Pathological Findings in Chronic Inflammatory Demyelinating Polyradiculoneuropathy: A Single-Center Experience

Abstract

Objective: Segmental demyelination is the pathological hallmark of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), but other elementary lesions are frequently observed, configuring a series of different pathological pictures. In this article, we review the pathological findings of a large series of sural nerve biopsies from our cohort of CIDP patients.

Patients and methods: Patients with CIDP who underwent nerve biopsy were retrospectively selected from those referred to the Institute of Neurology of the "Università Cattolica del Sacro Cuore" in Rome, Italy, from 1982 to February 2020. Sural nerve biopsy was performed according to standard protocols.

Results: Sural nerve biopsy was performed in 43/130 CIDP patients. Demyelinating abnormalities and axonal loss were found in 67.4% and 83.7% of biopsies, respectively. Conversely, onion bulbs and inflammatory infiltrates were rare (18.6% and 4.7%, respectively). In three cases, we observed normal pathological findings.

Conclusions: A pathognomonic pathological finding of CIDP cannot be established, but we confirm the utility of nerve biopsy in this setting to confirm the diagnosis (also in atypical phenotypes) and to elucidate pathogenic mechanisms.

Keywords: CIDP; axonal loss; inflammatory infiltrates; nerve biopsy; onion bulbs; regenerating clusters; segmental demyelination.

Figure 1

Distribution of clinical phenotypes in the entire chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) cohort.

Figure 2

European Federation of Neurological Societies and the Peripheral Nerve Society (EFNS/PNS) diagnostic category among CIDP patients that underwent a sural nerve biopsy.

Figure 3

Distribution of clinical phenotypes among CIDP patients that underwent a sural nerve biopsy.

Figure 4

Semithin section stained with toluidine blue. Sural nerve biopsy performed in a 66-year-old man with “typical” CIDP (a), and sural nerve biopsy from a normal subject matched per age (b). A moderate reduction of myelinated fibers is shown (a). Many fibers (75%) have a thin myelin sheath if compared with axon diameter (red arrows in (a)); few fibers (4%) are devoid of myelin sheath (“naked axons”, black arrows in (a)).

Figure 5

Teased fibers analysis from sural nerve biopsy performed in a 65-year-old man with “atypical” CIDP (multifocal acquired demyelinating sensory and motor neuropathy (MADSAM)) (a,b) and from sural nerve biopsy performed in an age-matched control with an axonal polyneuropathy (c). Segmental demyelination, found in about 40% of fibers, is shown (a,b).

Figure 6

Sural nerve biopsy from a 37-year-old man with “typical” CIDP (a–d) and normal age-matched controls (e,f). Electron microscopy. Macrophage-mediated demyelination. (a) A fiber with normal myelin appearance wrapped in a macrophage (ma) is observed; in the macrophage’s cytoplasm, there are numerous myelinated figures, expression of an early phase of the demyelination process. The arrows indicate the demarcation between the cytoplasm of the Schwann cell (Sc) and that of the macrophage. Separated from the fiber, another macrophage (m) participates in the “digestion” of the myelin. (b) Greater enlargement of a detail of (a). The macrophage has broken off the basement membrane (arrows) to attack the myelin. (c) Myelin begins to decompact and has a “beehive” (arrow) appearance. Also, in this case, the macrophage (ma) actively participates in the process of destruction of the myelin sheath. (d) Axon (ax) appears completely devoid of the myelin sheath. Also, in this case, there is a macrophage (ma) loaded with myelin debris. (e) Normal myelinated fiber. (f) Normal myelinated fiber surrounded by Schwann cell.

Figure 7

Different pathological alterations in CIDP (a–c) and normal age-matched control (e,f). (a–c) Semithin section from CIDP patients stained with toluidine blue. (a) Sural nerve biopsy from a 64-year-old woman with “typical” CIDP. Two contiguous fascicles with completely different aspects: in one, only a loss of myelin fibers is observed; while in the other, fibers are extremely reduced in number and are all surrounded by onion bulbs. (b) Sural nerve biopsy from a 47-year-old woman with “typical” CIDP: marked reduction of myelinated fibers, all surrounded by onion bulbs, is observed. (c) Sural nerve biopsy from a 65-year-old man with “atypical” CIDP (MADSAM, shown in Figure 5a,b): slight reduction of myelin fibers and active axonal degenerations (arrows) are observed. (d) Hematoxylin and eosin (H&E) staining from a CIDP patient. Sural nerve biopsy from a 53-year-old man with “typical” CIDP: an endoneural inflammatory infiltrate is present. (e) Semithin section from a normal subject stained with toluidine blue. (f) H&E staining from a normal subject.

Figure 8

Sural nerve biopsy from a 58-year-old man with “typical” CIDP (a). Semithin sections stained with toluidine blue (a). Numerous fibers appear vacuolated (arrows in (a)) and show a distension and thinning of the myelin sheath (a). Electron microscope (b–e). Sural nerve biopsies from a 63-year-old woman with “typical” CIDP (b); from a 58-year-old man with “typical” CIDP (shown in (a)) (c); from a 61-year-old man with “typical” CIDP (d); and from the 65-year-old man with “atypical” CIDP (MADSAM) shown in Figure 5a,b and Figure 7c (e). Intramyelinic edema appears as a finely granular fluid material that relaxes and deforms the myelin sheath. The fibers affected have a swollen appearance with a markedly increased diameter: myelin decompaction occurs at the level of the major dense line, and the axons invariably show a marked reduction in diameter, as shrunk by osmotic mechanisms. (f) Semithin section stained with toluidine blue from a normal age-matched control. (g) Electron microscope. Myelinated fibers from a normal age-matched control.