After reading this note you will be able to describe the clinical approach to peripheral neuropathy and Guillain‑Barre syndrome, list local aetiologies, recognise key examination findings, interpret basic investigations and outline immediate and definitive management – remembering to verify drug choices and dosing against the Kenya MoH guideline and your hospital formulary.
Definition
- Peripheral neuropathy – any disorder of the peripheral nerves (motor, sensory or autonomic) that produces dysfunction distal to the spinal cord.
- Guillain‑Barre syndrome (GBS) – an acute, immune‑mediated polyradiculoneuropathy characterised by rapidly progressive, symmetric weakness with areflexia, often preceded by an infection.
Anatomy and physiology you need
| Structure | Relevance to disease |
|---|---|
| Peripheral nerve fiber (myelinated A‑α, A‑β, A‑δ; unmyelinated C) | Determines pattern of loss (motor vs sensory) and speed of conduction. |
| Dorsal root ganglion | Site of sensory neuron bodies; vulnerable in toxic and metabolic neuropathies. |
| Spinal nerve roots | In GBS the immune attack targets myelin at the node of Ranvier in roots → conduction block. |
| Autonomic fibers | Involvement explains tachycardia, labile BP, urinary retention in severe GBS. |
| Blood‑nerve barrier | Disruption allows immune complexes, toxins or infections to reach nerve tissue. |
Causes and risk factors
| Category | Common Kenyan / tropical aetiologies |
|---|---|
| Infectious | HIV, TB (especially TB meningitis with nerve root involvement), malaria (cerebral malaria sequelae), hepatitis B/C, Campylobacter jejuni (classic GBS trigger), dengue, chikungunya |
| Metabolic / Nutritional | Diabetes mellitus, chronic alcohol excess, vitamin B12 deficiency, folate deficiency, thiamine deficiency (wet beri‑beri) |
| Autoimmune / Inflammatory | Systemic lupus erythematosus, rheumatoid arthritis, vasculitis, sarcoidosis |
| Toxic | Lead exposure (mining areas), organophosphates (agricultural), antiretroviral neurotoxicity, isoniazid (TB therapy) |
| Hematologic | Sickle cell disease (vaso‑occlusive neuropathy), sickle‑cell crisis‑related ischemia |
| Genetic / Hereditary | Charcot‑Marie‑Tooth disease (rare but relevant for family history) |
| Other | Chronic renal failure (uremic neuropathy), post‑surgical positioning injuries, malignancy‑related paraneoplastic neuropathy |
Pathophysiology
Peripheral neuropathy
- Trigger (infection, toxin, metabolic derangement) →
- Nerve injury (direct axonal degeneration or demyelination) →
- Impaired conduction (loss of sensory, motor or autonomic signals) →
- Clinical deficits (pain, numbness, weakness, autonomic dysfunction).
Guillain‑Barre syndrome
- Molecular mimicry after infection (e.g., Campylobacter LPS) →
- Auto‑antibody production against gangliosides (GM1, GD1a) →
- Complement activation at nodes of Ranvier →
- Myelin (or axonal) damage →
- Conduction block & segmental demyelination →
- Rapid, symmetric weakness with areflexia.
