DIAGNOSTIC VALUE OF THE NEAR-NERVE NEEDLE SENSORY NERVE
CONDUCTION IN SENSORY INFLAMMATORY DEMYELINATING
POLYNEUROPATHY
ZEKI ODABASI, MD,1,2and SHIN J. OH, MD1
1Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama, USA 2Department of Neurology, Ufuk University Medical School, Ankara, Turkey
Accepted 5 August 2017
ABSTRACT: Introduction: In this study we report the diag-nostic value of the near-nerve needle sensory nerve conduc-tion study (NNN-SNCS) in sensory inflammatory demyelinating polyneuropathy (IDP) in which the routine nerve conduction study was normal or non-diagnostic. Methods: The NNN-SNCS was performed to identify demyelination in the plantar nerves in 14 patients and in the median or ulnar nerve in 2 patients with sensory IDP. Results: In 16 patients with sensory IDP, routine NCSs were either normal or non-diagnostic for demyelination. Demyelination was identified by NNN-SNCS by dispersion and/or slow nerve conduction velocity (NCV) below the demyelination marker. Immunotherapy was initiated in 11 patients, 10 of whom improved or remained stable. Discussion: NNN-SNCS played an essential role in identifying demyelinaton in 16 patients with sensory IDP, leading to proper treatment.
Muscle Nerve 57: 414–418, 2018
A
mong the various forms of inflammatorydemye-linating polyneuropathy (IDP), the sensory form is
rare. Sensory Guillain–Barre syndrome (GBS) was
first described in 1992.1 The largest series of
patients with sensory GBS (8 patients) was
reported in 2001.2 Ten patients with chronic
sory demyelinating neuropathy (CSDN), the sen-sory form of chronic inflammatory demyelinating polyneuropathy (CIDP), were described by Oh
et al. in 1995.3 Subacute inflammatory
demyelinat-ing polyneuropathy (SIDP) was first described in 2008 and a few patients with the sensory form of
SIDP were also included.4
Nerve conduction studies (NCSs) are essential
in confirming the diagnosis of IDP.5The diagnosis
of demyelination usually has been based on motor NCS, and diagnostic criteria for this are well
established.5
However, motor NCS is either normal or non-diagnostic for demyelination in some patients with sensory IDP. In these patients, we have used the near-nerve needle–sensory nerve conduction study (NNN-SNCS) to detect demyelination for the
diag-nosis of demyelinating neuropathy.6 In this study,
we report on the essential role of the NNN-SNCS in the diagnosis of demyelination based on our experience in 16 patients with sensory IDP.
METHODS
During the 20-year period between 1985 and 2005, we observed 16 patients with sensory IDP diagnosed by the NNN-SNCS, whose routine NCSs were normal or non-diagnostic. Informed consent for participation in this study was obtained from all patients. As part of our standard of care, we performed NNN-SNCS in all patients with distal sensory neuropathy and normal routine NCS and in all clin-ically suspected sensory IDP patients with non-diagnostic routine NCS.7
Routine studies included the motor, sensory, and mixed NCS of 1 median and ulnar nerve, motor NCS of 2 fibular and tibial nerves, and sensory NCS of the right and left sural nerves.6
In 14 patients with a diagnosis of sensory neuropathy of the lower extremities, NNN-SNCS of the plantar nerve was performed in 1 foot according to Oh et al.’s method and the patients’ nerve conduction values were compared with age-matched normal values.6,8Six plantar nerves were tested in each foot with the recording needle at the tibial nerve above the tarsal tunnel behind the medial malleolus, and with surface stimulating electrodes over digits I and V, and I–II, II–III, III–IV, and IV–V interdigital nerves. None of our patients had a previous history of trauma in the tested nerves.
In 2 patients with predominant sensory neuropathy in the upper extremities, NNN-SNCS was performed in the ulnar nerve in 1 patient and in ulnar and median nerves in the other patient, according to the method of Odabasi et al. and Buchthal and Rosenfalck.9,10 Sensory nerve action potential (SNAP) was obtained with needle recording elec-trodes at the wrist and elbow with stimulation of the ulnar nerve in digit V and the median nerve in digit II.
