SHORT REPORT ABSTRACT: We present 3 patients with chronic inflammatory demyelinat-ing polyradiculoneuropathy (CIDP) with extensive and diffuse hypertrophy ofthe nerve roots and peripheral nerves. They exhibited slowly progressivesensory impairment and distally predominant limb weakness and muscularatrophy, and markedly enlarged palpable nerve trunks. They respondedbeneficially to corticosteroid. Magnetic resonance imaging demonstrated dif-fuse and extensive hypertrophy of the peripheral nerves in the four limbs andthe spinal nerve roots, with gadolinium enhancement in the nerve roots butnot in the peripheral nerves. These patients were considered to have ahypertrophic variant of CIDP. © 1998 John Wiley & Sons, Inc. Muscle Nerve21: 805–808, 1998Key words: chronic inflammatory demyelinating polyradiculoneuropathy(CIDP); nerve hypertrophy; magnetic resonance imaging (MRI); onion-bulbformation

CHRONIC INFLAMMATORYDEMYELINATINGPOLYRADICULONEUROPATHY WITHDIFFUSE AND MASSIVE PERIPHERALNERVE HYPERTROPHY: DISTINCTIVECLINICAL AND MAGNETICRESONANCE IMAGING FEATURES

KEIKO MIZUNO, MD,1 MASAAKI NAGAMATSU, MD, 1 NAOKI HATTORI, MD, 1

MASAHIKO YAMAMOTO, MD, 1 HIROSHI GOTO, MD,2

KAZUMASA KUNIYOSHI, MD, 3 and GEN SOBUE, MD 1*

1 Department of Neurology, Nagoya University School of Medicine, Nagoya 466,Japan2 Department of Internal Medicine, Minami Seikyo General Hospital, Nagoya Japan3 Department of Neurology, Okinawa Prefectural Hospital, Naha Japan

Accepted 5 October 1997

Chronic inflammatory demyelinating polyradiculo-neuropathy (CIDP) is a relapsing or chronic pro-gressive peripheral neuropathy.2,5,8,11,15 Thickenedperipheral nerves3,5,9,10,12–14 or enlarged nerveroots4,6,7,10,12,16 have been detected in subpopula-tions of CIDP, exhibiting unique symptoms such ascompression myelopathy.6,7,12,16 However, it is notwell understood why nerve hypertrophy occurs onlyin some patients with CIDP, and not in others.

Here, we describe 3 patients with CIDP with dif-fuse and extensive hypertrophy of the peripheral

nerve trunks and nerve roots. They shared commonclinical and magnetic resonance imaging (MRI) fea-tures, and are suggestive of a clinicopathologicalvariant of CIDP.

CASE REPORTS

Patient 1. A 52-year-old male noted tingling andnumbness in his feet, that progressed to affect hisforearms and calves over 4 years. Subsequently, limbweakness appeared and progressed to involve all ex-tremities over the course of a year. At 7 years afteronset he could not walk due to limb weakness andsensory ataxia. Neurological examination demon-strated symmetrical diffuse muscular atrophy andweakness of the four extremities, more pronounceddistally, general areflexia, and multimodal sensorydeficit predominant in deep sensation extending to

*Correspondence to: Dr. Gen Sobue

CCC 0148-639X/98/060805-04© 1998 John Wiley & Sons, Inc.

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his arms and midthighs. Enlarged peripheral nerveswere palpable over the nerve trunks at the axilla,elbow, and poplitea. The great auricular nerves werealso palpable. There were no evident autonomicsymptoms.

Normal investigations included baseline bloodchemistry, hematology, endocrine function, immu-noelectrophoresis of serum and urine, and autoan-tibody screen. Cerebrospinal fluid (CSF) protein was596 mg/dL, with two lymphocytes /mm3. Nerve con-duction studies revealed marked slowing [motorconduction velocity (MCV): 20 m/s; sensory nerveconduction velocity (SCV): 12 m/s], prolonged dis-tal latencies (29 ms), and temporal dispersion in theulnar nerves. No responses were elicited in the me-dian, tibial, and sural nerves. Conduction block wasnot observed.

T1-weighted MRI demonstrated massively en-larged cauda equina, with abnormal enhancementby gadolinium diethylenetriaminepentaacetic acid.MRI of the extremities showed markedly enlargedperipheral nerve trunks, which showed abnormalT2-weighted high intensity (Fig. 1A, B). Nerve trunkswere not enhanced by gadolinium.

Sural nerve biopsy showed severe loss of myelin-ated fibers (450/mm2), especially of large diameter,a strikingly hypertrophic change in fascicles withlarge onion-bulb formations, and marked endoneu-rial edema. Occasional lymphocytes were present inthe epineurial and endoneurial space. Teased fiberanalysis showed 100% of segmental demyelination.

His muscle strength gradually improved, with a3-day course of 1 g/day of intravenous methylpred-nisolone, followed by 40 mg/day of oral prednisone.In 2 months, he could walk without assistance. Nerveconduction studies after 4 months showed improve-ment in the ulnar nerve. MRI also showed less en-hancement of the cauda equina by gadolinium.

Patient 2. A 60-year-old female noted a tinglingsensation in her feet, associated with sensory ataxia.Subsequently, distally predominant limb weaknessdeveloped and progressed over 2 years to involve allextremities with general areflexia. At that time therewere moderately decreased superficial sensation,and severe loss of deep sensation in the distal ex-tremities. A positive Romberg test and pseudoatheto-sis of the fingers were noted. Peripheral nerves in thefour limbs were markedly thickened and palpable.

