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Clinical Case Analysis: Acute Flaccid Quadriparesis

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a) Diagnosis

• 30-year-old male
• Antecedent illness (fever + loose stools) 2 weeks prior - the typical post-infectious trigger
• Ascending weakness completed within 24 hours - rapid progression
• Areflexic quadriparesis - the invariable hallmark
• No sensory loss (pure motor), no bowel/bladder involvement - consistent with the motor-predominant form

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b) Differential Diagnosis and Laboratory / Imaging Features

GBS in Context

1. Progressive weakness of both legs and arms
2. Areflexia or hyporeflexia

• Progression over days to 4 weeks
• Relative symmetry
• Mild sensory symptoms/signs
• Bifacial palsies
• Autonomic dysfunction
• Absence of fever at onset
• Recovery beginning 2-4 weeks after progression ceases

GBS Subtypes (Box 106.11, Bradley & Daroff)

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Differential Diagnosis

• Myasthenia gravis (myasthenic crisis): fatigable weakness, ptosis, diplopia; CMAP decrement on slow repetitive stimulation; anti-AChR antibodies
• Botulism: descending paralysis, diplopia, dry mouth; contaminated food; presynaptic defect; incremental response on high-frequency stimulation; normal reflexes early
• Tick paralysis: ascending flaccid paralysis identical to GBS; tick found on scalp; resolves on tick removal

• Acute poliomyelitis / West Nile virus / enterovirus myelitis: asymmetric, fever throughout; CSF shows pleocytosis; no sensory loss; irreversible deficit

• Acute intermittent porphyria (AIP): ascending motor neuropathy; abdominal pain; urine turns dark; elevated urinary delta-ALA and porphobilinogen
• Diphtheritic polyneuropathy: palatal palsy first; history of pharyngitis; no prodromal diarrhea
• Critical illness polyneuropathy: axonal neuropathy in ICU patients with sepsis; normal CSF
• Vasculitic neuropathy: painful, asymmetric; mononeuritis multiplex; elevated ESR/CRP
• Heavy metal poisoning (arsenic, thallium): history of exposure; Mees' lines; elevated urine metals

• Transverse myelitis: upper motor neuron signs develop; sensory level on trunk; bladder/bowel involvement early; CSF pleocytosis; MRI shows cord signal change
• Cord compression / epidural abscess: spinal tenderness; sensory level; MRI definitive
• Anterior spinal artery infarction: sudden onset; pain at onset; spares dorsal columns (vibration/proprioception preserved)

• Hypokalemic periodic paralysis, severe hypophosphatemia, hypermagnesemia

• Bradley & Daroff's Neurology in Clinical Practice; Rosen's Emergency Medicine

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Laboratory and Imaging Features of GBS

1. CSF Examination (Lumbar Puncture)

• Elevated CSF protein (>45 mg/dL) - found in almost all patients after the first week
• Normal or near-normal cell count (<10 cells/µL)
• In the first week, CSF protein may still be normal in up to 50% of patients - so a normal early LP does not exclude GBS
• Transient oligoclonal IgG bands and elevated myelin basic protein may be detected
• Moderate pleocytosis (>50 cells) should raise suspicion for HIV or Lyme disease-associated GBS

2. Nerve Conduction Studies (NCS) / Electromyography (EDX)

• Reduced motor conduction velocities (<80% of lower limit of normal)
• Prolonged distal latencies
• Partial conduction block - hallmark of acquired demyelination
• Absent or prolonged F-wave latencies (reflecting proximal/root involvement)
• Normal or mildly reduced CMAP amplitudes (early)
• Sensory nerve action potentials (SNAPs) may be reduced or absent

• Low-amplitude CMAPs with preserved or near-normal conduction velocities
• Absent SNAPs

3. Serological / Other Blood Tests

• Anti-ganglioside antibodies:
  • Anti-GM1, anti-GD1a - associated with AMAN (post-Campylobacter)
  • Anti-GQ1b - Miller Fisher syndrome (>98% sensitivity)
• Stool culture / serology for C. jejuni
• CBC, electrolytes, LFTs (mild transient LFT elevation in ~1/3 of patients)
• Urine porphyrins (to exclude AIP)
• HIV, Lyme serology if CSF shows pleocytosis
• Anti-AChR antibodies if MG suspected
• Heavy metals (arsenic, thallium) if exposure suspected

