Transcript guillain-barre syndrome

MYOPATHIES AND
NEUROPATHIES IN
CRITICAL CARE
DEFINITION
Neuromuscular or myoneural disease is a very broad
term that encompasses many diseases and ailments
that impair the functioning of the muscles, either
directly, being pathologies of the muscle, or indirectly,
being pathologies of nerves or neuromuscular
junctions.
CLASSIFICATION
IMMUNE MEDIATED: Immune-mediated diseases include a variety of diseases
affecting the nerve & neuromuscular junction
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Myasthenia gravis
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Lambert-Eaton syndrome.
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Guillain-Barre syndrome .
TOXIC/METABOLIC : Abnormal energy metabolism by damaging or disabling
enzyme, or abnormal feed back system. Toxins effecting neuromuscular
junction functioning
• Critical Illness Polyneuropathy & Critical illness myopathy.
• Snake venom poisoning,
• Botulism, Fugu fish poisoning etc.
• Arthropod poisoning,
• Organophosphates and
• Hypermagnesemia
MYASTHENIA GRAVIS
• Acquired autoimmune or congenital disorder
• Clinically characterized by:
– Weakness of skeletal muscles
– Fatigability on exertion
PATHOPHYSIOLOGY
• Antibodies are directed toward the acetylcholine receptor at
the neuromuscular junction of skeletal muscles
• Results in decreased number of nAChR at the motor endplate with reduced postsynaptic membrane folds and
widened synaptic cleft.
• Anti- AChR antibody is found in 80-90% .
• MG may be considered a B cell-mediated disease.
• In the rare congenital form ,there is genetic defect in some
portion of the neuromuscular junction.
• Up to75% have Thymic hyperplasia and thymomas and
T-cell mediated immunity is implicated.
CLINICAL FEATURES
• Fluctuating weakness increased by exertion (Weakness
improves with rest) Usually spreads from ocular to facial to
bulbar to truncal and limb muscles .Often, symptoms may
remain limited to EOM and eyelid muscles for years
• Asymmetric ocular involvment
• lateral and medial recti weakness -- Limited adduction of one
eye with nystagmus of the abducting eye on attempted lateral
gaze ,
• Ptosis & Diplopia.
• Bulbar muscle weakness
“Nasal voice”, nasal regurgitation, Drop Jaw, difficult chewing ,
Swallowing may be difficult and aspiration may occur with fluids ,
Neck flexors affected more than extensor
• Upper limbs more common than lower limbs
• Weakness of the intercostal muscles and the diaghram may result in CO2
retention due to hypoventilation causing neuromuscular emergency .
• Weakness of pharyngeal muscles may collapse the upper airway
• Monitor negative inspiratory force, vital capacity and tidal volume
• Do NOT rely on pulse oximetry
Arterial blood oxygenation may be normal while CO2 is retained
• Remissions with treatment occur within the first three years
CO-EXISTING AUTOIMMUNE
DISEASES
– Hyperthyroidism
• Occurs in 10-15% MG patients
– Exopthalamos and tachycardia point to hyperthyroidism
– Weakness may not improve with treatment of MG alone in
patients with co-existing hyperthyroidism
– Rheumatoid arthritis
– Scleroderma
– Lupus
IMPLICATED DRUGS
• penicillamine exposure
• Antibiotics (Amino glycosides, ciprofloxacin,
ampicillin, erythromycin)
• B-blocker (propranolol)
• Lithium
• Magnesium
• Procainamide
• Verapamil
• Quinidine
• Chloroquine
• Prednisone
• Timolol
• Anticholinergics
COMPLICATIONS
• Respiratory failure
• Dysphagia
• Complications secondary to drug treatment
– Long term steroid use
• Osteoporosis, cataracts, hyperglycemia, HTN
• Gastritis, peptic ulcer disease
• Pneumocystis carinii.
DIFFERENTIAL DIAGNOSIS
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Amyotropic Lateral Sclerosis
Basilar Artery Thrombosis
Brainstem gliomas
Cavernous sinus syndrome.
Lambert-Eaton Myasthenic Syndrome
Multiple Sclerosis
Sarcoidosis and Neuropathy
Thyroid disease
Botulism
Oculopharyngeal muscular dystrophy
Brainstem syndromes.
LAB AND RADIOLOGY
• Lab studies : Anti-acetylcholine receptor antibody Positive , Anti-striated
muscle Present in of patients with thymoma , who are younger than 40
years
• Interleukin-2 receptors Increased in generalized and bulbar forms of MG
• Chest x-ray : thymoma as an anterior mediastinal mass. Chest CT scan is
mandatory to identify thymoma
• MRI of the brain and orbits may help to rule out other causes of cranial
nerve deficit
• Tensilon test : Edrophonium (Acetylcholine Esterase Inhibitor) muscle
contractility improves after Edrophonium administration.
