Peripheral neuropathy and Guillain-Barre syndrome

• Peripheral neuropathy is damage to the peripheral nerves; it is a symptom or syndrome with many causes, not one disease.
• The first question in every patient is whether the process is mainly axonal (loss of nerve fibres) or demyelinating (loss of myelin), and whether it is length-dependent or not, because this points to the cause.
• Diabetes is the most common cause of chronic distal symmetric polyneuropathy; vitamin B12 deficiency, alcohol, drugs, vasculitis, renal failure and inherited conditions are other common causes.
• Nerve conduction studies are the main test that separates axonal from demyelinating disease and focal from diffuse disease.
• Guillain-Barre syndrome is an acute autoimmune neuropathy that can weaken breathing muscles; it is treated with intravenous immunoglobulin or plasma exchange, and needs early respiratory monitoring.
• Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is the chronic counterpart: symmetric proximal and distal weakness over at least 8 weeks, treated first with intravenous immunoglobulin or corticosteroids.

By the end of this page you should be able to:

1. Classify a peripheral neuropathy as axonal or demyelinating, diffuse or focal, and length-dependent or not, and say what each pattern suggests.
2. List the common causes of distal symmetric polyneuropathy and the screening tests for each.
3. Explain what a nerve conduction study measures and how axonal loss differs on it from demyelination.
4. Recognise Guillain-Barre syndrome clinically, including variants, and state the diagnostic criteria, the treatment options with doses, and the rules for respiratory monitoring.
5. Recognise CIDP and its variants, state its diagnostic criteria, and outline induction and maintenance treatment.
6. Adapt management to low-resource settings.

Peripheral nerves carry motor, sensory and autonomic signals. Disease can hit them in different distributions, and the distribution is more informative than any single symptom:

• Mononeuropathy: one nerve, as in carpal tunnel syndrome.
• Mononeuropathy multiplex: several nerves in different places; the classic pattern of vasculitis.^[4]
• Polyneuropathy: many nerves symmetrically, usually length-dependent, which is the commonest pattern.
• Polyradiculoneuropathy: roots and nerves together, as in Guillain-Barre syndrome and CIDP.
• Neuronopathy (ganglionopathy): the cell body is the target, giving non-length-dependent, often severe sensory loss, as in Sjogren syndrome or paraneoplastic disease.

The second essential distinction is physiological:

• Axonal neuropathy: the nerve fibre (axon) is lost. It is the commonest result of metabolic, toxic and most genetic causes.
• Demyelinating neuropathy: the myelin sheath is damaged while the axon is relatively preserved. It is the hallmark of acquired immune-mediated disease (Guillain-Barre syndrome, CIDP, multifocal motor neuropathy) and of hereditary demyelinating neuropathies such as Charcot-Marie-Tooth disease type 1.

Most chronic peripheral neuropathies in practice are mixed to some degree, but labelling the dominant process guides both the search for a cause and treatment.^[3][4]

Peripheral neuropathy is common. It affects about 1 to 3% of the general population and roughly 7% of people older than 65 years.^[3] Diabetes is the most common cause in developed countries: about 40 to 50% of patients with diabetes mellitus develop a detectable neuropathy within 10 years of onset, and many cases are never clinically apparent unless tested.^[3][4]

Guillain-Barre syndrome is an acute polyradiculoneuropathy with an annual incidence estimated at 0.81 to 1.89 cases per 100,000 people worldwide. Respiratory failure requiring ventilation occurs in up to 30% of patients, and functionally significant residual deficits remain in about 15%.^[6][7]

CIDP is rarer and occurs at any age, most often between 40 and 60 years, and is more common in men.^[11]

The causes of chronic distal symmetric polyneuropathy cluster into a short list and should be worked through in every patient.^[3][4]

