Neuropathies — Inflammatory and Immune Neuropathies

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.

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, intravenous (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 central negative to remember in this disease.

Anti-MAG neuropathy and paraproteins

A paraprotein is a monoclonal immunoglobulin produced by a single abnormal clone of cells. 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.

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.

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 (vascular endothelial growth factor) 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.

Immunotherapy helps only when the neuropathy is immune-mediated. A slowly progressive demyelinating neuropathy with a positive family history points instead to an inherited cause, where immunotherapy has nothing to offer.