Neuromuscular diseases leading to respiratory failure
Upcoming SlideShare
Loading in...5
×
 

Neuromuscular diseases leading to respiratory failure

on

  • 2,646 views

 

Statistics

Views

Total Views
2,646
Views on SlideShare
2,646
Embed Views
0

Actions

Likes
0
Downloads
63
Comments
0

0 Embeds 0

No embeds

Accessibility

Categories

Upload Details

Uploaded via as Microsoft PowerPoint

Usage Rights

© All Rights Reserved

Report content

Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

Cancel
  • Full Name Full Name Comment goes here.
    Are you sure you want to
    Your message goes here
    Processing…
Post Comment
Edit your comment

    Neuromuscular diseases leading to respiratory failure Neuromuscular diseases leading to respiratory failure Presentation Transcript

    • Neuromuscular diseases leading to respiratory failure Jiann-Horng Yeh, M.D. Department of Neurology Shin Kong WHS Memorial Hospital
    • Respiratory muscles C4-8 Cranial XI, C2-3 Cranial XI, C2-4 Scalene Sternocleidomastoid Trapezoid T7-L1 Abdominal muscles T1-12 Intercostal muscles C3-5 Diaphragm AHC level Muscle groups
    • Neurological signs for D/D * Pain in polymyositis # ANS s/s in Bulbar poliomyelitis — + + / — — + / — EOM — — * + / — N Muscle + / — — + N NMJ + + +  Nerve — # — + / —  AHC + / — + / — + / —  UMN ANS Sensation Bulbar DTR Level
    • Common disorders of NMD GB syndrome Tick paralysis Nerve Endocrine myopathy OP poisoning ALS Trichinosis Botulism Poliomyelitis Polymyositis LE syndrome LMN Dystrophy Myasthenia gravis BS/cord lesion Muscle NMJ UMN
      • 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
      CNS disorders causing RF
      • Sedative drugs
      • Metabolic disorder
      • Central transtentorial herniation
    • Neuropathy with RF - I High calorie intake Liver transplant U/d-ALA H.tyrosinemia Antitoxin Throat swab Diphtheria IV hematin U /porphobilinogen Porphyria Steroid, Endoxan N biopsy Vasculitis-LE Cytotoxic N biopsy Lymphoma — — Critical illness PE, Steroid, IVIG NCV CIDP PE, IVIG NCV GBS
    • Toxic neuropathy with RF Withdrawal — Vincristine Hemodialysis Plasma level Lithium Na-Ca edetate, above — Gold Na-Ca edetate, above Blood level Lead Dimercaprol, DMSA 24h Urine level Arsenic Berline blue Blood level Thallium Atropine Pralidoxime RBC C-esterase P/pseudoC-esterase O-phosphate
      • General hints in initial symptoms
        • Vomiting
        • Altered level of consciousness
      • Thallium
        • Prominent cutaneous & muscular pain, esp. feet
        • Preserved DTR in the early stage
      Clues for toxic neuropathy
    • NM disorders with RF * snake, scorpion, spider, fish, shellfish, crab Removal Find the tick Tick paralysis PP, steroid Increment on RNS LE syndrome Antitoxin Identification Poisoning * Antitoxin Antibody, RNS Botulism IV calcium Plasma level, RNS Hypermagnesemia Withdrawal — Antibiotics Withdrawal Tensilon test — AC overdose PP, Steroid Tensilon test, AchRAb Myasthenia gravis
    • Muscle disorders with RF IV K + Mg sulfate, po Hemodialysis Plasma K + Barium intoxication — PAS stain (PB film) Acid maltase def. Phosphate Plasma level Hypophosphatemia Urine alkalinization CPK, EMG, biopsy Rhabdomyolysis Steroid CPK, EMG, biopsy Polymyositis K + Plasma level Hypokalemia
    • 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
      • Orthopnea, interrupted speech
      • Shallow & rapid respiration
      • Paradoxical respiration
      • Breathing sound
        • Reduced BS, sputum, crackle
      • Arterial blood gas
        • Hypoxemia, CO2 narcosis, respiratory acidosis
      AIRWAY MANAGEMENT Evaluate s/s of impending respiratory failure
      • Criteria for intubation
        • VC<15 mL/kg; Pimax < -25 cmH 2 O
      • 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 Monitor the changes of pulmonary function
      • 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
      AIRWAY MANAGEMENT Appropriate chest care
    • 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 ANS Intubation
    • 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 Investigational : Refsum disease, acquired neuromyotonia, Stiff-man syndrome, Cryoglobulinemic neuropathy, CNS lupus, ADEM III Established MG – preop & crisis I Established MS - acute; refractory to steroid II/III Possibly useful Lambert-Eaton syndrome I Investigational MGUS - IgM I Established MGUS - IgG/A I Established CIDP I Established GBS Class Definition Disease
    • GBS Study Group : PE vs No Tx Neurology 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.