CSF protein was 1985 mg/dL, with normal cellcount. MCV was 20 m/s in the median and 19 m/s inthe ulnar nerves, both with 1 mV of compound mo-tor action potential (CMAP), accompanied by exten-sive temporal dispersion, and 48 ms and 47 ms of

distal latency, respectively. Tibial nerve MCV andSCV were not elicited. F wave was absent, and con-duction block was not apparent.

MRI of the four extremities demonstrated mark-edly enlarged nerve trunks with minimal enhance-ment by gadolinium. The maximum diameter of theenlarged nerve trunk at the proximal thigh was 4 cm.The nerve trunk comprised fascicles with varying de-grees of high signal intensity in the T2-weighted im-age (Fig. 1C, D). MRI revealed massive enlargementof the cauda equina and dorsal root ganglia, withslightly high signal intensity in the T2-weighted im-age and conspicuous enhancement by gadolinium(Fig. 1E, F). Sural nerve biopsy showed strikinglyhypertrophic neuropathy, with severe loss of myelin-ated fibers (510/mm2), extensive onion-bulb forma-tions, and endoneurial edema.

Administration of oral corticosteroid and intra-venous immunoglobulin produced clear benefitwithin several weeks. She was able to stand withoutassistance and noted improvement of hand function,but MRI and electrophysiological findings were notnotably changed.

Patient 3. A 66-year-old male noted insidious onsetof numbness and tingling in his distal extremities,with slow progression over 4 years to involve up tothe knees and the forearms. Weakness also devel-oped in all distal extremities. Neurological examina-tion was notable for peripheral nerve thickening,muscle weakness and atrophy, general areflexia, andpronounced loss of vibratory sensation, predomi-nantly in his lower extremities. CSF protein was 342mg/dL, with normal cell count. MCV, distal latency,and CMAP were 16 m/s, 23 ms, and 2 mV in themedian nerve, and 26 m/s, 11 ms, and 1 mV in theulnar nerve, respectively, both with marked tempo-ral dispersion. Tibial nerve MCV and SCV were notelicited. F wave was absent, and conduction blockwas not apparent.

MRI documented extensive and diffuse hypertro-phy of the peripheral nerve trunks and the caudaequina. Sural nerve biopsy demonstrated extensivedemyelinating changes and onion-bulb formations,with marked fascicular hypertrophy and edema.

Oral prednisone, followed by 50 mg/day of oralcyclophosphamide, relieved the sensory symptomsand produced an improvement of gait. Nerve con-duction studies after 2 years also showed improve-ment in the median and the ulnar nerves.

All 3 patients had no family history of neuropa-thy, and were negative for PMP 22 gene duplicationby both fluorescent in situ hybridization (FISH) andpolymerase chain reaction techniques.17

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DISCUSSION

All 3 patients fulfilled the criteria for CIDP1 andwere negative for genetic abnormality for Charcot–Marie–Tooth syndrome 1A. However, the clinicalfeatures were fairly common to all 3: slow progres-sion of sensory impairment, pronounced in deepsensation, followed by distally predominant limbweakness and muscular atrophy, markedly high CSF

protein, and a beneficial response to corticosteroid.The most striking common feature was the dif-

fuse, marked enlargement of peripheral nervetrunks and nerve roots, demonstrated by MRI. Thesenerve trunks showed markedly high signal intensityin the T2-weighted images, with no or minimal en-hancement by gadolinium in the peripheral nervetrunks, and marked enhancement in the nerve roots.

FIGURE 1. (A, B): MRI of left distal (A) and proximal (B) arm, patient 1. (C, D): MRI of left distal (C) and proximal (D) thigh, patient 2.Left side shows T1-weighted images, right side T2-weighted images. Abnormally high intensities of nerve trunks are indicated by arrows.(E, F): MRI of axial T1-weighted images at L3 (E) and L5 (F) level, patient 2. Hypertrophy of cauda equina roots and dorsal root ganglia(arrows), enhanced by gadolinium. (repetition time/echo time: A, B: 400/15 and 7000/120; C, D: 550/10 and 3000/120; E, F: 450/15).

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The abnormal T2-weighted high signal intensity in-dicates massive endoneurial edema. These MRI find-ings of cauda equina and nerve trunks, palpable pe-ripheral nerves in the distal limbs, and sural nervebiopsy findings confirm the nerve hypertrophy asextensive and widespread along the peripheral ner-vous system in these patients.

Slow insidious progression of clinical symptoms,particularly predominant in sensory symptoms,could result in delayed initiation of treatment. A pro-longed course without treatment could have in-duced extensive nerve damage of demyelination andsubsequent hypertrophic change. Alternatively,these patients might intrinsically tend to developnerve hypertrophy based on some unknown geneticsusceptibility, resulting in a clinical and pathologicalvariant of CIDP of a certain pathologic background,different from that in typical CIDP.

In these cases, nerve hypertrophy was extensivelyand diffusely distributed, as identified by MRI. Weregard these cases as presumably a variant of CIDP,given the considerable clinical and radiological over-lap.

This work was partly supported by the grants from the Ministry ofWelfare and Health of Japan.

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