AMYOTROPHIC LATERAL SCLEROSIS

INTRODUCTIONMotor neuron diseases (MND) include a heterogeneous spectrum of inherited and sporadic (no family history) clinical disorders of the upper motor neurons (UMNs), lower motor neurons (LMNs), or a combination of both.

Subtype Nervous System PathologyAmyotrophic lateralSclerosis

Degeneration of the corticospinal tracts, neurons in the motor cortex and brainstem, and anterior horn cells in the spinal cord

Primary lateralSclerosis

Degeneration of upper motor neurons

Progressive bulbarPalsy

Degeneration of motor neurons of cranial nerves IX to XII

Progressive muscularAtrophy

Loss or chromatolysis of motor neurons of the spinal cord and brainstem

AMYOTROPHIC LATERAL SCLEROSIS ALS commonly known as Lou Gehrig’s disease It can be defined as a rapidly progressive neurodegenerative disease

characterized by weakness, spasticity, and muscular atrophy with subsequent respiratory compromise leading to premature death.

It is caused by the destruction of motor neurons in the primary motor cortex, brain stem, and spinal cord.

“Amyotrophy” refers to muscular atrophy occurring from the degeneration of anterior horn cells in the spinal cord with muscle fiber denervation.

“Lateral sclerosis” describes the resultant hardening of the anterior and lateral corticospinal tracts caused by replacement of dying motor neurons with subsequent gliosis.

EPIDEMIOLOGY The prevalence of ALS has been reported to be 4 to 10 cases per 100,000.

(O’Sullivan, 2014) It is estimated that 30,000 individuals in the US have ALS at any one time and

15 cases are diagnosed every day. ALS most often afflicts people between 40 and 60 years of age with a mean age

of onset of 58 years. This disease affects men slightly more than women, with an approximate

ratio of 1.7:1 (O’Sullivan) | 1.5:1 (Braddom) The worldwide prevalence is 5 to 7/100,000, making ALS one of the most

common neuromuscular diseases in the world. (Braddom, 2011) Three Classifications of ALS:1. Familial Amyotrophic Lateral Sclerosis2. Juvenile Amyotrophic Lateral Sclerosis3. Sporadic Amyotrophic Lateral Sclerosis

FAMILIAL ALS Approximately 5% to 10% of all ALS cases, however, are familial

(FALS) and most commonly have an autosomal dominant inheritance pattern.

The age of onset of FALS occurs a decade earlier than sporadic cases, and progression of the disease is more rapid.

Males and females are equally affected. About 20% of FALS cases result from a copper–zinc superoxide dismutase (SOD1) gene defect.

JUVENILE ALS It is by definition presents before age 25. It is a rarely occurring form of FALS. The progression of the disease is typically much slower than adult-

onset ALS and can present initially with either UMN or LMN signs. Two autosomal recessive (ALS5 and ALS2) and one autosomal

dominant (ALS4) form of juvenile ALS have been described:a. ALS5

• The disease-causing mutation has been mapped to chromosome 15q.• It typically presents in the teenage years with progressive limb spasticity,

distal limb weakness, and muscle atrophy.

JUVENILE ALSb. ALS2

The disease-causing mutation has been linked to chromosome 2q33. Disease onset typically begins before age 10. Prominent symptoms include limb and facial spasticity accompanied by

pseudobulbar affect.

c. ALS4 presents with severe distal muscle weakness and pyramidal signs in the

absence of bulbar and sensory abnormalities. It is caused by a mutation in the senataxin gene found on chromosome 9q34. The senataxin protein is known to have a role in RNA processing.

SPORADIC ALS The etiology of sporadic ALS is unknown and likely multifactorial with a

complex interplay of pathogenic cellular mechanisms. These mechanisms includes:

1. Oxidative stress2. Exogenous neurotoxicity3. Glutamate Excitotoxicity4. Impaired axonal transportation5. Protein aggregation6. Apoptosis (programmed cell death)7. Lifestyle factors (e.g. cigarette smoking, alcohol intake, anthropometric

measures), may be responsible for neuron degeneration in ALS.

ETIOLOGY

ETIOLOGY

ANATOMICAL & PHYSIOLOGICAL BACKGROUND Motor neurons are nerve cells

located in the brain, brain stem, and spinal cord that serve as controlling units and vital communication links between the nervous system and the voluntary muscles of the body.