• Diabetes mellitus is the most common cause in most populations. The risk rises with duration of disease, poor glycaemic control, and the presence of retinopathy or nephropathy.
• Alcohol causes a slowly progressive, painful, distal sensorimotor neuropathy that is thought to be a mix of direct toxicity and secondary vitamin deficiency (thiamine, folate, vitamin B12). It is largely irreversible.
• Vitamin B12 deficiency damages myelin and produces a sensory-predominant neuropathy, often with dorsal column and corticospinal tract involvement ("subacute combined degeneration"). It is seen after bariatric surgery and in strict vegetarians, among others.
• Other vitamin problems: deficiency or excess of vitamin B6 (pyridoxine) can both cause neuropathy; thiamine and vitamin E deficiency are rare causes.
• Renal failure: about 60% of patients with chronic renal failure (glomerular filtration rate below 12 mL/min) develop a sensorimotor polyneuropathy, and mononeuropathies such as carpal tunnel syndrome are common.^[4]
• Drugs and chemotherapy: vinca alkaloids, taxanes, platinum compounds, bortezomib, thalidomide and suramin among cytotoxic agents, and metronidazole, amiodarone, phenytoin, isoniazid, nitrofurantoin, dapsone, colchicine and others among non-cytotoxic drugs.^[3]
• Inherited neuropathies, of which Charcot-Marie-Tooth disease is the largest group; these usually begin in childhood or early adulthood with pes cavus, hammer toes and distal wasting.
• Vasculitis (primary or secondary, including connective tissue disease) classically presents as mononeuritis multiplex with acute pain.
• Infections: HIV, hepatitis C, leprosy, Lyme disease and others.
• Paraproteinaemic neuropathy and amyloidosis.
• Idiopathic (chronic idiopathic axonal polyneuropathy) remains the label in about 20 to 30% of cases after a thorough work-up.^[3]

Guillain-Barre syndrome (GBS) is an acute immune-mediated polyradiculoneuropathy. About two-thirds of patients have a prodromal illness in the preceding weeks, usually respiratory or gastrointestinal. Campylobacter jejuni is the most frequently associated bacterial infection and cytomegalovirus the most common viral one. The syndrome is thought to arise from molecular mimicry between microbial antigens and peripheral nerve gangliosides, triggering an immune attack on myelin (acute inflammatory demyelinating polyneuropathy, AIDP) and sometimes on axons (acute motor axonal neuropathy, AMAN) or both motor and sensory axons (acute motor-sensory axonal neuropathy, AMSAN).^[4]

A useful clinical rule is that GBS worsens for up to 4 weeks; if progression continues beyond 8 weeks, reconsider the diagnosis as acute-onset CIDP (A-CIDP), which occurs in about 5% of patients initially labelled GBS.^[10]

CIDP is an acquired immune-mediated neuropathy with an insidious or stepwise course over at least 8 weeks. Most patients have progressive, symmetric, proximal and distal weakness of the upper and lower limbs with numbness and paraesthesiae. It is more common in men and occurs at any age, most often between 40 and 60 years.^[4][11]

The right explanation of a symptom starts with the nerve fibre type and its length.

Large myelinated fibres carry proprioception, vibration and motor signals. Their loss produces numbness, imbalance, loss of joint position sense and weakness. Small fibres (unmyelinated C fibres and thinly myelinated A-delta fibres) carry pain and temperature and drive autonomic function; their loss produces burning pain, hyperalgesia, allodynia, and autonomic symptoms such as dry skin, orthostatic intolerance and gastroparesis. A patient can have severe pain with an entirely normal nerve conduction study, because small fibres are not measured by standard electrophysiology.^[3]

Length-dependence explains why symptoms start in the feet. Axons are longest to the toes; a toxic or metabolic insult that impairs axonal transport or energy supply affects the longest and thinnest fibres first. Hence the classic "stocking-glove" sensory loss: when sensory loss reaches the mid-calf, the fingertips are affected, because the nerve lengths are roughly equivalent. Weakness follows sensory loss, first in toe extension, then ankle dorsiflexion.^[3]

In axonal injury, if the axon is cut the distal portion undergoes Wallerian degeneration and regenerates slowly; in metabolic and toxic neuropathies the process is a "dying-back" from the terminals. Recovery is slow and often incomplete. In demyelinating disease the myelin is stripped but the axon survives, so remyelination can be rapid, and immune therapy often works well, provided treatment is not delayed so long that secondary axonal loss has occurred.^[4]

