Myasthenia gravis

• associated with serum IgG antibodies to acetylcholine receptors in the postsynaptic membrane of the neuromuscular junction. Classically, the muscles are easily fatigued.
• There are associations between myasthenia gravis and
  • thymic hyperplasia – 75% of cases
  • thymoma -15% of cases
• females are affected more often in the under 40 year old age group whereas men predominate in cases which develop in older age groups

Incidence

• non-thymoma cases have a peak incidence at 10-30 years and again, at 60-70 years of age;
• associated with thymoma have a peak incidence at 40-50 years of age

prognosis

• The prognosis in myasthenia gravis is very variable. The use of immunosuppressive drugs has steadily improved outcome in recent years.
• Remission or substantial improvement can be expected in 80% of patients. For those with associated thymoma, the 5 year survival is approximately 30 %.

associated immune disorders

• rheumatoid arthritis
• hyperthyroidism
• hypothyroidism
• polymyositis
• systemic lupus erythematosus
• pernicious anaemia
• pemphigus
• Sjogren’s syndrome

Triggers for Myasthenia Gravis and Myasthenia crisis

• Infection
  • Infection triggering myasthenia is common
  • Consider empiric antibiotics
• Electrolyte abnormalities
• Trauma
• Surgery
• Thyroid disease
• Pregnancy
• Drugs: penicillamine, lithium, aminoglycosides, and phenytoin

Clinical

• external ocular muscles
  • affected in over 90% of cases, and are the muscles first affected in 65% of cases
  • diplopia or ptosis, often asymmetrical, are typical
  • ocular myasthenia describes myasthenia confined to the eyes.
• Limb weakness
  • increased by exercise – easily fatigued; 
  • may complain of difficulty in raising their arms above their head, or of brushing their hair; arm flexion is often more strong than extension
  • Proximal Muscle Weakness are typically more affected than distal Muscles
  • Distal wrist extensors and foot dorsiflexors are most often involved
  • tone is normal and reflexes are often brisk
  • muscle wasting may occur in chronic disease.
• bulbar – loss of facial expression
  • unable to smile and may seem to snarl; inability to whistle;
  • dysarthria – often, slurring speech
  • difficulty in chewing and swallowing
  • weakness of the neck muscles may force the patient to sit with their jaw propped by a hand
• Bedside ice pack test helpful in patient with ptosis — not helpful to assess 

EXAMINATION

• swallow
• functional capacity
• effectiveness of cough
• jaw closure often weak and cannot be maintained against resistance
• airway assessment
• focused RESP and CVS examination
• evidence of proximal myopathy and strength

DIFFERENTIALS

Associated symptoms presented with muscle weakness

Disease	Symptoms
Dermatomyositis	Skin rash, e.g., upper eyelids (heliotrope rash), erythema of the knuckles (Gottron rash), anterior chest (v sign), or back (shawl sign) Weight loss, anorexia, bleeding tendency, abnormal vaginal bleeding, chronic cough (malignancy).
Inclusion body myositis	Frequent falls, dysphagia
Myasthenia gravis	Squint, dysphagia Compression symptoms of thymoma (cough, SOB)
Lambert-Eaton syndrome	Autonomic symptoms, e.g., dry mouth, impotence History of lung cancer
Mixed connective tissue disease and overlap syndrome	Other connective tissue disease’s symptoms; arthritis, skin rash
Rhabdomyolysis	History of trauma, seizure, dark urine