4. Imaging

• MRI of the spine: Perform urgently to exclude cord compression, transverse myelitis, or epidural abscess - the MRI in GBS is normal or may show gadolinium enhancement of the cauda equina/nerve roots (reflecting blood-nerve barrier disruption). This is a supportive finding, not diagnostic.
• MRI brain: Usually normal; rarely shows brainstem findings in Miller Fisher or overlap syndromes.
• Chest X-ray: To assess respiratory compromise and detect aspiration pneumonia.

5. Pulmonary Function Tests

• Forced vital capacity (FVC) - critical for monitoring
• Negative inspiratory force (NIF) - bedside assessment of diaphragmatic strength
• The "20-30-40 rule" for intubation: FVC <20 mL/kg, NIF <-30 cmH₂O, PaO₂ <40 (on air) signals impending respiratory failure

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c) Management

Management Flowchart (Bradley & Daroff's Neurology)

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Track 1: Monitoring and Supportive Care

• Measure FVC and NIF every 4-6 hours
• Indications for intubation and mechanical ventilation: FVC <12-15 mL/kg (or <1 L), NIF weaker than -20 to -25 cmH₂O, rising PaCO₂, hypoxia (PaO₂ <70 mmHg), inability to count to 20 on a single breath, or rapid clinical deterioration
• About 25-30% of hospitalized GBS patients require mechanical ventilation
• Tracheostomy if ventilation anticipated >2 weeks

• Continuous cardiac monitoring (ECG telemetry)
• Antihypertensives must be short-acting and titratable (e.g., IV labetalol for hypertensive surges)
• Treat hypotension with IV saline and vasopressors cautiously - autonomic instability means rapid swings
• Avoid tracheal suctioning without atropine pretreatment (vagal spells can cause asystole)

• Subcutaneous heparin or LMWH + pneumatic compression stockings in all immobilized patients

• Impaired swallowing → enteral tube feeding early
• High-caloric protein diet

• NSAIDs for radicular/back pain
• Opioids for severe pain

• Regular repositioning to prevent pressure sores
• Protect eyes in facial diplegia (artificial tears, tape eyelids shut at night)
• Pad ulnar and fibular nerve pressure points
• Physical therapy early - prevents contractures and venous stasis
• Establish a reliable communication method before intubation (letter/phrase board)
• Psychological support for patient and family

• Monitor for aspiration pneumonia and UTI (affect ~50% of ICU patients with GBS)
• Prompt treatment with antibiotics

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Track 2: Specific Immunotherapy

Option A: Intravenous Immunoglobulin (IVIG) - Preferred

• Dose: 0.4 g/kg/day for 5 days (total 2 g/kg)
• Timing: Start within 2 weeks of onset for maximum benefit; effective up to 4 weeks
• Mechanism: Neutralizes pathogenic antibodies, blocks Fc receptors, modulates complement
• Advantages: Ease of administration, no venous access requirements for apheresis
• Contraindications: IgA deficiency (risk of anaphylaxis), severe renal impairment, congestive cardiac failure (fluid load)

Option B: Therapeutic Plasma Exchange (Plasmapheresis)

• Schedule: 4-5 exchanges (40-50 mL/kg each) on alternate days over ~10-14 days
• Replacement fluid: Saline and albumin
• Timing: Most effective within 2 weeks; still beneficial up to 30 days from onset
• Even mildly affected patients benefit from 2 exchanges; 4 exchanges optimal for moderate-severe disease; 6 exchanges show no additional benefit (French Cooperative Group)
• Contraindications: Active sepsis/bacteremia, active bleeding, severe cardiovascular instability, recent MI
• Complications: Venous access problems, pneumothorax from central line insertion, catheter septicemia

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Track 3: Rehabilitation and Prognosis

