Neuromuscular diseases leading to respiratory failure

Jiann-Horng Yeh, M.D.

Department of Neurology

Shin Kong WHS Memorial Hospital

Respiratory muscles

Muscle groups AHC level

Diaphragm C3-5

Intercostal muscles T1-12

Scalene

Sternocleidomastoid

Trapezoid

C4-8

Cranial XI, C2-3

Cranial XI, C2-4

Abdominal muscles T7-L1

Neurological signs for D/D

Level DTR Bulbar EOM Sensation ANS

UMN +/— +/— +/— +/—

AHC +/— — — —#

Nerve + +/— + +

NMJ N + + — +/—

Muscle N +/— — —* —

* Pain in polymyositis# ANS s/s in Bulbar poliomyelitis

Common disorders of NMD

UMN NMJ Muscle

BS/cord lesion Myasthenia gravis Dystrophy

LMN LE syndrome Polymyositis

Poliomyelitis Botulism Trichinosis

ALS OP poisoning Endocrine myopathy

Nerve Tick paralysis

GB syndrome

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 drugsMetabolic disorderCentral transtentorial herniation

CNS disorders causing RF

Neuropathy with RF - IGBS NCV PE, IVIG

CIDP NCV PE, Steroid, IVIG

Critical illness — —

Lymphoma N biopsy Cytotoxic

Vasculitis-LE N biopsy Steroid, Endoxan

Porphyria U/porphobilinogen IV hematin

Diphtheria Throat swab Antitoxin

H.tyrosinemia U/d-ALA High calorie intake

Liver transplant

Toxic neuropathy with RF

O-phosphate RBC C-esterase

P/pseudoC-esteraseAtropine

Pralidoxime

Thallium Blood level Berline blue

Arsenic 24h Urine level Dimercaprol, DMSA

Lead Blood level Na-Ca edetate, above

Gold — Na-Ca edetate, above

Lithium Plasma level Hemodialysis

Vincristine — Withdrawal

General hints in initial symptomsVomitingAltered level of consciousness

ThalliumProminent cutaneous & muscular pain, esp. feetPreserved DTR in the early stage

Clues for toxic neuropathy

NM disorders with RF

Myasthenia gravis Tensilon test, AchRAb PP, Steroid

AC overdose Tensilon test — Withdrawal

Antibiotics — Withdrawal

Hypermagnesemia Plasma level, RNS IV calcium

Botulism Antibody, RNS Antitoxin

Poisoning * Identification Antitoxin

Tick paralysis Find the tick Removal

LE syndrome Increment on RNS PP, steroid

* snake, scorpion, spider, fish, shellfish, crab

Muscle disorders with RF Hypokalemia Plasma level K+

Polymyositis CPK, EMG, biopsy Steroid

Rhabdomyolysis 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

Differential tests

Physical and neurological examinationsLaboratory tests

Electrophysiology: NCV, RNS, EMG, SFEMGCPK, electrolyte, thyroid functionAntibody titerCSFBiopsy: nerve, muscle

Provocative test: Tensilon test

General Management in ICU

Orthopnea, interrupted speechShallow & rapid respirationParadoxical respirationBreathing sound

Reduced BS, sputum, crackle

Arterial blood gasHypoxemia, CO2 narcosis, respiratory acidosis

AIRWAY MANAGEMENT Evaluate s/s of impending respiratory

failure

Criteria for intubationVC<15 mL/kg; Pimax < -25 cmH2O

Paired VC test – supine & sitting positionNormal: Supine VC > 80% Sitting VCWeakness: Supine VC < 40% Sitting VC

Digit count at one breathCount <25: VC < 20 mL/kg

AIRWAY MANAGEMENTMonitor the changes of pulmonary

function

Chest physical therapyPercussion, postural drainage

Education for effective respiration/coughingElective intubation

Impaired swallowingSigns of aspiration pneumoniaHypoxemiaCritical level of lung function

AIRWAY MANAGEMENTAppropriate chest care

Prevention of complications

Careful posturing: entrapment neuropathyFrequent turn: bedsoresPassive exercise: disuse atrophyNG feeding: aspirationHeparin or pneumatic leg compression: DVTVital sign monitoring: ANS instabilityEmotional support: anxiety, depression

