Case Discussion C.C.: Cough for 3 days with progressive drowsy consciousness <Brief History >       This 71-year-old woman was first diagnosed as myasthesia gravis in 1993, when she developed ptosis but without diplopia, dysphagia or limbs weakness. Her ptosis improved after taking pyridostigmine, but recurred after she discontinued the drug. The chest CT revealed a thymoma and thyomectomy was suggested but she refused. She then received pyridostigmine and prednisolone at outpatient clinic.       She was well until Sep, 1994, when she developed proximal muscle weakness. She stopped taking pyridostigmine and prednisolone in the morning on Nov 2, 1994. Dyspnea with cyanosis developed soon. Symptoms improved but persisted after parenteral vagastigmine and increasing the dose of prednisolone. She then received plasma exchange for three times. Dyspnea subsided later.       She underwent a thymomectomy on Nov. 20 1994 and was followed up at outpatient clinic therefore, with oral medication of pyridostigmine and prednisolone.       She then remained in a disease-free status until Feb, 25, 2000, when an episode of myesthenic crisis occurred following a flu-like episode. She developed progressive dyspnea and was intubated due to CO2 narcosis. Plasmapheresis was performed and she was extubated on March 2 after 4 times of plasmapheresis. Her AchR Ab titer dropped from 55.94 nmole/l (Feb 25, 2000) to 29.16 nmole/l (Mar 6, 2000). She was discharged with oral medication of pyridostigmine and prednisolone.       Because of progressive left hip pain for 6 months, she underwent left total hip replacement (THR) revision on Jul. 11, 2002. She developed mild dyspnea after operation, so the dose of prednisolone was increased from 10 mg qod to 20 mg qd. However, dislocation of left hip joint occurred frequently and her dyspnea persisted. Three days prior to this admission, she sufferrede from cough with whitish sputum. Progressive drowsy consciousness was also noted. She was then brought to ER, and CO2 narcosis was found. She was then intubated, and was admitted to ICU for further care. 檢體發現 (Physical findings): Conscious: clear Vital sign: TPR: 37/ 70/12; BP: 104/52 mmHg (On ventilator) Eye: conjunctiva: not pale, sclera: not icteric Neck: supple, JVE (-), LAP (-) Chest: Symmetric expansion, Breath sound: clear Heart: regular heart beat; no murmur Abdomen: soft and flat, Bowel sound: normoactive                  Liver/ spleen: not palpable                  No tenderness, no rebound tenderness                  Shifting dullness (-)  Extremity: edema (-), cyanosis (-) 住院治療經過(Course and Management):       Ampicillin/subactam was administered at ER for suspected respiratory infection. Plasmapheresis was started on Sep. 5 once every other days. Prednisolone 30 mg per day was also given. Her muscle power improved significantly after the first plasmapheresis on Sep. 5. However, there was still CO2 retention during spontaneous breathing trials through a T-piece. The maximal inspiratory and expiratory pressures (Pimax and Pemax), tidal volume and vital capacity (VC) continued to improve during the course of plasmaphoresis. There was no CO2 retention after the 5th course of plasmaphoresis on Sep. 13. She was then extubation on Sep. 14, and was transfered to the general ward on Sep.17. <Laboratory data>   WBC RBC Hb Hct MCV MCHC PLT   /ul M/ul g/dl % fL g/dl /ul  9/5 11380 3.93 12.0 38.0 96.7 31.6 251K   Seg  Eos Baso Mono Lym 9/5 87.3 0.1 0.2 3.3 9.1     BUN Cre GOT Bil(T) Cl Ca Na K CK CRP   Mg/dl Mg/dl U/l Mg/dl Mmole Mmole Mmole Mmole U/l Mg/dl 9/5 23.2 0.63 21 0.38  76.0 1.98 132.2 2.88 59 1.82 9/5 AchR Ab 18.2 nmol/l (< 0.2)   Weaning parameter   9/5 9/7 9/9 9/9 9/11 9/11 9/13 9/13 Plasmapheresis 1st 2nd   3rd 4th   5th   Vt     310 ml     369 ml   445 ml RR     20 /min     18 /min   20 /min VE     6.2 l/min     6.6 l/min   8.9 l/min RSBI (f/Vt)     64.5     48.7   45 Pimax     -40 cmH2O     -52 cmH2O   -50 cmH2O PeMax      50 cmH2O     55 cmH2O   50 cmH2O VC     600 ml     550 ml   750 ml Vt: tidal volume; RSBI: rapid shallow breathing index; VC: vital capacity    本病例為一患有多年重症肌無力之女性病患。於接受胸腺切除後其症狀曾一度有較長時間的緩解。但最近幾年在接受骨科開刀或有上呼吸道感染時就會引起重症肌無力症狀惡化(crisis)，導致呼吸肌肉無力加重而引發呼吸衰竭。經抗生素治療，呼吸器輔助及血漿置換術治療後，血中抗Acetyecholine受體抗體值明顯下降，臨床症狀也迅速改善， 可順利脫離呼吸器。此病例之臨床表現可說是此疾病之典型案例。內科醫師在加護病房偶而會遇到這些呼吸衰竭之病患，對其適當處理應有基本認識。           