Guillain-Barre syndrome and CIDP are post-infectious or autoimmune disorders: in AIDP macrophages strip myelin from nerves; in AMAN and AMSAN antibodies against gangliosides (GM1, GD1a and others) bind to the axolemma at the nodes of Ranvier and cause conduction failure or axonal degeneration. This explains why AMAN patients tend to have purely motor, often very rapid, severe weakness and why their reflexes may initially be preserved.^[4][7]

Patients describe "pins and needles", burning, electrical or aching pain, numbness, cold or dead feet, or loss of balance in the dark (sensory ataxia). Weakness appears as tripping, difficulty with buttons or climbing stairs. Autonomic clues are orthostatic dizziness, constipation, diarrhoea, bladder symptoms, sweating changes, erectile dysfunction and blurry vision.

A useful bedside screen for an inflammatory cause is the onset-distribution-systemic tool: an inflammatory neuropathy is likely if at least one of the following is present: onset in under 8 weeks to reach plateau, a non-length-dependent distribution, or systemic signs (skin changes, weight loss, fever, joint swelling, autonomic symptoms). This screen is 96% sensitive and 85% specific for inflammatory neuropathies, including Guillain-Barre syndrome, CIDP, multifocal motor neuropathy, vasculitic and paraneoplastic neuropathies.^[3]

• Sensation in a glove-and-stocking distribution, with loss of pinprick, temperature, vibration and joint position; in mild cases only the toes and fingertips.
• Weakness distally; later, in severe chronic disease, proximal weakness too.
• Areflexia or hyporeflexia, usually starting at the ankles. A reflex that is lost on only one side suggests mononeuropathy or radiculopathy rather than a generalised polyneuropathy.
• In chronic cases: distal calf and intrinsic hand wasting, hammer toes, pes cavus and claw hands.^[3]

The classic picture is an acute illness over days to 4 weeks: paraesthesiae in the feet and hands, progressive symmetric weakness beginning in the legs and moving up (ascending paralysis), loss of reflexes early, and variable cranial nerve, sensory and autonomic involvement.^[4][7]

• Reflexes are usually reduced or absent, but can be normal in about 10% of patients early in the course, especially in AMAN.^[6]
• Facial weakness occurs in at least half of patients. ^{[7] [4]}
• Ophthalmoparesis and bulbar palsy raise the risk of aspiration and dysphagia.
• Respiratory insufficiency from diaphragm weakness is the life-threatening complication; it can develop without obvious dyspnoea.
• Autonomic dysfunction (heart rate and blood pressure lability) is a major cause of morbidity and mortality.^[4][7]
• Pain is common: 36% of patients have pain two weeks before weakness, and 66% during the acute phase.^[6]
• Miller Fisher syndrome is a variant with ophthalmoplegia, ataxia and areflexia (usually without limb weakness), often preceded by Campylobacter jejuni or Mycoplasma infection and associated with anti-GQ1b antibodies.^[4][7]
• Cranial variant (bilateral facial weakness with paraesthesiae) and pharyngeal-cervical-brachial variant are recognised less often.
• AMAN/AMSAN variants give motor deficits, often rapidly, with or without sensory loss. Tendon reflexes may be preserved until weakness is severe in AMAN. Axonal GBS carries a worse short-term prognosis.^[4][7]

Typical CIDP shows progressive symmetric proximal and distal weakness of upper and lower limbs with numbness and paraesthesiae. Reflexes are absent or markedly attenuated. Large-fibre modalities (vibration, proprioception) are lost. Cranial nerves are involved in about 15% of cases (facial, ophthalmoparesis or bulbar). Sensory CIDP is a recognised variant in which sensory ataxia dominates and motor findings are minimal. Hypertrophy of nerve roots can mimic lumbar stenosis.^[4][8]

The pattern tells you where to look.

Two traps matter in practice:

1. Myelopathy mimics neuropathy. Cervical myelopathy can produce a pyramidal pattern of weakness, hyperreflexia below the lesion, a sensory level and bladder or bowel dysfunction. A peripheral neuropathy should not be diagnosed without considering it.
2. Common diseases are not always the cause. Diabetes and hypothyroidism are common; a diabetic patient can still develop Guillain-Barre syndrome, CIDP, amyloidosis or vitamin B12 deficiency.

