Chapter 15. Neuropathology
A 33-year-old man with no significant past medical history presents with a 3-year history of fatigue, back pain, and recurrent lower extremity weakness. He describes the weakness as being equally present in both legs, both distally and proximally. Concomitantly, he also complains of numbness and paresthesias that started over his toes but now have ascended to his ankles. Physical examination demonstrates diminished vibration sense and light touch over both feet up to his ankles. Deep tendon reflexes are abolished.
Which of the following findings is most likely on nerve and/or muscle biopsy of this patient?
(A) Demyelination and remyelination with onion bulb appearance, denervation group atrophy, and endoneurial inflammation
(B) Denervation group atrophy with granulomatous reaction
(C) Endoneurial inflammation with granulomatous reaction
(D) Muscular fibrosis, endoneurial inflammation, and denervation group atrophy
(E) Reduction in myelinated fiber density with muscular fibrosis
(A) The patient in the vignette has symptoms consistent with chronic inflammatory demyelinating polyneuropathy (CIDP). He has lower motor neuron signs (such as abolishment of deep tendon reflexes) and both motor and sensory symptoms. His symptoms are not length-dependent, with no difference proximally versus distally. The diagnosis of CIDP typically requires either evidence via nerve conduction studies or biopsy. Nerve biopsies in CIDP classically demonstrate an “onion bulbs” appearance. Affected nerves undergo repeated episodes of demyelination and remyelination, with sections becoming enlarged because of whorls of overlapping and proliferating Schwann cell processes encircling bare axons, forming the described onion appearance.
A combination of autopsy, MRI, and ultrasound studies has demonstrated that the inflammatory lesions in CIDP occur predominantly in spinal roots, proximal nerve trunks and major plexuses, but can also be disseminated throughout the peripheral nervous system. Because of the relative inaccessibility of the proximal nerves and nerve roots, most biopsies are performed upon the sural nerve.
Nerve biopsy findings are variable, ranging from no abnormalities to edema, demyelination and remyelination, axonal degeneration, and perivascular or endoneurial inflammatory macrophage or T-cell infiltration. Granulomatous reaction and muscular fibrosis are incompatible with this condition. (Griffin, 64–68; Harbo, 1036–1045; Mathey, 973–985; Melter, 359–372; Webster, 276–299)
Griffin J, Stoll G, Chun Y, Tyor W, Cornblath D. Macrophage responses in inflammatory demyelinating neuropathies. Ann Neurol. 1990;27(Suppl 1):S64–S68.
Harbo T, Andersen H, Jakobsen J. Length-dependent weakness and electrophysiological signs of secondary axonal loss in chronic inflammatory demyelinating polyradiculoneuropathy. Muscle Nerve. 2008;38:1036–1045.
Mathey E, Park S, Hughes R, et al. Chronic inflammatory demyelinating polyradiculoneuropathy: from pathology to phenotype. J Neurol Neurosurg Psychiatry. 2015;86:973–985. doi:10.1136/jnnp-2014-309697
Melter N, Meuth SG. Disease-modifying therapy in multiple sclerosis and chronic inflammatory demyelinating polyradiculoneuropathy: ...