Peripheral nerve ultrasound changes in CIDP and correlations with nerve conduction velocity Antonella Di Pasquale, MD* Stefania Morino, MD, PhD Simona Loreti, MD Elisabetta Bucci, MD, PhD Nicola Vanacore, MD Giovanni Antonini, MD*
Correspondence to Prof. Antonini:
[email protected] ABSTRACT
Objective: To evaluate the ultrasound (US) characteristics of peripheral nerves in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and their correlations with electrodiagnostic (EDX) characteristics.
Methods: Nineteen patients with CIDP and 19 healthy controls matched by age and body mass index were included in a blind case-control, observational study. All patients underwent a neurologic examination (including inflammatory neuropathy cause and treatment [INCAT] and Medical Research Council [MRC] sum score) and an EDX study. Each patient and each control underwent a US study of 14 nerve segments, yielding a total number of 266 segments scanned in each group. Results: US changes, characterized by an increased nerve cross-sectional area (NCSA), were detected in 53% of the 266 patient nerve segments. Mean NCSA was higher in nerve segments of patients than in those of controls (p , 0.001). Nerve segments with abnormal US belonged to patients with longer disease duration, lower MRC sum score, higher INCAT score, and progressive disease form (all p , 0.0001). All the aforementioned variables were independently associated with the occurrence of US changes. Motor nerve conduction was significantly lower in nerve segments with increased NCSA than in those with normal NCSA (p , 0.0001). NCSA in segments with prevalent myelin damage was higher than that in segments with prevalent axonal damage (p 5 0.001) or in segments with normal EDX characteristics (p , 0.0001). NCSA and motor nerve conduction velocity were inversely correlated in nerve segments with EDX evidence of myelin damage (R 5 0.599; p , 0.0001). Conduction blocks were associated with increased NCSA (p 5 0.001). Conclusions: US may, similar to MRI, have a supporting role in the diagnosis of CIDP. US and EDX changes are correlated. Neurology® 2015;84:803–809 GLOSSARY BMI 5 body mass index; CI 5 confidence interval; CIDP 5 chronic inflammatory demyelinating polyradiculoneuropathy; CMAP 5 compound muscle action potential; EDX 5 electrodiagnostic; INCAT 5 inflammatory neuropathy cause and treatment; IQR 5 interquartile range; MRC 5 Medical Research Council; NCSA 5 nerve cross-sectional area; NCV 5 nerve conduction velocity; OR 5 odds ratio; US 5 ultrasound.
Supplemental data at Neurology.org
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an acquired immunemediated inflammatory peripheral neuropathy with an estimated prevalence of approximately 0.5 per 100,000 children and 1 to 7 per 100,000 adults.1,2 There are no gold standards for CIDP diagnosis, which derives from composite diagnostic criteria3 (European Federation of Neurological Societies criteria). Varying amounts of active demyelination associated with onion bulbs, endoneurial edema, and inflammatory infiltrates are the most common neuropathologic hallmarks of the disease.4,5 Neurophysiologic investigations reveal a demyelinating process characterized by slow nerve conduction, temporal dispersion, prolonged distal latencies, prolonged F-wave latencies, and conduction blocks.6 MRI studies have shown that these changes are frequently associated with *These authors contributed equally to this work. From the Department of Neuroscience, Mental Health and Sensory Organs (A.D.P., G.A.), and School of Rehabilitation Medicine (S.L.), Faculty of Medicine and Psychology, University of Rome Sapienza; Neuromuscular Disease Unit of Sant’Andrea Hospital (S.M., E.B.), Rome; and National Institute of Health (N.V.), Rome, Italy. Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article. © 2015 American Academy of Neurology
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hypertrophy and gadolinium enhancement of spinal roots, brachial plexus, and peripheral nerves.7–9 Recently, ultrasound (US) has been applied widely to diagnose peripheral nervous system lesions because of its capacity to detect morphologic changes in peripheral nerves.10–14 However, few studies have systematically evaluated US nerve changes in CIDP or assessed the relationship between such changes and electrophysiologic characteristics.15–22 To evaluate the US characteristics of peripheral nerves and their correlations with electrophysiologic characteristics in CIDP, we performed a blind case-control, observational study in a series of patients with CIDP. METHODS Subjects. All patients with the clinical and neurophysiologic criteria of CIDP3 attending the outpatient service of the Neuromuscular Clinic at Sant’Andrea Hospital (n 5 19) gave their informed consent to participate in this study. A similar number of healthy subjects, matched by age (62 years) and body mass index (BMI) (61 kg/m2), enrolled from our working environment, served as controls.