First confirm that the findings are neuropathic (take the history, test large and small fibres, check reflexes) and classify the pattern. Then choose tests to confirm the cause.

High-yield screening laboratory tests for distal symmetric polyneuropathy: full blood count; serum sodium, potassium, chloride and bicarbonate; urea and creatinine; liver function tests; fasting glucose and haemoglobin A1c; serum protein electrophoresis; vitamin B12 with or without methylmalonic acid (methylmalonic acid normal range 0.1 to 0.4 micromol/L, recommended when vitamin B12 is 150 to 300 pmol/L, normal range 145 to 569 pmol/L).^[3]

Add, according to the clinical picture: thyroid function; glycaemic testing with a 2-hour glucose tolerance test if haemoglobin A1c is 6.0 to 6.4%; copper and vitamin E levels; heavy metal screening; autoantibody testing for Sjogren syndrome, lupus and rheumatoid arthritis; HIV and hepatitis B/C serology; cryoglobulins; and, when vasculitis or amyloidosis is suspected, nerve or combined nerve-muscle biopsy. Genetic testing is appropriate for suspected hereditary neuropathy.^[1][3]

Lumbar puncture in suspected Guillain-Barre syndrome or CIDP looks for albuminocytological dissociation (raised cerebrospinal fluid protein with a normal or near-normal cell count). This is present in over 80% of Guillain-Barre syndrome patients after 2 weeks.^[4][7]

Nerve conduction studies are the single most useful test in neuropathy: they confirm that a peripheral nerve problem exists, determine whether it is axonal or demyelinating, motor or sensory, diffuse or multifocal, and gauge severity and acuity.

Axonal loss. The amplitude of the compound muscle action potential (CMAP) correlates with the number of motor axons, and the amplitude of the sensory nerve action potential (SNAP) with the number of sensory axons. Axon-loss lesions reduce these amplitudes; conduction velocity is only mildly or moderately slowed once the largest, fastest fibres are lost. A drop in CMAP amplitude between distal and proximal stimulation of more than 20% implies conduction block, and an increase in CMAP duration of more than 15% signifies temporal dispersion; both are hallmarks of demyelination rather than axon loss.^[2][4]

Demyelination. Loss of myelin produces marked slowing of conduction velocity (slower than 75% of the lower limit of normal), marked prolongation of distal latency (longer than 130% of the upper limit of normal), or both, plus prolonged F-wave latency. Conduction block and temporal dispersion at non-entrapment sites differentiate acquired demyelinating neuropathy (Guillain-Barre syndrome, CIDP) from hereditary demyelinating neuropathy such as Charcot-Marie-Tooth disease type 1, where slowing is uniform and block is absent.^[2][4]

Patterns in common conditions. Diabetes typically gives a length-dependent mixed axonal and demyelinating sensorimotor polyneuropathy. Alcohol and most toxins give a diffuse axonal sensorimotor polyneuropathy. Vasculitis gives a multifocal axonal (mononeuritis multiplex) pattern. Guillain-Barre syndrome (classically AIDP) gives a multifocal demyelinating neuropathy, motor more than sensory. CIDP gives diffuse demyelination.^[2][4]

Needle electromyography complements the study: positive sharp waves and fibrillation potentials indicate active denervation; recruitment falls early; and long, large, polyphasic motor unit potentials appear later as reinnervation proceeds. Chronicity, severity and prognosis can be inferred.^[2]

Small-fibre neuropathy escapes routine nerve conduction studies because these only measure large fibres. In patients with pure small-fibre symptoms, skin biopsy measuring intraepidermal nerve fibre density is the gold standard test (sensitivity 45 to 90%, specificity 95 to 97%).^[3]