• Recovery begins 2-4 weeks after progression stops (plateau phase lasts 2-4 weeks)
• Prognosis:
  • 15% mild course, remain ambulatory, recover fully
  • 70% complete recovery within 12 months; 82% by 24 months
  • 20% have residual motor weakness at 1 year
  • 2-5% mortality (from autonomic complications, respiratory failure, nosocomial infections)
  • Up to 5% relapse
• Poor prognostic indicators: Age >60, preceding diarrheal illness (as in this patient), rapid progression to nadir in <7 days, ventilator dependence, low distal CMAP amplitudes, CMV infection, hyponatremia
• Physical therapy and rehabilitation are started as early as clinically feasible

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Summary Table for this Patient

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Diagnostic Approach to Peripheral Neuropathy

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Step 1: Confirm the Lesion is in the Peripheral Nervous System

• Central nervous system (CNS) disorders - upper motor neuron signs (spasticity, hyperreflexia, extensor plantar response, sensory level), bladder/bowel involvement
• Neuromuscular junction (NMJ) disorders - fatigable weakness, no sensory involvement, normal reflexes
• Myopathies - proximal > distal weakness, normal sensation, elevated CK

• Weakness is flaccid with hyporeflexia or areflexia
• Sensory loss follows a nerve/root distribution or a "stocking-glove" pattern
• Fasciculations may be present (anterior horn cell or motor axon)
• No extensor plantar responses, no spasticity

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Step 2: Determine the Topographic Pattern

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Step 3: The Seven Key Questions (Harrison's Framework)

Q1. What systems are involved?

• Motor only → motor neuropathy, NMJ disorder, myopathy; if asymmetric consider MND or multifocal motor neuropathy (MMN)
• Sensory only → most neuropathies are predominantly sensory; consider metabolic, toxic, hereditary
• Sensorimotor → most common pattern; acquired and hereditary
• Autonomic → especially amyloid, diabetes, GBS, porphyria; prominent autonomic dysfunction without diabetes should raise suspicion of amyloidosis

Q2. What is the distribution of weakness?

• Symmetric proximal + distal → acquired demyelinating (GBS, CIDP)
• Symmetric distal only → most acquired polyneuropathies (diabetes, toxic, metabolic)
• Asymmetric distal, multifocal → vasculitis, leprosy, mononeuropathy multiplex
• Asymmetric proximal + distal → polyradiculopathy, plexopathy

Q3. What is the nature of sensory involvement?

• Large fiber (vibration, proprioception loss, positive Romberg) → metabolic, CIDP, vitamin B12 deficiency
• Small fiber (pain, temperature loss; burning neuropathic pain; normal NCS) → diabetes/glucose intolerance, amyloid, idiopathic
• Both large and small fibers → most polyneuropathies
• Sensory ataxia predominant, non-length-dependent → sensory neuronopathy/ganglionopathy (Sjögren's, paraneoplastic anti-Hu, cisplatin)

Q4. Is there UMN involvement?

• UMN + peripheral neuropathy = combined system degeneration
• Most common cause: vitamin B12 deficiency (subacute combined degeneration)
• Others: adrenomyeloneuropathy, Friedreich's ataxia, HSP-plus, copper deficiency

Q5. What is the temporal evolution?

Q6. Is there a hereditary neuropathy?

• Family history of neuropathy
• Onset in childhood or adolescence
• Foot deformities (pes cavus, hammer toes) suggesting long-standing disease
• Lack of sensory symptoms despite sensory signs (sensory ataxia without pain)
• Uniform slowing on nerve conduction studies (CMT type 1: MCV <38 m/s)
• Consider genetic testing for CMT (PMP22 duplication/deletion, MPZ, GJB1/Cx32)

Q7. Are there associated medical conditions?