Clinical assessment. Each patient underwent a neurologic examination (including the inflammatory neuropathy cause and treatment [INCAT] disability scale and MRC score of arm abductors, elbow flexors, wrist extensors, first dorsal interosseous, thumb abductor, hip flexors, knee extensors, foot dorsiflexors, and extensor hallucis longus), neurophysiologic study (electrodiagnostic [EDX]), and US study on the same day. An expanded version of the MRC sum score (MRC-80) was calculated by summing the MRC grades of the aforementioned muscles (except thumb abductor) on each side. The score ranges from 0 (total paralysis) to 80 (normal strength).23 The INCAT disability scale assesses the efficiency of patients’ arms and legs by means of a semistandardized interview. Daily arm activities (using cutlery, buttons and zippers, washing or brushing hair, and handling coins) are scored as “not affected,” “affected but not prevented,” or “prevented.” The leg scale measures walking difficulties, based on the use of aids. The INCAT score ranges from 0 (no signs of disability) to 10 (most severe disability).24 Control subjects underwent a neurologic examination and US study. US imaging. Two US evaluators (A.D.P. and S.L.), who were blinded to the clinical and neurophysiologic data, performed the US study using a General Electric Voluson E6 imaging system (GE Healthcare, Waukesha, WI) with a broadband linear transducer (frequency band 10–18 MHz) in both patients and controls. To ensure blinded status of the US examiners, a random number was assigned to patients and controls, who were scanned and recorded anonymously by the first evaluator (A.D.P.). The second evaluator (S.L.) subsequently performed the measurements on the US recordings. A third author (E.B.) attributed the US data collected to each subject. The median, ulnar, and peroneal nerves were scanned on both sides at the axilla, arm, forearm, and popliteal fossa. More proximal segments, such as trunks of the brachial plexus, were not recorded. Entrapment sites (wrist, elbow, and fibular head) 804
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were excluded to avoid confounding local traumatic factors. A total of 14 nerve segments were quantitatively and qualitatively evaluated in each subject, recording both transverse and longitudinal images along the entire length of each segment. For the quantitative evaluation, we measured the nerve cross-sectional area (NCSA) by tracing the nerve just inside the hyperechoic rims. The NCSA was measured by means of the “ellipse formula,” or the “tracing technique” when the nerve was irregular in shape. The largest NCSA of each nerve segment was used for the statistical comparisons. For the qualitative evaluation, we studied the single nerve fascicles and defined a nerve as abnormal when it was possible to detect at least 3 nerve fascicles with cross-sectional area $2 mm2, regardless of the NCSA value (figures e-1 and e-2 on the Neurology® Web site at Neurology.org). Nerve segments with the NCSA within the range values of controls and without fascicular changes were defined as normal. Power-Doppler indices in the nerve segments were not measured.
