Neuromuscular diseases leading to respiratory failure Jiann-Horng Yeh, M.D. Department of Neurology Shin Kong WHS Memorial Hospital Respiratory muscles Muscle groups Diaphragm Intercostal muscles Scalene Sternocleidomastoid Trapezoid Abdominal muscles AHC level C3-5 T1-12 C4-8 Cranial XI, C2-3 Cranial XI, C2-4 T7-L1 Neurological signs for D/D Level UMN AHC DTR Bulbar +/— +/— EOM Sensation ANS +/— +/— +/— — — —# Nerve + +/— + + NMJ N + + — +/— Muscle N +/— — —* — * Pain in polymyositis # ANS s/s in Bulbar poliomyelitis Common disorders of NMD UMN NMJ BS/cord lesion Myasthenia gravis Muscle Dystrophy LMN LE syndrome Polymyositis Poliomyelitis Botulism Trichinosis ALS OP poisoning Endocrine myopathy Nerve Tick paralysis GB syndrome CNS disorders causing RF Brainstem lesions Stroke Extrinsic compression Intrinsic tumor Encephalitis MS, CPM Motor neuron disease Spinal cord lesions Cord compression Motor neuron Dz, Polio Intrinsic tumor MS, Myelitis Rabies Sedative drugs Metabolic disorder Central transtentorial herniation Neuropathy with RF - I GBS CIDP Critical illness Lymphoma Vasculitis-LE Porphyria Diphtheria H.tyrosinemia NCV NCV — N biopsy N biopsy U/porphobilinogen Throat swab U/d-ALA PE, IVIG PE, Steroid, IVIG — Cytotoxic Steroid, Endoxan IV hematin Antitoxin High calorie intake Liver transplant Toxic neuropathy with RF O-phosphate RBC C-esterase Thallium Arsenic Lead Gold Lithium Vincristine Atropine P/pseudoC-esterase Pralidoxime Blood level Berline blue 24h Urine level Dimercaprol, DMSA Blood level Na-Ca edetate, above — Na-Ca edetate, above Plasma level Hemodialysis — Withdrawal Clues for toxic neuropathy General hints in initial symptoms Vomiting Altered level of consciousness Thallium Prominent cutaneous & muscular pain, esp. feet Preserved DTR in the early stage NM disorders with RF Myasthenia gravis AC overdose Antibiotics Hypermagnesemia Botulism Poisoning * Tick paralysis LE syndrome Tensilon test, AchRAb Tensilon test — — Plasma level, RNS Antibody, RNS Identification Find the tick Increment on RNS PP, Steroid Withdrawal Withdrawal IV calcium Antitoxin Antitoxin Removal PP, steroid * snake, scorpion, spider, fish, shellfish, crab Muscle disorders with RF Plasma level K+ CPK, EMG, biopsy Steroid CPK, EMG, biopsy Urine alkalinization Hypophosphatemia Plasma level Phosphate Acid maltase def. PAS stain (PB film) — Barium intoxication Plasma K+ IV K+ Mg sulfate, po Hemodialysis Hypokalemia Polymyositis Rhabdomyolysis Differential tests Physical and neurological examinations Laboratory tests Electrophysiology: NCV, RNS, EMG, SFEMG CPK, electrolyte, thyroid function Antibody titer CSF Biopsy: nerve, muscle Provocative test: Tensilon test General Management in ICU AIRWAY MANAGEMENT Evaluate s/s of impending respiratory failure Orthopnea, interrupted speech Shallow & rapid respiration Paradoxical respiration Breathing sound Reduced BS, sputum, crackle Arterial blood gas Hypoxemia, CO2 narcosis, respiratory acidosis AIRWAY MANAGEMENT Monitor the changes of pulmonary function Criteria for intubation VC<15 mL/kg; Pimax < -25 cmH2O Paired VC test – supine & sitting position Normal: Supine VC > 80% Sitting VC Weakness: Supine VC < 40% Sitting VC Digit count at one breath Count <25: VC < 20 mL/kg AIRWAY MANAGEMENT Appropriate chest