118 NEUROMUSCULAR DISEASE / Upper Motor Neuron Diseases

walk at 1 year. Thus, of the two modalities, IVIg is

now considered the treatment of first choice due to
its efficacy, ease of administration, and low incidence
of side effects. Although plasma exchange clearly removes presumed blood-borne factors involved in the
pathogenesis of the disease, the mechanisms of action
of IVIg administration are less certain, but may include binding of Fc receptors, increased clearance of
immunoglobulins, and/or stimulation of remyelination. Unlike CIDP, steroids have not been shown to
be helpful in treatment of GBS.

Prognosis

Overall, the prognosis for recovery of patients with

GBS is favorable with the majority of patients (65%)
experiencing little or no disability. Of the remaining
patients, less than 5% will die in the acute stages of
the illness, usually from cardiac arrhythmias or pulmonary embolism while those who do survive will be
left with persistent deficits. The percentage of patients
experiencing chronic impairments has not been significantly altered by the introduction of IVIg or
plasma exchange, which both shorten time to recovery but not the proportion of patients attaining a good
recovery. Factors associated with a poor outcome include advanced age, rapid progression of symptoms,
need for ventilatory support, and severely diminished
muscle action potential amplitude on electromyography. Also, a more severe course and poorer prognosis are associated with the AMSAN subtype.
See also: Autoantibodies. Myoglobin. Neurophysiology: Neurons and Neuromuscular Transmission.

Further Reading
Asbury AK (2005) Approach to the patient with peripheral neuropathy. In: Kasper DL, Braunwald E, Fauci AS, et al. (eds.)
Harrisons Principles of Internal Medicine, 16th edn., pp. 2500
2510. New York: McGraw-Hill.
Asbury AK and Thomas PK (eds.) (1995) Peripheral Nerve Disorders II. Oxford: ButterworthHeinemann.
Bennett CL and Chance PF (2001) Molecular pathogenesis of hereditary motor, sensory and autonomic neuropathies. Current
Opinion in Neurology 14: 621627.
Chalela JA (2001) Pearls and pitfalls in the intensive care management of GuillainBarre syndrome. Seminars in Neurology
21: 399405.
Donofrio PD (2003) Immunotherapy of idiopathic inflammatory
neuropathies. Muscle and Nerve 28: 273292.
Kieseier BC and Hartung HP (2003) Therapeutic strategies in the
GuillainBarre syndrome. Seminars in Neurology 23: 159168.
Kieseier BC, Kiefer R, Gold R, Hemmer B, Willison HJ, and
Hartung HP (2004) Advances in understanding and treatment of
immune-mediated disorders of the peripheral nervous system.
Muscle & Nerve 30: 131156.

Paparounas K (2004) Anti-GQ1b ganglioside antibody in peripheral nervous system disorders: pathophysiologic role and clinical
relevance. Archives of Neurology 61: 10131016.
Rabinstein AA and Wijdicks EFM (2003) Warning signs of imminent respiratory failure in neurological patients. Seminars in
Neurology 23: 97104.
Victor M and Ropper AH (2001) Adams and Victors Principles of
Neurology, 7th edn. New York: McGraw-Hill.
Willison HJ and Yuki N (2002) Peripheral neuropathies and antiglycolipid antibodies. Brain 125: 25912625.
Winer JB (2001) GuillainBarre syndrome. Molecular Pathology
54: 381385.
Yuki N, Susuki K, Koga M, et al. (2004) Carbohydrate mimicry
between human ganglioside GM1 and Campylobacter jejuni
lipooligosaccharide causes GuillainBarre syndrome. Proceedings of the National Academy of Sciences 101: 1140411409.

Upper Motor Neuron Diseases

E Servera, J Marn, and J Sancho, Valencia
University, Valencia, Spain
& 2006 Elsevier Ltd. All rights reserved.

