Supervisor : VS

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Myasthenia Gravis

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• Supervisor VS???
• 2007.06.04

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Case 1

• Name ?O?
• Age 67 y/o
• Gender male
• Admission date 96/4/24
• Chief Complaint
• Dysphagia and easy-choking for 3 weeks,
  bilateral ptosis was also noted , exertional
  dypnea and mild weakness at bilateral lower limbs.

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Myasthenia gravis is a neuromuscular disease
leading to fluctuating muscle weakness and
fatiguability. It is one of the lesser known
autoimmune disorders.
Myasthenia Gravis
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Myasthenia Gravis
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Common symptoms

• A drooping eyelid
• Blurred or double vision
• Slurred speech
• Difficulty chewing and swallowing
• Weakness in the arms and legs
• Chronic muscle fatigue
• Difficulty breathing

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Diagnostic

• Acetylcholine Receptor Antibody
• A blood test for the abnormal antibodies can
  be performed to see if they are present.
  Acetylcholine Receptor Antibody testing -
  Approximately 85 of MG patients have this
  antibody and, when detected, is a guaranteed
  diagnosis.

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Diagnostic

• Anti-MuSK Antibody testing
• a blood test for the remaining 15 of
  seronegative (SN) MG patients, those who have
  tested negative for the acetylcholine antibody,
  40-70 test positive for the anti-MuSK antibody.
  The remaining patients have an unidentified
  antibody causing their MG.

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Diagnostic

• Tensilon test --
• The edrophonium chloride (Tensilon) test is
  performed by injecting this chemical into a vein.
  Improvement of strength immediately after the
  injection provides strong support for the
  diagnosis of MG.

Acetylcholinesterase inhibitor
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Diagnostic

• Electromyography
• EMG studies can provide support for the
  diagnosis of MG when characteristic patterns are
  present. Repetitive Nerve Stimulation to check
  for a post-synaptic defect.

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Diagnostic

• Single Fiber EMG
• studies can provide support for the diagnosis
  of MG when characteristic patterns are present

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Case 1
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Thymoma

• Thymoma is a neoplasm of the thymus. It is a
  rare disease, best known for its enigmatic
  association with the neuromuscular disorder
  myasthenia gravis. About one MG patient in ten
  has a thymoma.

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Symptoms

• Patients with a thymoma, 1/3 1/2 are
  asymptomatic
• 1/3 of patients present with local symptoms
  related to the tumor encroaching on surrounding
  structures. These patients may present with
  cough, chest pain, superior vena cava syndrome,
  dysphagia, and hoarseness if the recurrent
  laryngeal nerve is involved.
• 1/3 of cases are found incidentally on
  radiographic examinations during a workup for
  MG.

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Diagnostic

• The diagnosis of thymoma usually is clinically
  based on radiological findings

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Case 1
Requesting CT study without and with contrast
enhancement shows a well-defined soft-tissue
mass at the superior anterior mediastinum.
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Current therapies for MG

• Anticholinesterase Therapy
• Immunosuppressant Therapy
• Plasma Exchange (plasmapheresis)
• Intravenous Immune Globin
• Thymus Thymectomy

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Anticholinesterase Therapy
Boost the body's ACh by blocking the enzyme which
usually breaks down ACh.

• Anticholinesterase drugs include
• - Pyridostigmine ( Mestinon )- Neostigmine
  ( Prostigmin )- Ambenonium chloride (Mytelase
  )

Neostigmine Methylsulfate Vagostin 0.5
mg/1 mL /amp
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Mestinon

• The most commonly used anticholinesterase is
  "Mestinon". This comes in 60mg tablets .
• An increase in muscle strength is usually
  noticeable within 20 to 40 mins after taking the
  medication, and they produce their maximal
  effects about 12 hours after ingestion (although
  muscle strength rarely returns to normal). The
  effects start wearing off after 34 hours.
• The need for anticholinesterases varies from
  infection, menstruation, emotional stress, and
  hot weather.

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Side effects

• Stomach cramps
• Queasiness and nausea
• Gut hyperactivity and diarrhea
• Vomiting
• Increased perspiration
• Increased salivation
• Muscle twitching and muscle cramps
• Palpitations
• Increased urinary frequency
• The muscle controlling the pupil of the eye is
  also affected, and there may be difficulty in
  focusing
• There are Acetylcholine receptors in the heart
  and so Mestinon may cause a very slow heart beat,
  which can, in turn, cause dizziness

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Side effects

• To lessen the side effects, the drug can be taken
  with bland foods such as crackers and milk.
• ?SMP
• Other symptoms of overdose could include the
  worsening of generalized weakness, swallowing
  difficulties and respiratory failure.

