ACUTE NEUROPATHIESBY:SYED IRSHAD MURTAZA TRAINEE TECHNOLOGIST NEUROPHYSIOLOGY AGA KHAN UNIVERSITY HOSPITAL KARACHI DATE: 08-10-2012
INTRODUCTION NEUROPATHY:- Dysfunction or disorder of peripheral nerves. The type of neuropathy is always determined by the temporal course of the disease. Acute (Days to weeks). Sub-acute, (Weeks to Months) Chronic (Months to Years) Progressive (Getting worse day by day). stepwise (involving a region completely then next) and relapsing/remitting. (Attacking and Recovery)
How to obtain temporal course? By the history alone and often confirmed by EDX studies. Acute polyneuropathies are notably less common.e.g Guillaine-Barre Syndrom (GBS), Which is immune mediated acute inflammatory demyelinating Polyneuro(radiculo)pathy.
GUILLAIN BARRE SYNDROME (GBS) 08-10-2012 by MURTAZA
Acute polyneuropathies In 1916, three French neurologists Georges Guillain, Jean-Alexandre Barre, and Andre Strohl described two soldiers with acute areflexic paralysis followed by recovery, refferred as Guillain Barr’e Syndrome. Guillain Barre Syndrome refers to an “acute immune-mediated polyneuropathy. It is an acute inflammatory demyelinating polyneuropathy characterized by acute onset of peripheral and cranial nerve dysfunction (and progressive muscle weakness and areflexia)
CONT’D Other Symptoms and signs include rapidly progressive symmetric weakness, loss of tendon reflexes, facial diplegia, oropharyngeal and respiratory paresis, and impaired sensation in the hands and feet
Causes/ PATHOGENESISEtiology unknownMay be cell-mediated immunological reaction directed at the peripheral nervesFrequently preceded by viral infection, trauma, surgery or other immune system stimulation.Humoral factors and cell-mediated immune phenomena have been implicated in the damage of myelin and/or the myelin-producing Schwann cells T-cell sensitization occurs which causes loss of myelin which disrupts nerve impulses.
CLINICAL FEATURES Progressive symmetric muscle weakness Absent / depressed deep tendon reflexes Weakness starts in the legs in 90% of cases Parasthesia in legs and arms is common Wide range of weakness • Two-thirds of patients develop the neurologic symptoms 2-4 weeks after viral infections
The initial symptoms are SENSORY CHANGES: paresthesia, numbness; usually mild; 70% patients have sensory abnormalities on electrodiagnostic• DYSESTHESIAS: burning, tingling, shock like, persistent in 5- 10% WEAKNESS: oascending and symmetrical, lower limbs involved first, distal muscles involved earlier ; develops acutely and progresses.
CONT’D wide variations in severity; Deficits peak by 4 weeks after initial Symptoms;recovery begins 2-4 weeks after progression stops.Hypotonic and areflexia (absence of reflexes)More than 90% of patients reach the nadir of their function within two to four weeks, with return of function occurring slowly over weeks to monthsInvolvement of lower brainstem leads to facial and eye weakness
Clinical Features RESPIRATORY: 40% patients have respiratory or oropharyngeal weakness AUTONOMIC CHANGES: Tachycardia, or bradycardia, facial flushing, paroxysmal HTN, orthostatic hypotension, urinary retention, Ileus (painful obstruction of the intestine) dizziness (light-headedness and feeling faint) more common if severe weakness or respiratory failure
CLINICAL FEATURS (DETAIL) A. “Typical” GBS GBS is an acute, predominantly motor neuropathy involving distal limbs paresthesias, relatively symmetric leg weakness, and frequent gait ataxia. 1. Most cases will have subsequent arm weakness, and possibly weakness of facial, ocular, and oropharyngeal (oral airway) muscles.
B. Weakness Weakness is always bilateral, although some asymmetry in onset and severity is common. i. Proximal muscles weakness very frequent, especially initially, with subsequent distal arm and leg weakness. ii. GBS with a descending pattern of weakness seen in 14% cases; onset initially with cranial nerve or arm muscle weakness, followed by leg weakness. iii. In 1/3 of cases, the degree of weakness in the arms and legs is roughly equal.
C. Reduced or absent reflexes characterizeGBS. i. Early loss of reflexes may be due to desynchronization of afferent impulses in reflex arc due to non-uniform demyelination. ii. About 70% of patients present with loss of reflexes; less than 5% retained all reflexes during the illness; iii. The presence of intact reflexes should suggest an alternative diagnosis other than GBS.