• Diabetes mellitus, glucose intolerance
• Malignancy (paraneoplastic, direct infiltration, treatment-related)
• Connective tissue disease (Sjögren's, SLE, RA, vasculitis)
• Infections: HIV, Lyme, leprosy, hepatitis B/C, CMV, EBV
• Medications and toxins (see below)
• Alcohol use (direct toxicity + B1/B12 deficiency)
• Monoclonal gammopathy / plasma cell dyscrasia
• Preceding events (viral illness → GBS; vaccination)

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Step 4: Fiber Type and Pathological Classification

By fiber type:

• Large myelinated fibers (Aα, Aβ): motor power, vibration, proprioception, deep tendon reflexes - assessed by NCS
• Small myelinated fibers (Aδ): pain, temperature, autonomic
• Unmyelinated fibers (C): pain, temperature, autonomic - assessed by skin biopsy IENFD, QSART

By pathology:

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Step 5: Electrodiagnostic Studies (NCS / EMG)

1. Confirm PNS pathology
2. Determine axonal vs. demyelinating pathology
3. Localize the lesion (root, plexus, nerve)
4. Assess severity and prognosis
5. Guide further workup

• CMAP amplitude - proportional to number of functioning motor axons
• Conduction velocity - reflects myelin integrity
• Distal latency - terminal segment conduction
• F-wave latency - proximal/root segment
• SNAP amplitude and latency - sensory axons

• Fibrillations and positive sharp waves - active denervation (axonal loss)
• Large polyphasic motor units - chronic reinnervation
• Reduced recruitment - motor unit loss
• Paraspinal fibrillations - polyradiculopathy

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Diagnostic Flowcharts

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Step 6: Laboratory and Special Investigations

Tier 1 - All patients with generalized symmetric polyneuropathy (Harrison's):

Tier 2 - Mononeuropathy multiplex / asymmetric / vasculitis suspected:

Tier 3 - Specific situations:

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Step 7: Special Tests for Specific Situations

Small-Fiber Neuropathy (normal NCS)

• Skin punch biopsy - intraepidermal nerve fiber density (IENFD) with anti-PGP 9.5 staining; loss of intraepidermal fibers confirms small-fiber neuropathy (diagnosis if ≥2 tests abnormal)
• Quantitative sensory testing (QST) - heat/cold pain thresholds
• Quantitative sudomotor axon reflex test (QSART) - 80% sensitivity for autonomic small-fiber involvement

Nerve Biopsy (sural or superficial peroneal sensory nerve)

• Vasculitis (combined nerve + muscle biopsy increases yield from ~50% to 60-70%)
• Amyloidosis (light chain or hereditary)
• Sarcoidosis
• Leprosy / Hansen's disease
• Giant axonal neuropathy
• Tumor infiltration

• CMT type 1 and 3
• CIDP
• IgM paraprotein neuropathy (anti-MAG)

Neuromuscular Ultrasound

• Increasingly used; non-invasive
• Focal nerve enlargement (cross-sectional area) at entrapment sites: carpal tunnel, ulnar at elbow
• Multifocal enlargement at non-entrapment sites and brachial plexus trunks → highly specific for CIDP; distinguishes acquired from axonal/hereditary neuropathy
• • Bradley & Daroff's Neurology in Clinical Practice

MRI

• MRI spine/nerve roots: Enhancement of cauda equina/roots in GBS, CIDP, lymphomatous radiculopathy
• MRI brachial plexus: Plexopathy (neoplastic, idiopathic, post-radiation)
• MRI brain: When central involvement or paraneoplastic syndrome suspected

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Common Causes by Pattern - Practical Summary

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Skin, Hair, and Nail Clues on Examination

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Key Take-Home Points

1. The history and examination alone narrow the differential dramatically - use the 7 key questions systematically.
2. EDx (NCS + EMG) is the single most important test - it distinguishes axonal from demyelinating, localizes the lesion, and guides all further workup.
3. HbA1c and glucose tolerance testing should be ordered in virtually all patients with distal sensory polyneuropathy - diabetes and prediabetes are the most common identifiable causes.
4. Acute demyelinating neuropathy → GBS until proven otherwise; urgent CSF and hospital admission.
5. Prominent autonomic dysfunction without diabetes → think amyloidosis.
6. Non-length-dependent sensory ataxia → think sensory neuronopathy/ganglionopathy - screen for occult malignancy and Sjögren's.
7. Uniform NCS slowing + family history + foot deformities → hereditary neuropathy (CMT) - genetic testing not biopsy.
8. Conduction block on NCS → acquired demyelination; never seen in hereditary neuropathy.