care Chest physical therapy Percussion, postural drainage Education for effective respiration/coughing Elective intubation Impaired swallowing Signs of aspiration pneumonia Hypoxemia Critical level of lung function Prevention of complications Careful posturing: entrapment neuropathy Frequent turn: bedsores Passive exercise: disuse atrophy NG feeding: aspiration Heparin or pneumatic leg compression: DVT Vital sign monitoring: ANS instability Emotional support: anxiety, depression Guillain-Barré syndrome Guillain-Barré Syndrome (Acute inflammatory demyelinating polyneuropathy) Acute/subacute motor paralysis for days/wks Arefelexia or hyporeflexia Mild sensory symptoms or signs CSF: albuminocytological dissociation NCV: conduction slowing or block Pathology Focal segmental demyelination Inflammatory cells infiltration Clinical course Course Progression: 4 wk (90%) Plateau: 4 wk (85%) Recovery: 4-6 months (80%) Outcome Permanent residua: 15% Permanently disabled: 5% Mortality: 2-5% Relapse: 3% Clinical features - I Spectrum: mild ataxia to total paralysis Limb involvement Leg onset: arm & face are possible Proximal > distal involvement Symmetric pattern Absence of DTR even in minimally involved m. External urethral sphnicter 10-20% retention > incontinence Clinical features - II Cranial N involvement VII: asymmetric: 50% (esp. upper lip/perioral) EOM: 10% Isolated cranial N: 5% Oropharngeal involvement: 40% (herald of impending respiratory failure) Respiratory muscle involvement Major cranial N involvement frequently associated Weakness of shoulder elevation & neck flexion parallels diaphragmatic weakness & resp. failure Clinical features -III Autonomic involvement: 65% Sinus tachycardia: > 50% SIADH, (DI) Orthostatic hypotension (20%) & hypertension Sweating disturbance Cardiac dysautonomia may correlate with sensory dysfunction ( Raphael JC, 1986 ) Muscular of neuropathic pain: 30-55% follow vigorous exercise (chaley horse) distributed in thigh, buttock & low back 73 F AIDP onset: May 27,1996 7 ANS Intubation 6 5 4 3 2 1 Grade MRC-sum score *10 0 1 2 3 4 5 6 7 8 9 10 11 12 14 16 18 20 22 24 26 28 GBS之處置 呼吸道: 插管 肺活量監控, VC<15mL/Kg, Pimax < -20mmHg 輸液: N/S 2L/天 營養: 腸道營養。如有腸堵塞才改靜脈營養 特殊處置 IVIG (免疫球蛋白), 0.4g/Kg/天 x 5天 PE (血漿交換) 隔日一次 x 5次 如使用呼吸器或同時使用 aspirin/NSAID病人, 投予Sucralfate 10mL bid. 肌肉疼痛可投予肌肉注射類固醇 Plasmaphresis in Neurology Disease GBS CIDP MS - acute; refractory to steroid MGUS - IgG/A MG – preop & crisis MGUS - IgM Lambert-Eaton syndrome Definition Class Established I Established I Established I Established I Established III Investigational I Possibly useful II/III Investigational: Refsum disease, acquired neuromyotonia, Stiff-man syndrome, Cryoglobulinemic neuropathy, CNS lupus, ADEM GBS Study Group : PE vs No Tx Neurology 1985,35,1094-1104 245 patients; 40-50 cc/kg for 3-5 PE Parameters Improve > 1 grade at 4 wks Mean grade change at 4 wks Median time to improve 1 G Median time to walk unaided Median time on ventilator Failed to improve 1 G at 6M PE 59% 1.1 G 19 D 53 D 24 D 3% No Tx 39% 0.4 G 40 D 85 D 48 D 13% Plasmapheresis appears to be of benefit in patients with GBS of recent onset (within 7 days). p * ** ** ** * * Change of MRC-sum score during plasmapheresis in GBS Chen et al; J Clin Apheresis 1999;14:126-9. 