The 2023 European Academy of Neurology / Peripheral Nerve Society guideline sets out the current diagnostic approach. Diagnosis rests on the characteristic clinical picture of an acute or subacute polyradiculoneuropathy with progression for up to 4 weeks, decreased or absent reflexes, and supportive findings (cerebrospinal fluid albuminocytological dissociation, or nerve conduction study abnormalities) that are often absent very early. The guideline recognises AIDP, the axonal variants AMAN and AMSAN, and Miller Fisher syndrome, among others.^[10][7]

Supportive and diagnostic pointers from reviews and the guideline summary:

• Cerebrospinal fluid albuminocytological dissociation is present in over 80% of patients after 2 weeks and in up to 90% by the third week.^[4][6]
• Nerve conduction study at 3 to 4 weeks after onset differentiates axonal from demyelinating GBS.^[6]
• Antiganglioside antibodies: GM1 IgG in some AIDP; anti-GM1 or anti-GD1a in most AMAN and AMSAN; anti-GQ1b in many Miller Fisher syndrome.^[4][7]
• Spine MRI may show enhancement of nerve roots in AIDP.^[4]
• The guideline advises testing for anti-ganglioside antibodies mainly in atypical cases (not needed for typical motor-sensory GBS) and considering autoimmune nodopathy antibodies when the phenotype suggests a nodopathy.^[10]
• If weakness is still progressing after 8 weeks, consider acute-onset CIDP (about 5% of cases initially diagnosed as GBS).^[10]

The 2021 EAN/PNS CIDP guideline (second revision) is the current standard. It recognises "typical CIDP" and well-characterised CIDP variants (distal, multifocal or focal, motor, motor-predominant, sensory, sensory-predominant) instead of the old "atypical CIDP" label; autoimmune nodopathies are no longer classified as CIDP.^[8][11]

Diagnostic categories are now only two: CIDP and possible CIDP. For typical CIDP, at least 2 motor nerves must show demyelination on nerve conduction study, with sensory conduction abnormalities in at least 2 nerves. Possible CIDP can be diagnosed when a patient fulfils clinical criteria but meets criteria in only 1 motor nerve, or fails electrodiagnostic criteria altogether but shows objective improvement with IVIg, corticosteroids or plasma exchange and at least one supportive criterion (elevated CSF protein, ultrasound or MRI abnormalities, or nerve biopsy). Sensory CIDP can be diagnosed only as "possible sensory CIDP", because sensory criteria alone cannot be upgraded.^[8][11]

Two scores are in routine use and are recommended by the 2023 guideline for estimating risk and outcome.

• mEGOS (modified Erasmus GBS Outcome Score) predicts the probability of being unable to walk independently at 6 months. ^[10]
• mEGRIS (modified Erasmus GBS Respiratory Insufficiency Score) estimates the risk of needing mechanical ventilation, using MRC (Medical Research Council) sum score, facial or bulbar weakness, and the time from onset to admission. ^[10]

Clinical predictors of needing ventilation are fast progression, bulbar palsy, neck and hip flexor weakness, severe disease and autonomic instability.^[10][6]

All patients with suspected GBS should be admitted to hospital; the speed of progression and the respiratory risk make observation on a neurology or intensive care unit appropriate. The intensity of monitoring depends on severity and trajectory. ^[5][6]

Respiratory monitoring rules from the 2023 EAN/PNS guideline and supporting reviews: ^[10][5][6]

• Measure forced vital capacity (FVC) three to six times a day depending on severity, and until significant worsening seems unlikely; hourly or four-hourly while the patient is still declining.^[10]
• A fall in FVC of more than 30% below the predicted baseline should raise concern; a fall of more than 30% within 24 hours likely warrants immediate transfer to the intensive care unit; a 50% decline within 24 hours likely indicates the need for ventilation.^[5][6][10]
• Consider elective ventilation when FVC is 20 mL/kg or less; ventilation is almost inevitable at 10 mL/kg or less.^[5][10]
• Single breath count (counting aloud on one full breath) under 20 is a useful bedside screen for transfer to intensive care.^[10]
• If measured, maximal expiratory pressure under 30 cmH2O or maximal inspiratory pressure under 40 cmH2O indicates that elective ventilation should be considered imminently.^[10]
• Continue close monitoring after discharge from intensive care, because up to two-thirds of GBS deaths occur during recovery, mostly from cardiovascular and respiratory events. ^[5]

