Acute Peripheral Neurologic disorder
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Transcript of Acute Peripheral Neurologic disorder
Acute Peripheral Neurologic disorder
Praween Lolekha, MDThammasat University
Outline
• Neural Control of Breathing• Signs and Symptoms of acute peripheral
neurologic disorder and respiratory failure
• Clinical pattern of neuromuscular failure – Guillain Barré Syndrome (GBS)– Myasthenia Gravis (MG)– Lambert-Eaton Myasthenic Syndrome (LEMS)– Botulism– Acute intermittent porphyria– Neurotoxic marine poisoning – Organophosphate poisoning
Neural Control of Breathing
• Diaphragm• Accessory muscles of inspiration
– External intercostal muscle– Scalene muscle– Sternocleidomastoid muscle
• Accessory muscles of expiration– Internal intercostal muscle– Abdominal wall muscles
• Upper airway musculature
Neural Control of Breathing
• Mechanical aspect of respiration (Ventilation)– PNS (Nerve, NMJ, Muscle)– CNS (Brainstem, Cervicomedullary
junction)• Alveolar gas exchange
(Oxygenation)– CNS: Neurogenic pulmonary edema
in subarachnoid hemorrhage, status epilepticus, head injury, brain death
Neural Control of Breathing
Mechanoreceptors-Respiratory muscle-Lungs: Pulmonary stretch receptor
Chemoreceptors-Carotid bodies-Aortic bodies
Medullary respiratoryCenter (RC center)
CN IX,X
CN X
-Phrenic n (C3-5)- Intercostal n (T2-T12)
Larygopharyngeal m.Bronchoconstrictors CN IX
Symptoms
• Acute/ Subacute onset– Dyspnea, orthopnea– Respiratory arrest– Bulbar weakness: dysarthria (nasal voice),
dysphagia– Secretion aspiration
• Gradually onset– Noctunal hypoventilation– Broken sleep pattern– Nightmares, daytime fatigue– Somnolence
Signs
• Using accessory muscles of respiration• Inability to speak in complete sentences
or count 1-20 in a single breath– 1-10 (FVC ~1000cc) , 1-25 (FVC~2000cc)
• Paradoxical abdominal motion• Mental clouding, alteration of
consciousness• Facial muscles weakness (oral, orbital)• Ptosis, ophthalmoparesis
Respiratory Investigations
• Spirometry : FVC (Forced Vital Capacity)– Normal 20-30 cc/kg– Impending respiratory failure:
FVC<15-20 cc/kg (~1000cc)• Peak flow
– Normal is ~360-840 L/min– Respiratory weakness : PF <160-200
L/min
Respiratory Investigations
• Arterial blood gases– Late feature in neuromuscular
disease– Hypoxemia, compensated
respiratory acidosis• Mouth pressure
– Maximum inspiratory pressure (MIP)<30 cmH2O
– Maximum expiratory pressure (MEP)<40 cmH2O
Neurological Disorders and respiratory failure
• Acute Ventilatory failure– CNS : Brainstem and
cervicomedullary junction lesion– PNS: Neuromuscular disease
• Motor neuron disease : ALS• Polyneuropathy : GBS , Porphyria• Neuromuscular junction disorders : MG ,
LEMS, Botulism, Organophosphate• Myopathy: DM, PM, muscular dystrophy
Peripheral neurology and respiratory failure
• Acute / Subacute– Neuropathy: Guillain Barré syndrome
(GBS) Tetrodo toxin, Prophyria– NMJ: Myasthenia gravis (MG),
Botulism,Organophosphate, Snake venoms
– Muscle: Inflammatory myopathy• Chronic progressive
– ALS (Amyotrophic lateral sclerosis)– Muscular dystrophy
Guillain-Barré syndrome
Guillain-Barré syndrome
• Self-limited, autoimmune disease• The main clinical feature
– Motor weakness (proximal > distal)– Areflexia– Paresthesia with slight sensory loss– Increased protein in CSF without
pleocytosis “Albuminocytological dissociation”
Epidemiology
Annual Incidence• 0.4-4.0 (median 1.3) : 100,000Age and Sex• Occur at all ages (8mo - 81yr)• 2 peak
– Late adolescence and young adulthood
– Elderly• Men : women = 1.25 : 1
Guillain-Barré syndrome
GBS
AIDP AMAN MFS
AIDP with 2 degeneration AMSAN
AIDP = Acute inflammatory demyelinating polyneuropathy
AMAN = Acute motor axonal neuropathy
AMSAN = Acute motor sensory axonal neuropathy
MFS = Miller Fisher syndrome (Ophthalmoparesis, ataxia, areflexia)
Etiology
• 2/3 of patients are preceded by symptoms of upper respiratory tract infection or gastroenteritis.