Latency was measured from the onset of the stimulus to the initial positive peak of the potential for the maxi-mum sensory nerve conduction velocity (NCV) calculation and to the highest negative peak of the potential for the negative peak sensory NCV calculation. The amplitude of
Abbreviations: CIDP, chronic inflammatory demyelinating polyneurop-athy; CSDN, chronic sensory demyelinating neuroppolyneurop-athy; CSF, cerebrospi-nal fluid; GBS, Guillain–Barre syndrome; IDP, inflammatory demyelinating polyneuropathy; IVIg, intravenous immunoglobulin; MSDN, multifocal sen-sory demyelinating neuropathy; NCV, nerve conduction velocity; NNN-SNC, near-nerve needle sensory nerve conduction; NP, negative peak; NCV, nerve conduction velocity; ONN, on-nerve needle; SNAP, sensory nerve action potential; SIDP, subacute inflammatory demyelinating poly-neuropathy; SPGP, sulfated glucuronic para-globoside
Key words: inflammatory demyelinating polyneuropathy; near-nerve nee-dle recording; near-nerve neenee-dle sensory nerve conduction; nerve conduc-tion study; plantar nerve conduction study; sensory inflammatory demyelinating polyneuropathy
Correspondence to: Z. Odabasi, Ufuk Universitesi Tip Fakultesi Noroloji AD, Mevlana Blv. No. 86 Balgat, 06520 Ankara, Turkey; e-mail: odabasi@ gmail.com
This article was published online on 23 November 2017. After online publi-cation text was updated. This notice is included in the online and print ver-sions to indicate that both have been corrected on 29 December 2017.
VC 2017 Wiley Periodicals, Inc.
Published online 10 August 2017 in Wiley Online Library (wileyonlinelibrary. com). DOI 10.1002/mus.25761
the potential was measured from peak to peak. The dura-tion of the SNAP was measured from the onset of the first positive deflection to the return of the last component to baseline.6
Diagnostic criteria for demyelination in NNN-SNCS were slow negative peak (NP) sensory NCV below the demy-elination marker (mean 2 mean 3 0.36) and/or dispersion of the SNAP (multiple peaks duration > normal limit).11 For the plantar nerve, demyelination criteria were: duration > 6.8 ms (indicating temporal dispersion) and NP-NCV < 23.0 m/s. For the ulnar nerve, the criteria were dura-tion >10.0 ms and NP-NCV < 34.4 m/s.6
RESULTS
Clinical Features. The clinical features of 16 patients (10 males and 6 females, age range 36–59 years) are summarized in Table 1. Duration of symp-toms ranged from 10 days to 15 years. The predomi-nant chief complaints were numbness, tingling, or pain in the feet and/or legs in 15 patients. Muscle strength was normal in all. Deep tendon reflexes were either diminished or absent in 14 patients. All patients had clinically pure sensory peripheral neu-ropathy that was symmetric in the feet or legs in 15 and in the hands in 3. One patient demonstrated prominent astereognosis in the hands. The final diagnosis was sensory GBS in 1 patient, multifocal sensory demyelinating neuropathy (MSDN) in 1,
sensory SIDP in 3, and CSDN in 11.2–4,12
Spinal Fluid Findings and other Laboratory Tests. Pro-tein was elevated (>55 mg/dl) in 8 (57%) of 14 tested patients. Lymphocytes and glucose were normal in all tested patients. In 4 patients, oligoclonal bands or an increased IgG index was present. One patient each
had IgM monoclonal gammopathy, low vitamin B12
level, GD1A antibody, or diabetes mellitus. Sulfated glucuronic para-globoside (SPGP) was positive in 2 patients.
Routine Nerve Conduction Findings. Routine NCSs were normal in 9 patients, with mild motor sensory polyneuropathy in 6 patients and sensory polyneur-opathy in 1 patient. Electrophysiological evidence of demyelination (abnormal temporal dispersion, conduction block, >150% prolongation of normal mean distal latencies and F-wave latencies, and/or NCVs slower than 60% of normal means) was not
detected in any patient.6We also analyzed routine
NCS data by the recent diagnostic criteria of demy-elination by the European Federation of
Neurolog-ical Societies/Peripheral Nerve Society CIDP
guidelines.5 None of our patients met definite,
probable, or possible criteria. SNAPs were absent in routine NCS of the median and ulnar nerves in 1 patient. In 1 other patient (patient 5), SNAP amplitude was low in the ulnar nerve. These 2 patients had predominant symptoms in the hands
and forearms, and thus underwent NNN-SNCS of the ulnar and/or median nerves.