Cholinergic Crisis
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Immunosuppressant Therapy

• Prednisolone
• Azathioprine ("Imuran")
• Cyclophosphamide ("Cytoxan")
• Cyclosporine ("Sandimmune").

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Prednisolone

• Starting with a low dose of prednisolone and
  gradually working up to a recommended amount of
  5060 mg / day for several months.
• Onset of improvement in muscle strength usually
  occurs within 2 weeks but may take as long as 2
  months.
• 30 of MG on high-dose prednisolone therapy
  experience a drug-dependent symptom-free
  remission, and another 50 obtain marked
  improvement. However, 25 of patients also
  experience serious complications from this drug.

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Side effects

• Risk of developing osteoporosis
• Increased susceptibility to diabetes
• Thinning of skin and wasting of muscles
• Sodium and water retention
• Increased appetite and weight gain
• high blood pressure
• Acne on the face, back, and chest
• Decreased resistance to infectionCandida.

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Case 1

• Mestion 1 tid since 4/9
• Prednisolone 1 tid since 4/25
• 4/26 consult Neurology

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5


5


5
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Plasma Exchange (plasmapheresis)

• To stabilize the condition of patients in
  myasthenic crisis where the condition is life
  threatening.
• To reduce moderate to severe muscle weakness
  before thymectomy.
• Some myasthenics do not respond sufficiently to
  more traditional forms of treatments, and so
  plasmapheresis offers their only relief from near
  paralysis and life-threatening respiratory
  problems.

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Plasma Exchange (plasmapheresis)

• Plasmapheresis does not cure MG - it only
  temporarily reduces the level of circuiting
  antibodies that attack the neuromuscular
  junction.
• Plasma Exchange NT.5500
• Double filtration plasmapheresis NT.15000
• Immunoadsorption plasmapheresis NT.36000
• The recommended plasmapheresis prescription is 5
  treatments over a one-week period. Each treatment
  should equal 1.5 plasma volume (PV), which can be
  re-placed with 5 albumin or fresh frozen plasma
  (FFP).

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Case 1
Plasma Exchange
Operation
Weaning ventilation on 5/8
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Intravenous Immune Globin

• Intravenous immune globin (IVIG) is the opposite
  of plasmapheresis .
• The process does not require special equipment,
  and the usual dose is small (eg 400 mg / kg / day
  infused for 5 successive days).
• The mechanism of action remains unknown, IVIG is
  thought to have a nonspecific suppressive effect
  upon the production of antibody by the immune
  system.
• The process is quite expensive, and like
  plasmapheresis, the treatment is short term.

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Thymus Thymectomy

• It is accepted that there is a connection between
  the thymus and Myasthenia Gravis but the reason
  for the connection is not fully understood.
• A thymectomy is the removal of the thymus gland
  by surgery. The goal of thymectomy as a treatment
  for MG is to induce remission, or at least
  improvement, permitting a reduction in
  immunosuppressive medication. Remission is the
  complete elimination of symptoms without
  medication.

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Thymectomy

• Principle radically removal of thymus tissue

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Surgical Approaches

• Full Sternotomy
• Partial Sternotomy
• Thoracoscopic Thymectomy
• Transcervical Thymectomy

Transsternal Thymectomy
Minimally Invasive Thymectomy
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Transsternal Thymectomy
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Thoracoscopic Thymectomy(VATS)
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Transcervical Thymectomy
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Case 1

• Pre-operation Evaluation

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Case 1

• Operation on 5/4
• Op Method
• 1.Radical thymothymectomy via VATS
• 2.Partial pericardiaectomy and repair by
  equine pericardial patch
• Op Finding
• 1. A 63 cm thymoma with invasion to the
  pericardium and L't
• side pleura
• 2. A 66 cm defect of the pericardium,
  repaired by equine
• pericardium
• 3. Severe adhesion of the thymoma and
  pericardium
• 4. Air leakage from L't lung

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Case 1

• Post-op Course
• Solu-medrol 500mg during op
• Solu-medrol 40mg Q8H after op since 5/4
• Mestinon 1 tid po since 5/7
• 5/8 Start Weaning Ventilator
• 5/9 R/O Mestinon Overdose
• Bradycardia HR40 bpm
• Hyperactive bowel sound
• Salivation increase
• 5/10 Extubation

? DC Mestinon
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Complication

• 
  
• 1. Subcutaneous
• emphysema
• 2. Persist Air leak

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Case 2

• Name ??O?
• Age 76 y/o
• Gender female
• Admission date 96/5/11
• Chief Complaint
• Dysphagia since Feb 2007. Ptosis in the
  afternoon has been noted for years, but the
  situation worsened 2 months ago.
• MG was diagnosed and treatment in??.