• C oncept of “molecular mimicry”– Campylobacter jejuni– Haemophilus influenzae– CMV, EBV– Mycoplasma pneumoniae
• Prodromal infection between 1 week and 3 weeks (averaged 11 days)
Clinical Features
• Paresthesias and numbness are frequent and early symptoms
• Major clinical manifestation is muscle weakness
• Maximum deficit develop over days and nadir in 2 wks. (no progression after 4 wks.) followed by a plateau phase and gradual recovery
Motor symptoms
• Symmetrical limb weakness initially be proximal > distal muscles or global
• Usually the lower extremities before the upper (ascending paralysis)
• Trunk, intercostals, neck, bulbar and cranial nerves may be affected later
• Respiratory muscle weakness (25%)• Facial diplegia • Areflexia• Muscle wasting (after 2 wks.)
Sensory symptoms
• Pain and an aching discomfort in the muscles, mainly those of the hips, thighs and backs
• Numbness, paresthesia• Lost of joint position sense,
vibration, touch and pain distally• Ataxia
Autonomic dysfunctions
• Fluctuation of heart rate and blood pressure
• Tonic pupil• Hypersalivalation• Excessive sweating• Paralytic ileus• Urinary retention• Constipation
Electrophysiologic study
• Diagnosis of AIDP
Patients must have one of the following in two or more nerves during the first 2 weeks of illness– i) Conduction velocity <90% of lower limit of normal if amplitude i
s >50% of the lower limit of normal; <85% if amplitude is <50% of lower limit of normal.
– ii) Distal latency >110% of upper limit of normal if amplitude is normal; >120% of upper limit of normal, if the amplitude is less than lower limit of normal.
– iii) Evidence of unequivocal temporal dispersion.
– iv) F-response latency >120% of normal
“Evidence of demyelination”
CSF analysis
• Typical– Normal pressures– Few cells (typically mononuclear)– Elevated protein concentration (greater
than 50 mg/dL)– Normal sugar
• Less than one week, protein levels may not yet be elevated
• If CSF pleocytosis (>10/mm3), other diseases should be considered : HIV, malignancy
“Albuminocytological
dissociation”
Treatment
Supportive Treatment• 25-30% require i ntubation and mechan
ical ventilation• Continuous monitoring of blood pressur
e and heart rateImmunomodulating treatment• Plasma exchange• IVIg• Corticosteroid : no benefit
• PE recommended for patients– Unable to walk unaided– Worsening vital capacities– Require mechanical ventilation– Significant bulbar weakness
• Removes a total of 200-250ml/kg in 4-6 treatments on alternate days
Plasma Exchange
Immunoglobulin
• Plasma exchange and IVIg have equivalent efficacy
• Advantages of lower risk and ease of application
• IVIg is more efficacious than plasma exchange in patients with axonal GBS
• Dosage : 0.4 g/kg/day for 5 days consecutively
Myasthenia gravis (MG)
• An autoimmune disorder caused by autoantibodies against the nicotinic acethycholine recetors on the postsynaptic membrane at the NM junction
• Characterised by weakness and fatigability of the voluntary muscles.
