Transcript Neuromuscular diseases leading to respiratory failure Jiann-Horng Yeh, M.D. Department of Neurology

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