A single breath count of 19 or fewer independently predicts the need for mechanical ventilation; this and the 20/30/40 rule come from well-quoted teaching. ^[5]

Additional criteria for intensive care admission are rapid progression of respiratory muscle weakness, evolving respiratory distress, severe autonomic disturbance or severe dysphagia, and an mEGRIS score greater than 4. ^[6]

Intensive care monitoring also includes heart rate, rhythm, blood pressure, oxygen saturation, vital capacity, blood gases, biochemistry and swallowing, checked every 2 to 4 hours when the patient is deteriorating; temporary pacing for severe dysautonomia or arrhythmia; VTE prophylaxis; and careful positioning and airway suctioning. ^[6][4]

• Intravenous immunoglobulin: 0.4 g/kg body weight per day for 5 consecutive days (or 1 g/kg for 2 days) is the standard regimen. ^[5][6][10]
• Plasma exchange: 40 to 50 mL plasma per kg per session for 5 sessions over 7 to 14 days, exchanging a total of 12 to 15 L of plasma; the guideline gives the recommendation as four to five exchanges, total 12 to 15 L, over 1 to 2 weeks. ^[5][6][10]
• Intravenous immunoglobulin and plasma exchange are equally effective in patients unable to walk unaided. ^[7][9][10]
• Choose IVIg or PE on availability, patient factors and local expertise; IVIg is easier to give and is often preferred in practice, while PE may be used when IVIg is unavailable or contraindicated. ^[5][9]
• Start IVIg as soon as possible within the first 2 weeks (good practice point also 2 to 4 weeks) in patients unable to walk unaided; start PE within 4 weeks. ^[10]
• Corticosteroids should not be used, alone or as add-on, because they do not hasten recovery and oral corticosteroids may delay it. ^[7][9][6]
• Do not combine IVIg and plasma exchange in sequence; it adds complications without benefit. ^[7][9]
• A second course of IVIg in patients with a poor prognosis is not recommended. ^[10]

AAN perspective. The American Academy of Neurology practice parameter (2003, reaffirmed 2025) recommends plasma exchange for non-ambulant adults within 4 weeks and IVIg for non-ambulant adults within 2 (possibly 4) weeks, regards the two as equivalent, and states that corticosteroids are not recommended and sequential treatment is not recommended. ^{[9] [11]}

EAN/PNS perspective. The 2023 EAN/PNS guideline and the 2021 EAN/PNS CIDP guideline inform both the diagnostic criteria and the treatment choices above and below. ^[10][11]

Neuropathic pain in GBS is common and can dominate the illness. Gabapentinoids, tricyclic antidepressants or carbamazepine are weakly recommended for pain control, together with standard analgesia; the 2023 guideline does not recommend a specific treatment for fatigue. ^[10][6]

Physiotherapy, early mobilisation once stable, prevention of contractures, VTE prophylaxis, and management of swallowing, secretion clearance and autonomic disturbance are essential; most GBS deaths in the recovery phase are from cardiovascular and respiratory causes. ^[5][6]

In children with severe GBS, both IVIg and plasma exchange are treatment options, with the choice made by the specialist paediatric team; the evidence base in children is limited. ^[9][7]

Treatment should start when there is disabling disease. Both intravenous immunoglobulin and corticosteroids are first-line; plasma exchange is similarly effective but is less well tolerated and harder to arrange, so it is usually offered after failure of the first-line options or when rapid reversal is needed. ^[8][11]