Clinical features
History – key questions
| Domain | Questions | Rationale |
|---|---|---|
| Onset & progression | “When did symptoms start? Sudden vs. gradual? Has it spread proximally?” | Guillain‑Barre (GBS) is usually acute (days‑weeks) with rapid ascending spread; chronic peripheral neuropathy evolves over months‑years. |
| Distribution | “Are the feet, hands, legs, arms affected first? Any facial or bulbar weakness?” | Distal‑to‑proximal pattern suggests length‑dependent neuropathy; facial/bulbar involvement points toward GBS or certain infectious neuropathies. |
| Sensory profile | “Do you feel numbness, tingling, burning, or loss of vibration? Is it glove‑and‑stocking?” | Small‑fiber dysfunction gives burning/tingling; large‑fiber loss gives loss of proprioception and vibration, typical of many metabolic/tropical neuropathies. |
| Motor impact | “Any weakness, difficulty climbing stairs, lifting objects, or walking?” | Motor weakness is hallmark of GBS; in diabetic or toxic neuropathy motor loss is usually mild and distal. |
| Autonomic symptoms | “Do you have dizziness on standing, palpitations, sweating, urinary retention, or constipation?” | Autonomic dysfunction is common in GBS and in some toxic or HIV‑related neuropathies; helps gauge severity. |
| Pain | “Is pain present? Where and what type (sharp, aching, electric)?” | Neuropathic pain is frequent in distal symmetric polyneuropathy; severe radicular pain may suggest vasculitic or infectious causes. |
| Preceding events | “Recent infection (respiratory, GI), vaccination, travel, malaria treatment, TB therapy, HIV seroconversion, trauma?” | GBS often follows Campylobacter, CMV, HIV, or recent vaccination; toxic neuropathies follow antitubercular drugs, antiretrovirals, or anti‑malaria agents. |
| Systemic illnesses | “Do you have diabetes, renal failure, liver disease, hypothyroidism, sickle cell disease, rheumatic fever?” | Metabolic and systemic diseases are common causes of chronic peripheral neuropathy in Kenya. |
| Drug & toxin exposure | “Current or recent meds (isoniazid, dapsone, stavudine, quinine), alcohol, heavy metals?” | Identifies iatrogenic or toxic neuropathies. |
| Family history | “Any relatives with neuropathy, Charcot‑Marie‑Tooth, hereditary sensory neuropathy?” | Screens for inherited neuropathies. |
| Occupational / environmental | “Work in agriculture, exposure to pesticides, repeated heat?” | Pesticide‑related neuropathy is relevant in rural settings. |
Examination – what to look for and why
| Finding | What it indicates | Pathophysiologic basis |
|---|---|---|
| Sensory map (pinprick, temperature, vibration, proprioception) | Distal loss > proximal; stocking‑glove pattern | Length‑dependent axonal degeneration of longest fibers. |
| Muscle strength (MRC scale) | Symmetric proximal > distal weakness in GBS; distal weakness in metabolic neuropathy | Demyelination in GBS impairs conduction to proximal muscles first; axonal loss spares proximal muscles initially. |
| Deep tendon reflexes | Absent or markedly reduced in both GBS and chronic polyneuropathy; may be brisk early in demyelinating variants | Reflex arc interruption by sensory or motor fiber dysfunction. |
| Cranial nerve exam | Facial weakness, dysphagia, ophthalmoplegia | GBS (Miller‑Fisher variant) or HIV‑related neuropathy; helps differentiate from pure peripheral neuropathy. |
| Autonomic testing (heart rate variability, blood pressure response) | Orthostatic hypotension, tachycardia, arrhythmias | Autonomic fiber involvement, especially in GBS. |
| Gait assessment | Ataxic gait from proprioceptive loss; foot drop from peroneal weakness | Large‑fiber loss or motor weakness. |
| Skin & nail changes | Ulcers, trophic changes, loss of hair | Chronic sensory loss leads to unnoticed trauma. |
| Upper limb coordination (finger‑nose, rapid alternating movements) | Dysmetria if proprioception impaired | Large‑fiber sensory loss. |
| Respiratory assessment (vital capacity, chest expansion) | Reduced vital capacity in GBS | Diaphragmatic and intercostal weakness from motor fiber involvement. |
Differential diagnosis
| Condition | Points toward it | Distinguishing features |
|---|---|---|