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Case 2

• Pre-operation Medication
• Mestinon 60mg 2 q12h
• Pre-operation Evaluation

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Case 2

• Operation on 5/14
• Op Method
• VATS extensive thymectomy
• Op Finding
• A 3x3 cm multilobular, firm mass was noted at
  right anterior mediastinum with mild adhesion to
  lung.

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Case 2

• Post-op Course
• Solu-medrol 500mg during op
• Solu-medrol 40mg Q8H after op since 5/14
• Complain ???, MP4 ?
• Mestinon 2 bid po since 5/15
• Increased perspiration
• Start Weaning Ventilator on 5/15
• Af with RVR attacked on 5/16 5AM? Aminodarone
• Extubation on 5/16 3PM
• Transfer to 8B on 5/17 and DC Mestinon due to
  diarrhea

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Case 2

• 5/17 transfer to 8B
• Immediately complain ???? , general weakness
• Dyspnea (RR 2832) combine Tachy-arrhythmia (HR
  150 160) ? BiPAP use
• Calm down , bed rest , HR 65 70
• Irritation and insomnia
• CO2 retention PCO2 51
• PSVT (HR 170 190) ?Aminodarone
• Add Mestinon 1 bid on 5/18
• Neostigmine 0.5 mg im stat on 5/18 4 20 pm
• But still Dyspnea reentry ICU

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Case 2

• 5/18 in 4C2 PICU
• Intubation and sedation
• DC Mestinon
• SBP drop to 58 mmHg R/O sedation induce or
  Infection ? Dopamine
• Remove CVP ? tip culture , sputum culture
• 5/19 transfer to 4B1
• Vital sign stable , Dopamine off
• Medication
• 1. Solu-Medrol 40mg IV Q8H
• 2. Mestinon 1 PO BID

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• In 4B1 ICU
• Respiratory condition had been improved
• But diarrhea ? Pecolin use on 5/20
• Taper Mestinon 0.5 PO BID
• Solu-medrol 40 mg Q12H
• Extubation on 5/22
• Still diarrhea hyperactive bowel sound
• DC Mestinon on 5/22
• Respiratory pattern smooth
• Swallowing smooth without choking
• Transfer to general ward on 5/24
• Discharge on 5/29 only prednisolone use

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Whats happen in this patient ?
Respiratory failure is a life-threatening
complication of MG

• Myasthenic Crisis
• or
• Cholinergic Crisis

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Myasthenic Crisis

• A myasthenic crisis occurs when weakness affects
  the muscles that control breathing.
• In individuals whose respiratory muscles are
  weak, infection, fever, a reaction to medication,
  or emotional stress can trigger a crisis.
• Plasma exchange may be performed to treat
  myasthenic crisis.

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Cholinergic Crisis

• A cholinergic crisis, muscles stop responding to
  the bombardment of Ach, leading to flaccid
  paralysis, respiratory failure, and other signs
  and symptoms reminiscent of organophosphate
  poisoning.
• Other symptoms include increased sweating,
  salavation, bronchial secretions along with
  miosis.
• This crisis may be masked by the concomitant use
  of atropine along.

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Myasthenic VS Cholinergic Crisis

• Both can be present as respiratory failure
• Cause
• Myasthenia crisis disease exacerbation,
  noncompliance with medication, adverse of other
  medications, fever, and emotion stress
• Cholinergic crisis excess cholinesterase
  inhibitor medication
• Differentiate myasthenia vs. cholinergic crisis
• ? history and associated symptoms and signs

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Differentiate myasthenic crisis vs.
cholinergic crisis
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Take home massage

• Myasthenia Gravis (MG) is a neuromuscular
  autoimmune disease .
• Diagnosis by Clinical History ,Neurological Exam,
  Serum Antibodies to AChR
• MG patient 10 has a thymoma , around 1/3 of all
  thymoma patients get MG .
• Therapies for MG include
• 1. Anticholinesterase Therapy
• 2. Immunosuppressant Therapy
• 3. Plasma Exchange
• 4. Intravenous Immune Globin
• 5. Thymus Thymectomy

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Thank you for your attention