• Induction with IVIg: 2 g/kg total dose, divided over 2 to 5 days. Two to five repeated doses of 1 g/kg every 3 weeks may be needed before judging it ineffective, or a second 2 g/kg course a few weeks after the first. ^[8][11]
• Maintenance IVIg: most patients need it. The common trial regimen is 1 g/kg every 3 weeks; in practice lower doses and longer intervals are used, for example 0.4 to 1 g/kg every 2 to 6 weeks. ^[8][11]
• Subcutaneous immunoglobulin (SCIG) is an option for maintenance in IVIg-responsive patients (2021 guideline recommendation), at a starting conversion of 1:1 weekly dose from the IVIg dose; trial doses studied were 0.2 and 0.4 g/kg per week, with fewer relapses at the higher dose. ^[8]
• Corticosteroids: pulsed regimens (for example 40 mg oral dexamethasone daily, or 500 mg intravenous methylprednisolone daily, each for 4 days per month for 6 months) may induce remission more often than daily prednisone or prednisolone, with fewer side effects; the best regimen is unknown. Motor CIDP can worsen after steroids, so IVIg is preferred first in motor CIDP. ^[8][11]
• Plasma exchange: an effective induction option when IVIg and corticosteroids fail or are contraindicated; dosing and schedules follow local practice and the treating team. ^[11]
• Refractory disease: azathioprine, mycophenolate or cyclosporine may be used as steroid- or immunoglobulin-sparing agents; refractory cases are treated with rituximab, cyclophosphamide or cyclosporine after re-evaluating the diagnosis (including autoimmune nodopathies, POEMS, lymphoma, amyloidosis). ^[8][11]
• Maintenance principle: continue the effective agent until maximal benefit, then taper or space the dose to find the lowest effective maintenance dose; test for active disease versus fixed deficits from chronic axonal loss before escalating. ^[8][11]
• Neuropathic pain is uncommon in CIDP but treat with standard neuropathic pain agents (gabapentinoids, tricyclic antidepressants, SNRIs, carbamazepine). ^[8][11]
• Rehabilitation, orthoses, foot care, physiotherapy, occupational therapy and psychosocial support should accompany medical therapy. ^[8][11]

Systemic or non-systemic vasculitis needs immunosuppression (usually corticosteroids with or without cyclophosphamide, depending on severity) after confirmation by nerve biopsy. Diabetic or renal-failure patients must also have vasculitis excluded rather than attributing everything to the common disease. ^[4]

Across causes, first-line oral options for neuropathic pain are tricyclic antidepressants, SNRIs, sodium-channel blockers (such as carbamazepine/oxcarbazepine) and gabapentinoids; efficacy is similar and the choice follows comorbidity, side-effect profile and cost. Opioids are discouraged for long-term use. Patients should be counselled to expect reduction, not abolition, of pain. ^[3]

• Progression to respiratory failure in Guillain-Barre syndrome (up to 30%).^[6]
• Autonomic dysfunction with arrhythmia, severe hypertension or hypotension, ileus, urinary retention.
• Aspiration pneumonia from bulbar weakness.
• Deep vein thrombosis and pulmonary embolism from immobility.
• Pressure injuries and contractures in severe or prolonged disease.
• Persistent disability: about 15% of GBS patients have functionally significant residual deficits. ^[7]
• CIDP complications: treatment-related complications of chronic immunotherapy, steroid side-effects, secondary axonal loss if treatment is delayed.
• Chronic neuropathic pain in many chronic polyneuropathies.

Guillain-Barre syndrome reaches its worst point (nadir) within 1 month in over 90% of patients; a plateau phase precedes recovery. Recovery may take months to a year and can be incomplete. Predictors of poor outcome are older age, rapid progression, severe weakness at nadir and axonal loss on nerve conduction study. Immunotherapy hastens recovery but does not change the ultimate prognosis. ^[4][7]

CIDP follows a relapsing or progressive course; as a rule most patients improve with immune therapy, and early treatment prevents permanent axonal loss. Many need long-term maintenance, but some achieve lasting remission. ^[4][8]

There is no primary prevention of most peripheral neuropathies. Secondary prevention means:

• Early and good glycaemic control to delay diabetic neuropathy.
• Alcohol cessation to prevent progression of alcoholic neuropathy.
• Routine vitamin B12 replacement after bariatric surgery, during treatment of pernicious anaemia, and in at-risk diets.
• Annual foot examination and patient education in diabetes, including monofilament testing, to prevent ulcers and amputation.
• Medication reconciliation to avoid or monitor neurotoxic drugs (isoniazid with pyridoxine, dose-adjustment in renal impairment).
• Screening for neuropathy in newly diagnosed diabetes is recommended by diabetes guidelines and is best done with clinical examination and, when indicated, nerve conduction studies.