Messages from motor neurons in the brain (called upper motor neurons) are transmitted to motor neurons in the spinal cord (called lower motor neurons) and from them to particular muscles.

ANATOMICAL & PHYSIOLOGICAL BACKGROUNDUMN The upper motor neurons are located on the surface of

the brain and exert control over the lower motor neurons, which are in the brainstem and the spinal cord.

LMN The lower motor neurons are directly attached to

muscles through “wires” called axons. Bundles of these axons leave the spinal cord and extend out to the muscles.

Bulbar Motor Neuron Those that control the muscles of speaking, swallowing

and facial expression are in the brainstem. They’re sometimes called bulbar motor neurons, because the part of the brainstem that houses them has a bulblike shape.

PATHOLOGICAL BACKGROUND ALS is marked by progressive and highly selective degeneration and

loss of upper and lower motor neurons in the brain and spinal cord leading to paralysis of voluntary muscles and loss of ability to swallow, speak, and breathe.

As motor neurons degenerate, they can no longer control the muscle fibers they innervate. Healthy, intact surrounding axons can sprout and reinnervate the partially denervated muscles, in essence assuming the role of the degenerated motor neuron and preserving strength and function early in the disease; however, the surviving motor units undergo enlargement. Reinnervation can compensate for the progressive degeneration until motor unit loss is about 50%. As the disease progresses reinnervation cannot compensate for the rate of degeneration, and a variety of impairments develop.

PATHOLOGICAL BACKGROUND When these cells gradually die in ALS,

muscles atrophy (shrink) and become progressively weaker and eventually unable to contract, resulting in paralysis.

When upper motor neurons are lost and lower motor neurons remain, movements are still possible but can become tight (spastic) and less precise. In ALS, a combination of these effects is usually seen because both upper and lower motor neurons are dying. People with ALS can have weak and atrophied muscles with tightness (spasticity). Muscle twitches (called “fasciculations”) and cramps are common; they occur because degenerating nerves become irritable.

CLINICAL MANIFESTATIONS Clinical manifestations of ALS vary depending on the localization and extent of motor neuron loss, the degree and combination of LMN and UMN loss, pattern of onset and progression, body region(s) affected, and stage of the disease. At onset, signs or symptoms are usually asymmetrical and focal. Progression of the disease leads to increasing numbers and severity of impairments.

SYMPTOMS Early signs and symptoms of ALS include:

Difficulty walking, tripping or difficulty doing your normal daily activities Weakness in your leg, feet or ankles Hand weakness or clumsiness Slurring of speech or trouble swallowing Muscle cramps and twitching in your arms, shoulders and tongue Difficulty holding your head up or keeping a good posture

The disease frequently begins in your hands, feet or limbs, and then spreads to other parts of your body. As the disease advances, your muscles become progressively weaker. This weakness eventually affects chewing, swallowing, speaking and breathing.

However, ALS doesn't usually affect your bowel or bladder control, your senses, or your thinking ability. It's possible to remain actively involved with your family and friends.

COMMON IMPAIRMENTS ASSOCIATED WITH ALSPathology Impairments

LMN Muscle weakness, hyporeflexia, hypotonicity, atrophy, muscle cramps, fasciculations

UMN Spasticity, pathological reflexes, hyperreflexia, muscle weaknessBulbar Bulbar muscle weakness, dysphagia, dysarthria, sialorrhea,

pseudobulbar affectRespiratory

Respiratory muscle weakness (inspiratory and expiratory), dyspnea, exertional dyspnea, nocturnal respiratory difficulty, orthopnea, hypoventilation, secretion retention, ineffective cough

Others Rare impairments: sensory impairments, bowel and bladder dysfunction, ocular palsyIndirect and composite impairments: Fatigue, weight loss, cachexia, decreased ROM, tendon shortening, joint contracture, joint subluxation, adhesive capsulitis, pain, balance and postural control impairments, gait disturbances, deconditioning,depression, anxiety

IMPAIRMENTS RELATED TO LMN PATHOLOGY The most frequent presenting impairment, occurring in the majority of

patients, is focal, asymmetrical muscle weakness beginning in the lower extremity (LE) or upper extremity (UE), or weakness of the bulbar muscles.