Abstract
Upper motor neuron diseases are a heterogeneous group of disorders in which a degeneration of motor neurons of the cortex
and tronchoencephalic motor nucleus occurs. Clinically, these
disorders are characterized by weakness, motor clumsiness,
spasticity, and hyperreflexia. The major cause of morbidity and
mortality in these disorders is due to the involvement and dysfunction of respiratory muscles. Amyotrophic lateral sclerosis is
the most characteristic example of motor neuron disease in
which both the upper and lower motor neuron are involved;
when only the upper motor neuron is affected, it is called primary lateral sclerosis. Other diseases with upper motor neuron
dysfunction are spinal cord injury, multiple sclerosis, and stroke.
In Parkinsons disease, the upper motor neuron is indirectly affected. Respiratory muscle involvement entails alveolar hypoventilation, decreased cough capacity, and the risk of aspiration
due to bulbar dysfunction. The use of respiratory muscle aids,
noninvasive mechanical ventilation, and manually and mechanically assisted cough can improve survival, quality of life, and
avoid hospitalization when respiratory muscles are involved.
Moreover, during acute respiratory episodes, the combined use
of inspiratory and expiratory muscle aids can avoid endotracheal intubation; this means continuous noninvasive ventilation
with adequate respiratory secretions management if different
interfaces are correctly used.

Introduction
Upper motor neuron diseases are a heterogeneous
group of disorders in which a degeneration of motor
neurons of the cortex and tronchoencephalic motor
nucleus occurs. Clinically, these disorders are characterized by muscular weakness, particularly of the extensor musculature of the upper limb and of the flexor
musculature of the lower limb, motor clumsiness,

NEUROMUSCULAR DISEASE / Upper Motor Neuron Diseases 119

spasticity, and hyperreflexia; they may be associated

with clonus and pathological reflexes (e.g., Babinski
sign). When these disorders affect the corticobulbar
way bilaterally, the most characteristic symptom is
emotional lability. In these disorders, dysfunction of
the respiratory muscles (the inspiratory and expiratory muscles) and the upper airway muscles accounts
for the major cause of morbidity and mortality.

Etiology
Amyotrophic lateral sclerosis (ALS) is the most characteristic example of motor neuron disease. In ALS,
both upper and lower motor neuron diseases are involved. When the dysfunction is selective of the
upper motor neuron, it is called primary lateral sclerosis (PLS); this is a sporadic disease with a lower
incidence than ALS.
Spinal cord injury (SCI) is another important cause
of upper motor neuron affection and is the main
cause of chronic hypoventilation failure in young
people. Other disorders that can affect upper motor
neurons are multiple sclerosis (MS) and strokes in
which corticospinal and bulbospinal tracts are involved. Another serious disorder in which the upper
motor neuron is indirectly affected is Parkinsons
disease (PD). In PD, the excessive inhibition of the
talamocortical pathway produces a diminution of the
stimulus of motor and premotor cortical areas.

Pathology and Physiopathology

Primary Lateral Sclerosis and Amyotrophic Lateral
Sclerosis

In PLS, there is a selective degeneration of the Betz

motor neuron in lamina V of the cortex and a degeneration of corticospinal tracts. In ALS, the abnormality spreads to the anterior horn of the medulla
and bulbar motor centers. In both diseases, the respiratory problems are related to weakness of respiratory muscles; respiratory complications are more
severe in ALS than in PLS because in the former both
upper and lower motor neurons are affected.
Inspiratory muscle weakness produces hypoventilation. In the early stages of the disease, hypoventilation is present only in the rapid eye movement
phase of sleep, but worsening gas exchange abnormalities contribute to frequent arousals, reducing
sleeping time and sleeping efficiency, and result in
daytime symptoms of sleep deprivation. As the disease worsens, hypoventilation extends to total sleeping time and then to the period during which
the patient is awake. Moreover, due to inspiratory
muscle weakness, the elastic load of the chest wall

gradually increases, which is related to the inability

to achieve a full inhalation and contributes to increase the effort required for breathing. This loss of
the capacity to perform maximum inflations produces structural changes of the lung and the thoracic
cage. Deformities associated with the disease, such as
kyphoscoliosis, also contribute to chest wall stiffness
and increase the effort required for breathing.
Cough capacity decreases due to inspiratory muscle weakness that inhibits a deep inspiration at the
beginning of the cough effort, expiratory muscle
weakness that inhibits an energetic contraction, unstable upper airway dysfunction, and inability to
close the glottis (Figure 1).
Involvement of the bulbar muscles produces inadequate respiratory protection and a risk of aspiration.
Spinal Cord Injury