45 32.6 50 Score 0 Pre-PP Post-PP Plasmapheresis in GBS Chen et al; J Clin Apheresis 1999;14:126-9. Author Y Country No Osterman Sweden 84 GBS study 85 French 87 Van der Meche 92 Bril 96 PES/GBS 97 SKH 98 USA France Neth Canada UK Taiwan G at Time to Tx entry 18 4.6 6.9 122 4.3 11.1 109 ND 6.3 73 3.9 5.6 24 4.1 4.7 121 3.9 6.9 16 3.6 8.1 Plasmapheresis in GBS Chen et al; J Clin Apheresis 1999;14:126-9. Author 1G at W4(%) G at W4 Osterman 59 2.1 1.1 34 61 81 GBS study French Van der Meche Bril PES/GBS SKH Time to Fail to G2 G2 at M6 OFF respirator 53 70 21 18 9 0.4 1 1.1 1.5 69 40 19 13.7 13 22.6 11.2 GBS病情惡化之成因 病情持續惡化 病情穩定後再復發(relapse) 自律神經異常(dysautonomia) 好發於急速癱瘓且合併眼肌麻痺者 血壓不穩 心律不整 呼吸器相關之併發症 Myasthenic Crisis Onset - MG Presenting symptoms Ocular (50%): ptosis; diplopia Weakness (35%): bulbar; leg; arm Fatigue (10%) Progression: generally insidious over wks to months Aggravating factors Systemic disease: infection, thyroid Emotional stress Pregnancy Medications Clinical pattern - MG Ocular Ptosis & ophthalmoplegia Usually asymmetric & bilateral Bulbar Dysarthria, dysphagia, weak mastication Complicated with aspiration pneumonia Facial: > 95% Respiratory failure Life-threatening Etiology Systemic Typical: symmetric diaphragmatic & intercostal muscle weakness vocal cord paralysis Proximal > distal Arms > legs Selective weakness Posterior neck Occasional distal Severity classification of MG Grade 1 Osserman/71 Drachman/82 Ocular Focal Grade 2 a: Mild generalized Mild generalized b: Severe generalized Grade 3 Acute fulminating Severe generalized Grade 4 Late severe Crisis Diagnosis - MG 3 mainstays of diagnostic testing Pharmacological (Tensilon test) Serological (acetylcholine receptor antibody) Electrodiagnostic (RNS & SFEMG) Diagnosis a characteristic history /PE two positive diagnostic tests, preferably serological and electrodiagnostic. Edrophonium (Tensilon) test 2 mg IV observation for 2 min 8 mg IV A positive test requires objective improvement in muscle strength. Most myasthenic muscles respond in 30 to 45 seconds after injection Sensitivity: 60% False positive results in patients with LES, ALS or even localized, intracranial mass lesions Repetitive Nerve Stimulation Electric stimulation 6-10 times at 2 or 3 Hz. Positive: (R1-R5) /R1>10% Sensitivity: 75% (generalized MG) 50% (ocular MG) False positive Lambert-Eaton syndrome Motor neuron diseases Single Fiber EMG (SFEMG) Rationale increased variability of the latencies at which the muscle fibers innervated by an individual axon Sensitivity: 95% in both generalized and ocular MG the test site includes facial muscles. False positive Lambert-Eaton syndrome Motor neuron diseases Polymyositis Clinical significance of AchRAb Diagnostic aid Monitor the clinical status Evaluate the efficacy of immune therapies Assess the functional capacity of plasmapheresis column quantitatively AchRAb Adults with generalized MG: 85 to 90% Positive Childhood MG: 50% Ocular MG: 50% to 70% MG with thymoma: nearly 100% Some patients taking penicillamine +/- MG AchRAb Thymoma without MG False + Immune liver disorders Lambert-Eaton syndrome (13%) Primary lung cancer: 3% Older patients (> 70 years): 1% to 3% Neuromyotonia AchRAb titers in Osserman stages (n=699) 100% 80% 60% 40% 20% 80.2 88.8 96.3 100 IIb-80 III-27 