Classification of Polyneuropathy

Primary Classification Methods

Polyneuropathy is primarily classified based on pathophysiology, inheritance pattern, and etiology, with electrodiagnostic studies and genetic testing being essential for accurate classification, as recommended by the American Academy of Physical Medicine and Rehabilitation 1, 2
Demyelinating polyneuropathies are characterized by damage to the myelin sheath surrounding nerve fibers, resulting in slowed nerve conduction velocities on electrodiagnostic testing, according to the American Academy of Neurology 2
Axonal polyneuropathies are characterized by damage to the nerve axon itself, with relatively preserved conduction velocities but reduced amplitude on nerve conduction studies, as stated by the American Academy of Physical Medicine and Rehabilitation 2

Autosomal dominant is the most common pattern in hereditary neuropathies, as reported by the American Academy of Neurology 2, 3
X-linked inheritance pattern is seen in conditions like CMTX (Cx32/GJB1 mutations), according to the American Academy of Physical Medicine and Rehabilitation 2, 3

Hereditary polyneuropathies are genetically determined, most commonly variants of Charcot-Marie-Tooth disease with a prevalence of approximately 1:2,500 people, as stated by the American Academy of Neurology 3, 4

Distal symmetric polyneuropathy (DSP) is the most common presentation, with "glove and stocking" distribution, as reported by the American Academy of Physical Medicine and Rehabilitation 5, 4

Electrodiagnostic studies are essential for distinguishing between demyelinating and axonal polyneuropathies, and provide critical information to guide subsequent genetic testing in suspected hereditary cases, according to the American Academy of Neurology 2, 4
Genetic testing is established as useful for accurate diagnosis and classification of hereditary polyneuropathies (Level A evidence), as stated by the American Academy of Physical Medicine and Rehabilitation 5, 6
First-tier genetic testing should focus on the most common abnormalities, including CMT1A duplication/HNPP deletion, Cx32 (GJB1) mutations, and MFN2 mutations, as recommended by the American Academy of Neurology 2, 3, 6

Failure to perform electrodiagnostic studies is a common pitfall, as these are essential for proper classification and subsequent management, according to the American Academy of Physical Medicine and Rehabilitation 2, 4
Overlooking hereditary causes in sporadic cases is another pitfall, as up to 30% of hereditary neuropathy mutations are de novo, as reported by the American Academy of Neurology 2
Incomplete genetic testing is also a pitfall, as following the tiered approach to genetic testing is crucial for cost-effective diagnosis, according to the American Academy of Physical Medicine and Rehabilitation 2, 3