In SCI, respiratory muscle impairment depends on the

level of the medullary lesion. High cervical cord lesions (C1C2) and middle cervical cord lesions (C3
C5) cause paralysis of the diaphragm, intercostal,
scalene, and abdominal muscles. These lesions result
in severe hypoventilation, reduced ability to clear secretions (due to the loss of the ability to hyperinflate
the lungs and an ineffective cough), and atelectasis.
Low cervical lesions (C6C8) and upper thoracic
cord lesions denervate the intercostal and abdominal
muscles but leave the diaphragm and neck muscles
intact. Although phrenic nerves remain completely, or
at least partially, intact at these levels, the intercostal
activity necessary to stabilize the ribcage is lost, resulting in a compromised ventilation. Moreover,
cough capacity is decreased due to weakness of expiratory muscles. Prognosis improves as lesions move
downwards. When the lesion is lower in the spinal
cord, the expiratory muscles, and thus cough capacity,
are often more affected than the inspiratory muscles.
Multiple Sclerosis

The pathological hallmark of MS is the presence of

multiple areas of nerve demyelination, which may
vary in size and localization. When MS affects
the motor pathway, it causes muscle weakness and
spasticity. Respiratory failure is a late manifestation
of advanced disease, although acute respiratory failure can occur due to demyelination lesions of the
cervical spinal cord or the respiratory centers of the
medulla. Patients usually develop the insidious onset
of chronic respiratory failure due to weakness of
the respiratory muscles, especially the expiratory
muscles. This weakness is produced due to demyelination, inactivity, and the effects of treatment with
steroids. The respiratory dysfunction in MS may be

120 NEUROMUSCULAR DISEASE / Upper Motor Neuron Diseases

Malnutrition
Fatigue

Weakness
Bulbar dysfunction

Thoracic cage
deformities

Decreased cough capacity

Decreased
parenchima

Alveolar hy
hypoventilation

Loss
of
compliance
Bronchial
obstruction

Sleep disturbances

Figure 1 Factors determining respiratory failure in motor neuron disease. Figure reprinted from Archivos de Bronconeumologa 2003;
39(9): 418427. Permission granted by Ediciones Doyma S.L.
Table 1 Patterns of respiratory involvement in multiple sclerosis depending on demyelinating plaque localization

Table 2 Indications for noninvasive mechanical ventilation in

neuromuscular diseases

Abnormality

Anatomic localization

Paralysis of voluntary
breathing
Paralysis of automatic
breathing

Bilateral corticospinal tracts,

brainstem, or cervical cord
Dorsomedial medulla, nucleus
ambiguus, and medial
lemnisc
Upper cervical cord
Lower brainstem
Lower brainstem
Tegmentum of medulla
Medulla in region of nucleus
tractus solitarius and floor of
fourth ventricle

Symptoms: e.g., fatigue, dyspnea, and morning headache

Physiologic criteria (one of the following):
PaCO2445 mmHg
Nocturnal oximetry demonstrating oxygen saturation o88% for
5 consecutive min
For progressive neuromuscular disease, maximal inspiratory
pressures o60 cmH2O or FVC o50% predicted

Diaphragmatic paralysis
Apneustic breathing preserved
Paroxysmal hyperventilation
Obstructive sleep apnea
Neurogenic pulmonary edema

caused by respiratory muscle weakness (hypoventilation and ineffective cough), bulbar dysfunction,
obstructive sleep apnea, abnormalities in respiratory
control, and paradoxical hyperventilation (Table 1).
Stroke

The two most important motor pathways for respiratory control are the corticospinal tracts and the bulbospinal tracts. The former is responsible for voluntary
breathing and the latter for automatic breathing.
Hemispheric ischemic strokes influence respiratory
function to only a modest degree; reduced chest wall
movement and diaphragmatic excursion contralateral to the stroke have been reported. Therefore,
vascular accidents of the cortex do not cause significant diaphragmatic impairment; however, in capsular stroke with extensive damage of the pyramidal
respiratory fibers, the voluntary control of breathing

Source: American College of Chest Physicians; Goldberg AC,

Legger P, Hill NS, et al. (1999). Clinical indications for noninvasive positive pressure ventilation in chronic respiratory failure due
to restrictive lung disease, COPD and nocturnal hypoventilation.
A consensus conference report. Chest 116: 521534.

can be impaired with inability to change breathing

voluntarily in the presence of preserved autonomic
respiratory function.
Damage to the bulbospinal tract eliminates autonomic control of breathing but leaves voluntary
control intact (Ondines syndrome). In this situation,
severe hypoventilation is produced during resting.
Lateral medullary strokes can cause hypoventilation,
apneustic breathing, ataxic breathing, and hyperventilation.
Parkinsons Disease