IV-1 56.9 0% I-348 IIa-243 <0.2 <0.5 >0.5 Thymus relationship - MG Thymoma: 10% to 15% Mostly in MG patients > 30 years AChRAb 95% to 100% Hyperplasia:60% to 80% Younger age groups Female HLA: B8 & DR3 Atrophy: 20% Usually > 50 years 重症肌無力危象之處置 呼吸道:插管 吞嚥困難, 咳嗽乏力, 吸入性肺炎, VC<15mL/Kg 疑有肺炎時, 先投予第3代Cephalosporin 輸液: N/S, 發燒時加量 營養: 嚴重吞嚥障礙時, NG餵食 特殊處置: 使用呼吸器時, Pyridostigmine停用 血漿交換, 隔日一次 x 5次 IVIG, 0.4g/Kg/天 x 5天 大量類固醇1mg/Kg, 視情況而定 Precipitants (n=20) Yeh et al; Acta Neurol Scand 2001; in press Characteristic Pneumonia/pneumonitis Bronchitis URI Sepsis Surgery No obvious precipitant % 40 30 5 15 10 15 no 8 6 1 3 2 3 Drugs interfere NM transmission Variety Drug Antibiotic Aminoglycoside, Fluoroquinolone, Tetracycline, Sulfonamide, Penicillin, Macrolide, Lincomycin, Colistin, Polymyxin, Quinocrine, Chloroquine Transquillizer, Barbiturate, Anticonvulsant, Lithium, Mg salt, TCA, Haloperidol Anesthesic Halothane, Ether, Trichloroethylene CNS CV Others B-blocker, Verapamil, Quinidine, Procainamide Narcotic, Penicillamine, Iodinated contrast Time to produce a 50% AchRAb (m) Thymectomy 24 18 AZA+steroid 12 Azathioprine 10 Cyclophosphamide 6 CTX+steroid Steroid PP+steroid 4 0.5 Plasmapheresis 0.3 Tindall RSA/1982 Plasma Exchange - MG Dose: 5 exchanges over 9 to 10 days Indications: Acutely ill MG patient Pre-thymectomy (respiratory/bulbar involvement) Advantages Very short onset of action (3 to 10 days) Probably more effective in crisis than IVIG Disadvantages Requires specialized equipment & personnel Complications more frequent in elderly High cost with short-term effects (weeks) Blood Plasma Purified P Double-filtration plasmapheresis Clinical response Yeh et al, Acta Neurol Scand 1999;100:305-9 Poor 16% Good 22% Fair 62% Poor Fair Good 0: 2 2:12 5:3 1: 5 3:8 6:2 4:8 >:5 Clinical response: plasmapheresis Author-year Dau-81 Fornasari-85 Mantegazza-87 Antozzi-91 Kornfeld-92 no 60 33 37 70 43 Method PE PE PE PE PE Response 74% 61% 87% 70% 91% Shibuya-94 Yeh-99 20 45 IAP DFP 55% 84% Change of MG score during DFP 9.9 4.2 10 5 Score 0 Pre-PP Post-PP Change of AchRAb titer during DFP 1 0.78 0.8 0.6 0.71 0.61 0.67 0.4 0.56 0.2 0 1st 0.44 Blood Filtrate 2nd 3rd Session of plasmapheresis 4th Pulmonary function tests during DFP 1.86 1.49 1.40 2 1.5 1 1.85 1.37 1.55 Pimax 0.5 0 1st Vital capacity 2nd 3rd Session of plasmapheresis 4th Proportion remaining intubated 1.00 5 days 0.75 9 days 0.50 26 days 0.25 0.00 0 7 14 21 28 35 42 Time (days) 49 56 63 70 Favorable prognostic parameters Yeh et al, Acta Neurol Scand 1999;100:305-9 High MG score Pathology of non-thymoma type Young age at onset Daily apheresis High removal rate for IgG Clinical response of DFP Yeh et al; Acta Neurol Sin 1995;4:107-12. Dyspnea group Non-dyspnea group 1 0.8 0.6 0.4 1 0.7 0.2 0 Response rate 0.53 0.47 Effective duration > 2 Months Botulism Botulinum Toxin Clostridium botulinum Gram positive bacilli Spore producing Anaerobic: obligate Botulinum Toxin Sequence homology (30% to 40%) to tetanus toxin Produced as a protoxin withMW 150 kDa 7 types of neurotoxin: A-G Clinical Features - Botulism Type A Most common outbreaks in Rocky Mountains & West Ca++ level in synaptosomes overcomes blockade More severe & long-lasting paralysis: 67% intubation Type B Most common outbreaks in