Epidemiology
• The commonest disorder in NMJ • Annual incidence 0.25-2/100,000• Present in any age
– A bimodal peak• First peak in 3rd decade ( women >
men )• Second peak in 6th-7th decade ( men > women )
Pathophysiology
Modified Osserman Classification
• Class I: Ocular weakness• Class II: Mild weakness
– IIa : limb and/or axial involvement– IIb : oropharyngeal and/or respiratory involvement
• Class III: Moderate weakness – IIIa : limb and/or axial involvement– IIIb : oropharyngeal and/or respiratory involvement
• Class IV: Severe weakness– IVa : limb and/or axial involvement– IVb : oropharyngeal and/or respiratory involvement
• Class V: Defined by intubation c/s mechanical ventilator
Clinical features
• Weakness and fatigability of muscles on sustained or repeated activity that improves after rest
• Insidious onset• Often fluctuation • Progression
– Craniocaudal direction
Clinical features
• The most commonly affecting muscles – Levator palpebrae (ptosis)– Extraocular muscles (diplopia)– Muscle of facial expression (“Snarl” face)– Neck muscles (drop neck myopathy)– Bulbar muscles (dysphagia, nasal voice)– Proximal limb muscles
Clinical features
• Can first present during– Pregnancy or post natally– Post general anesthesia– ICU care
• Diaphragmatic weakness• Weakness can remain localized to
one group of muscle for many years eg. Ocular MG
“Myasthenic snarl”
Associated disorder
• Thymic hyperplasia 50-70%• Thymoma 10-15%• Thyroid disease 10%• Rheumatoid arthritis• Pernicious anemia• SLE
Diagnosis of MG
• Serology: – Anti-AchR (sensitivity 80%, high specificity)
• EMG: Repetitive nerve stimulation– CMAP decremental >10% at 3 Hz (sensitivity
75%)• SFEMG:
– increase jitter +/- blocking (most sensitive but not specific)
• Edrophonium/ Tensilon test – (sensitivity 80%, not specificity)
• Ice test – (80% sensitivity, high specificity)
Repetitive Nerve Stimulation
“Decrement response”
Precipitating factors
• Physical exertion• Hot temperature• Emotional upsets• Infections• Hyperthyroidism• Surgery• Menstruations• Pregnancy (1st
trimester)• Postpartum• Hypokalemia
• Drugs induced MG– Aminoglycoside– Fluoroquinolones – B-blockers– Ca Channel blocker– High dose steroid– D-penicillamine– Chloroquine– Quinine– Quinidine– Lithium– Clopromazine– Procainnamide
Treatment
• Improve neuromuscular transmission – Acethycholineaterase inhibitors : Mestinon
• Suppress immune response– Corticosteroid– Immunosuppressant: AZA, MTX, MM etc.– IVIg
• Remove antibodies– Plasmapheresis
• Thymectomy
MG crisis
• Occur 15-20% of MG patients• Plamapheresis is the treatment of
choice except– Hemodynamic instability– Sepsis– Coagulopathy– Unavailable– First trimester of pregnancy
• Then IVIg
Diagnosis of MG
Evaluate for Thymectomy
Anticholinesterase
CrisisGeneralizedOccular
Low risk
If unsatifactory
MRI
Anticholinesterase
Intensive CareRespiratoryInfection
High risk
ImproveThymectomy
PrednisoloneImmunosuppressive
Plasmapheresis / IVIg
Not improve
Prognosis
• Ocular MG 10% 90% turn to Generalized (usually in 2 years)
• Untreated weakness fixed and atrophic
• Spontaneous remission rate 20%• 20-30% will die within 10 years
without treatment
MG crisis vs Cholinergic crisis
• Myasthenic crisis– Respiratory distress– Increased pulse and
blood pressure– Poor cough– Secretion aspiration– Dysphagia– Weakness– Improve with
edrophonium
• Cholinergic crisis– Abdominal cramps– Diarrhea– Nausea and
vomiting– Excessive secretions– Miosis– Fasciculations– Weakness– Worse with
edrophonium
Lambert-Eaton Myasthenic Syndrome (LEMS)
• Autoimmune disease producing antibodies against presynaptic voltage-gated calcium channels
• Paraneoplastic syndrome (50-70%)– Small cell lung cancer– Lymphoma, Leukemia
• Usually presents in adulthood > 40 years with smoker
Pathophysiology
• P/Q-type VGCC antibodies attack presynaptic NMJ
Clinical Features
• Symptoms– Proximal limb weakness (Leg>arms)– Rarely, cranial nerve symptoms– Rarely, respiratory failure– Autonomic dysfunction (75%)
• Dry mouth, constipation,dilated pupils with poor reactive to light, impair sweating, orthostatic hypotension, impotence
– Lambert’s sign • Grip becomes more powerful over several
seconds
– Absent DTR but obtainable after exercise
Repetitive Nerve Stimulation
Posttetanic facilitation - incremental response >200%
Treatment
• Treating the cancer– Screened for small cell lung CA every 6
months with chest imaging for at least 2 years
• Pyridostigmine alone is usually ineffective
• 3,4 Diaminopyridine is usually beneficial, and usually enhanced by pryidostigmine
• Plasma exchange/ IVIg temporary improvement
Botulism
• Botulism is a rare, but seriousparalytic illness caused by atoxin that is produced by the bact
eria Clostridium botulinum .• C. botulinum is an anaerobic, Gra
- m positive, spore forming rod.
• 3 main kinds of botulism– The classic (food-borne) botulism
• Ingestion of toxin in food contaminated with toxin-producing bacteria.
– Infant botulism• Ingestion of spores that then germinate
and produce toxin in the infant’s gastrointestinal tract.