NNN-SNCS. NNN-SNCS was abnormal in all 16
patients, in plantar nerve studies in 14, and by ulnar and/or median nerve study in 2. In the plan-tar nerve studies, SNAP was obtained in at least 2 plantar nerves in all patients. A definite neuropa-thy pattern (abnormality in > 3 digital or interdigi-tal nerves) was found in plantar NNN-SNCS in all 14 patients. As a whole, slow NCVs were found in 15 patients, low amplitudes in 13, and dispersion in 14. In 1 patient (patient 5), dispersion (22.3 ms) was observed in the ulnar nerve, indicating demyelination. In 1 patient (patient 12) with absent SNAPs in the routine study, NNN-SNCS showed a low SNAP amplitude (1.5 mV), dispersion (13.3 ms), and NCV in demyelinating range (23.4 m/s) in the ulnar nerve. Among 14 patients with plantar NNN-SNCS, NP-NCV showed slow NCV below the demyelination marker (13.7– 22.6 m/s) in 11 patients and dispersion (6.9–12.7 ms) in 10 patients (Fig. 1). Demyelination was documented by slow NCV below the demyelination marker and dispersion in 11 patients, by slow NCV below the demyelination marker alone in 2 patients and by dispersion alone in 3 patients. Thus, electrophysiological evidence of demyelin-ation was documented in all 16 patients by NNN-SNCS. Routine and NNN-SNCS data are summa-rized in Table 2.
Nerve Biopsy Findings. Sural nerve biopsy was per-formed in 9 patients. Final histological diagnosis
was demyelinating neuropathy in 4 patients,
inflammatory demyelinating neuropathy in 3, end-stage neuropathy in 1, and normal findings in 1. Thus, nerve biopsy confirmed demyelinating neu-ropathy in 7 of 9 biopsied patients. This included 3 (patients 10, 13, and 17) patients with normal cerebrospinal fluid (CSF) protein.
Treatment. Spontaneous improvement occurred
without any treatment in 1 sensory GBS patient.2
In 3 sensory SIDP patients, clinical improvement was documented in conjunction with corticosteroid treatment in 2, and with corticosteroids and
intra-venous immunoglobulin (IVIg) in 1 patient.4 In 1
MSDN patient, mild improvement was sustained on
treatment with IVIg and cyclosporine.12 Of 11
CSDN patients, 2 were not followed up, 2 remained stable without any treatment, and 2 remained
stable with immunotherapy.3 In 1 CSDN patient,
symptoms progressed despite immunotherapy. Par-tial or complete recovery was observed in 4 patients who received immunotherapy with corticosteroids, IVIg, azathioprine, and mycophenolate mofetil, either singly or in combination. Ten of 11 patients
Ta b le 1 . Clinic al featu res, CS F finding s, and respon ses to treatme nt A ge/gen der Duration Sym ptoms Sensory loss Refle xes CSF Tr eatme nt/out come Sen sory GBS Patien t 1 41/M 10 days Nu mb feet after viral illne ss PP , V on feet N Spon taneous improve me nt Sen sory SIDP Patien t 2 45/M 6 weeks Tingl ing in legs PP below shin V, P o n toes Ø A , K 68/4*, high IgG OCB Improve d with IVIg and steroid, asymp toma tic in 1 year Patien t 3 57/M 6 weeks Burn ing in hand s, feet, and left abd omen PP on feet/h and Ø A 119, high IgG Asym pt omatic with ste roid in 5 mont hs Patien t 4 43/F 7 weeks Burn ing in feet PP on to es Ø A , K 110, high IgG Improve d with ste roid. Failed with IVIg and PE MSD N Patien t 5 42/M 3 years Numbn ess in hand s P P o n han ds, V on finger s/toes, astreog nosis ØA , 1 1 ot hers 40 Stabl e with IVIg and cycl osporin e CS DN Patien t 6 49/M 1 years Numb ness/p ain toes PP on legs, V o n toes Ø A 1 1 K 6 5 Impro ved with IVIg and azath ioprin e Patien t 7 54/F 2 years Burn ing in hand s and legs PP on feet, V o n to e s Ø A , K 4 7 S table for 18 years, mild improv emen t with IVIg in the recen t worse ning Patien t 8 57/F 3 years Tinglin g o n feet PP on feet, V o n to e s 1 1 A, K Stabl e, no trea tment Patien t 9 55/M 15 years Burn ing in legs PP on legs , V on ankle, Po nt o e s ØA , 1 1 K 8 4 Stable with IVIg Patien t 1 0 55/F 1.5 years Stabb ing pa in on feet PP on feet, V o n ankle 1 1 A 34/4, OC B N o follow-up Patien t 1 1 36/M 3 years Burn ing on legs, fing ers and face PP on feet N 3 6 Mild im prove ment with IVIg and steroid Patien t 1 2 59/M 8 years Pain in arm s and legs PP/V below knee/ elbow , P toes Ø all 98/7 Dram atic improv emen t with IVIg Patien t 1 3 40/F 1.5 years Pai n o n feet PP be low kne e/ elbow , V toe N 67, high IgG No follow-up Patien t 1 4 52/F 10 years Pai n o n feet PP on to es, V ankle 1 1 A 6 0 N o resp onse to immu nothera py Patien t 1 5 45/M 1.5 years Nu mbness on feet PP on feet, V toes 1 1 A 4 8 Faile d with IVIg , improv ed with myco pheno late mofeti l Patien t 1 6 37/M 3 years Burn ing feet V toes 1 1 A N Stabl e, no immu nothe rapy All reflexes are normal, except where indicated. CSF, cerebrospinal fluid; Ø, absent; 1 1 , decreased; A, ankle; K, knee; GBS, Guillain–Barr esyndrome; F, female; M, male; IVIg, intravenous immunoglobulin; CSDN, chronic sensory demyelinating neuropathy; N, normal; OCB, oligoclonal band; PP, pinprick; V, vibration; P, position. *Protein (mg/dl) / cell (mm).