East, especially Allegheny Has most structural homology to tetanus toxin Require assembled intracellular microtubule for action Somewhat less severe paralysis than Type A Clinical Features - Botulism Time course Incubation period: average: 18 to 38 hours Extremes: 2 hours to 1 week Weakness Diffuse; Usually symmetric; Proximal > distal Bulbar: dysphagia; dysarthria Extraocular: ptosis; EOM weakness Sensory loss: never prominent Tendon reflexes: reduced Cholinergic ANS involvement Pupils: dilated, blurred vision Bradycardia; hypotension Skin: Hypohydrosis Urinary retention Gastrointestinal Nausea & vomiting with contaminated food Constipation: first sign, especially in infants Diarrhea may occur early Diagnosis - Botulism Analysis of serum, feces & implicated food Passive transfer of serum/body fluid to mice Toxicity to mice Selectively prevented by anti-toxin Stool or wound culture Foodborne Botulism Food Contaminated with spores in anaerobic conditions Home canned vegetable/potato & preserved sea food Toxin Resistant to proteolysis in stomach Absorption Alkaline pH of intestine dissociates toxin from proteins Absorption into circulation Usually adults Foodborne Botulism in Taiwan 1986; 9 cases (2 fatalities) in Chang-Hwa city Type A foodborne botulism Canned peanuts from a unlicensed cannery Malaise, ptosis, diplopia, dysphagia, dysarthria and proximal weakness Implications Poor governmental supervision of canned food Inadequate quantities of orphan drug stored Inefficient system for recalling the problem products Delayed broadcasting of warnings to the public Wound Botulism Toxin is produced locally Drug abuse: most common cause IM or SC heroin for subcutaneous abscesses (50%) Incubation: 4-14 D, longer when wound is debrided Onset: blurred vision & bulbar weakness Progression Generalized weakness Dysarthria; dysphagia Pupillary reactivity Botulinum types A > B Treatment - Botulism Supportive care: respiratory; wound debridement Early Emetics: avoid magnesium containing Lavage Enemas: not when paralytic ileus Antitoxin Most useful in 1st 24 hours Use on clinical diagnosis Lowers fatality rate & shortens illness (Type A) Complications (immune): 9% ? 3,4-diaminopyridine Prognosis - Botulism Ventilator dependence frequency Type A > B > E Slow improvement in strength over weeks to months 1 year: Most near normal ± fatigue ANS function may improve later than weakness Mortality: 5% to 10% Prevention - Botulism Canning or preserving foods with appropriate heat, pressure, & low pH Spores Survive 2 hr at 100 °C; inactivated at 120 °C Factors favoring spore germination: Low acidity (pH > 5.0); Low O2; High water content Toxin: inactivated 1 min at 85 °C, or 5 min at 80 °C Avoid exposure of infants to honey (may contain Clostridium botulinum spores) Periodic Paralysis Periodic Paralysis Hypokalemic Hereditary Ca++ channel (CACNA1S)1q31 K+ channel (KCNE3)11q13-14 Na+ channel (SCN4A)17q13 Distal RTA (ASLC4A1)17q21-22 Thyrotoxic Acquired: K+ wasting Hyperkalemic Hereditary (AD) Na+ channel (SCN4A)17q35 Hereditary Hypokalemic PP l L-type Calcium Channel, a1 subunit (CACNA1S) 1q31: R528H; R1086C; R1086H; R1239G; R1239H AD inheritance penetrance: M 100%; F 50% Onset: early childhood to 30's; 60% < 16 years Attacks begin in early morning hours Weak