繼續教育考題 1. (C) Which description about myasthenia gravis is WRONG? A characterized by weakness and fatigability of skeletal muscles B An autoimmune response mediated by specific anti-Ach receptor antibodies C Loss of reflexes or impairment of sensation are typical findings D All of the above 2. (D) Which description about the distribution of muscle weakness in MG is WRONG? A The cranial muscles are often involved early B The lids and extraocular muscles are particularly involved C In approximately 85% of patients, the weakness becomes generalized, affecting the limb muscles as well. D The limb weakness in MG is often distal 3. (D) Which description about the role of thymoma in MG is WRONG? A Surgical removal is necessary because of the possibility of local tumor spread, although most thymomas are benign B Up to 85% of patients experience improvement after thymectomy; C Thymectomy offers the possibility of long-term benefit, D Thymectomy is of little benefit in patients with MG. 4. (C) Which description about the diagnosis of MG is WRONG? A Diagnosis is suspected on the basis of weakness and fatigability in the typical distribution, B Diagnosis should be confirmed definitively before treatment C Diagnosis of MG can be excluded if anti-AchR Ab is negative. D Anti-AChR radioimmunoassay: ~90% positive in generalized MG; 50% in ocular MG 5. (D) Which laboratory test below is of help in the diagnois of MG ? A Edrophonium chloride (Tensilon) test B Repetitive nerve stimulation C Single-fiber electromyography D All of the above 6. (D) Which description about the clinical course of MG is correct ? A The course of MG is often variable; exacerbations and remissions may occur B Remissions are rarely complete or permanent C Myasthenic crisis is defined as an exacerbation of weakness sufficient to endanger life D All of the above 7. (D) Which description about the changes in pulmonary function is not typical for MG during crisis? A Decreased PImax B Decreased FEV1 C Decreased vital capacity D Increased airway resistance 8. (D) Which description about myasthenic crisis is correct ? A The most common cause of crisis is infection. B Respiratory failure is common C Overdose of anticholinesterase medication may induce"cholinergic crisis" D All of the above 9. (C) Which description about the treatment of myasthenic crisis is WRONG ? A Treatment should be carried out in an intensive care unit B Patients with infection should be treated in like other immunocompromised patients. C Plasmapheresis is not useful in hastening recovery. D Early and effective antibiotic therapy and respiratory assistance are essentials 10. (B) The cause of CO2 retention in this case is most likely due to: A Overproduction of CO2 B Decreased alveolar ventilation C Increased airway resistance D Increased dead space

答案解說 (C)  There is no loss of reflexes or impairment of sensation in MG. (D)  The limb weakness in MG is often proximal (D)  The available evidence suggests that up to 85% of patients experience improvement after thymectomy; of these, ~35% achieve drug-free remission. However, the improvement is typically delayed for months to years. The advantage of thymectomy is that it offers the possibility of long-term benefit, nagement, anesthesia, and surgical techniques of total thymectomy. (C)  The cranial muscles, particularly the lids and extraocular muscles, are often involved early, and diplopia and ptosis are common initial complaints. (D) All descriptions are correct. (D)  Diagnosis is suspected on the basis of weakness and fatigability in the typical distribution described above, without loss of reflexes or impairment of sensation or other neurologic function. The suspected diagnosis should always be confirmed definitively before treatment is undertaken; this is essential because (1) other treatable conditions may closely resemble MG, and (2) the treatment of MG may involve surgery and the prolonged use of drugs with adverse side effects. (D)  Neuromuscular weakness is a type of restrictive ventilatory disorder. The airway resistance is normal. (D)  Myasthenic crisis is defined as an exacerbation of weakness sufficient to endanger life; it usually consists of respiratory failure caused by diaphragmatic and intercostal muscle weakness. (C)  The myasthenic patient with fever and infection should be treated like immunocompromised patients. Early and effective antibiotic therapy, respiratory assistance, and pulmonary physiotherapy are essentials of the treatment program. Plasmapheresis or IVIG is frequently helpful in hastening recovery. (B)  Respiratory muscle weakness → Decreased tidal volume →Decreased alveolar ventilation → hypercapnia