Neurophysiologic studies. All the patients underwent a complete EDX according to standard techniques performed by one of the authors (S.M.), who was blinded to the US study. Skin temperature was measured and maintained between 29°C and 32°C. Motor nerve conduction was studied on the median, ulnar, and peroneal nerve bilaterally, by recording the compound muscle action potential (CMAP), respectively, at the abductor pollicis brevis, abductor digiti minimi, and extensor digitorum brevis muscles. The median nerve was stimulated at the wrist, elbow, and axilla; the ulnar nerve was stimulated at the wrist, below and above the elbow, and axilla. Erb’s point stimulation was considered unreliable for the EDX. The peroneal nerve was stimulated at the ankle, fibular head, and knee. CMAP amplitude, distal latency, nerve conduction velocity (NCV), and F-wave latency were recorded. Conduction blocks were considered if CMAP proximal/distal ratio was #50%. The electrophysiologic characteristics of each nerve segment were stratified in 3 categories: (1) predominant myelin damage: motor conduction velocity ,70% of lower normal limit if CMAP amplitude ,80%, or motor conduction velocity ,80% of lower normal limit if CMAP amplitude .80%, or evidence of conduction blocks; (2) predominant axonal damage: motor conduction velocity .70% of lower normal limit if CMAP amplitude ,80%; and (3) motor conduction velocity within normal range. Similar to the US study, entrapment sites were excluded from the EDX. Sensory nerve conduction was studied on the median, ulnar, and sural nerve bilaterally by measuring sensory action potential amplitude and conduction velocity. Statistics. For the statistical analysis, we considered each of the 14 scanned nerve segments in each subject on its own (i.e., the forearm, arm, axilla for the ulnar and median nerves, and popliteal fossa for peroneal nerves). Both the quantitative and qualitative characteristics of the nerve segments in patients and controls were compared. Disease duration, MRC-80, INCAT score, and clinical form of CIDP were compared with the number of nerve segments with US changes in each patient, as well as with the NCSA of the overall number of nerve segments in all the patients. MRC score of thumb abductor, first dorsal interosseous, and extensor hallucis longus was compared with US characteristics of median, ulnar, and peroneal nerves, respectively. Because the entrapment sites were excluded from the study and the conduction velocity of the peroneal nerve at the popliteal fossa was considered to be unreliable because of the limited length of this segment, the correlation between NCV and US was analyzed for only the median and ulnar nerves in the arm and
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forearm. None of the other neurophysiologic parameters (i.e., distal latency, F-wave latency, CMAP amplitude, or sensory nerve conduction) were analyzed. The NCSA was compared in the 3 categories identified by the neurophysiologic stratification. Frequencies of US abnormalities in patients’ proximal and distal nerve segments were also compared. Chi-square test was used for categorical variables. Mann– Whitney U test was used for continuous variables, which showed a nonnormal distribution and significantly different variance (as evaluated by the Levene test). A 95% confidence interval (CI) of the mean NCSA value was calculated for each stratification. Linear regression analysis was used to test for a linear correlation among NCSA disease duration, MRC sum score, and motor nerve conduction velocity. Logistic regression analysis was used to test which of the patients’ characteristics were independently associated with US nerve changes. Corrections for multiple testing were not performed because the aim of our study was to investigate any differences in US between patients with CIDP and controls, as well as any association between the patients’ US nerve morphology and their clinical/neurophysiologic characteristics in the context of an exploratory study. Two-sided p values were calculated for all analyses; values of #0.05 were considered significant. Data were analyzed with SPSS 21.0 (IBM Corp., Armonk, NY) for Mac.
Standard protocol approvals, registrations, and patient consents. The study obtained the institutional review board/ethical approval. Written informed consent was obtained from all participants in the study.
Nineteen patients (11 men, 8 women) aged 55.74 6 13.55 years (range 5 28–78, median 5 60, interquartile range [IQR] 5 48–65 years) with BMI 5 24.60 6 4.93 kg/m2 and 19 controls (12 men, 7 women) aged 55.84 6 13.25 years (range 5 30–76, median 5 61, IQR 5 48.5–65.5 years) with BMI 5 24.38 6 4.60 kg/m2 were included in the study. Patients’ characteristics are shown in table e-1. Disease duration ranged from 1 to 18 years (median 5 7, RESULTS Clinical and US characteristics.