Muscle weakness is considered the cardinal sign of ALS and may be caused by LMN or UMN loss.

Initial muscle weakness usually occurs in isolated muscles, most often distally, and is followed by progressive weakness and activity limitations.

DIAGNOSIS No definite diagnostic test No diagnostic biological marker exists

For individual with clinical presentation: Laboratory studies EMG Nerve Conduction Velocity studies Muscle and nerve biopsies Neuroimaging studies

DIAGNOSIS Diagnosis of ALS requires the presence of1. LMN signs by clinical, electrophysiological, or neuropathological

examination2. UMN signs by clinical examination3. Progression of the disease within a region or to other regions by clinical

examination or via the medical history The absence of1. Electrophysiological and pathological evidence of other diseases that

may explain the UMN and LMN sign and2. Neuroimaging evidence of other disease processes that may explain the

observed clinical and electrophysiological signs are also evaluated

DISEASE COURSE ALS has a progressive and deteriorating trajectory Disease course varies among individuals From time of onset to death ranging from several months to 20 years

Average duration of ALS between 27 months to 43 months Median duration between 23 and 52 months Five-year and ten-year survival rates range from 9% to 40% and 8% to 16%

A 50% survival probability after the first symptom of ALS appears is slightly greater that 3 years

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

PROGNOSIS Age at time of onset has the strongest relationship to prognosis Patients <35 to 40 years of age at onset had better 5-year survival rates that older individual Individuals with limb-onset have a better prognosis that bulbar-onset 5-year survival rates were reported to be 37% and 44%, compared to survival rates of 9% to

16% for patients with bulbar-onset ALS

Other factor affecting prognosis Less sever involvement at the time of diagnosis Longer interval between onset and diagnosis No symptoms of dyspnea at onset A study of 144 individuals with ALS found that those individuals with psychological well-being

had significantly longer survival times compared to those with psychological distress. Mortality rates were found to be 6.8 times greater

MANAGEMENTDisease-Modifying Agents Currently, there is no cure for ALS, although a number of clinical drug trials are

ongoing. In 1995, the FDA approved riluzole (Rilutek), a glutamate inhibitor, for the treatment of ALS. The standard dose of riluzole is one 50 mg tablet two times a day, and side effects include liver toxicity (which requires discontinuation), asthenia, nausea, vomiting, and dizziness. Evidence suggests the effects of riluzole to be modest, extending survival for 2 to 3 months.

Symptomatic Management Because the pathological process cannot be reversed and is progressive in nature,

the context of medical management for individuals with ALS may be considered palliative. As defined by the WHO, palliative care is “an approach that improves the quality of life of patients and their families facing the problem associated with life-threatening illness, through the prevention and relief of suffering by means of early identification and impeccable assessment and treatment.

Management of Dysphagia Speech-language pathologists conduct swallowing examinations such as

video fluoroscopy to determine the degree and nature of the swallowing impairment and to assist in formulating a plan of care

Nutritionists provide counseling and diet management throughout the course of the disease.

Management of Respiratory Impairments Important management considerations include (1) pneumococcal and yearly

influenza vaccinations;68 (2) prevention of aspiration; and (3) effective oral and pulmonary secretion management.

supplemental oxygen is recommended only for individuals with concomitant pulmonary disease or as a comfort measure for patients who decline ventilator support.

When VC decreases to 50% of predicted, positivepressure noninvasive ventilation (NIV) is recommended.

Management of Sialorrhea and Pseudobulbar Affect Management of sialorrhea in people with ALS and other diseases is often directed

toward prescription of anticholinergic medications that decrease saliva production. Examples include:

glycopyrrolate (Robinul) benztropine (Cogentin) transdermal hyoscine (scopolamine), atropine and trihexyphenidyl hydrochloride (Artane).

For patients with associated thick mucus production beta-blockers such as propranolol (Inderal) or metoprolol (Toprol) are often prescribed.

For patients with pseudobulbar affect, tricyclic antidepressants, such as amitriptyline (Elavil), or selective serotonin reuptake

inhibitors (SSRIs), such as fluvoxamine (Luvox), are often prescribed

Management of Dysarthria Dysarthria impairments are managed primarily by a speech-language

pathologist. Initial speech changes are usually managed with intelligibility strategies

Management of Muscle Cramps, Spasticity, Fasciculations, and Pain Anticonvulsant medication such as phenytoin (Dilantin) and carbamazepine

(Atretol, Tegretol) may be prescribed for muscle cramps, if they are not relieved with a program of muscle stretching and adequate hydration and nutrition.

