Hereditary and inflammatory neuropathies: a review of reported associations, mimics and misdiagnoses

Abstract

International audienceDistinguishing between hereditary and inflammatory neuropathy is usually straightforward on clinical grounds with the help of a family history. There are nevertheless cases where the distinction is less clear. The advent of molecular genetics has in the past several years aided confirmatory diagnosis for an increasing proportion of patients with genetic neuropathy. Various reports have described associations of Charcot-Marie-Tooth disease with a suspected or confirmed inflammatory neuropathy occasionally responding to immunotherapy. Possible predisposition to an inflammatory component was suggested in a subset of patients. Such reports have, however, been relatively few in number, suggesting the rarity of such associations and of such a predisposition if it exists. There have been a number of publications detailing clinical presentations suggestive of inflammatory neuropathy in patients with a known or later proven genetic aetiology, and subsequently felt to be part of the phenotype rather than representing an association. A number of genetically mediated multisystemic diseases with neuropathy have otherwise been reported as mimicking chronic inflammatory demyelinating polyneuropathy (CIDP). The most common example is that of familial amyloid polyneuropathy, of particular concern for the clinician when misdiagnosed as CIDP, in view of the therapeutic implications. We review the literature on reported associations, mimics and misdiagnoses of hereditary and inflammatory neuropathy and attempt to determine a practical approach to the problem in clinical practice using clinical features, electrophysiology, histopathology and targeted early genetic testing. The issue of attempting immunomodulatory therapy is discussed in view of the published literature

Sporadic hereditary neuropathies misdiagnosed as chronic inflammatory demyelinating polyradiculoneuropathy: Pitfalls and red flags

“…2 Moreover, they may also be observed in patients without CIDP 6 and in demyelinating CMT. [25][26][27] However, it is well known that CSF protein values may be normal in reported also in conditions different from CIDP. 6 However, patients with CMT1A and concomitant CIDP responsive to immunomodulatory therapies have been described.…”

“…Increased CSF proteins with leukocyte count <10/mm 3 are common but not constant in CIDP, and represent a supportive criterion . Moreover, they may also be observed in patients without CIDP and in demyelinating CMT . However, it is well known that CSF protein values may be normal in patients with the distal CIDP variant (Distal Acquired Demyelinating Symmetric polyradiculoneuropathy) or with Lewis‐Sumner syndrome, regardless of the age.…”

Chronic inflammatory demyelinating polyneuropathy misdiagnosis: A clinical more than electrophysiogical problem?

“…Thirteen (45%) were found to have initially correctly interpreted electrophysiological data, but only 1, with CMT4C, demonstrated demyelinating electrophysiology. The authors did not detail whether this patient had, albeit asymmetrical, proximal weakness, which may explain a misdiagnosis or concurrent diagnosis of CIDP . The other patients surprisingly had normal results, axonopathy, or motor neuron disease.…”

Anti‐neurofascin 155 antibody‐related neuropathy

“…In 28 Japanese patients with anti-NF155 antibodies, mean CSF levels were approximately 300 mg/dL, and no patients had CSF levels <100 mg/dL. 7,9 Because the CSF protein levels of patients with multifocal acquired demyelinating sensory and motor neuropathy (MADSAM), 49 diabetic neuropathy 50 or Charcot-Marie-Tooth disease 51 were usually <100 mg/dL, this finding can help us differentiate anti-NF155 antibody-positive CIDP from MADSAM or other non-inflammatory polyneuropathies. Furthermore, we studied two anti-NF155 antibody-positive CIDP patients whose CSF protein levels fluctuated along with their clinical disease courses, suggesting that CSF protein levels might reflect disease activity.…”