Table 1
IQR 5 3–10 years). MRC sum score ranged from 58 to 80 (median 5 78, IQR 5 70–80) and INCAT score ranged from 0 to 4 ($1 in 9 patients). Sixteen patients had a progressive type of disease, while the remaining 3 had a relapsing type. Thirteen patients were under treatment, which included prednisone (8 patients), immunosuppressant (4 patients), and IV immunoglobulins (6 patients). Six patients were not taking any immunologic treatment: 5 had been treated previously, while the sixth was enrolled in the study before treatment started. A total of 532 nerve segments were scanned, in both patients and controls. When the 266 nerve segments scanned in patients were considered, 141 (53%) revealed US changes, which were both quantitative and qualitative in 112 segments and quantitative alone in the remaining 29. The NCSA of both the median and ulnar nerves in the forearm, arm, and axilla, and of the peroneal nerves in the popliteal fossa, was significantly higher in patients than controls (table 1). Patients’ nerve segments with US abnormalities were more frequent in the axilla (56%) and arm (63%) than in the forearm (38%) (odds ratio [OR] 5 2.11, 95% CI 5 1.10–4.03, p 5 0.017 and OR 5 2.77, 95% CI 5 1.44–5.35, p 5 0.02, respectively). The number of nerve segments with US changes in each patient ranged from 0 to 14 (median 5 8, IQR 5 2–13). Two patients did not display US changes in any of the segments, while 4 displayed US changes in all the segments. Nerve segments with abnormal US characteristics belonged to patients with a significantly longer disease duration, lower MRC sum score, and higher INCAT score (p , 0.0001) (table 2). US abnormalities in ulnar and median nerve segments were associated with a lower MRC score of
Nerve cross-sectional area of 532 nerve segments scanned in 19 patients and 19 healthy controls Patients
Controls
Mean (SD)
Range
95% CI
Mean (SD)
Range
95% CI
pa
Forearm
15.10 (14.39)
4–61
10.37–19.83
6.02 (1.30)
4–9
5.59–6.45
0.0001
Arm
22.65 (22.33)
6–102
15.31–29.99
7.07 (1.74)
5–11
6.50–7.65
0.0001
Axilla
21.84 (23.15)
6–98
14.22–29.45
7.73 (1.62)
5–11
7.20–8.27
0.0001
Forearm
11.10 (11.34)
4–63
7.37–14.83
5.50 (1.20)
3–9
5.10–5.89
0.0001
Arm
16.36 (14.28)
4–52
11.67–21.06
5.94 (1.08)
4–9
5.58–6.30
0.0001
Axilla
15.63 (15.11)
5–69
10.66–20.60
6.23 (1.07)
4–9
5.88–6.59
0.0001
15.15 (7.47)
7–36
12.70–17.61
8.81 (2.12)
3–12
8.11–9.51
0.001
Site Median nerve
Ulnar nerve
Peroneal nerve Popliteal fossa
Abbreviation: CI 5 confidence interval. a Mann–Whitney U test. Neurology 84
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Table 2
Differences of clinical characteristics in patients with CIDP according to the US evidence of nerve morphologic changes Nerve segments with abnormal US (n 5 141)
Nerve segments with normal US (n 5 125)
Mean (SD)
Median (IQR)
95% CI
Mean (SD)
Median (IQR)
95% CI
p
Disease duration, y
9.55 (6.15)
7 (5–18)
8.53–10.58
5.69 (2.99)
6 (3–7)
5.16–6.22
,0.0001
MRC sum score 80
73.33 (7.79)
78 (62–78)
72.04–74.63
76.54 (5.90)
80 (76–80)
75.50–77.59
,0.0001
INCAT score
1.20 (1.34)
1 (0–2)
0.98–1.42
0.55 (0.80)
0 (0–1)
0.41–0.70
,0.0001
Abbreviations: CI 5 confidence interval; CIDP 5 chronic inflammatory demyelinating polyradiculoneuropathy; INCAT 5 inflammatory neuropathy cause and treatment; IQR 5 interquartile range; MRC 5 Medical Research Council; US 5 ultrasound.
the first dorsal interosseous and thumb abductor (p 5 0.003 and p 5 0.035, respectively); by contrast, no difference in MRC score of extensor hallucis longus emerged between peroneal nerve segments with and without US changes (figure e-3). Regarding the clinical type, 134 of 224 (60%) of the nerve segments in patients with progressive CIDP and 7 of 42 (16%) of the nerve segments in patients with relapsing CIDP displayed US abnormalities (OR 5 7.4, 95% CI 5 3.16–17.49, p , 0.0001). Logistic regression analysis showed that disease duration, MRC sum score, INCAT score, and clinical type were independently associated with the occurrence of US changes in nerve segments, after correction for sex and age (table 3). Electrophysiologic and US characteristics. At the time of the study, 5 patients displayed myelinopathic EDX features in all nerve segments, one patient displayed normalized NCV in all nerve segments, while the remainder displayed a varying percentage of myelinopathic (10%–90%), axonopathic (10%–60%), and normal (20%–80%) segments, whose distribution varied within individual patients. No patient had axonal features alone. Nerve segments with US changes ranged between 70% and 100% in patients with all myelinopathic nerves, while none of the nerve segments showed US abnormalities in the patient with normalized NCV. The 2 patients with prevalently axonopathic nerve segments showed US abnormalities in 86% and 93% of segments.