• Electrodiagnostic studies
– Repetitive nerve stimulation
– Single fiber electromyography (SFEMG)
– SFEMG is more sensitive than RNS in MG
MANAGMENT
• AChE inhibitors:-Pyridostigmine bromide (Mestinon)
• Starts working in 30-60 minutes and lasts 3-6 hours
– 60-960mg/d PO (2mg IV/IM q2-3h)
• Caution:-Check for cholinergic crisis
• Others: Neostigmine Bromide
• Immunomodulating therapies:- Prednisone
Significant improvement in 1-4 month , Clearance
may be decreased by estrogens or digoxin ,concurrent
diuretics use should be monitored for hypokalemia
• Plasmapheresis
• Thymectomy.
OUT COME
• Untreated MG carries a mortality rate of 2531%
• Treated MG has a 4% mortalitiy rate
• 40% have ONLY occular symptoms
– Only 16% of those with occular symptoms at onset
remain exclusively occular at the end of 2 years
GUILLAIN-BARRE
SYNDROME
It is acute immune-mediated polyneuropathy
• Peripheral nerve myelin is target of an immune
attack
• Starts at level of nerve root leading to
conduction blocks & muscle weakness
• Eventually becomes widespread patchy
demyelination and causes increased paralysis
PATHOPHYSIOLOGY
• Usually post infectious immune - mediated (Ab
against specific gangliosides /glycolipids)
• Lymphocytic infiltration of spinal roots/peripheral
nerves F/B macrophage-mediated, multifocal
stripping of myelin
• Results faulty propagation of nerve impulses, with
eventual conduction block and flaccid paralysis .
CLINICAL FEATURES
• Progressive, fairly symmetric muscle weakness
-typically starts in proximal legs
-10% will 1st develop weakness in face or arms
-severe resp muscle weakness in 10-30% pts
-oropharyngeal weakness in ~ 50%
• Absent or depressed DTR
• Often prominent severe pain in lower back
• Common to have paresthesias in hands and
feet
• Autonomic : tachycardia, urinary retention,
hypertension alternating with hypotension,
paralytic ileus.
DIAGNOSIS
Progressive weakness of > than 1 limb
with Areflexia
Supportive Features:
• Progression of symptoms over days to 4 weeks.
• Relative symmetry.
• Involvement of b/l facial nerve weakness.
• Autonomic dysfunction (EMG features prolonged or
absent F waves .
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CSF elevated protein with normal WBC (80-90%
pts)
(Albuminocytologic dissociation) .
DIFFERENTIAL DIAGNOSIS
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Arsenic poisoning
N-Hexane (glue sniffing)
Vasculitis
Lyme Disease
Tick paralysis
Sarcoidosis
Leptomeningeal disease .
Paraneoplastic disease .
Critical Illness
VARIANTS
• ACUTE INFLAMMATORY
DEMYLINATING Polyneuropathy commonest
type accounting for 85-90% of cases.
• Miller Fisher Syndrome: ophthalmoplegia,
ataxia, and areflexia (5%). GQ1b antibody. Only
1/4th with extremity weakness
• ACUTE MOTOR AXONAL NEUROPATHY:
selective motor nerves involvement , DTRs are
preserved almost all preceded by Campylobacter
infection.
• ACUTE MOTOR SENSORY AXONAL
NEUROPATHY: more severe form of AMAN
+sensory
MANAGMENT
• Close monitoring of respiratory status , up to 30% may
require ventilatory support
• In severe cases, I/arterial monitoring may be necessary
for significant B.P fluctuations.
• Neuropathic pain : Gabapentin or Carbamazepine
• IVIG : typically given for 5 d at 0.4 gram/kg/d (may
need to extend course depending on response)
• Plasmapheresis: usually 4-6 treatments over 8-10 days.
Because of ease of administration, IVIG is frequently
preferred.
Glucocorticoids
: no role except for coexisting
morbidity.
OUT COME
• 65% can walk independently after 6 mths.
• Overall, 80% usually recover completely.
• 5-10% have prolonged course with incomplete
recovery, abt 3% wheelchair bound.
• Approx 5% die despite ICU care.
• 2% will develop chronic relapsing Chronic
Inflammatory Demylinating
Polyradiculoneuropathy (CIDP).
Critical Illness
Polyneuropathy
Critical Illness
Myopathy
first described by Bolton and colleagues in 1986
SPECTRUM OF ILLNESS
• Peripheral neuropathy
– Critical illness polyneuropathy
– Acute motor neuropathy
• Neuromuscular junction dysfunction
– Transient neuromuscular blockade
(pharmacologic)
• Myopathy
– Disuse / Type II muscle fiber atrophy
– Thick-filament myopathy
– Necrotizing myopathy
DIFFERENTIAL DIAGNOSIS
• Spinal cord dysfunction
• Critical illness myopathy
• Guillain-Barre syndrome
• Motor neuron disease
• Porphyria
• Pre-existing neuropathy
• Myasthenia
PATHOPHYSIOLOGY
The cause of CIP and CIM are unknown, though they are
thought to be a possible neurological manifestation of systemic
inflammatory response syndrome .