In PD, there is a degeneration of the compact part of

the nigra substance resulting in a degradation of the
dopaminergic nigrostriatal pathway that produces a
dopaminergic denervation of the striatum nucleus.
This results in an increase in acid g-aminobutiric inhibitory activity due to an increase in the activity of
inner palidus nucleus neurons. The dysfunction of

NEUROMUSCULAR DISEASE / Upper Motor Neuron Diseases 121

Figure 2 (a) Noninvasive mechanical ventilation via mouthpiece and (b) mechanical aids to coughing with the Emerson InExsufflatorTM for a hospitalized patient with ALS and a pulmonary infection. Reproduced from Servera E, Sancho J, Gomez-Merino E,
et al. (2003) Noninvasive management of an acute chest infection for a patient with ALS. Journal of Neurological Science 209: 1113,
with permission from Elsevier.

respiratory muscles results in alveolar hypoventilation, a decrease in cough effectiveness, and upper
airway dysfunction.
Inspiratory muscle strength decreases with the
progression of the disease due to impaired neural
drive of the muscles. Inspiratory muscle endurance
decreases in early PD due to impaired activation of
the motor cortex for the respiratory muscles, a shift
in the fibers fatigue-resistant type I and IIa to the
more fatigable type IIb, mitochondrial abnormalities,
and lack of coordination between inspiratory and

expiratory muscles. Expiratory muscle weakness

produces a decrease in cough capacity. Upper airway dysfunction can produce occasional sudden and
intermittent airway closure.

Clinical Features
Respiratory symptoms in disorders that damage
upper motor neurons are related to alveolar hypoventilation, impaired cough capacity, and upper airway dysfunction. Dyspnea, orthopnea, restless sleep,

122 NEUROMUSCULAR DISEASE / Upper Motor Neuron Diseases

nightmares, early morning headaches, and daytime

hypersomnolence are related to alveolar hypoventilation. When respiratory impairment progresses, pulmonary hypertension with cardiac failure (cor
pulmonale) can be present with increased orthopnea
and dyspnea and lower extremity edema.
Impaired cough capacity produces retained respiratory secretions that increase airway resistance and
alter the respiratory mechanics. Moreover, these retained secretions can produce atelectasis and there is
a high risk of superinfection and pneumonia. With
the involvement of the upper airway, speaking and
swallowing are affected and the risk of aspiration is
greater, contributing to the impairment of cough
effectiveness. This results in inadequate nutrition,
weight loss, drooling, choking episodes and recurrent
pulmonary infections due to aspiration episodes. In
PD, the upper airway muscle dysfunction with closure can produce stridor, sudden death by apnea, and
obstructive sleep apnea.
During an acute respiratory episode such as a banal chest cold, respiratory muscle weakness is increased, impairing hypoventilation and cough
capacity. In this way, these episodes can lead to
acute respiratory failure.

In order to view the drop in pulseoxihemoglobin

saturation during sleep, a nocturnal pulse oximetry
must be performed. A polysomnographic record
is appropriate when obstructive sleep apnea is suspected. To study swallowing disorders related to
bulbar dysfunction, videofluoroscopy is performed.

Management of Respiratory Problems

Management of respiratory problems in motor neuron disorders must be centered on three key points:
alveolar hypoventilation, respiratory secretions, and
swallowing disorders.
Alveolar Hypoventilation

Noninvasive mechanical ventilation (NIV) has been

used successfully to treat hypoventilation in neuromuscular patients (Table 2). NIV provides mechanical
ventilation without access to the trachea and relieves
dyspnea, and it also improves survival, cognitive
function, and quality of life. The most common
method of NIV is positive pressure ventilation with a
pressure or volume ventilator. Initially, NIV is administered nocturnally and as needed during the daytime. A combination of different interfaces can be
used to maintain NIV continuously throughout the

Lung Function Tests

Arterial blood gases show hypoxemia and, with the

progression of the disease and impairment of hypoventilation, hypoxemia and hypercapnia. Spirometry
and lung volumes show a restrictive pattern with decreased vital capacity and forced expiratory volume in
1 s and total lung capacity. Vital capacity has been
shown to be a good prognostic factor; however, maximum insufflation capacity (MIC) is proposed to be a
more useful prognostic measurement. MIC is the maximum volume of air that can be stacked in lungs with
the glottis closed. MIC lower than 1500 ml indicates
great difficulty in attaining an effective cough. Respiratory muscle force tests, such as static maximum
pressures at the mouth (PImax and PEmax) and transdiaphragmatic pressure (Tdi), are infrequently used.
Measurement of flows generated during a coughing effort has been proposed as an effective and useful parameter of cough capacity because peak flows
generated during the expulsive phase of cough (PCF)
are responsible for airway secretion removal. PCF
lower than 2.7 l s 1 probably results in an ineffective
cough, and PCF lower than 4.5 l s 1 in a stable patient indicates a high risk that the cough will become
ineffective during an acute chest episode. Another
test for measuring cough capacity is gastric pressure
during a cough effort (PgaCo); however, this causes
discomfort to the patient.