Table 3
Logistic regression analysis of clinical characteristics in patients with CIDP according to the US evidence of nerve morphologic changes p
OR
95% CI
Disease type
4.49
1.67–12.07
Disease duration
1.24
1.11–1.38
,0.0001
MRC sum score
1.22
1.09–1.35
,0.0001
INCAT score
2.85
1.73–4.67
,0.0001
0.003
Abbreviations: CI 5 confidence interval; CIDP 5 chronic inflammatory demyelinating polyradiculoneuropathy; INCAT 5 inflammatory neuropathy cause and treatment; MRC 5 Medical Research Council; OR 5 odds ratio; US 5 ultrasound. Data corrected for sex and age. 806
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Motor nerve conduction was significantly lower in nerve segments with increased NCSA (35.61 6 14.51 mm2) than in those with normal NCSA (47.69 6 11.09 mm2) (p , 0.0001). Seventy (46%) of the 152 nerve segments analyzed for the comparison of US and EDX fulfilled the electrophysiologic criteria for myelin damage, 29 (19%) for axonal damage, while the EDX of the remaining 53 segments (35%) was normal. The NCSA in myelinopathic segments was higher than that in axonopathic (p 5 0.001) or normal (p , 0.0001) segments. By contrast, the NCSA was similar in axonopathic and normal segments (table 4). An inverse linear correlation was observed between NCSA and NCV (R 5 0.599, p , 0.0001) in myelinopathic segments; by contrast, no correlation emerged between the NCSA and NCV in nerve segments that did not fulfill the criteria for myelin damage (R 5 0.108, p 5 0.33) (figure 1). When each of the nerve segments was considered on its own, the NCSA was found to be higher in 49 (70%) myelinopathic, in 13 (45%) axonopathic, and in 15 (28%) neurophysiologically normal segments. Conduction blocks were observed in 28 nerve segments. The mean NCSA of nerve segments with conduction blocks was 31.28 mm2 (SD 5 28.21), while that of nerve segments without conduction blocks was 12.92 mm2 (SD 5 9.80) (p 5 0.001). DISCUSSION An enlargement of the spinal roots, brachial and lumbar plexus, and peripheral nerves has been reported as a macroscopic feature in the few postmortem studies previously performed in CIDP.25 Such changes have been attributed to the proliferation of Schwann cells, caused by repeated demyelination and remyelination, and to the accumulation of an amorphous substance in the endoneurium, probably deriving from secondary products associated with nerve degeneration.25 Nerve swelling in both the cervical and lumbar spinal roots and brachial plexus in CIDP has been extensively demonstrated in vivo by MRI studies, which have shown that approximately 50% of patients with CIDP display hypertrophy, increased signal intensity on T2-weighted images, and abnormal enhancement after gadolinium administration.7,9,26–28
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Table 4
Distribution of NCSA values regarding the characteristics of the neurophysiologic damage in 152 nerve segments of median and ulnar nerves from 19 patients with CIDP NCSA
EDX characteristics
No.
Mean
SD
Range
Median
IQR
95% CI
Myelin damage
70
23.34
21.09
5–102
15
8.0–31.5
18.31–28.37
Nonmyelin damage
82
10.30
6.97
4–40
8
5.0–14.0
8.77–11.83
Axonal
29
11.65
7.63
4–35
9
5.5–17.0
8.75–14.55
Normal
53
9.56
6.53
4–40
7
5.0–12.5
7.76–11.36
Abbreviations: CI 5 confidence interval; CIDP 5 chronic inflammatory demyelinating polyradiculoneuropathy; EDX 5 electrodiagnostic; IQR 5 interquartile range; NCSA 5 nerve cross-sectional area. Myelin vs nonmyelin p , 0.0001; myelin vs axonal p 5 0.001; myelin vs normal p , 0.0001; axonal vs normal p 5 0.181 (Mann–Whitney test).