Guillain-Barré syndrome

Guillain-Barré Syndrome(Acute inflammatory demyelinating polyneuropathy)

Acute/subacute motor paralysis for days/wksArefelexia or hyporeflexiaMild sensory symptoms or signsCSF: albuminocytological dissociation

NCV: conduction slowing or block

Pathology Focal segmental demyelination Inflammatory cells infiltration

Clinical courseCourse

Progression: 4 wk (90%)Plateau: 4 wk (85%)Recovery: 4-6 months (80%)

OutcomePermanent 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 - IICranial 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 associatedWeakness of shoulder elevation & neck flexion

parallels diaphragmatic weakness & resp. failure

Clinical features -IIIAutonomic involvement: 65%

Sinus tachycardia: > 50%SIADH, (DI)Orthostatic hypotension (20%) & hypertensionSweating disturbanceCardiac 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

0

1

2

3

4

5

6

7

1 2 3 4 5 6 7 8 9 10 11 12 14 16 18 20 22 24 26 28

GradeMRC-sum score *10

ANSANS

IntubationIntubation

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 Definition Class

GBS Established I

CIDP Established I

MS - acute; refractory to steroid Established I

MGUS - IgG/A Established I

MG – preop & crisis Established III

MGUS - IgM Investigational I

Lambert-Eaton syndrome Possibly useful II/IIIInvestigational: Refsum disease, acquired neuromyotonia,

Stiff-man syndrome, Cryoglobulinemic neuropathy, CNS lupus, ADEM

GBS Study Group : PE vs No TxNeurology 1985,35,1094-1104

245 patients; 40-50 cc/kg for 3-5 PE

Parameters PE No Tx p

Improve > 1 grade at 4 wks 59% 39% *

Mean grade change at 4 wks 1.1 G 0.4 G **

Median time to improve 1 G 19 D 40 D **

Median time to walk unaided 53 D 85 D **

Median time on ventilator 24 D 48 D *

Failed to improve 1 G at 6M 3% 13% *

Plasmapheresis appears to be of benefit in patients with GBS of recent onset (within 7 days).

Change of MRC-sum score during plasmapheresis in GBS

Chen et al; J Clin Apheresis 1999;14:126-9.

32.6

45

0

50

Pre-PP Post-PP

Score

Author Y Country No G at entry

Time to Tx

Osterman 84 Sweden 18 4.6 6.9GBS study 85 USA 122 4.3 11.1

French 87 France 109 ND 6.3Van der Meche 92 Neth 73 3.9 5.6

Bril 96 Canada 24 4.1 4.7PES/GBS 97 UK 121 3.9 6.9

SKH 98 Taiwan 16 3.6 8.1

Plasmapheresis in GBSChen et al; J Clin Apheresis 1999;14:126-9.

Plasmapheresis in GBSChen et al; J Clin Apheresis 1999;14:126-9.

Author 1G at W4(%)

G at W4

Time to G2

Fail to G2 at M6

OFF respirator

Osterman 2.1 GBS study 59 1.1 53 21 9

French 70 18 Van der Meche 34 0.4 69 22.6

Bril 61 1 PES/GBS 1.1 40 13.7

SKH 81 1.5 19 13 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 - MGOcular

Ptosis & ophthalmoplegia

Usually asymmetric & bilateral

Bulbar Dysarthria, dysphagia,

weak mastication Complicated with

aspiration pneumonia Facial: > 95%

Respiratory failure Life-threatening Etiology

diaphragmatic & intercostal muscle weakness

vocal cord paralysis

Systemic Typical: symmetric

Proximal > distal Arms > legs

Selective weakness Posterior neck Occasional distal

Severity classification of MG

Osserman/71 Drachman/82

Grade 1 Ocular Focal

Grade 2 a: Mild generalized

b: Severe generalized

Mild 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.