truncal muscle; spared cranial nerves Duration of attack: hours to days Triggers: carbohydrate-rich meal; cold Permanent weakness: often develops over years Diagnosis - HOPP Laboratory Serum CK ; K+ during attacks Electrodiagnostic CMAP during attacks Amplitude after sustained maximal contraction Progressively (40%) during rest 20-40 min after initial (80% of patients) Provocative test: Glucose ± insulin Muscle pathology Vacuoles: clear; central and tubular aggregates Myopathy: varied mf size; split fiber; internal nuclei Angular muscle fibers K wasting syndrome – urinary loss Alkaline urine & metabolic acidosis Hyperaldosteronism Angiotensin converting enzyme dysfunction Licorice intoxication Mineralocorticoid excess Renal tubular acidosis Sjögren's, Fanconi's syndrome Alkaline urine & azotemia: Amphotericin B K wasting syndrome – urinary loss Acidosis Ammonium chloride ingestion Ureterocolostomies: bilateral Diabetic coma: recovery Renal tubular necrosis: recovery Distal renal tubular acidosis Other Gossypol toxicity (with low K+ diet) Tea: excessive amounts K wasting syndrome – GI loss Non-tropical sprue Laxative abuse Severe diarrhea or vomiting Draining GI fistula Thyrotoxic Periodic Paralysis Incidence Asians: ~ 2%; North America: 0.1% Male predominance (83% to 95%) Onset: 20 to 40 years; Proximal weakness Weakness Duration of episodes: hours to days Distribution: legs > arms; proximal > distal Severe attack may involve resp/bulbar function Sphincters not involved Clinical features - TPP Attacks Often occur in random pattern Precipitating factor: carbohydrate challenge; muscle cooling; rest after exercise Single or multiple episodes Abate when thyrotoxicosis resolves Systemic Thyrotoxicosis: may be subclinical ± Cardiac arrhythmias Diagnosis & Treatment - TPP Laboratory Usually hypokalemia; occasionally normal Hypophosphatemia: occasional Renal: retention of Na+ & K+; oliguria Electrophysiology CMAP reduced during attacks Muscle pathology Vacuolar dilation of sarcoplasmic reticulum Treatment Correct thyrotoxicosis b-adrenergic blocking agents Polymyositis Polymyositis Muscle weakness Proximal > distal; symmetric Selective: dysphagia, post.neck; quadriceps Onset age: usually > 20 years Progression: months Pain 30%; especially with connective tissue disease R/O: polymyalgia; arthritis; fasciitis; rhabdomyolysis PM associated disorders Cardiac Arhythmias Inflammatory cardiomyopathy Pulmonary Respiratory muscle weakness, 4% for initial feature Interstitial lung disease Esophageal paresis Upper 1/3 with muscle weakness Lower 2/3 with scleroderma Malignancy: mild increased risk Autoimmune: Lupus; Sjögren's; APAS; thyrotoxicosis Respiratory involvement in PM Interstitial lung diseaes Aspiration pneumonia Alveolar hypoventilation Ventilatory insufficiency PM-RF Case 1: 61M Selva-O’Callaghan et al, Spain, Rheumatology 2000;39:914-6 Progressive girdle & neck weakness for 1 M Paradoxical dysphagia CPK: 1494 IU/l; ESR: 48 mm/h EMG & muscle biopsy: confirmed Hypercapnic respiratory failure at D3 Tx: Prednisone 1mg/kg/d, IVIG, Cyclosporin 150 bid Extubation 20 days later PM-RF Case 2: 43F Selva-O’Callaghan et al, Spain, Rheumatology 2000;39:914-6 18 y/o: diagnosed PM (EMG, biopsy) 34 y/o: wheelchair bound (P+A treatment) 39 y/o: acute URI