Neuromuscular Disorders

Amyotrophic Lateral Sclerosis

• Amyotrophic Lateral Sclerosis (ALS) or Lou Gehrig Disease

– Neuromuscular disorder characterized by

progressive degeneration of upper and lower

motor neurons leading to loss of skeletal muscle

strength, including the respiratory muscles

– http://www.youtube.com/watch?v=3cmk4cbgTCU

Amyotrophic Lateral Sclerosis

• Etiology

– Heredity – 8 to 10% of cases are familial

– More common in males than females (2:1)

– Most common in ages 40 – 60

– 1 - 2 persons/100,000 in the U.S.

– Prognosis is poor

Amyotrophic Lateral Sclerosis

• Etiology

– Exact etiology unknown

• Genetic mutation present in 10 – 15% of patients

increases the susceptibility of neurons to oxidative

stress

• Possible links to pesticides and other neurotoxic

chemicals

Amyotrophic Lateral Sclerosis

• Etiology

• Susceptibility to glutamate-induced neurotoxicity –

glutamate is the principal excitatory brain

neurotransmitter; decrease in uptake of glutamate may

lead to overstimulation of glutamate receptors leading

to increased intracellular calcium, triggering production

of a proteolytic enzymes causing cell membrane injury

Amyotrophic Lateral Sclerosis

• Pathophysiology

– Progressive death of both upper and lower motor neurons in

the motor cortex of the brain, the brain stem, and the spinal

cord

– Begins usually with weakness of large muscle groups or the

bulbar muscles (those supplied by nerves in the upper spinal

cord, such as those controlling swallowing and speaking)

Amyotrophic Lateral Sclerosis

• Pulmonary Function Findings

– Progressive decrease in FVC

– Decreased MVV

– Increase in RV

– Decrease in NIF

Amyotrophic Lateral Sclerosis

• Pulmonary Function Findings

– Will require ventilatory assistance when criteria are met

• PaCO2 > 45 mmHg

• VC < 20 ml/kg

• NIF < -20mmHg

• VT < 5 ml/kg

Amyotrophic Lateral Sclerosis

• Clinical Findings

– Progressive weakness of distal extremities

– If early involvement of phrenic nerve, then nocturnal hypoventilation followed by acute respiratory failure

– Progressive deterioration of pulmonary function results

– Difficulty in swallowing

– Difficulty in speech

– Prognosis is poor with 80% mortality within five years of diagnosis

ALS diagnosis• No test can provide a definite diagnosis of ALS, although the presence of upper

and lower motor neuron signs in a single limb is strongly suggestive. Instead, the diagnosis of ALS is primarily based on the symptoms and signs the physician observes in the patient and a series of tests to rule out other diseases. Physicians obtain the patient's full medical history and usually conduct a neurologic examination at regular intervals to assess whether symptoms such as muscle weakness, atrophy of muscles, hyperreflexia, and spasticity are getting progressively worse.

• MRI demonstrates increased T2 signal within the posterior part of the internal capsule, consistent with the clinical diagnosis of ALS.

• Because symptoms of ALS can be similar to those of a wide variety of other, more treatable diseases or disorders, appropriate tests must be conducted to exclude the possibility of other conditions. One of these tests is electromyography (EMG), a special recording technique that detects electrical activity in muscles

ALS treatment

• Slowing progression of disease, no cure exist• RT treatment: bronchial hygiene, trachestomy,

continuous mechanical ventilation

Neuromuscular Disorders - Guillain-Barre Syndrome

• is an acute polyneuropathy, a disorder affecting the peripheral nervous system. Ascending paralysis, weakness beginning in the feet and hands and migrating towards the trunk, is the most typical symptom, and some subtypes cause change in sensation or pain as well as dysfunction of the autonomic nervous system. It can cause life-threatening complications, in particular if the breathing muscles are affected or if there is autonomic nervous system involvement. The disease is usually triggered by an infection.