| Guillain‑Barre syndrome (acute inflammatory demyelinating polyradiculoneuropathy) | Acute onset ≤4 weeks, rapid ascending weakness, areflexia, preceding infection, autonomic signs | CSF albumin‑cytologic dissociation, nerve‑conduction slowing, need for ventilatory monitoring |
| Diabetic distal symmetric polyneuropathy | Long‑standing diabetes, gradual onset, stocking‑glove sensory loss, mild distal weakness | Stable course, glycemic control correlation, absence of cranial nerve involvement |
| HIV‑associated neuropathy | HIV infection, CD4 count, antiretroviral therapy, painful burning distal symptoms | Often small‑fiber predominant, may improve with ART change |
| Antitubercular drug (isoniazid) neuropathy | TB treatment, pyridoxine deficiency, sensory loss, ataxia | Improves with pyridoxine supplementation |
| Toxic/medication‑induced (e.g., quinine, dapsone, stavudine) | Recent exposure to offending drug, dose‑related, often painful | Reversibility after drug withdrawal |
| Nutritional deficiency (B12, folate) | Malnutrition, vegetarian diet, malabsorption, macrocytosis | Presence of dorsal column signs, megaloblastic anemia |
| Sickle cell disease neuropathy | Sickle cell history, vaso‑occlusive crises, acute painful neuropathy | Episodic pain crises, hemolysis labs |
| Tropical neuropathies (e.g., leprosy, filariasis) | Residence in endemic area, skin lesions, nodules | Skin changes, positive skin smears, eosinophilia |
| Chronic inflammatory demyelinating polyneuropathy (CIDP) | Relapsing‑remitting course >8 weeks, proximal weakness, sensory ataxia | Responds to steroids/IVIG, nerve‑conduction shows demyelination but slower progression |
Investigations
| Test | What it answers | Interpretation |
|---|---|---|
| Nerve conduction studies / EMG | Demyelination vs axonal loss, distribution, severity | Slowed conduction velocity, prolonged distal latencies → demyelination (GBS, CIDP); reduced amplitudes → axonal neuropathy (diabetes, toxic) |
| Cerebrospinal fluid analysis | Presence of albumin‑cytologic dissociation, infection | Elevated protein with normal cell count supports GBS; pleocytosis suggests infectious meningitis |
| Full blood count & peripheral smear | Anemia, eosinophilia, sickle cells | Macrocytosis → B12/folate deficiency; sickle cells → sickle cell disease |
| Glycated hemoglobin | Chronic hyperglycemia | >7 % suggests diabetic neuropathy |
| HIV serology / viral load | HIV infection status | Positive → HIV‑related neuropathy; viral load guides ART |
| Hepatitis B/C serology | Co‑infection, immune‑mediated neuropathy | Positive may indicate cryoglobulinemic neuropathy |
| Serum B12, folate, copper, zinc | Nutritional deficiencies | Low B12 → subacute combined degeneration; low copper → myeloneuropathy |
| Renal & liver function tests | Uremic or hepatic neuropathy | Elevated creatinine or transaminases suggest metabolic cause |
| Antitubercular drug levels (if available) | Isoniazid toxicity | High levels correlate with neuropathy |
| Autoimmune panel (ANA, ENA, anti‑GM1) | Autoimmune neuropathy | Positive anti‑GM1 supports GBS; ANA suggests connective‑tissue disease |
| Imaging – MRI spine (contrast) | Nerve root enhancement | Root enhancement typical of GBS; compressive lesions excluded |
| Chest X‑ray / CT | Underlying TB, malignancy | Pulmonary TB may precede GBS; malignancy can cause paraneoplastic neuropathy |
Diagnosis and severity
Diagnostic criteria (GBS)
- Progressive weakness of more than one limb, reaching nadir within 4 weeks.
- Areflexia or hyporeflexia in affected limbs.
- Supportive evidence: CSF albumin‑cytologic dissociation, nerve‑conduction slowing, or recent antecedent infection.
If the above are met, label as Guillain‑Barre syndrome.
Severity grading (for GBS) – use the Hughes Functional Grading Scale:
| Grade | Clinical picture |
|---|---|
| 0 | Healthy, no symptoms |
| 1 | Minor symptoms, able to run |
| 2 | Able to walk 10 m independently |
| 3 | Able to walk 10 m with assistance |
| 4 | Bed‑ridden or chair‑bound |
| 5 | Requires assisted ventilation |
| 6 | Death |
For chronic peripheral neuropathy, severity is staged by:
- Mild – sensory symptoms only, normal strength, preserved ADLs.