Figure 3 Complete atelectasis due to aspiration solved after

6 h with intensive use of mechanical in-exsufflation.

NEUROMUSCULAR DISEASE / Upper Motor Neuron Diseases 123

day (mouthpiece during day and nasal, oronasal, or

lipseal during sleep) (Figure 2). In patients with severe
bulbar involvement, NIV is often ineffective and
poorly tolerated. When NIV is ineffective or poorly
tolerated or refused by the patient, a tracheostomy is
mandatory to initiate invasive mechanical ventilation.
During acute episodes, continuous NIV can avoid
endotracheal intubation with adequate respiratory
secretions management and if different interfaces are
correctly used. In patients with severe bulbar dysfunction, NIV tends to fail in acute episodes.
Respiratory Secretions

When the patient is unable to perform an effective

cough effort (PCFo2:70 l s 1 ), there is a high risk of
major complications, such as atelectasis, superinfection
of retained secretion, pneumonia, increased difficulty
in breathing with acute respiratory failure, and failure
of NIV. Several approaches are available to increase
cough capacity in neuromuscular patients; however,

manually and mechanically assisted techniques have

proved effective in removing respiratory secretions.
In manually assisted cough, a thoracic and/or abdominal thrust is applied in synchrony with the patients cough effort, leading to enhanced expiratory
flow rates. The effectiveness of manually assisted
cough is greater if the patients lungs are insufflated before the highest volume that can be retained
with a closed glottis with a manual resuscitator or a
portable volume-limited ventilator. This technique
requires patient cooperation and good bulbar function to close the glottis.
When manually assisted cough cannot generate an
effective cough effort, mechanically assisted cough
TM
with Cough Assist is the best alternative (Figures 3
TM
and 4). Cough Assist delivers a deep insufflation
using positive pressure followed immediately by an
equal negative pressure that produces a forced exsufflation (MI-E). If a thoracic and/or abdominal
thrust is applied during the exsufflation cycle, the
PCF generated will be greater. MI-E does not require

12
4

12
1

(b)

(a)
12
8

12
(c)

PCFMI-E
PCFMIC
PCF

6
1

7
(d)

Figure 4 Flowvolume loops during coughing show unassisted and assisted peak cough flow (PCF). (a) No respiratory muscle
involvement with effective unassisted PCF. (b) Ineffective unassisted PCF. It is effective, however, when manual and mechanical aids
are applied: Both have the same values. (c) Ineffective unassisted PCF. Mechanically assisted PCF are clearly greater than manually
assisted ones, but both are effective. (d) Severe bulbar dysfunction with ineffective assisted PCF.

124 NEUROMUSCULAR DISEASE / Myasthenia Gravis and Other Diseases

the patients collaboration; in severe bulbar dysfunction, however, MI-E can be ineffective due to a dynamic upper airway collapse during the exsufflation
cycle (Figure 4(d)).
When assisted coughing techniques cannot remove
airway secretions, a tracheostomy must be performed in order to gain direct access to them. MI-E
can be applied through a tracheostomy to avoid
complications related to aspiration with a catheter.
Moreover, aspiration with a conventional catheter
through a tracheostomy tube fails to enter the main
left stem bronchus in 90% of cases, but MI-E, when
it is applied through the tracheostomy tubes, is able
to clear the central, medium, and small bronchi of
both left and right airways.
Swallowing Disorders

When bulbar dysfunction produces aspiration, a percutaneous endoscopic gastrostomy must be performed in order to provide adequate nutrition and
avoid the risk of respiratory problems related to an
incompetent glottis.
See also: Arterial Blood Gases. Carbon Dioxide. Neuromuscular Disease: Inherited Myopathies; Lower
Motor Neuron Diseases; Acquired Myopathies; Peripheral Nerves; Upper Motor Neuron Diseases; Myasthenia
Gravis and Other Diseases of the Neuromuscular Junction. Neurophysiology: Neurons and Neuromuscular
Transmission. Respiratory Muscles, Chest Wall,
Diaphragm, and Other. Signs of Respiratory Disease: Breathing Patterns. Sleep Disorders: Central
Apnea (Ondines Curse); Hypoventilation. Ventilation,
Mechanical: Negative Pressure Ventilation; Noninvasive
Ventilation; Positive Pressure Ventilation.