Common signs with specific myopathies

	Head and neck	Hands	Chest and abdomen
Dermatomyositis	–  Upper eyelids (heliotrope ash) –  Lymphadenopathy or any mass (malignancy)	–  Erythema of the knuckles (Gottron rash) –  Clubbing (lung cancer)	–  Erythema of anterior chest (v sign), or back (shawl sign) –  Axillary lymphadenopathy, breast lump or abdominal mass
Overlap syndrome and MCTD	–  Fish mouth, pinched nose (in scleroderma) –  Malar rash, discoid lupus (in SLE)	Sclerodactyly, Raynaud’s (in scleroderma). Arthritis (in SLE)	Signs of lung fibrosis and serositis
Lambert-Eaton syndrome	–  Dry mouth and skin (autonomic neuropathy)	–  Clubbing (lung cancer)	–  Chest finding if there are complications for lung cancer e.g. pleural effusion, lymphadenopathy
Myasthenia gravis	SVC syndrome (thymoma)	–	–

Correlation between findings and suggestive diagnoses of weakness

Findings	Suggestive diagnosis
Acute focal weakness decreased muscle power, hyperreflexia, hypertonia, positive Babinski sign, ± sensory deficit, ± loss of bladder/bowel control	Stroke, or spinal cord injury
Diffuse or localized peripheral weakness, muscle atrophy, fasciculations, hypotonia, loss of reflexes	Lower motor neuron disease
Asymmetrical distal weakness, muscle atrophy, hypotonia, loss of reflexes, sensory deficit “Glove and stocking” distribution	Peripheral neuropathy Diabetic neuropathy
Acute onset of combined weakness (ascending), fasciculations, loss of deep tendon reflexes, sensory deficit	Guillain-Barre syndrome
Facial weakness, fatigability, ptosis	Myasthenia gravis
Symmetrical weakness of proximal muscles, muscle wasting, with some types, muscle tenderness, normal reflexes, no sensory level	Proximal myopathies
Symmetrical distal weakness, with myotonic contractions	Myotonic dystrophy
Cardiomyopathy, and proximal muscle weakness	Inflammatory myopathies, hereditary myopathies
Mental status changes with proximal weakness	Myopathy-inducing electrolyte disorder (calcium or magnesium)

Investigations

• Acetylcholine receptor antibody – will be present in 85%
• Consider
  • CT chest – for thymoma
  • Brain MRI – exclude other intracranial abnormality with a neurological presentation
  • Thyroid function test
  • Electrophysiological studies – helpful if seronegative
  • Lumbar puncture

 Complications

1. Aspiration Pneumonia
2. Cholinergic crisis (excessive Acetylcholinesterase Inhibitor)
3. Myasthenia Crisis (30% of cases)

treatment

• oral anticholinesterase medication
  • pyridostigmine
  • neostigmine
• thymectomy
  • required if there is a thymoma because of the risk of local infiltration
• immunosuppression with corticosteroids +/- cytotoxic agents
• intravenous immunogobulin (IVIg) or plasmapheresis 
• rituximab

Advice for Patients

1. Understanding the Disease:
   • Knowledge is Power: Understanding MG helps in managing the disease better and recognizing when to seek medical intervention.
   • Stay Informed: Keep up with new research and treatment options through reputable sources and medical consultations.
2. Energy Conservation:
   • Plan and Prioritize: Organize daily tasks to distribute energy throughout the day.
   • Rest Periods: Incorporate regular rest periods between activities to avoid fatigue.
3. Diet and Nutrition:
   • High-Calorie, Nutritious Foods: Focus on nutrient-dense foods that are easy to swallow.
4. Exercise and Physical Therapy:
   • Moderation is Key: Engage in regular, moderate exercise tailored to your capabilities.
   • Professional Guidance: Work with physical and occupational therapists to develop a safe exercise regimen.
5. Speech and Swallowing:
   • Therapeutic Techniques: Follow prescribed exercises from speech and swallowing therapists to improve function.
   • Safe Eating Practices: Use techniques to reduce aspiration risk, such as eating slowly and ensuring proper food texture.
6. Psychosocial Support:
   • Join Support Groups: Participate in support groups for shared experiences and emotional support.
   • Mental Health Care: Seek counseling or therapy for coping strategies and stress management.
7. Avoiding Triggers:
   • Identify Personal Triggers: Keep a diary to track and identify triggers that exacerbate symptoms.
   • Infection Control: Practice good hygiene and take preventive measures to avoid infections.
8. Lifestyle Adjustments:
   • Adaptive Devices: Use assistive devices to maintain independence and safety.
   • Stress Reduction: Practice relaxation techniques and manage stress proactively.