After these findings, MRI changes in spinal roots and brachial or lumbar plexus have been included as additional criteria for the diagnosis of CIDP.3 The potential contribution made by MRI to the detection of enlarged peripheral nerves outside the root and plexus regions has not, however, been systematically examined. In recent years, US has been applied widely to diagnose peripheral nervous system lesions. Few studies have systematically evaluated US nerve changes in CIDP.15–21 Indeed, a total of only 166 patients with CIDP under therapy have been examined in 8 different studies (3 blind case-control,15,17,20 1 unblind case-control,16 and 4 observational18,19,21,22), 5 of which also tested the correlation between NCSA and EDX.16,17,20–22 While an increased NCSA was observed in all these studies, the correlation between NCSA and EDX, as well as between NCSA and patients’ clinical characteristics Figure 1
(INCAT score, MRC sum score, and disease duration), remains controversial.16–21 In our study, 53% of nerve segments examined in the CIDP group displayed the US evidence of focal fascicular and/or trunk hypertrophy, which, according to neurophysiologic studies,29 occurred more frequently in the most proximal nerve segments. US detected morphologic changes in at least one nerve segment in 17 of 19 patients (89%), in at least half of nerve segments in 10 (52%), in all segments in 4 patients. Disease duration, the chronic form of CIDP, INCAT score, and MRC sum score were independent factors found to correlate with the increase in NCSA, suggesting that US abnormalities may be the result of an “over time” accumulation of morphologic changes, which interfere with nerve function. Noteworthy, the US abnormalities
Correlation between motor conduction velocity and NCSA in nerve segments of median and ulnar nerves from patients with chronic inflammatory demyelinating polyradiculoneuropathy
(A) Nerve segments with EDX evidence of myelin damage. (B) Nerve segments with EDX evidence of axonal damage and nerve segments with normal MCV. EDX 5 electrodiagnostic; NCSA 5 nerve cross-sectional area; NCV 5 nerve conduction velocity. Neurology 84
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in single nerves (i.e., median and ulnar nerves) showed a correlation with MRC score of their respective muscles (the lack of a similar correlation for peroneal nerve may be attributed to the fact that this nerve was scanned in only one segment). The EDX study showed that myelinopathic nerve segments had a greater NCSA than axonopathic and normal segments, which virtually overlapped. Lastly, the motor conduction velocity in myelinopathic nerve segments was inversely correlated with the NCSA. These results suggest that US is sensitive to anatomical nerve changes that are functionally associated with prevalently myelinopathic damage. It should be borne in mind, however, that NCSA was also increased in 45% of nerve segments with NCV within axonopathic range and in 28% of segments with normal NCV. The fact that the majority of patients in the study were already being treated for the disease might have
Comment: A growing role for nerve ultrasound in diagnosis and management of CIDP? Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an immune-mediated polyneuropathy characterized by segmental demyelination, sometimes accompanied by axonal loss. Nerve size and architecture are altered. Despite composite criteria, diagnosis can be challenging. Furthermore, objective measurements to follow disease activity are limited. High-resolution nerve ultrasound could potentially aid in diagnosis and disease monitoring; it is inexpensive, widely available, noninvasive, and can rapidly image long segments of multiple nerves. However, few studies have examined the relationship between nerve morphology and function in CIDP using ultrasound.1 This blinded, cross-sectional study by Di Pasquale et al.2 describes nerve ultrasound findings at noncompressible sites in the median, ulnar, and peroneal nerves in 19 patients with CIDP compared to controls. The authors examined the relationship between both total cross-sectional nerve area and enlargement of individual nerve fascicles and assessed electrodiagnostic measures. They also correlate abnormal ultrasound segments with clinical measures of strength and disability. Consistent with prior studies, the primary findings were that (1) ultrasound is sensitive and specific for detecting abnormality in CIDP, although the number of segments with ultrasound abnormalities was highly variable; (2) abnormal ultrasound segments were associated more frequently with demyelinating than with axonal electrophysiology; and (3) abnormality within a nerve segment was correlated with longer disease duration, lower Medical Research Council sumscore, higher Inflammatory Neuropathy Cause and Treatment disability score, and progressive disease. While providing a substantive contribution to the literature, this study also had several limitations. Eighteen of 19 patients had already undergone treatment for CIDP. Effects of these therapies on nerve morphology remain unknown.3 Additionally, the study included only ultrasound of distal nerve segments and measured nerve areas. Proximal segments and nerve vascularity and echogenicity may also be abnormal in CIDP.1 To further elucidate ultrasound’s role in the diagnosis and management of CIDP, large-scale, multimeasure prospective, longitudinal studies in treatment-naive patients are needed. 1. 2. 3.
Hobson-Webb LD. Neuromuscular ultrasound in polyneuropathies and motor neuron disease. Muscle Nerve 2013;47:790–804. Di Pasquale A, Morino S, Loreti S, Bucci E, Vanacore N, Antonini G. Peripheral nerve ultrasound changes in CIDP and correlations with nerve conduction velocity. Neurology 2015;84:803–809. Zaidman CM, Pestronk A. Nerve size in chronic inflammatory demyelinating neuropathy varies with disease activity and therapy response over time. Muscle Nerve 2014;50:733–738.