Plasmaphoresis• Plasmapheresis is the removal, treatment,

and return of (components of) blood plasma from blood circulation. It is thus an extracorporeal therapy (a medical procedure which is performed outside the body). The method is also used to collect plasma, to preserve it frozen and to keep it fresh. Finally, the frozen plasma is manufactured into a variety of medications.

GB• Polyneuropathy is a neurological disorder that occurs

when many nerves throughout the body malfunction simultaneously.

• The diagnosis is usually made by nerve conduction studies and with studies of the cerebrospinal fluid. With prompt treatment by intravenous immunoglobulins or plasmapheresis, together with supportive care, the majority will recover completely. Guillain–Barré syndrome is rare, at 1–2 cases per 100,000 people annually, but is the most common cause of acute non-trauma-related paralysis in the world.

Neuromuscular Disorders - Guillain-Barre Syndrome

• Most common peripheral neuropathy causing respiratory

deficiency; characterized by paralysis and hyporeflexia with

or without sensory symptoms

• Affects 1 – 2/100,000

• All ages and genders affected

Guillain-Barre Syndrome

• Etiology

– Believed to be caused by an autoimmune defect that destroys the myelin sheath of the neuron

– Can have had a history of upper respiratory infection or flu-like illness preceding onset of symptoms

– The Epstein-Barr virus may be implicated

Guillain-Barre Syndrome

• Pathophysiology

– Progressive loss of myelin sheath

– Paralysis usually begins in lower extremities with or without dysesthesia (abnormal sensations from damaged nerves)

– Progresses upward over hours or days to arms and facial muscles

– Lower cranial nerves may be affected, leading to drooling, difficulty swallowing, and/or maintaining an open airway

Guillain-Barre Syndrome

• Pathophysiology

– 30% of patients require ventilatory support

– Generally, spontaneously resolves, though sometimes with sequelae

– Mortality range of 3 to 6%.

Guillain-Barre Syndrome

• Clinical Findings

– Ascending symmetrical muscle weakness or paralysis

– Drooling

– Difficulty in speech

– Decreased vital capacity

– Respiratory failure

GB

• RT treatment trach and bronchial hygeine • Mechaincal ventilation• Plasmaphoresis• Protein therapy

Myasthenia gravis

• Myasthenia gravis is a chronic autoimmune neuromuscular disease characterized by varying degrees of weakness of the skeletal (voluntary) muscles of the body. The name myasthenia gravis, which is Latin and Greek in origin, literally means "grave muscle weakness." With current therapies, however, most cases of myasthenia gravis are not as "grave" as the name implies. In fact, most individuals with myasthenia gravis have a normal life expectancy.

• The hallmark of myasthenia gravis is muscle weakness that increases during periods of activity and improves after periods of rest. Certain muscles such as those that control eye and eyelid movement, facial expression, chewing, talking, and swallowing are often, but not always, involved in the disorder. The muscles that control breathing and neck and limb movements may also be affected.

• http://www.youtube.com/watch?v=YtypsBCjuyQ

Neuromuscular Disorders - Myasthenia Gravis

• A chronic autoimmune disorder of the neuromuscular junction

characterized by fatigue and weakness, with improvement

following rest

• Sensory function is not lost

• Loss of strength may be confined to an isolated group of

muscles or as a generalized weakness

• Affects 20,000 – 70,000 people in the U.S. annually

• Peak age of onset: females 15-35 yrs, males 40-70yrs

Neuromuscular Disorders - Myasthenia Gravis

• Etiology

– Thymic tumors are present in 10% of patients

– Antibodies to acetylcholine receptors is seen in 80% of patients

Causes• Myasthenia gravis is caused by a defect in the transmission of nerve

impulses to muscles. It occurs when normal communication between the nerve and muscle is interrupted at the neuromuscular junction—the place where nerve cells connect with the muscles they control. Normally when impulses travel down the nerve, the nerve endings release a neurotransmitter substance called acetylcholine. Acetylcholine travels from the neuromuscular junction and binds to acetylcholine receptors which are activated and generate a muscle contraction.

