Differentials
Guillain-Barre syndrome (GBS)
SIGNS / SYMPTOMS
GBS typically progresses for <4 weeks. In cases that progress for 4-8 weeks, distinction can be difficult, because these cases mimic acute- or subacute-onset CIDP.[7][81][82]
Some subacute presentations of CIDP can be monophasic, as in GBS.[4][8][40]
GBS is associated with more frequent antecedent infection, respiratory failure, cranial nerve involvement, motor greater than sensory involvement, and autonomic dysfunction.[81][82][83][84]
Charcot-Marie-Tooth disease (CMT)
SIGNS / SYMPTOMS
Also known as hereditary motor and sensory neuropathy.
Early age of onset, slow progression of weakness, skeletal deformities (e.g., pes cavus, hammer toes), and extremely distal weakness.[34]
INVESTIGATIONS
Electrodiagnostic features include uniform slowing of conduction velocities and usually absence of conduction block.[87]
Terminal latency index, the modified F ratio, and dispersion of the compound muscle action potential amplitude may also differentiate.[88][89]
Nerve ultrasound shows more diffuse nerve enlargement, especially in CMT1A, compared with multifocal cross-sectional area enlargement in CIDP.[51][52][86]
Nerve biopsy more often shows areas of abnormally thickened or folded (tamaculous) myelin or areas of hypomyelination in CMT.[90]
Anti-myelin-associated glycoprotein (anti-MAG) neuropathy
SIGNS / SYMPTOMS
Patients tend to be older, more often male, have a more indolent course, and have only distal weakness or sensory ataxia with gait imbalance or action tremors.[11][91]
Most common presentation is a distal acquired symmetrical demyelinating (DADS) phenotype.[11][91]
INVESTIGATIONS
Conduction block and abnormal temporal dispersion rarely occur.[92]
Electrodiagnostic finding of prolonged distal latencies out of proportion to slowed conduction velocities is a hallmark.[93]
The presence of anti-MAG antibodies by enzyme-linked immunosorbent assay (ELISA) and Western blot is seen in essentially all patients.[11]
Widely spaced myelin is the classic pathological finding.[11]
Patients do not respond as well to corticosteroids, intravenous immunoglobulin, or plasma exchange.[94]
Rituximab has been widely used and is the treatment of choice despite limited evidence of efficacy.[11][94][95]
Monoclonal gammopathy of unknown significance (MGUS)-associated neuropathy
SIGNS / SYMPTOMS
Patients with CIDP and MGUS (usually IgA, IgG, or IgM) tend to be older and have more distal weakness, a more indolent course, and more sensory involvement.[11][62]
IgA/IgG MGUS without CIDP has a better response to plasma exchange compared with IgM MGUS in the context of the distal variant of CIDP.[96]
INVESTIGATIONS
Testing should include serum protein electrophoresis and immunofixation, spot urine immunofixation for light chains, and serum free light chains.[1][70]
For IgA or IgG lambda paraproteinaemia, testing of vascular endothelial growth factor (VEGF) serum levels is indicated, especially in patients with clinical suspicion of polyneuropathy-organomegaly-endocrinopathy-M-protein-skin changes (POEMS) syndrome.[1]
For IgM paraproteinaemia, testing for anti-MAG antibody is warranted.[1]
If immunoglobulin level is >15 g/L (>1.5 g/dL), check for a haematological malignancy.[97]
Multifocal motor neuropathy
SIGNS / SYMPTOMS
Distal asymmetrical weakness and the lack of sensory signs or symptoms are seen.[98]
European Academy of Neurology/Peripheral Nerve Society (EAN/PNS) guidelines consider this a distinct entity from CIDP.[1]
INVESTIGATIONS
Electrodiagnostic studies show multifocal conduction block as the major demyelinating feature. Sensory nerve conduction studies are normal.[98]
Anti-GM1 antibodies are found in 30% to 80% of patients.[99][100]
Nerve ultrasound often shows milder, more asymmetrical nerve enlargement with greater side-to-side intra-nerve variability.[86][101]
Responds to treatment with intravenous immunoglobulin, but no response to corticosteroids or plasma exchange.[62][98]
Autoimmune nodopathy
SIGNS / SYMPTOMS
Demyelinating polyneuropathy with acute or subacute aggressive onset, resembling Guillain-Barre syndrome or acute-onset CIDP.[63]
Low-frequency tremor, ataxia disproportionate to the sensory involvement or other cerebellar features, or predominantly distal weakness.[63]
May be associated with nephrotic syndrome.[63]
Central nervous system demyelination has been reported.[102][103]
INVESTIGATIONS
Antibodies (mostly IgG4 subtypes) present against nodal and paranodal antigens, such as neurofascin-155 (NF155), contactin-1 (CNTN1), contactin-associated protein 1 (Caspr1), and neurofascin isoforms NF140/186.[62][63]