- Moderate – sensory loss with mild distal weakness, some limitation in ADLs.
- Severe – marked weakness, loss of ambulation, autonomic instability, ulceration risk.
Severity guides urgency of immunotherapy (IVIG or plasma exchange for moderate‑severe GBS) and need for intensive monitoring (respiratory function, cardiac rhythm).
Management
Immediate stabilisation
- Airway, breathing, circulation – watch for respiratory muscle weakness; if vital capacity < 20 mL/kg or rapid shallow breathing, prepare for non‑invasive ventilation or intubation.
- Cardiac monitoring – autonomic dysfunction may cause tachyarrhythmia or bradycardia; have atropine and temporary pacing available.
- Pain control – start neuropathic analgesics (e.g., gabapentinoids, tricyclics) and opioid rescue for severe nociceptive pain.
- Prevent secondary injury – keep limbs in neutral position, use splints if severe motor loss, and start early passive range‑of‑motion exercises.
Definitive treatment
| Situation | First‑line disease‑modifying therapy | Adjunctive measures |
|---|---|---|
| Classic Guillain‑Barre (rapidly progressive ≤4 weeks) | Intravenous immunoglobulin (IVIG) – 2 days course | Monitor renal function, avoid volume overload |
| Same as above | Plasma exchange (PE) – 4‑5 exchanges over 1‑2 weeks | Ensure central line patency, replace electrolytes |
| Chronic inflammatory demyelinating polyneuropathy (CIDP) | IVIG or PE (induction) → oral steroids or steroid‑sparing immunosuppressants (azathioprine, mycophenolate) | Physiotherapy, occupational therapy |
| Metabolic/toxic neuropathy (e.g., diabetes, HIV, antiretroviral toxicity) | Treat underlying cause (optimise glycaemia, switch offending drug) | Vitamin supplementation (B‑complex), analgesia |
| Infectious neuropathy (e.g., leprosy, TB) | Appropriate antimicrobial regimen (rifampicin‑based for leprosy; anti‑TB therapy) | Corticosteroids for nerve inflammation when indicated |
Monitoring & follow‑up
- Daily bedside assessment of motor strength (MRC scale) and respiratory function (vital capacity, negative inspiratory force).
- Autonomic signs: heart‑rate variability, blood pressure lability; treat with fluids, vasoactive drugs as needed.
- Laboratory: CBC, renal & liver panels (especially with IVIG/PE), serum electrolytes, glucose.
- Rehabilitation: start active physiotherapy once strength improves; occupational therapy for ADL training.
Contra‑indications & safety
- IVIG: avoid in patients with severe IgA deficiency, known hyper‑viscosity, or uncontrolled hyper‑coagulable states.
- Plasma exchange: contraindicated in severe hemodynamic instability, active bleeding, or uncontrolled anticoagulation.
- High‑dose steroids: caution in uncontrolled diabetes, active infection, or severe osteoporosis.
Complications and prognosis
- Respiratory failure – leading cause of early mortality; early ventilatory support improves survival.
- Autonomic dysfunction – arrhythmias, labile blood pressure, urinary retention; may persist for weeks.
- Deep‑vein thrombosis / pulmonary embolism – immobilisation; prophylactic low‑molecular‑weight heparin unless contraindicated.
- Long‑term weakness – up to 30 % retain some motor deficit at 1 year; intensive rehab reduces disability.
- Chronic pain – neuropathic pain may persist; requires long‑term gabapentinoids or antidepressants.
- Relapse – more common in CIDP; monitor for re‑emergence of weakness after tapering immunotherapy.
Overall prognosis is good when respiratory failure is averted early; most patients recover functional independence within 6‑12 months, but residual sensory deficits are common.
High‑yield exam points
- Key differentiator: Guillain‑Barre is acute (<4 weeks) with albumin‑cytologic dissociation; CIDP is chronic (>8 weeks) and often responds to steroids.