Management of Anxiety and Depression Pharmacotherapy and psychological counseling are important

management strategies for addressing the anxiety and depression that can develop. Individuals with depression may be prescribed an SSRI, such as fluoxetine (Prozac) or sertraline (Zoloft).

Benzodiazepines, such as chlordiazepoxide (Librium), clorazepate, diazepam, and flurazepam (Dalmane), may be prescribed for anxiety or for patients with depression and insomnia.

COGNITION No ALS-specific cognitive test or measure exists If dementia or cognitive impairments are suspected, executive function,

language comprehension, memory, and abstract reasoning should be examined.

The Mini-Mental State Examination has been used in clinical studies, although it may not be sensitive to frontotemporal function impairments.

Referral for a neuropsychological evaluation may also be indicated to identify specific cognitive impairments.

PSYCHOSOCIAL FUNCTION As depression and anxiety are common in individuals with ALS, screening is important

and referral to a psychologist or psychiatrist for further evaluation may be indicated. The Beck’s Depression Inventory, The Center of Epidemiologic Study Depression Scale The Hospital Anxiety and Depression Scale (HADS) The State-Trait Anxiety Inventory

Pain Pain is common in individuals with ALS and should be examined subjectively and

objectively, using a Visual Analogue Scale (VAS)Joint Integrity, Range of Motion,and Muscle Length Functional ROM, active, active-assisted, and passive range ROM, muscle length, and

soft tissue flexibility and extensibility using standard methods

MUSCLE PERFORMANCE Specific deficits of muscle strength, power and endurance, and muscle

performance during functional activities, can be measured through: manual muscle testing (MMT), Isokinetic muscle strength testing handheld dynamometry

Maximum voluntary isometric contraction (MVIC) using a strain gauge tensiometer system. This eliminates muscle length and velocity

MVIC is considered the most direct technique for investigating motor unit loss, and has been used extensively for examining muscle strength in individuals with ALS for the past 10 years.

MOTOR FUNCTION Impairments in dexterity, coordination of large movement patterns, as well

as gross and fine motor control may be evident owing to spasticity and muscle weakness.

Hand function and initiation, modification, and control of movement patterns

TONE AND REFLEXES Muscle tone may be examined using the Modified Ashworth Scale. Deep tendon and pathological reflexes should be tested to distinguish

between UMN and LMN involvement.

CRANIAL NERVE INTEGRITY The cranial nerves commonly affected by ALS include V, VII, IX, X, and XII. Cranial nerves should be tested to determine the extent of bulbar

involvement. Screening for oral motor function, phonation, and speech production can be

accomplished through the interview and observation. Referral to a speech-language pathologist is recommended.

SENSATION If the patient complains of sensory symptoms or if sensory involvement is

suspected, sensory testing should be completed.

POSTURAL ALIGNMENT, CONTROL, AND BALANCE Static and dynamic postural alignment and body mechanics during self-care,

functional mobility skills, functional activities, and work conditions and activities

Postural stability, reactive control, anticipatory control, and adaptive postural control should also be determined.

No ALS-specific balance test or measure exists. A variety of balance status measures, originally designed for use with other

patient populations, including: the Tinetti Performance Oriented Mobility Assessment (POMA) The Berg Balance Scale The Timed Up and Go Test (TUG) The Functional Reach Test

GAIT Documentation of gait within a particular time period (e.g., within 15

seconds) or over a certain distance (e.g., 10 feet [3 meters]) has been measured in clinical trials.

Gait stability, safety, and endurance should be examined. Energy expenditure, alignment, fit, practicality, safety, and ease of use of

orthotic and assistive devices should also be examined at regular intervals.

RESPIRATORY FUNCTION Determination of respiratory status and function includes examination of

respiratory symptoms and muscle function, breathing pattern, chest expansion, respiratory sounds, cough effectiveness, and VC or forced vital capacity (FVC) using a handheld spirometer.