– Wound botulism• W ound infected with Clostridium botulinu
m• IVDU
Botulism
C. botulinum
• Pathogenic bacterium that found in the soil.
• Proliferates under anaerobic and alkaline conditions
• The spores can survive extreme weather and temperature conditions (>120c may be required to kill the spores).
• Toxin is heat labile (>85c inactivates the toxin)
• Toxins A,B,C1,C2,D,E,F,G
Pathophysiology
Clinical presentations
• Cranial nerve palsies (2-36hr)– Diplopia, ptosis, blurred vision– Dysarthria, dysphagia
• Descending weakness of the limbs – Upper limbs Lower limbs– Usually bilateral but can be
asymmetric.
• Respiratory paralysis• Autonomic dysfunction
Autonomic dysfunction
• Dilated pupils (<50% of patients)• Constipation, diarrhea• Nausea and vomiting• Dry mouth• Postural hypotension• Urinary retention• Heart rate R-R interval variation• Recovery of autonomic function may
take longer than NM transmission.
Diagnostic methods
• NCV and EMG– Small CMAP amplitude– Decremental response of the MAP to slow
rated of nerve stimulation (2-3 Hz)– Posttetanic facilitation (PTF) (50Hz) or post
isometric exercise incremental response to 30-100%
• Detection of toxin– Serum (30-40%) (<30% after day 2)– Stool (60%) (36% after day 3)– wound
Treatment
• Supportive care (weeks – months)• Antitoxin
– Dose not reverse paralysis when the toxin is internalized and bound at the nerve terminal.
– Lack of efficacy in some cases– Allergic reactions and serious side
effect 20%
Vincent van Gogh
Porphyria
• A heterogeneous group of inherited disorders of haem biosynthesis
• Deficiency of one of the enzyme of the haem biosynthetic pathway
• 7 main types of prophyria, classified into acute neuropsychiatric, cutaneous and mixed forms
• Acute intermittent prophyria is the commonest.
Pathway of Haem Synthesis
Acute intermittent prophyria
• Autosomal dominant (AD, 11q23)• 10-15% of gene carriers develop
symptom• 1/3 have no family history or
unidentified for several generations• Often misdiagnosed and life-
threatening condition• Deficient activity of
hydroxymethylbilane synthase• More common in women than men• Rare attacks before puberty
Clinical features
• Severe abdominal pain back• Proximal muscle weakness (arms)
quadriparesis• Peripheral motor neuropathy (wrist / foot drop)• Respiratory failure• Seizure• Hypoesthesia of a bathing-trunk distribution• Spare ankle reflexes• Autonomic neuropathy
– Tachycardia, hypertension, postural hypotension – Constipation, nausea, vomiting,
• Dehydration and hyponatremia
Precipitating factors
• Exposure to exogenous drugs– Amphetamines, cocaine– Barbiturates, phenytoin, carbamazepine,
diazepam, sodium valpoate– Estrogens, progesterones– Sulphonylureas– Tetracyclines, chloramphenicol, isoniazid– Antihistamine
• Fasting, alcohol• Stress, smoking, pregnancy• Infection
Laboratory diagnosis
• Increase urine aminolaevulinic acid and porphobilinogen
• Urine is often dark during an attac k or upon standing in the light
Management
• About 1% may be death• Avoidance of precipitating agents
– Severe pain : Opiates– Tachycardia, hypertension: propanolol– Sedation : Chlopromazine– Convulsion : gabapentin
• High carbohydrate diet or 10%glucose
• Haem arginate/ Haematin
Neurotoxic marine poisoning
• Ingestion of marine animals that contain toxic substances– Ciguatera poisoning (Ciguatoxin) – Puffer fish poisoning (Tetrodotoxin) – Paralytic shellfish poisoning (Saxitoxin)
• Affect voltage-gated Na+ channels in myelinated and unmyelinated nerves peripheral neurological effects
Puffer fish poisoning
Puffer fish poisoning
• Southeast Asia and Japan• Ingestion of fish contain
tetrodotoxin• Highest concentrations in the
liver, ovary, intestine and skin• Blockade of voltage-sensitive Na+
channels at the nodes of Ranvier.
Puffer fish poisoningGrade 1 Perioral numbness and
paraesthesia, ± GI symptoms (N/V)
5-45 min
Grade 2 Lingual and face numbness, early motor paralysis and incoordination. Slurred speech. Normal reflexs
10-60 min
Grade 3 Generalized flaccid paralysis, respiratory failure, aphonia, fixed or dilated pupils, patient is conscious.