Myasthenic Crisis

Overview

Myasthenic crisis is a severe complication of myasthenia gravis (MG) characterized by respiratory muscle weakness leading to respiratory failure. It is a medical emergency requiring prompt recognition and intervention.

Pathophysiology

Myasthenic crisis occurs due to exacerbation of the underlying autoimmune process of MG, which targets the neuromuscular junction. In MG, autoantibodies attack acetylcholine receptors (AChRs) or other components involved in neuromuscular transmission, impairing signal transmission from nerves to muscles.

Several factors can precipitate a myasthenic crisis, including:

• Infection: Respiratory or systemic infections can exacerbate MG symptoms.
• Surgery: Postoperative stress and medications used during surgery can worsen MG.
• Medications: Certain drugs, such as aminoglycoside antibiotics, beta-blockers, and others, can impair neuromuscular transmission.
• Emotional Stress: Physical or emotional stress can trigger a crisis.
• Inadequate Medication: Suboptimal dosing or sudden discontinuation of MG medications.

Clinical Presentation

Patients in myasthenic crisis typically present with:

• Severe Generalized Weakness: Worsening of existing muscle weakness, including bulbar muscles (affecting speech and swallowing).
• Respiratory Distress: Dyspnea, reduced tidal volume, and inability to clear secretions.
• Dysphagia and Dysarthria: Difficulty swallowing and speaking due to bulbar muscle weakness.

Diagnosis

Diagnosis is clinical and supported by:

• Pulmonary Function Tests: Decreased forced vital capacity (FVC) and negative inspiratory force (NIF) indicating respiratory muscle weakness.
• Arterial Blood Gases (ABGs): May show hypoxemia and hypercapnia.
• Electrophysiological Studies: Repetitive nerve stimulation or single-fiber electromyography (EMG) may show characteristic findings of MG.

Treatment

The goals of treatment are to support respiration, reverse the crisis, and address the underlying causes or triggers.

Respiratory Support

• Noninvasive Ventilation (NIV): BiPAP or CPAP may be used initially in less severe cases.
• Intubation and Mechanical Ventilation: Indicated for severe respiratory failure or when NIV is inadequate. Early intubation should be considered to avoid emergency situations.

Pharmacological Treatment

1. Intravenous Immunoglobulin (IVIG) or Plasmapheresis:
   • IVIG: Given at a dose of 2 g/kg over 2-5 days.
   • Plasmapheresis: Typically, 3-5 exchanges over 7-14 days.
   • Both therapies aim to reduce circulating autoantibodies.
2. Corticosteroids:
   • High-dose steroids may be initiated, but care must be taken as they can initially worsen symptoms.
   • Start with a low dose and gradually increase to minimize the risk of steroid-induced exacerbation.
3. Cholinesterase Inhibitors:
   • Pyridostigmine: Typically continued but may be withheld temporarily if there is significant bulbar weakness due to the risk of excessive secretions.

Addressing Precipitating Factors

• Infections: Prompt diagnosis and treatment of underlying infections.
• Medication Review: Discontinue or adjust any offending drugs.
• Electrolyte Imbalances: Correct any underlying electrolyte abnormalities.

Supportive Care

• Nutritional Support: Enteral feeding may be required for patients with significant bulbar weakness.
• Physiotherapy: To prevent complications of immobility.

Monitoring and Follow-up

• Continuous monitoring in an intensive care unit (ICU) setting is often required.
• Regular reassessment of respiratory function and muscle strength.
• Gradual weaning off mechanical ventilation as respiratory function improves.
• Long-term immunosuppressive therapy may be optimized to prevent future crises.