precipitate resp. failure PO2: 40 mmHg, PCO2: 68 mmHg Tracheostomy with home ventilator Stable status with normal ABG at home PO2: 83 mmHg, PCO2: 45 mmHg Diagnosis - PM Serum CK: High (3 to 30 X ) EMG: Irritative myopathy Small amplitude, brief, polyphasic motor units Fibrillations; positive sharp waves Antibodies: disease specific & non-specific Muscle biopsy Variation in size of muscle fibers Necrosis; phagocytosis & regeneration of fibers Mild, patchy increase in endomysial connective tissue Inflammation: endomysial & perivascular Focal invasion of non-necrotic muscle fibers Classification of PM Idiopathic Proximal weakness; CK; inflammatory myopathy Collagen vascular disease Myalgias; scleroderma & MCTD Anti-t-RNA synthetase antibodies;Jo-1 antibodies Interstitial pneumonitis; Raynauds; arthritis Signal recognition particle antibody Acute onset; severe weakness MAS antibody Acute onset; rhabdomyolysis Drug-induced: D-penicillamine Classification of PM Familial: Homozygosity at HLA-DQA1 locus Graft-vs-host disease: 7 to 24 months post BMT Granulomatous: sarcoid; immune; infection Malignancy (necrotic) Rapid onset; older patients; necrotic myopathy Mitochondrial (P-COX) Quadriceps weakness; steroid resistant; Age Other systemic disorders: HIV; fasciitis Treatment - PM Corticosteroid Oral Prednisone 100 mg q.d.; latency: 1 to 6 months Solumedrol (iv): Fewer side effects than oral prednisone Azathioprine 2.5 - 3mg/kg/day; for prednisone dose Latency: 6 to 12 months Methotrexate 7.5 to 22.5 mg/wk; 1 or 2 doses on weekends Latency: 3 to 6 months Cyclosporine Starting dose: 2.5 mg/kg b.i.d Latency: 2 to 6 months Case Demonstration 73 M Progressive malaise, acronumbness for 4 days ER: 970814 144/92mmHg, PR 92/min, RR 14/min No edema or dehydration Quadriplegia/malaise: UE:3/LE:0 Generalized areflexia [Na]: blood 121 mEq/L, urine 155 mEq/L Osmolality: blood 260 mosm/kg, urine 716 mosm/kg PH: ASD, gout 4565238 Clinical course 970817 in MICU: respiratory failure HIV: negative Complement & ANA: WNL Serum protein electrophoresis: No M-protein CEA, AFP, CA 19.9 & CA 125: WNL CXR: no pneumonic patch Nerve conduction study D14 DML CMAP NCV F-wave Median 14.9/16.5 0.7/0.6 37.0/31.3 41.7/— Ulnar 6.7/6.1 0.4/0.3 17.4/39.8 —/ — Peroneal 5.8/7.3 0.8*/1.3* 39.3/44.0 —/ — Tibial 7.0/8.2 0.7/0.3 38.6/42.4 —/ — *: conduction block All SAPs were absent. 70 SIADH MRC sumscore 60 6 50 40 4 30 MRC Grade 20 10 2 0 8/9 12 15 17 19 21 23 25 27 29 9 / 1 3 5 8 10 N/S cc/hr 60 cc/hr Water restriction cc/d Plasmapheresis 40 Lasix mg/d 40 cc/hr 1000 1500 QOD * 5 1000 140 Na 135 130 125 UNa 155 / Uosm 716 120 15 16 19 21 UNa 165 22 25 28 1 4 5 8 55 F Acute worsening of dyspnea on 8/10, 1996 Present illness General weakness, SOB, dysphagia for 2 months BW loss 20 kg/2 months Cathay General Hospital Severe restrictive lung disease Gastric erosion (PES) Past history: DM for 5 years NE & ABG Neurological exam Clear consciousness No ptosis EOM: OK MP: 3/3 DTR: ++/++ Blood gas ABG 8/10 8/11 pH 7.366 7.185 PO2 166.3 113.5 PCO2 58.0 88.0 HCO3 33.4 33.4 SaO2 99.4 96.7 Chest PA Laboratory tests Glu(pc) Ketone Cr Na K Osmol 435 T3 54.8 CPK 402 + T4 6.8 AchRAb 46.01 0.7 TSH 0.14 ESR 15/hr 145 Hb 16.5 EF 55% 3.8 Platelet 263K LA 52mm 309 WBC 9200 EKG NSR Mediatinal CT Contrast