Amanda C. Guidon, MD From the Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston. Study funding: No targeted funding reported. Disclosure: The author reports no disclosures. Go to Neurology.org for full disclosures.
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biased these findings. Indeed, the only patient in our sample who underwent US before receiving any form of therapy (a 44-year-old woman with a chronic form of CIDP, whose symptoms had started approximately 1 year before) exhibited both quantitative and qualitative changes in all nerve segments, associated with myelinopathic EDX changes. By contrast, the 2 patients with normal NCSA had a relatively brief disease duration (1 and 5 years) with good clinical response to treatment and displayed the highest percentage of nerve segments with normalized EDX (80% and 100%, respectively). Of note, a recent study showed that NCSA in enlarged CIDP nerves normalizes or even decreases with disease remission.22 All these findings point, in most of our patients, to a complex pathophysiologic scenario that evolved over time and was probably biased by treatment and different disease aggressiveness, characterized by the accumulation of different pathologic processes. The increase in “demyelinating lesion load” and/or connective tissue within the nerve, the intraneural deposition of amorphous proteinaceous substance, and the secondary axonal loss with, in some cases, a “pseudo-normalization” of nerve size, may explain the different nerve changes and their variable association with EDX characteristics in our patients. This study has some limitations. Because of its cross-sectional design, our study was conducted on a series of patients with varying disease duration, whose clinical characteristics may have been influenced by therapies. It should thus be considered that the data do not accurately reflect the characteristics of a population with CIDP, but those of patients with CIDP undergoing medical treatment. Moreover, we limited the study to the evaluation of NCSA and fascicular enlargement in the most easily accessible sites of 3 nerves; the study of proximal nerve segments (i.e., trunks of brachial plexus) and of pure sensory segments, as well as the measurement of echogeneity30 and vascularity,18 would provide a better understanding of the potential contribution of US in CIDP. Despite the aforementioned limitations, our data indicate that US may, similar to MRI, have a supporting role in the diagnosis of CIDP. The fact that US is considerably cheaper, much more widely available, and easier to apply than MRI highlights the important role this technique may have in the diagnosis of inflammatory neuropathies and warrants prospective studies to assess morphologic changes in nerves, both at diagnosis and during the course of the disease. AUTHOR CONTRIBUTIONS Antonella Di Pasquale: analysis and interpretation of ultrasound data and manuscript drafting. Stefania Morino: analysis and interpretation of electrodiagnostic data. Simona Loreti: blind measurement of ultrasound recordings and interpretation of the data. Elisabetta Bucci: patient and control collection, check of protocol, file preparation, and data analysis.
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Nicola Vanacore: statistical analysis and interpretation. Giovanni Antonini: study design, drafting, and revising of the manuscript.
15. STUDY FUNDING No targeted funding reported.
DISCLOSURE
16.
A. Di Pasquale received contribution from Genzyme for congress participation. S. Morino received contribution from Genzyme for congress participation. S. Loreti, E. Bucci, and N. Vanacore report no disclosures relevant to the manuscript. G. Antonini received honoraria for conferences from Kedrion SpA and contributions for congress participation from Kedrion SpA, Genzyme, and Boerhing. Go to Neurology.org for full disclosures.
17.
18.
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Neurology 84
February 24, 2015
809
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Peripheral nerve ultrasound changes in CIDP and correlations with nerve conduction velocity Antonella Di Pasquale, Stefania Morino, Simona Loreti, et al. Neurology 2015;84;803-809 Published Online before print January 28, 2015 DOI 10.1212/WNL.0000000000001291 This information is current as of January 28, 2015
Neurology ® is the official journal of the American Academy of Neurology. Published continuously since 1951, it is now a weekly with 48 issues per year. Copyright © 2015 American Academy of Neurology. All rights reserved. Print ISSN: 0028-3878. Online ISSN: 1526-632X.
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Neurology ® is the official journal of the American Academy of Neurology. Published continuously since 1951, it is now a weekly with 48 issues per year. Copyright © 2015 American Academy of Neurology. All rights reserved. Print ISSN: 0028-3878. Online ISSN: 1526-632X.