2 mg IV observation for 2 min 8 mg IVA 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

Edrophonium (Tensilon) test

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 aidMonitor the clinical statusEvaluate the efficacy of immune therapiesAssess the functional capacity of

plasmapheresis column quantitatively

Adults with generalized MG: 85 to 90% Childhood MG: 50% Ocular MG: 50% to 70%MG with thymoma: nearly 100% Some patients taking penicillamine +/- MG Thymoma without MG Immune liver disordersLambert-Eaton syndrome (13%)Primary lung cancer: 3%Older patients (> 70 years): 1% to 3% Neuromyotonia

AchRAbPositive

AchRAbFalse +

AchRAb titers in Osserman stages (n=699)

56.980.2 88.8 96.3 100

0%

20%

40%

60%

80%

100%

I-348 IIa-243 IIb-80 III-27 IV-1

<0.2

<0.5

>0.5

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

Thymus relationship - MG

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

Characteristic % no

Pneumonia/pneumonitis 40 8

Bronchitis 30 6

URI 5 1

Sepsis 15 3

Surgery 10 2

No obvious precipitant 15 3

Precipitants (n=20)Yeh et al; Acta Neurol Scand 2001; in

press

Drugs interfere NM transmission

Variety Drug

Antibiotic Aminoglycoside, Fluoroquinolone, Tetracycline, Sulfonamide, Penicillin, Macrolide, Lincomycin, Colistin, Polymyxin, Quinocrine, Chloroquine

CNS Transquillizer, Barbiturate, Anticonvulsant, Lithium, Mg salt, TCA, Haloperidol

Anesthesic Halothane, Ether, Trichloroethylene

CV B-blocker, Verapamil, Quinidine, Procainamide

Others Narcotic, Penicillamine, Iodinated contrast

0.3

0.5

4

6

10

12

18

24

Plasmapheresis

PP+steroid

Steroid

CTX+steroid

Cyclophosphamide

Azathioprine

AZA+steroid

Thymectomy

Time to produce a 50% AchRAb (m)

Tindall RSA/1982

Plasma Exchange - MGDose: 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)

Double-filtration plasmapheresis

PlasmaBlood Purified P

Clinical responseYeh et al, Acta Neurol Scand 1999;100:305-9

Poor16%

Fair62%

Good22%

Poor Fair Good0: 2 2:12 5:31: 5 3:8 6:2

4:8 >:5

Clinical response: plasmapheresis

Dau-81 60 PE 74%

Fornasari-85 33 PE 61%

Mantegazza-87 37 PE 87%

Antozzi-91 70 PE 70%

Kornfeld-92 43 PE 91%

Author-year no Method Response

Shibuya-94 20 IAP 55%Yeh-99 45 DFP 84%

Change of MG score during DFP

9.9

4.2

0

5

10

Pre-PP Post-PP

Score

Change of AchRAb titer during DFP

1st2nd

3rd4th

Filtrate

Blood

0.670.56

0.440

0.2

0.4

0.6

0.8

1

Session of plasmapheresis

0.780.71

0.61

Pulmonary function tests during DFP

1st2nd

3rd4th

Vital capacity

Pimax1.37 1.55 1.85

0

0.5

1

1.5

2

Session of plasmapheresis

1.40 1.49 1.86

Favorable prognostic parameters

Yeh et al, Acta Neurol Scand 1999;100:305-9

High MG scorePathology of non-thymoma typeYoung age at onsetDaily apheresisHigh removal rate for IgG

Clinical response of DFPYeh et al; Acta Neurol Sin 1995;4:107-12.

1 0.70.53 0.47

0

0.2

0.4

0.6

0.8

1

Response rate Effective duration > 2Months

Dyspnea groupNon-dyspnea group

Botulism

Botulinum Toxin

Clostridium botulinum Gram positive bacilli Spore producingAnaerobic: obligate

Botulinum Toxin Sequence homology (30% to 40%) to tetanus toxinProduced as a protoxin withMW 150 kDa7 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

Time course Incubation period: average: 18 to 38 hoursExtremes: 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

Clinical Features - Botulism

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 miceSelectively prevented by anti-toxin

Stool or wound culture

Foodborne Botulism

FoodContaminated with spores in anaerobic conditionsHome canned vegetable/potato & preserved sea food