Aerobic capacity and cardiovascular–pulmonary endurance may be tested in the early stages of ALS using standardized, modified protocols to evaluate and monitor responses to aerobic conditioning.

INTEGUMENT Skin inspection should be used to examine contact points between the

body and assistive, adaptive, orthotic, protective, and supportive devices, mobility devices, and the sleeping surface

Such inspection is especially important when the patient’s mobility becomes increasingly more dependent.

If present, swelling should also be examined and monitored. Swelling of the distal limb may develop owing to lack of muscle pumping

action in a weakened extremity.

FUNCTIONAL STATUS Functional mobility skills, safety, and energy expenditure are important

considerations The Functional Independence Measure (FIM) has been used to document

functional status in clinical trials. The Schwab and England Activities of Daily Living Scale is an 11-point

global measure of functioning that asks the rater to report activities of daily living (ADL) function from 100% (normal) to 0% (vegetative functions only), and has been used to examine function in individuals with ALS

ENVIRONMENTAL BARRIERS The patient’s home and work environments should be examined for current

and potential barriers, access, and safety.

FATIGUE Fatigue is very common in individuals with ALS. No ALS-specific measures exist; the Fatigue Severity Scale has been used in

clinical trials.

DISEASE-SPECIFIC MEASURES The ALS Functional Rating Scale (ALSFRS) and the revised version, ALSFRS-

R examine the functional status of patients with ALS. The patient is asked to rate his or her function using a scale from 4 (normal function) to 0 (unable to attempt the task).

The ALSFRS-R was expanded to include additional respiratory items, and was found to have internal consistency and construct validity, and to have retained the properties of the original scale.

Other disease-specific scales include the: Appel ALS Scale (AALS), ALS Severity Scale (ALSSS), Norris Scale

QUALITY-OF-LIFE MEASURES The Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-40),

an ALS-specific quality of life measure, contains 40 items that represent five distinct areas of health: mobility (10 items), ADL (10 items), eating and drinking (3 items), communication (7 items), and emotional functioning (10 items)

The questions refer to the patient’s condition during the past 2 weeks and responses are given on a five-point Likert scale.

The ALSAQ-40 measures health status in each domain using a summary score from 0 (best health status) to 100 (worst health status).

PHYSICAL THERAPYINTERVENTIONS Restorative intervention

directed toward remediating or improving impairments and activity limitations. Compensatory intervention

directed toward modifying activities, tasks, or the environment to minimize activity limitations and participation restrictions.

Preventative intervention is directed toward minimizing potential impairments such as loss of ROM, aerobic

capacity, or strength, preventing pneumonia or atelectasis, and activity limitations.

1. CERVICAL MUSCLE WEAKNESS Progressive cervical extensor weakness will cause the head to fall forward,

resulting in overstretching of the posterior musculature and soft tissues. For mild to moderate cervical weakness, a soft foam collar may be worn

during specific activities. Soft collars are comfortable and usually well tolerated.

For moderate to severe weakness, a semirigid or rigid collar is prescribed. Usually

made of padded rigid plastic or leather and provide very firm support.

2. DYSARTHRIA AND DYSPHAGIA In collaboration with the SLP and nutritionist, the physical therapist can

play a role in managing dysarthria and dysphagia by addressing the patient’s head and trunk control and position in sitting

Physical therapist can reinforce the use of strategies for eating and swallowing (e.g., chin tuck), the use of prescribed communication devices, and the need for food consistency modifications.

3. UE MUSCLE WEAKNESS Weakness of the UEs greatly affects the patient’s ability to carry out ADL. Splinting of the wrist or hand may be indicated to prevent contractures or

to improve the patient’s function, such as the ability to grasp.

4. SHOULDER PAIN Individuals with ALS may develop shoulder pain and present with capsular

patterns of restriction caused by several factors: abnormal scapulohumeral rhythm secondary to spasticity or weakness causing imbalance that may lead to impingement; overuse of strong muscles; muscle strain; faulty resting position; glenohumeral subluxation secondary to weakness; or a fall.

Interventions may include modalities, ROM exercises, passive stretching, joint mobilizations, and education about proper joint support and protection.

Recommendations for managing the pain and decreased ROM included a protocol of an intra-articular analgesic and anti-inflammatory cocktail injection, followed by a course of aggressive ROM exercises.