• In myasthenia gravis, antibodies block, alter, or destroy the receptors for acetylcholine at the neuromuscular junction, which prevents the muscle contraction from occurring. These antibodies are produced by the body's own immune system. Myasthenia gravis is an autoimmune disease because the immune system—which normally protects the body from foreign organisms—mistakenly attacks itself.

Neuromuscular Disorders - Myasthenia Gravis

• Pathophysiology

– Normally acetylcholine is stored in pre-synaptic vesicles. it is released into the synaptic space and binds to the receptor on the post-synaptic membrane, depolarizing the nerve and leading to contraction of the muscle

– Binding of cholinesterase to the acetylcholine receptors blocks the impulse of the nerve, preventing muscle contraction

Neuromuscular Disorders - Myasthenia Gravis

• Clinical Findings

– Intermittent weakness of voluntary muscles

– Respiratory symptoms dependent upon severity of disease

• Upper airway obstruction due to muscle weakness

• Dyspnea on exertion

• Ventilatory failure in severe cases

• Decrease in VC, TLC, IRC, and ERV

• Most deaths occur secondary to pulmonary infections

Symptoms• Although myasthenia gravis may affect any voluntary muscle, muscles that control

eye and eyelid movement, facial expression, and swallowing are most frequently affected. The onset of the disorder may be sudden and symptoms often are not immediately recognized as myasthenia gravis.

• In most cases, the first noticeable symptom is weakness of the eye muscles. In others, difficulty in swallowing and slurred speech may be the first signs. The degree of muscle weakness involved in myasthenia gravis varies greatly among individuals, ranging from a localized form limited to eye muscles (ocular myasthenia), to a severe or generalized form in which many muscles—sometimes including those that control breathing—are affected. Symptoms, which vary in type and severity, may include a drooping of one or both eyelids (ptosis), blurred or double vision (diplopia) due to weakness of the muscles that control eye movements, unstable or waddling gait, a change in facial expression, difficulty in swallowing, shortness of breath, impaired speech (dysarthria), and weakness is the arms, hands, fingers, legs, and neck.

Diagnosis

• Because weakness is a common symptom of many other disorders, the diagnosis of myasthenia gravis is often missed or delayed (sometimes up to two years) in people who experience mild weakness or in those individuals whose weakness is restricted to only a few muscles.

• The first steps of diagnosing myasthenia gravis include a review of the individual's medical history, and physical and neurological examinations. The physician looks for impairment of eye movements or muscle weakness without any changes in the individual's ability to feel things. If the doctor suspects myasthenia gravis, several tests are available to confirm the diagnosis.

• A special blood test can detect the presence of immune molecules or acetylcholine receptor antibodies. Most patients with myasthenia gravis have abnormally elevated levels of these antibodies. Recently, a second antibody—called the anti-MuSK antibody—has been found in about 30 to 40 percent of individuals with myasthenia gravis who do not have acetylcholine receptor antibodies. This antibody can also be tested for in the blood. However, neither of these antibodies is present in some individuals with myasthenia gravis, most often in those with ocular myasthenia gravis.

Diagnosis• The edrophonium test uses intravenous administration of edrophonium chloride to

very briefly relieve weakness in people with myasthenia gravis. The drug blocks the degradation (breakdown) of acetylcholine and temporarily increases the levels of acetylcholine at the neuromuscular junction. Other methods to confirm the diagnosis include a version of nerve conduction study which tests for specific muscle "fatigue" by repetitive nerve stimulation. This test records weakening muscle responses when the nerves are repetitively stimulated by small pulses of electricity. Repetitive stimulation of a nerve during a nerve conduction study may demonstrate gradual decreases of the muscle action potential due to impaired nerve-to-muscle transmission.

• Single fiber electromyography (EMG) can also detect impaired nerve-to-muscle transmission. EMG measures the electrical potential of muscle cells when single muscle fibers are stimulated by electrical impulses. Muscle fibers in myasthenia gravis, as well as other neuromuscular disorders, do not respond as well to repeated electrical stimulation compared to muscles from normal individuals.

Tensilon Test

• http://www.youtube.com/watch?v=k7YX9kuWrxA