D. Sensory disturbance i.>50% will present with symmetric distal limb paresthesias, before clinically evident limb weakness. Early finger paresthesias suggest a patchy process, unlike the pattern seen with distal axonopathies. 1. paresthesias of trunk or face unusual, but sensory loss over the trunk frequent and a psuedo level may be evident a. beware if definite sensory level present as this may suggest structural cord disease. 3. an early sensory ataxia may not be obscured (indistinct) by concurrent (simultaneous) limb weakness
E. Pain i. Some discomfort reported in 2/3 of patients which may take one of the following forms: 1. deep muscle aching in back, hips or proximal legs, 2. sharp radicular pain into the legs, 3. severe burning dysesthetic pain (with urning, aching and/or tingling sensation) in feet or hands. ii. Radicular pain can occasionally be a presenting complaint obscuring (indistinct) the true diagnosis.
f. Cranial nerve involvement i. 1/2 of GBS patients have some degree of cranial nerve dysfunction during their illness. ii. Facial weakness most common, especially if substantial (considerable) limb weakness present. 1. normal facial strength in the presence of marked quadriparesis (all 4 limbs weakness) is very unusual in typical GBS. 2. facial weakness is usually bilateral but may be unequal in severity; only rarely truly unilateral. iii. Ophthalmoplegia is seen in 10-20% of patients. 1. Abducens palsy/vi cranial nerve palsy most common; usually bilateral.
g. Respiratory dysfunction Due to diaphragmatic weakness occurs in about 1/3 of patients. i. Diaphragmatic weakness common in patients with severe quadriparesis; may also occur early on in patients with bi-brachial weakness. ii. Patients with weakness of neck muscles, tongue and palate often have concommitant (simultaneously) diaphragmatic and respiratory muscle involvement. iii. Pathogenesis of respiratory failure: 1. Atelectasis (collapse of lung tissue) results from reduced vital (life-sustaining) capacity, inspiratory force and required volume due to diaphragmatic weakness.
h. Dysautonomia i. Occurs in about 65% of cases ii. more frequent in patients with severe paralysis and ventilatory difficulties but may develop in mild cases. iii. Most common manifestations include cardiac dysfunction such as sinus tachycardia, sinus bradycardia, sinus arrest and other paroxysmal hypertension, and hypotension etc
Variations Of GBSFollowings are the typical variants of GBSa. Acute Motor and Sensory Axonal Neuropathy (AMSAN)b. Acute Motor Axonal Neuropathy (AMAN)c. Miller-Fisher Variantd. Pure Motor Variantse. Pure Sensory Variants
a. Acute Motor and Sensory Axonal Neuropathy(AMSAN) i. Initially described by Feasby as axonal GBS. ii. Characterized by acute quadriparesis (Weakness of all four limb), areflexia, distal sensory loss, and respiratory insufficiency. iii. CSF with increased CSF; EDX shows loss of motor and sensory potentials with diffuse active denervation. No evidence of primary demyelination. . EDX studies differentiate from typical GBS by showing evidence of only axonal degeneration , without demyelination. iv. Condition is now labeled acute motor-sensory axonal neuropathy (AMSAN) . AMSAN is usually severe with quadriplegia, respiratory insufficiency and delayed, incomplete recovery.
b. Acute Motor Axonal Neuropathy (AMAN) I. Characterized by acute/subacute onset of relatively symmetric limb weakness, diffuse areflexia, facial and oropharyngeal muscle weakness, and respiratory insufficiency. iii. Clinically purely motor deficits; normal EOMs. (extraocular muslce/movement) iv. EDX studies show evidence of motor axonal loss, sparing sensory fibers. No evidence of demyelination. Needle EMG shows diffuse denervation. Elevated CSF protein. v. Pathogenesis unclear; possible antibody and complement mediated attack at terminal motor nerve endings vi. Occasionally, some patients make relatively rapid recovery, possibly due to reversible changes at nodes of Ranvier, or regeneration of intramuscular nerve endings.
c. Miller-Fisher Variant i. Classic triad of ophthalmoplegia, ataxia, and areflexia described by C. Miller Fisher in 1956 ii. Occurs in about 5% of GBS cases. some of what appears to be Fisher syndrome subsequently incorporate findings of typical GBS raising the possibility of a clinical spectrum between GBS and Fisher syndrome. iii. Diplopia usually initial symptom, followed by limb or gait ataxia. iv. Occasionally there may be mild sensory symptoms, swallowing difficulties, or proximal limb weakness in up to 1/3 or 1/2 of cases. v. abducens palsy (inability of an eye to turn outward which results in diplopia) usually initial EOM deficit, which may progress to complete ophthalmoplegia.
CONT’D,, 1. ptosis frequent, but papillary function usually spared. vi. Limb and gait ataxia common, although possibly asymmetric limb involvement initially. 1. limb ataxia may resemble that seen with cerebellar disease vii. Areflexia is usual. viii. Although CSF protein is mildly elevated, it is less so than in typical GBS. ix. EDX shows loss of sensory potentials, with milder axonal degeneration. Some studies have shown a demyelinating neuropathy, while others suggest purely an axonal process. x. May clinically resemble brainstem inflammatory or ischemic disease
d. Pure Motor Variants i. Acute, progressive, symmetric limb weakness, no sensory loss, areflexia. ii. Diagnosis suggested by acute, predominantly distal limb weakness, iii. normal cranial nerve function iv. Course and recovery similar to typical GBS. v. CSF protein elevated (decreased). vi. EDX shows marked axonal degeneration with some accompanying demyelinating features. vii. Differential Dx: poliomyelitis (viral disease that affects nerve & leads to partial or full paralysis) , porphyria (inherited disease where heme, is not made properly), acute myasthenia gravis, tick paralysis.