15min-several hrs.
Grade 4 Severe respiratory failure and hypoxia, hypotension, bradycardia, unconsciousness
15min- 24 hr
• The clinical effects develop rapidly and severity depend on the amount of ingestion
Puffer fish poisoning
• Most cases resolve after 5 days but may be longer in severe poisoning.
• Clinical diagnosis• Urine (5days) and serum (<24 hr)
tetrodotoxin for confirmation• Nerve conduction studies: reduced
amplitudes of compound motor and sensory potentials, slow conduction velocities. Prolong distal and F wave latencies
Management
• No antidote• Supportive and careful observation • Life-threatening effects are
unlikely after 24 hrs.• Atopine can be used to treat
bradycardia.• Respiratory support may be
needed for a period of 24-72 hrs.
Organophosphate Poisoning
• Well absorbed by dermal, respiratory and gastrointestinal
• Irreversible binding to cholinesterase enzymes
• Excess cholinergic stimulation
Acetylcholine in PNS
Acute intoxication
• DUMBBELS– Defecation– Urination– Miosis– Bronchorrhea– Bradycardia– Emesis– Lacrimation– Salivation
• SLUDGE– Salivation– Lacrimation– Urination– Defecation– Gastric secretion– Emesis
Receptor Organ Clinical EffectAutonomic -Postgang. Muscarinic(Parasympathetic)
-Postgang. Muscarinic(Sympathetic)-Pregang. Nicotinic(Sympathetic)
EyeMouthLungsHeartsGI tractGU tractSweat glands
Adrenal
Miosis, LacrimationSalivationBronchorrhea, bronchospasmBradyarrhythmia, prolong QTDiarrhea, emisis, increase motilityUrinary incontinenceDiaphoresis
Increase catecholamines
NMJ-Nicotinic Skeletal
muscleFasciculation, weakness, paralysis
CNS-Muscarinic/ nicotinic Brain Seizure, coma, depression,
agitation
Intermediate syndrome
• 5-65% in patients with organophosphate poisoning
• A myasthenia-like syndrome• Down-regulation of overstimulated AchR (pre
and postsynaptic dysfunction)• Occur 1-3 days after the acute cholinergic
Hallmarks– Proximal muscle weakness– ± Respiratory failure– Motor cranial nerve dysfunction– Diminished reflexes
• Recovery occurs 5-18 days
Organophosphate-induced delayed polyneuropathy
• 1-4 wks after cholinergic signs• Cramping muscle pains in the legs• Progressive weakness of the lower
extremities upper extremities• Distal > Proximal • Loss of reflexes• Axonopathy with Wallerian
degeneration and spinal cord atrophy• No treatment
Management
• Serum cholinesterase ± red cell cholinesterase
• Adequate decontamination– Clothing– Activated charcoal, Gastric lavage (<2hrs),
• Treatment of the parasympathetic– Clearing pulmonary secretions– Atropine (antimuscarinic) 2-5mg iv q 5-15 min until
secretions clear / drip 0.02-0.08mg/kg/hr.• Treatment in reversing nicotinic signs (motor
weakness, fasciculation)– Pralidoxime (<24 hr, reactivate AchE)
• Treatment seizure– Benzodizepines
Neurological Respiratory Failure
Level of consciousness
History of Drugs, Toxic substance
Normal consciousnessPoor, Unconsciousness
Long tract signs Brain stem signs
-Brainstem lesion: infraction-Increase ICP-Brain herniation
PNS
AcuteChronic
Polyneuropathy : GBSNMJ : MG crisis
BotulismToxin : Porphyria
Tetrodotoxin
-Drugs-Metabolic-Infection-Other systems
ALSMuscular dystrophyMyopathyCritical illness myopathy,neuropathy
Others
Other systemsYes
No
Airway:-COPD, asthmaAlveoli:-Pneumonia
CNS
Onset Tone Motor Sensory DTR Autonomic
Ant. horn cell- ALS
Chronic
Asymmetric
Normal -
Neuropathy-GBS-Porphyria-Tetrodotoxin
AcuteAcuteAcute
SymmetricAssending
DistalMildMild
Distal, perioral
Normal
+++
NMJ-MG -LEMS-Botulism-Organophosphate
Gradual
Gradual
AcuteAcute
SymmetricProximalProximal
Dessending
Proximal
NormalNormalNormalDelay distal
Normal
-+++
Muscle-Myopathy-Muscular dystrophy
Chronic
Chronic
SymmetricProximalProximal
NormalNormal
Normal
Normal
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The END