Corticosteroids and neuromuscular blocking agents
vasopressors, catecholamines, parenteral nutrition may
contribute to development of CIP and CIM as may raised
blood sugar.
A muscle biopsy may show loss of myosin and / necrosis
when muscles lose stimulation from neurons,
It may not be solely due to loss of innervation some times in
critical illness myopathy, no other cause of the muscle
degeneration can be found.Generally there is no
demyelization of neurons.
Systemic Inflammatory Response causes CIP/CIM by
• Altering microcirculation
• Pro-inflammatory cytokines released causing increased
micro vascular permeability
• Axonal degeneration due to glucose-induced phosphate
depletion
• Damage from parenteral lipids
• Impaired transport of axonal proteins
• End neural edema and/or hypoxia
CRITERIA FOR CIP DIAGNOSIS
• Presence of sepsis, multi-organ failure, respiratory
failure, or septic inflammatory response syndrome
(SIRS).
• Difficulty weaning from ventilator or limb
weakness
• Decreased amplitudes of compound muscle and
sensory action potentials
• Widespread denervation potentials in muscle
• Normal or mildly increased levels of blood CPK
SIGNS AND SYMPTOMS
• Progressive, generalized and symmetric muscle weakness in
critical ill and immobilsed patients.
• Hip and shoulder muscles are especially affected, in rare cases
there is ophthalmoplegia.
• Prolonged weaning time (7 – 13 days) due to atrophy of
diaphragm and degeneration of pherenic nerve.
• Deep tendon reflexes may be lost or diminished.
• Bilateral symmetric flaccid paralysis of upper and lower limbs.
MANAGMENT
As CIP/CIM not only causes difficult weaning but
also causes prolonged rehabilitation, it icauses inc
morbidity after surviving acute illness therefore
aggressive treatment of sepsis, minimal use CSs
and NMBAs. managing difficulty in weaning
from mechanical ventilation as well as
rehabilitation programs and avoiding additional
pressure neuropathies by careful positioning are
also considered to be major issues.
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DVT prophylaxis.
Temperature and sugar control (<180mg/dl): insulin therapy to maintain strict
glycemic control therefore may be beneficial to prevent CIP/CIM. Insulin itself has some
potential beneficial effects, including anti-inflammatory effects , endothelial protection ,
improvement of dyslipemia, and neuroprotective .
Regular monitoring for HCAP /VAP.
Hand heigene .
Daily weaning trials according to protocol.
Optimized Nutrition : nutrition schemes and nutritional interventions , supplement therapies ,
anti-oxidant therapy , and the use of testosterone derivates , growth hormone , and
immunoglobulins
Guard against pressure sores.
Sepsis control - with importance to daily monitoring for renal impairment - dose adjustments
of all meds.
BOTULINSM
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Botulism is a rare and potentially fatal paralytic illness caused by a toxin
produced by the anaerobic gram positive bacteria Clostridium botulinum.
The illness initially effects cranial nerves and progress to involve
extremities . The disease does not usually affect consciousness or cause a
fever, in severe forms botulism leads to paralysis of the inspiratory muscles
and causes respiratory failure.
• Toxins :Toxin is produced by the bacteria in anaerobic, low-salt, low-acid,
low-sugar environment and warm temperatures . There are eight distinct
toxins (A,B,C1,C2,D,E,F&G) except C2 all have neurotoxin activity. Type
G is associated with sudden death.
• Mechanism : proteolysis of neuroexocytosis apparatus of presyneptic
nerve cells and prevent release of acetylcholine.
• Epidemiology : Human botulism is rare but occurs world wide
TYPES
• Food born: occurs due to preformed toxin, illness is mild to severe.
Incubation 18 to 36 hrs,Characterized by descending paralysis may
lead to respiratory failure and death.
s/s- Nausea,
vomiting , abdominal pain, diplopia, dysarthria, dysphonia,
dysphagia,Ptosis , Pupil- sluggish reaction to dilated, gag reflex
suppressed ,deep tendon reflex normal/ decreased paralytic ileus,
severe constipation, urinary retention. Sensory findings are absent.
• Wound Botulism: by wounds contaminated by spores, similar to
food born except G.I symptoms (IV drug abusers of black tar
Heroin, traumatic injuries contaminated by soil ).
• Intestinal: due to germination of spores in intestine, seen in infants
due to feeding contaminated Honey.
• Bio terrorism : by mechanism of inhalation.
Diagnosis : demonstration of toxin / bacteria in food, wound, stool and
vomitus .In serum of mice after inoculation.
Electromyography : Characteristic electromyographic findings in
patients with botulism include the following:
Brief, low-voltage compound motor-units
Small M-wave amplitudes
Overly abundant action potentials
Treatment/ management: close monitoring of patients for developing
respiratory failure. Intubation and mechanical ventilation in pts
where vital capacity is < 30% of predicated.
• Tri or Bi valent horse antitoxin for adults and Human botulin
immunoglobulin for infants.
• Prevention : Pentavalent vaccine for highly exposed Individual.