of Onufrowicz nucleus/ Onuf’s nucleus located in the ventral margin of the anterior horn of S2 are also spared

- control striated muscles of pelvic floor including sphincters

PATHOPHYSIOLOGY- Sensory system and Spinocerebellar tracts spared

- Denervation is compensated by reinnervation of healthy axons

- Progression of ALS is contigous

- Cervical segments to cervical segments first- Spread locally within regions- Onset is usually assymetrical and focal at first

CLINICAL MANIFESTATIONS- Impairments related to LMN pathology

- Most frequent presenting impairment: focal, assymetrical, muscle weakness either in LE or UE or bulbar muscles

- Cardinal sign: Muscle weakness- Weakness associated with LMN loss causes more significant

dysfunction than UMN loss- Cervical Extensor weakness is typical- Muscle weakness predispose to other secondary imp

CLINICAL MANIFESTATIONS- Impairments related to LMN pathology

- Muscle weakness predispose to other secondary impairments:- Decreased ROM- Joint subluxation- Tendon shortening- Joint contractures commonly (claw-hand deformity)- Adhesive Capsulitis- Ambulation difficulties, deconditioning, impaired postural control

and balance

- Losses of muscle force distal first before proximal

CLINICAL MANIFESTATIONS- Impairments related to LMN pathology

- Fatigue- Atrophy- Fasciculations- Hyporeflexia, flaccidity, muscle cramping- Craps occur in uncommon site such as tongue, jaw, neck,

abdomen, UEs, hands, calf/ thigh- Paresthesias, pain in limbs

CLINICAL MANIFESTATIONS- Impairments related to UMN pathology

- Spasticity, hyperreflexia, babinski, hoffman sign, clonus- Impairments related to Bulbar Pathology

- Spastic bulbar/ Flaccid bulbar palsy- Dysarthria

- weakness of tongue, muscles of lips, jaw, larynx and pharynx- Initial symptoms: inability to project voice (shouting, singing)- Nasal tone- Anarthric

- Dysphagia- Sialorrhea- Pseudobulbar Affect

CLINICAL MANIFESTATIONS- Respiratory Impairments

- Loss of respiratory muscle strength- Decrease in VC- Eventual orthopnea, use of accessory muscles, dyspnea at rest,

weak cough- Cognitive Impairments

- Mild deficits to severe frontotemporal dementia (FTD)- 35.6% shoed significant cognitive impairment- More likely in bulbar onset than limb onset

CLINICAL MANIFESTATIONS- Impairments related to UMN pathology

- Spasticity, hyperreflexia, babinski, hoffman sign, clonus- Impairments related to Bulbar Pathology

- Spastic bulbar/ Flaccid bulbar palsy- Dysarthria

- weakness of tongue, muscles of lips, jaw, larynx and pharynx- Initial symptoms: inability to project voice (shouting, singing)- Nasal tone- Anarthric

- Dysphagia- Sialorrhea- Pseudobulbar Affect

DIAGNOSIS- With the exception of one genetic test, no definitive diagnostic

test or diagnostic biological marker exists for ALS

- Laboratory studies, EMG, NCV, muscle and nerve biopsies, neuroimaging techniques

- Presence of (1) LMN signs by clinical, electrophysiological, neuropathological examination, (2) UMN signs by clinical examination, (3) progression of disease within a region or to other regions

- El Escorial Criteria

DISEASE COURSE- Progressive and deteriorating disease trajectory

- In most patients, death occurs within 3 to 5 years after diagnosis and usually results from respiratory failure

PROGNOSIS- Patients less than 35 to 40 years of age at onset had better 5-

year survival rates

- Limb onset have a better prognosis

MANAGEMENT- Disease modifying agents

- No cure for ALS- Riluzole (Rilutek) glutamate inhibitor for treatment of ALS- 50 mg 2x a day, side effects: Liver toxicity, nausea, vomiting,

dizziness - Effects only survive for 2 to 3 months

MANAGEMENT- Symptomatic Management

- Anti-cramping medications, Anti-spasticity medications, antidepressants, Percutaneous Endoscopic Gastrotomy, Ventilatory Support

- Management of cognitive and behavioral impairments- Management of Sialorrhea and Pseudobulbar Affect

- Anti-cholinergic medications- For thick mucus production: beta blockers- Tricyclic anti-depressants for pseudobulbar affect

MANAGEMENT- Management of Dysphagia

- Dietary modifications- Maintaining adequate calories and hydration- PEG

MANAGEMENT- Management of Muscle Cramps, Spasticity, Fasciculations, and

pain

- Anticonvulsant medications such as phenytoin and carbamazepine

- Lorazepam for fasciculations, minimize caffeine and nicotine- NSAIDs for pain, analgesics- Morphine for terminal stages of ALS