Neuropathies — Inflammatory and Immune Neuropathies

Educational scope notice: This is a study note for medical students, not medical advice, diagnosis, or treatment guidance. Clinical management should follow local protocols and current guidelines.

Inflammatory neuropathies matter out of proportion to their frequency because most improve with appropriate immunotherapy. Missing CIDP or multifocal motor neuropathy leaves a treatable disease untreated.

CIDP

CIDP (chronic inflammatory demyelinating polyradiculoneuropathy) is the chronic counterpart of Guillain-Barre syndrome: a similar immune attack on myelin, but evolving over months rather than days. It is the most common acquired demyelinating neuropathy. The acute emergency is covered separately under Guillain-Barre syndrome (/notes/neurology/neuropathies-guillain-barre-syndrome/).

Several variants exist along one spectrum. Classic disease combines symmetric proximal and distal weakness with sensory loss and areflexia. Pure motor and pure sensory forms affect only one modality. Lewis-Sumner syndrome is multifocal and asymmetric, so it resembles mononeuritis multiplex clinically, but conduction studies show demyelinating conduction blocks rather than axonal damage, and it answers to immunotherapy. Focal disease stays in one limb or region, and distal symmetric disease (DADS) often travels with an IgM paraprotein.

First-line treatment uses corticosteroids, IV immunoglobulin, or plasma exchange, chosen by severity and comorbidity. Unlike Guillain-Barre syndrome, CIDP frequently needs maintenance therapy rather than a single course.

Multifocal motor neuropathy

Multifocal motor neuropathy (MMN) mimics motor neuron disease but responds to treatment, which makes the distinction critical. It produces progressive, asymmetric, predominantly distal weakness, usually in the arms, with minimal or no sensory loss. Conduction studies show persistent multifocal partial motor conduction blocks, and anti-GM1 IgM antibodies appear in roughly a third to half of patients. Hand wasting with intact sensation is the bedside picture that should trigger the thought.

Treatment is IV immunoglobulin as first line, effective in most patients, followed by maintenance infusions when it works. Corticosteroids are not recommended and may worsen the disease, which is the key negative to carry into exams and practice.

Anti-MAG neuropathy

Anti-MAG (myelin-associated glycoprotein) neuropathy is an IgM paraprotein-associated disease, typically in men between 50 and 70. It progresses slowly and distally with predominant sensory loss and gait ataxia, sometimes with an arm tremor. The electrophysiological signature is disproportionately prolonged distal latency relative to conduction slowing, and conduction block is rare.

POEMS syndrome and plasma cell disorders

POEMS is a rare paraneoplastic syndrome tied to a monoclonal plasma cell disorder, usually with lambda light chains.

Osteosclerotic bone lesions and markedly raised serum VEGF support the diagnosis. The neuropathy itself is sensorimotor, demyelinating, and CIDP-like but severe, and it does not answer to standard CIDP immunotherapy. Treatment targets the underlying clone with radiation for solitary lesions or systemic therapy including transplantation pathways.

A broader rule helps with paraproteins generally: an IgM monoclonal protein often attacks nerves directly (anti-MAG, anti-GM1), while IgG or IgA paraproteins are usually bystanders, so the search for another cause continues. Any neuropathy patient with a monoclonal protein belongs in joint hematology follow-up, since even benign gammopathy carries a small annual progression risk.

Chemotherapy-induced neuropathy

Chemotherapy-induced peripheral neuropathy grows more important as chemotherapy use grows. Vincristine produces distal sensory loss in roughly a third of patients, usually reversible between cycles. Platinum drugs accumulate in dorsal root ganglia and cause cumulative damage that can keep worsening after treatment stops (the coasting effect), with symptoms occasionally surfacing years later. Taxanes, bortezomib, and thalidomide are other recognized culprits. Because coasting exists, early dose adjustment matters more than rescue medication, and rehabilitation for balance, foot drop, and hand function carries much of the management. Pain and dose decisions are covered under treatment (/notes/neurology/neuropathies-treatment/).

Hereditary amyloid and Charcot-Marie-Tooth disease

Familial amyloid polyneuropathy from transthyretin (TTR) mutations deposits misfolded protein in nerves, producing progressive sensorimotor disease with prominent autonomic failure. Beyond historical liver transplantation, current options include TTR stabilizers, gene-silencing infusions, and antisense therapy, which have changed the outlook.

Charcot-Marie-Tooth disease remains the hereditary reference point: demyelinating type 1 most often from PMP22 duplication, axonal type 2 from genes including mitofusin-2, and X-linked disease from connexin-32. Diagnosis rests on family history and genetic testing, and care is supportive with physiotherapy and orthotics, since no disease-modifying therapy exists.

Evidence anchors

• NINDS. Peripheral Neuropathy: https://www.ninds.nih.gov/health-information/disorders/peripheral-neuropathy
• NINDS. Charcot-Marie-Tooth Disease: https://www.ninds.nih.gov/health-information/disorders/charcot-marie-tooth-disease