e. Pure Sensory Variants i. Rare occurrence of acute sensory poly-- neuropathy with elevated CSF protein, and demyelinating features on EDX studies. ii. Rapid onset of large fiber sensory loss with resultant sensory ataxia. iii. Positive Romberg sign, pseudoathetosis (abnormal writhing movements, usually of the finger s, caused by a failure of joint position sense), tremor,(involuntary vibratory movement) lesser involvement of small fiber sensory function; dysautonomia. iv. Sensory dysfunction may involve the face and torso in severe cases.
Diagnosis 2 ways to diagnose: 1. ELECTRODIAGNOSTIC (EMG/NCs) 2. Clinical Assessment 1. EMG/NCS EMG/NCs reveals markedly prolonged Or absent late responses, prolonged distal latencies with marked decrease in CMAP amplitudes of upper and lower extremities.
2. Clinical diagnosis – Clinical diagnosis Must include the following sign and symptoms: Progressive weakness in one or more limb, ranging from minimal weakness to full body paralysis Areflexia ranging from biceps and patella to whole body areflexia.
Electrophysiology (EMG and NCs) a. Diagnostic in 95% cases b. May be normal early on perhaps reflecting involvement of proximal nerve segments not accessible to conduction studies. c. Nature and severity of physiologic findings dependent on timing of study, number of nerves studied, and whether proximal nerve segments investigated.
NCS findingsd. Typically, there is multifocal demyelination affecting proximal and distal nerve segments.i. Earliest findings may be abnormalities of F waves and H reflex latencies. Prolonged or absent F waves may be initial sole abnormality in about 30-50% of cases studied.ii. Conduction block in about 1/3 of cases; conduction slowing and temporal dispersion reflect demyelination.
Cont’d NCS findingse. Evidence of sensory axon demyelination seen in about 25% of cases when studied in the first week, increasing to 75% after 3 weeks.f. Characteristic pattern is abnormal median and ulnar sensory potentialswith spared sural potentials, reflecting random, multifocal demyelination.i. Most important predictor of recovery is the degree of axonal degeneration, best reflected by the amplitude of the compound muscle action potential (CMAP).
Cont’d i. Motor potentials with amplitudes less than 20% normal suggest a prolonged, and often incomplete recovery. ii. No correlation between the degree of conduction slowing and eventual recovery. iii. Electrophysiologic evidence of demyelination may persist for years, despite adequate clinical recovery.
EMG FindingsMost common needle EMG finding is reduced voluntary motor unitrecruitment.i. Active denervation present in 20-64% of cases by week 4.ii. Myokymia, reflecting demyelination, occasionally present. Severe axonal GBS will show diffuse loss of sensory and motor responses with widespread active denervation.
Note Later in the first week or two, sensory studies may show so-called sural Sparing (i.e., the sural sensory response is normal whereas the median and ulnar sensory potentials are reduced or absent). This pattern is very unusual in the typical axonal, dying-back polyneuropathy. Many believe that sural sparing in the presence of a typical clinical picture is virtually diagnostic of AIDP.
Cont’dWhy sural sparing occurs is not completely known,but it is likely related to the preferential, earlyinvolvement of the smaller myelinated fibers inAIDP.Although it is not intuitively obvious, the recordedsural sensory fibers actually are larger, andaccordingly have more myelin, than the medianand ulnar sensory fibers.The routine median and ulnar sensory potentialsare recorded distally over the fingers, where thenerve diameters are more tapered than those of thesural nerve.
Treatment and Management1 Supportive Care Ventilatory Support Nutritional support ii. Intravenous immunoglobulin (IVIg) Plasmaphrasis
Prognosis a. Majority have progressive illness with nadir of clinical deficits at 4 weeks. i. 3/4 reach nadir by 1 week. b. 15% have mild illness, remain ambulatory, and recovery after few weeks. c. 5-20% have fulminant course, develop flaccid paralysis, ventilator dependence, and axonal degeneration. i. Such patients have delayed and incomplete recovery. d. Residual deficit (remaining part of the abnormality): about 1/3 of cases require ventilator assistance, 1/2 are either chair or bed bound, and 7% have trouble walking. The remainder are ambulatory. e. Recovery at 1 year follow-up: 62% had recovered completely, 14% could walk but not run, 9% could not walk without assistance, 4% remained bed bound or ventilated, 8% died.
Poor prognostic features:i. age greater than 60ii. history of preceding diarrhea illnessiii. ventilator dependenceiv. greatly reduced CMAP amplitudes or inexcitable nervesg. Mortality about 5-10% with aggressive ICU care.h. About 3-6% of patients with typical GBS have developed a chronic relapsing course consistent with CIDP.i. No distinguishing features.ii. Most relapses responsive to steroids.