• Children. GBS is uncommon and often follows infection; Miller Fisher syndrome and AMAN are proportionally more common than in adults. Hereditary neuropathies presenting in childhood are not GBS and should not be treated with immunotherapy.
• Older adults. Chronic idiopathic axonal polyneuropathy becomes more common after age 60; diabetes and renal impairment are frequent amplifiers. Polypharmacy magnifies drug-induced neuropathy.
• Pregnancy. Acute neuropathies in pregnancy need care by a neurology and obstetric team, especially when respiratory function is involved; the principles of GBS management are unchanged and IVIg or plasma exchange can be given when indicated.
• Immunocompromised patients. HIV, lymphoma and immunosuppression can themselves cause neuropathy and complicate treatment; investigate rather than attribute.

• The diagnosis is clinical first. Recognise the glove-and-stocking loss, absent ankle reflexes and, for GBS, ascending weakness and areflexia. Early unsafe diagnosis causes more harm than late testing.
• A single breath count and vital capacity are cheap and reproducible screens for GBS respiratory compromise; transfer early if the single breath count is under 20 or FVC is under 20 mL/kg.
• Plasma exchange requires a machine and staff that may not exist; IVIg may be unaffordable in many settings. Good supportive care (positioning, suction, feeding, DVT prophylaxis) reduces mortality even without immunotherapy.
• Cheap aetiology tests: fasting glucose/HbA1c, renal function, B12 level before B12 treatment, thyroid function and a medication review. HIV and hepatitis testing where prevalence is high.
• Nerve conduction studies and lumbar puncture equipment may be scarce; suspected GBS or CIDP then depends more on clinical diagnosis and response to therapy, and on referral links.
• Treatment may need referral to a centre with IVIg, plasma exchange or intensive care capacity; delayed referral for Guillain-Barre syndrome increases mortality.

• Peripheral neuropathy is a syndrome, not a diagnosis; classify by distribution (mononeuropathy, polyneuropathy, mononeuritis multiplex, polyradiculoneuropathy) and by physiology (axonal vs demyelinating).
• Diabetes is the most common cause of chronic distal symmetric polyneuropathy; about 40 to 50% of patients with diabetes develop a detectable neuropathy within 10 years of onset.^[3]
• Small-fibre symptoms (burning pain, temperature loss, autonomic symptoms) can exist with a normal nerve conduction study, because standard electrophysiology does not test small fibres.
• Vitamin B12 deficiency and excess of vitamin B6 both cause neuropathy; screen B12 in every polyneuropathy.
• Nerve conduction study differentiates axonal from demyelinating, motor from sensory, and diffuse from focal disease; demyelinating patterns are 75% (below the lower limit of normal) slowing of velocity or 130% (above the upper limit of normal) prolongation of distal latency, with temporal dispersion and conduction block.^[2][4]
• An inflammatory cause is likely with acute or subacute onset under 8 weeks, non-length-dependent distribution or systemic signs; this screen is 96% sensitive and 85% specific.^[3]
• Guillain-Barre syndrome worsens over up to 4 weeks; treat with IVIg 0.4 g/kg daily for 5 days or plasma exchange (12 to 15 L over 1 to 2 weeks), monitor respiration with the 20/30/40 rule, and never use corticosteroids.^{[5][6][9][10]}
• Both IVIg and plasma exchange are equally effective in GBS and should not be combined in sequence. ^[6]
• CIDP is the chronic counterpart (minimum 8 weeks) with symmetric proximal and distal weakness; first-line therapy is IVIg or corticosteroids, with maintenance as needed; plasma exchange is second-line.
• IVIg induction in CIDP is 2 g/kg over 2 to 5 days; maintenance 1 g/kg every 3 weeks, often tapered, and SCIG is an effective maintenance option.^[8][11]
• Up to 30% of GBS patients need ventilation; most deaths in the recovery phase are cardiovascular or respiratory.^[6][5]
• About 15% of GBS patients are left with functionally significant deficits; early, correct treatment improves recovery speed.^[7]

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