Very high CSF protein levels may be present.[63]
Poor response to intravenous immunoglobulin and corticosteroids.[1]
Chronic immune sensory polyradiculoneuropathy (CISP) and CISP-plus
SIGNS / SYMPTOMS
Chronic and progressive sensory ataxia. Preferentially affects large myelinated fibres of the sensory nerve roots proximal to dorsal root ganglions.[105]
CISP-plus was described in patients with CISP and mild distal weakness due to the extension of involvement distal to the dorsal root ganglions.[106]
There is not enough evidence to determine whether CISP is demyelinating or related to sensory CIDP.[1]
INVESTIGATIONS
Electrodiagnostic studies typically show normal nerve conduction. In CISP-plus, nerve conduction studies may show mild abnormality due to axonopathy.[105][106]
Abnormal somatosensory evoked potential.[105]
Nerve root enlargement on MRI.[105]
Elevated CSF protein.[105]
Lumbar sensory rootlet biopsy can show inflammatory hypertrophic changes.[105]
Response to intravenous immunoglobulin or corticosteroids.[62][105]
Neuropathy associated with lymphoproliferative disorders
SIGNS / SYMPTOMS
Neuropathy associated with multiple myeloma, polyneuropathy-organomegaly-endocrinopathy-M-protein-skin changes (POEMS) syndrome, osteosclerotic myeloma, Waldenstrom's macroglobulinaemia, and Castleman's disease tends to be predominantly distal.[107][108] Neuropathy associated with cryoglobulinaemia and lymphoma can be multifocal.[109]
INVESTIGATIONS
Serum and urine immunofixation, quantitative immunoglobulin levels, skeletal survey, and bone marrow biopsy will usually find the haematological abnormality.[97]
Testing of vascular endothelial growth factor (VEGF) serum levels, especially in patients with IgA or IgG lambda paraproteinaemia, is indicated.[1]
Nerve biopsy may be needed in lymphoma.[109]
Electrodiagnostic studies may have features of axonal degeneration and demyelination, although axonal degeneration may predominate.[107][108][109]
Nerve ultrasound may show nerve enlargement only at the entrapment sites with distinct echogenicity pattern (hypoechoic fascicles with hyperechoic interfascicular tissue).[86][110]
POEMS syndrome is associated with more severe reduction in lower extremity compound muscle action potential and sensory nerve action potential amplitudes, less temporal dispersion and conduction block, fewer prolonged distal motor latencies, higher terminal latency index in median nerve, and more evidence of active denervation in a length-dependent manner.[111][112][113]
Diabetic neuropathies
SIGNS / SYMPTOMS
Typical neuropathy is more axonal than demyelinating, and is distal, symmetrical, and sensory more than motor.[3]
Proximal diabetic neuropathies are often asymmetrical and can be painful.[114]
Acute diabetic neuropathy is often related to rapid glycaemic reduction.[115][116]
Diabetic neuropathy and CIDP may co-exist.[117]
Vasculitic neuropathy
SIGNS / SYMPTOMS
Manifests as subacute, progressive, asymmetrical sensorimotor polyneuropathy, or mononeuropathy multiplex.
May be associated with systemic lupus erythematosus.[119]
May mimic multifocal CIDP (Lewis-Sumner syndrome).[12]
May present as part of systemic vasculitis or remain clinically restricted to the peripheral nerve.
INVESTIGATIONS
Laboratory tests for systemic vasculitis may include antinuclear or antineutrophil cytoplasmic antibodies, erythrocyte sedimentation rate, CRP, anti-double-stranded DNA, cryoglobulin, etc.
Electrodiagnostic studies show axon loss, although pseudoconduction block can be seen with early lesions.[120]
Repeat nerve conduction studies often show later features typical of axon loss.
Nerve and/or muscle biopsy may be needed to document evidence of nerve inflammation.[121]
Drug-induced neuropathy
Mitochondrial disorders (MNGIE syndrome)
SIGNS / SYMPTOMS
Neuropathy is predominantly distal.
Look for associated features: gastrointestinal neuropathy, ophthalmoplegia, cachexia, hearing loss, or leukoencephalopathy.[122]
Leukodystrophies
Infection-associated neuropathy
Sarcoidosis
SIGNS / SYMPTOMS
Cranial neuropathy is most common.[123]
Peripheral nerve involvement consists of granulomatous neuropathy (rare) and non-granulomatous small-fibre neuropathy (more common).[124]
Granulomatous neuropathy may present as distal symmetrical polyneuropathy and asymmetrical polyradiculoneuropathy.[124]
Small-fibre neuropathy can manifest as non-length-dependent paraesthesias and pain.[124]
Thyroid disease
SIGNS / SYMPTOMS
Neuropathy with hypothyroidism or hyperthyroidism is predominantly distal and sensory, and usually improves with correction of thyroid status.[40]
Use of this content is subject to our disclaimer