Further Reading
Bach JR (1994) Update and perspectives on noninvasive respiratory muscle aids. Part 1: The inspiratory aids. Chest 105(4):
12301240.
Bach JR (1994) Update and perspective on noninvasive respiratory
muscle aids. Part 2: The expiratory aids. Chest 105(5):
15381544.
Bach JR (2004) Noninvasive respiratory muscle aids: intervention
goals and mechanisms of action. In: Bach JR (ed.) Management
of Patients with Neuromuscular Disease, pp. 211270. Philadelphia: Hanley & Belfus.
Brown LK (1994) Respiratory dysfunction in Parkinsons disease.
Clinical Chest Medicine 15: 715722.
Goldberg AC, Legger P, Hill NS, et al. (1999) Clinical indications
for noninvasive positive pressure ventilation in chronic respiratory failure due to restrictive lung disease, COPD and nocturnal
hypoventilation. A consensus conference report. Chest 116:
521534.
Gosselink R, Kovacs L, and Decramer M (1999) Respiratory muscle involvement in multiple sclerosis. European Respiratory
Journal 13: 449454.

Hadjikoutis S and Wiles CM (2001) Respiratory complications

related to bulbar dysfunction in motor neuron disease. Acta
Neurologica Scandinavia 103: 207213.
Laghi F and Tobin MJ (2003) Disorders of the respiratory muscles.
American Journal of Respiratory and Critical Care Medicine
168: 1048.
Make BJ, Hill NS, Goldberg AL, et al. (1998) Mechanical ventilation beyond the intensive care unit. Report of a consensus
conference of the American College of Chest Physicians. Chest
113(5 supplement): 289S344S.
Mausel JK and Norman JR (1990) Respiratory complications and
management of spinal cord injuries. Chest 97: 14461452.
Miller RG, Rosenberg JA, Gelinas DF, et al. (1999) Practice
parameter: the care of the patient with amyotrophic lateral
sclerosis (an evidence based review): report of the quality standards subcommittee of the American Academy of Neurology:
ALS Practice Parameters Task Force. Neurology 52: 13111323.
Perrin C, Uterborn J, Dambrosio C, et al. (2004) Pulmonary complications of chronic neuromuscular diseases and their management. Muscle & Nerve 29: 527.
Servera E, Sancho J, and Zafra MJ (2003) Cough and neuromuscular diseases. Noninvasive airway secretions management.
Archivos de Bronconeumologa 39: 418427.
Servera E, Sancho J, Gomez-Merino E, et al. (2003) Noninvansive
management of an acute chest infection for a patient with ALS.
Journal of Neurological Science 209: 1113.
Vingerhoest F and Bogousslavsk J (1994) Respiratory dysfunction
in stroke. Clinical Chest Medicine 15: 729737.
Winslow C and Rozovsky J (2003) Effect of spinal cord injury on
the respiratory system. American Journal of Physical Medicine
and Rehabilitation 82: 803814.

Myasthenia Gravis and Other

Diseases of the Neuromuscular
Junction
H M DeLisser, University of Pennsylvania School of
Medicine, Philadelphia, PA, USA
& 2006 Elsevier Ltd. All rights reserved.

Abstract
Processes that target the neuromuscular junction may result
in clinical syndromes characterized by muscle weakness. Among
these disorders, the most common is myasthenia gravis (MG),
an acquired, autoimmune disease in which the acetylcholine
receptor is targeted in the majority of affected patients. The
underlying cause of MG, however, remains unknown. Fluctuating muscle weakness is the hallmark feature of MG. Ocular,
facial, oropharyngeal, axial and limb muscles may be differentially involved, leading to a variety of clinical presentations.
Ventialtory support may be required for up to 20% of patients
who develop respiratory insufficiency due to inspiratory muscle
weakness and/or inability to maintain a patent upper airway.
MG must be distinguished from a number of other disorders
including, the LambertEaton myasthenic syndrome, botulism,
and non-immune genetic congenital myasthenic syndromes.
In addition to several general measures, a number of treatments
are available for MG with differing onsets, peaks and durations
of effects.