    • Plasmapheresis in GBS Chen et al; J Clin Apheresis 1999;14:126-9. 8.1 3.6 16 Taiwan 98 SKH 6.9 3.9 121 UK 97 PES/GBS 4.7 4.1 24 Canada 96 Bril 5.6 3.9 73 Neth 92 Van der Meche 6.3 ND 109 France 87 French 11.1 4.3 122 USA 85 GBS study 6.9 4.6 18 Sweden 84 Osterman Time to Tx G at entry No Country Y Author
    • Plasmapheresis in GBS Chen et al; J Clin Apheresis 1999;14:126-9. 11.2 13 19 1.5 81 SKH  13.7 40 1.1  PES/GBS    1 61 Bril 22.6  69 0.4 34 Van der Meche  18 70   French 9 21 53 1.1 59 GBS study    2.1  Osterman OFF respirator Fail to G2 at M6 Time to G2  G at W4  1G at W4(%) Author
    • 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
          • diaphragmatic & intercostal muscle weakness
          • vocal cord paralysis
      • Systemic
        • Typical: symmetric
          • Proximal > distal
          • Arms > legs
        • Selective weakness
          • Posterior neck
          • Occasional distal
    • Severity classification of MG Crisis Late severe Grade 4 Severe generalized Acute fulminating Grade 3 Mild generalized a: Mild generalized b: Severe generalized Grade 2 Focal Ocular Grade 1 Drachman /82 Osserman /71
    • 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 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
      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 aid
      • Monitor the clinical status
      • Evaluate the efficacy of immune therapies
      • Assess 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 disorders
      • Lambert-Eaton syndrome (13%)
      • Primary lung cancer: 3%
      • Older patients (> 70 years): 1% to 3%
      • Neuromyotonia
      AchRAb Positive AchRAb False +
    • AchRAb titers in Osserman stages (n=699)
      • 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
    • Precipitants (n=20) Yeh et al; Acta Neurol Scand 2001; in press 3 15 No obvious precipitant 2 10 Surgery 3 15 Sepsis 1 5 URI 6 30 Bronchitis 8 40 Pneumonia/pneumonitis no % Characteristic
    • Drugs interfere NM transmission Narcotic , Penicillamine, Iodinated contrast Others B-blocker , Verapamil , Quinidine, Procainamide CV Halothane, Ether, Trichloroethylene Anesthesic Transquillizer , Barbiturate , Anticonvulsant, Lithium, Mg salt, TCA, Haloperidol CNS Aminoglycoside , Fluoroquinolone , Tetracycline, Sulfonamide, Penicillin, Macrolide, Lincomycin, Colistin, Polymyxin, Quinocrine, Chloroquine Antibiotic Drug Variety
    • Time to produce a 50% AchRAb  (m) 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)
    • Double-filtration plasmapheresis Plasma Blood Purified P
    • Clinical response Yeh et al, Acta Neurol Scand 1999;100:305-9 Poor Fair Good 0: 2 2:12 5:3 1: 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
    • Change of AchRAb titer during DFP 0.78 0.71 0.61
    • Pulmonary function tests during DFP 1.40 1.49 1.86
    •  
    • 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.
    • 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
      • 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
      Clinical Features - Botulism
    • Cholinergic ANS involvement
      • Pupils: d ilated, 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: r espiratory; 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 O 2 ; 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
      • Hyperkalemic
        • Hereditary (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
          • Thyrotoxic
        • Acquired: 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 - 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
      • 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 – 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 - 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
        • PO 2 : 40 mmHg, PCO 2 : 68 mmHg
        • Tracheostomy with home ventilator
      • Stable status with normal ABG at home
        • PO 2 : 83 mmHg, PCO 2 : 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 - 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 , u rine 1 55 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
      • *: conduction block
      • All SAPs were absent.
      — / — 38.6/42.4 0.7/0.3 7.0/8.2 Tibial — / — 39.3/44.0 0.8*/1.3* 5.8/7.3 Peroneal — / — 17.4/39.8 0.4/0.3 6.7/6.1 Ulnar 41.7/ — 37.0/31.3 0.7/0.6 14.9/16.5 Median F-wave NCV CMAP DML D14
    • 2 4 6 SIADH 8/ 9/
    • QOD * 5 1000 1500 1000 60 cc/hr 40 cc/hr Lasix mg/d N/S cc/hr Water restriction cc/d Plasmapheresis U Na 155 / U osm 716 U Na 165 40
    • 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
      96.7 99.4 SaO 2 33.4 33.4 HCO 3 88.0 58.0 PCO 2 113.5 166.3 PO 2 7.185 7.366 pH 8/11 8/10 ABG
    • Chest PA
    • Laboratory tests NSR EKG 9200 WBC 309 Osmol 52mm LA 263K Platelet 3.8 K 55% EF 16.5 Hb 145 Na 15/hr ESR 0.14 TSH 0.7 Cr 46.01 AchRAb 6.8 T4 + Ketone 402 CPK 54.8 T3 435 Glu(pc)
    • Mediatinal CT Contrast