ToxinResistant to proteolysis in stomach

AbsorptionAlkaline pH of intestine dissociates toxin from

proteins Absorption into circulation

Usually adults

Foodborne Botulism in Taiwan

1986; 9 cases (2 fatalities) in Chang-Hwa cityType A foodborne botulismCanned peanuts from a unlicensed canneryMalaise, 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 locallyDrug 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

HyperkalemicHereditary (AD)

Na+ channel (SCN4A)17q35

Hypokalemic Hereditary

Ca++ channel (CACNA1S)1q31

K+ channel (KCNE3)11q13-14

Na+ channel (SCN4A)17q13

Distal RTA (ASLC4A1)17q21-22

ThyrotoxicAcquired: K+ wasting

Periodic Paralysis

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 - HOPPLaboratory

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 HyperaldosteronismAngiotensin converting enzyme dysfunctionLicorice intoxicationMineralocorticoid excessRenal tubular acidosis

Sjögren's, Fanconi's syndrome

Alkaline urine & azotemia: Amphotericin B

Acidosis Ammonium chloride ingestionUreterocolostomies: bilateralDiabetic coma: recoveryRenal tubular necrosis: recovery Distal renal tubular acidosis

Other Gossypol toxicity (with low K+ diet) Tea: excessive amounts

K wasting syndrome – urinary loss

Non-tropical sprue Laxative abuse Severe diarrhea or vomiting Draining GI fistula

K wasting syndrome – GI loss

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 - TPPLaboratory

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 disordersCardiac

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 diseaesAspiration pneumoniaAlveolar hypoventilationVentilatory insufficiency

PM-RF Case 1: 61MSelva-O’Callaghan et al, Spain, Rheumatology

2000;39:914-6

Progressive girdle & neck weakness for 1 MParadoxical dysphagiaCPK: 1494 IU/l; ESR: 48 mm/hEMG & muscle biopsy: confirmedHypercapnic respiratory failure at D3Tx: Prednisone 1mg/kg/d, IVIG, Cyclosporin 150 bid

Extubation 20 days later

PM-RF Case 2: 43FSelva-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 mmHgTracheostomy with home ventilator

Stable status with normal ABG at homePO2: 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

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

Classification of PM

Treatment - PMCorticosteroid

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 MProgressive malaise, acronumbness for 4 daysER: 970814

144/92mmHg, PR 92/min, RR 14/minNo edema or dehydrationQuadriplegia/malaise: UE:3/LE:0Generalized areflexia [Na]: blood 121 mEq/L, urine 155 mEq/LOsmolality: blood 260 mosm/kg, urine 716 mosm/kg

PH: ASD, gout 4565238

Clinical course

970817 in MICU: respiratory failureHIV: negativeComplement & ANA: WNLSerum protein electrophoresis: No M-proteinCEA, AFP, CA 19.9 & CA 125: WNLCXR: 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 blockAll SAPs were absent.

0

10

20

30

40

50

60

70

9 12 15 17 19 21 23 25 27 29 1 3 5 8 10

MR

C s

umsc

ore

MRCGrade

2

4

6SIADH

8/ 9/

120

125

130

135

140

15 16 19 21 22 25 28 1 4 5 8

Na

QOD * 5

1000 1500 1000

60 cc/hr 40 cc/hr

Lasix mg/d

N/S cc/hr

Water restriction cc/d

Plasmapheresis

UNa 155 / Uosm 716 UNa 165

40

55 F

Acute worsening of dyspnea on 8/10, 1996Present illness

General weakness, SOB, dysphagia for 2 monthsBW loss 20 kg/2 monthsCathay General Hospital

Severe restrictive lung diseaseGastric erosion (PES)

Past history: DM for 5 years

NE & ABG

Neurological examClear consciousnessNo ptosisEOM: OKMP: 3/3DTR: ++/++

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

Blood gas

Chest PA

Laboratory tests

Glu(pc)

435 T3 54.8 CPK 402

Ketone + T4 6.8 AchRAb 46.01

Cr 0.7 TSH 0.14 ESR 15/hr

Na 145 Hb 16.5 EF 55%

K 3.8 Platelet 263K LA 52mm

Osmol 309 WBC 9200 EKG NSR

Mediatinal CT

Contrast