5. RESPIRATORY MUSCLE WEAKNESS Patients and caregivers must be taught how to balance activity and rest and

educated about energy conservation techniques. Patients and caregivers should also be educated about signs and symptoms of

aspiration; positioning to avoid aspiration, such as upper cervical spine flexion during eating; causes and signs of respiratory infection; and strategies for managing oral secretions (use of oral suction device) or choking episodes (Heimlich maneuver).

Specific breathing exercises and positioning to optimize ventilation/perfusion matching may also be incorporated, although their effectiveness in ALS has not been determined.

Airway clearance techniques may be necessary when conditions that cause secretion retention, such as pneumonia or atelectasis, arise.

To compensate for a weakened cough, the patient and caregiver may be instructed in the use of manually assisted coughing techniques

6. LE MUSCLE WEAKNESS AND GAITIMPAIRMENTS Orthoses may be recommended to improve function by offering support to

weakened muscles and the joints they surround, decrease the stress on remaining functioning or compensatory muscles, conserve energy, or minimize local or general muscle fatigue.

Important thing to consider is the weight of the orthosis as individuals with ALS will have energy expenditure issues, and it may be more fatiguing for the patient to ambulate with a heavy orthosis than to ambulate without the impairment being corrected.

The type of ambulatory assistive device prescribed is dependent on the degree of proximal muscle strength or instability; function of the UEs; the pattern, extent, and rate of disease progression; acceptance by the patient; and financial constraints.

Wheeled walkers, are usually recommended. In general, individuals with ALS are rarely prescribed crutches. If crutches are

warranted, Loftstrand (Canadian) crutches are preferred.

7. ACTIVITIES OF DAILY LIVING As the disease progresses and proximal shoulder weakness increases, a

mobile arm support may be incorporated to allow the patient to maintain independence in eating.

In the late stage of ALS when the patient is dependent on the caregiver for eating, a long straw and straw holder may be recommended to assist the caregiver with the activity.

A large variety of adaptive equipment is available to assist individuals with muscle weakness perform everyday tasks.

8. DECREASED MOBILITY Patients with LE weakness may have difficulty with sit-to-stand or car

transfers. Simple interventions includes: placing a firm cushion 2 to 3 in (5 to 7.6 cm) thick under the buttocks in the chair or

elevating the chair by placing the legs in prefabricated blocks Self-powered lifting cushions are relatively inexpensive and portable, but the individual

needs adequate trunk control and balance in order to use the device safely Upholstered reclining chairs with powered seat lifts may also be recommended, but are

more expensive. Transfer boards may be used for transfers once the individual is unable to

stand, either alone if the person has adequate arm strength and good sitting balance, or the caregiver can be instructed in how to assist the patient.

In the early or early-middle stage of ALS a manual wheelchair, preferably lightweight, may be used for traveling long distances as an energy conservation technique.

9. MUSCLE CRAMPS AND SPASTICITY Cold can temporarily decrease spasticity. Physical therapists can perform and instruct caregivers in slow prolonged

stretches and passive ROM exercises to address spasticity. Postural and positioning techniques can be incorporated to decrease

spasticity and splinting may be necessary to prevent contractures.

10. PSYCHOSOCIAL ISSUES The emotional responses of the person experiencing the disease, family

members, and individuals caring for the patient are multifaceted and may fluctuate throughout the stages of the disease.

The physical therapist must be able to recognize the patient’s ability to cope and adapt, and his or her psychological reactions, level of acceptance, and willingness and ability to integrate therapeutic recommendations.

PATIENT AND FAMILY/CAREGIVER EDUCATION Providing accurate, factual information about the disease process and clinical

manifestations, and their significance in terms of management. Give only as much information as the patient, family, and caregivers need; information should be provided in a manner appropriate to their understanding.

Instructing patients, family members, and caregivers regarding interventions that can be carried out independently such as monitoring the effects and side effects of medications, use of assistive devices and adaptive equipment, and preventing secondary complications.

Advising the patient about methods to promote general health. Instruction regarding energy conservation, balancing rest and activity, and relaxation techniques may be beneficial in assisting the patient to cope with the daily constraints of the disease.

Counselling regarding care and life decisions, if the patient asks about these issues. Referring patients to support groups or psychological counselling. Providing information on health and available social and support services