- Look‑alike conditions: spinal cord compression, poliomyelitis, acute transverse myelitis, severe vitamin B12 deficiency.
- Common wrong first step: ordering MRI before assessing respiratory function; examiners expect immediate assessment of vital capacity.
- Bedside exam question: “What three signs would make you suspect autonomic involvement in this patient?” (e.g., tachycardia, labile BP, urinary retention).
- Management query: “If IVIG is unavailable, what is the next best disease‑modifying therapy?” – answer: plasma exchange.
- Safety focus: “List two contraindications to plasma exchange.”
Clinical case
Case: A 27‑year‑old male farmer presents with a 3‑day history of ascending weakness. He reports tingling in the feet, difficulty walking, and shortness of breath when climbing stairs. Examination shows symmetric flaccid paresis (MRC 3/5) in the lower limbs, absent ankle reflexes, preserved sensation to pinprick, and a vital capacity of 1.8 L. CSF shows protein 110 mg/dL with normal cell count.
Questions
- What is the most likely diagnosis?
Answer: Guillain‑Barre syndrome, acute inflammatory demyelinating polyneuropathy.
- What immediate intervention is mandatory?
Answer: Assess and support respiratory function; prepare for non‑invasive ventilation or intubation because vital capacity is below the safety threshold.
- Which disease‑modifying therapy should be started first, assuming both are available?
Answer: Intravenous immunoglobulin (IVIG) – it is easier to administer, has comparable efficacy to plasma exchange, and avoids central line complications.
Practice questions
Question 1
A 45‑year‑old woman with HIV on antiretroviral therapy develops symmetric distal numbness and foot drop over 2 months. Nerve conduction studies show demyelination. What is the next best step?
A. Start high‑dose steroids
B. Switch antiretroviral regimen
C. Begin IVIG
D. Order MRI spine
Answer: B. Switch antiretroviral regimen
Explanation: HIV‑associated neuropathy is often drug‑induced (e.g., stavudine); removing the offending agent is first‑line.
Question 2
A patient with confirmed Guillain‑Barre has a blood pressure that swings from 90/60 mmHg supine to 170/100 mmHg sitting. Which complication does this reflect?
A. Cardiac tamponade
B. Autonomic dysreflexia
C. Pulmonary embolism
D. Sepsis
Answer: B. Autonomic dysreflexia
Explanation: Labile hypertension with positional changes is classic autonomic dysfunction in GBS.
Question 3
A 60‑year‑old man presents with progressive weakness over 10 weeks, areflexia, and CSF protein 95 mg/dL. Which therapy is contraindicated as first‑line?
A. IVIG
B. Plasma exchange
C. Oral prednisolone
D. Azathioprine
Answer: C. Oral prednisolone
Explanation: Steroids alone are ineffective and may worsen outcomes in acute GBS; they are used in CIDP, not acute GBS.
Question 4
Which of the following is the most reliable bedside test to predict impending respiratory failure in Guillain‑Barre?
A. Sniff nasal inspiratory pressure
B. Forced vital capacity measurement
C. Pulse oximetry alone
D. Respiratory rate
Answer: B. Forced vital capacity measurement
Explanation: A falling vital capacity is the best predictor of need for ventilatory support.
Question 5
A child from a malaria‑endemic area develops acute flaccid paralysis after a febrile illness. Nerve biopsy shows axonal loss. Which diagnosis should be considered?
A. Guillain‑Barre syndrome
B. Cerebral malaria
C. Acute motor axonal neuropathy (AMAN) variant of GBS
D. Poliomyelitis
Answer: C. Acute motor axonal neuropathy (AMAN) variant of GBS
Explanation: AMAN is an axonal form of GBS seen after infections such as Campylobacter or malaria, characterised by pure motor axonal loss.
Drafted with AI assistance from standard references and reviewed for structure. Check details against your lecture notes and the Kenya MoH guideline.