treated with immunotherapy improved or were stable.
DISCUSSION
Even in sensory IDP, demyelinating findings in motor NCSs are common and a key to the
diagno-sis of demyelinating neuropathies.2,3 This is
because the electrophysiological data do not neces-sarily correlate with neuropathic symptoms and
deficits.13 Although sensory nerve conduction is
known to be more sensitive than motor nerve con-duction in detection of neuropathy, the difficulty in demonstrating demyelination in sensory NCSs is due to the technical limitations of routine, surface
electrode–based sensory studies.6 Diagnostic
crite-ria of demyelination based on sensory NCSs with surface electrodes were not well-established until recently. In 2016, Oh et al. proposed such criteria based on ONN-NCS of the sural nerve during the
nerve biopsy.11 In the surface electrode sensory
NCSs, slow NCV below the demyelination marker (normal mean – mean 3 0.36) and dispersion (duration of SNAP > 2.8 ms) are recommended as the diagnostic criteria of demyelination. In the NNN-SNCS, slow NCV below the demyelination marker and dispersion (multiple peaks with dura-tion >4.8 ms in the sural nerve) are recommended as the diagnostic criteria of demyelination. Routine NCSs for peripheral neuropathy also have limita-tions, because the most commonly affected seg-ments—those in the feet—are not tested with
sensory nerve conduction.6,7
In sensory IDP, motor nerve conduction is nor-mal or non-demyelinating in some patients. In such patients, the only way to document the demy-elinating nature of neuropathy is to use NNN-SNCS, which can document temporal dispersion
and slowing in NCV in the demyelinating
range.6,11 In the present study, the routine NCS
was completely normal in 9 patients and was abnormal but non-diagnostic for demyelination in 7 patients: mild motor sensory neuropathy in 6 and sensory neuropathy in 1.
In all patients except 2, we studied NNN-SNCS in the plantar nerves of 1 foot because of clinical FIGURE 1. Sensory nerve action potential (SNAP) in the digit 1
plantar nerve by near-nerve needle sensory nerve conduction study in a 41-year-old patient with sensory Guillain–Barre syn-drome. Maximum nerve conduction velocity (NCV) (38.8 m/s) is normal for his age. Negative peak NCV (22.6 m/s) is slower than the demyelination marker. Duration (9.2 ms) is longer than nor-mal (6.8 ms), indicating dispersion. Amplitude (3.3 mV) is nornor-mal.
Table 2. Routine and near-nerve needle sensory nerve conduction data
Patient Routine NCS NNN-SNCS NP-NCV (m/s) Amplitude (mV) Duration (ms)
1 Normal Plantar 22.6 3.3 9.2
2 M neuropathy Plantar 19.7 1.0 4.6
3 MS neuropathy Plantar 13.7 0.4 10.6
4 Normal Plantar 17.6 0.9 10.0
5 S neuropathy in left hand Ulnar* 47.4 1.1 22.3
6 Normal Plantar 22.3 0.8 10.0 7 Normal Plantar 19.3 0.5 5.6 8 Normal Plantar 20.6 0.9 9.0 9 M neuropathy Plantar 20.6 3.1 10.9 10 Normal Plantar 14.4 0.7 12.5 11 Normal Plantar 23.8 6.8 11.3 12 MS neuropathy Ulnar 23.4 1.5 13.3 13 MS neuropathy Plantar 23.3 0.6 6.9 14 Normal Plantar 17.0 0.7 7.5 15 MS neuropathy Plantar 27.9 0.5 9.7 16 Normal Plantar 18.4 0.4 12.7
Bold values indicate demyelinating range: duration >6.8 ms and NCV <23.0 m/s for plantar nerve and duration >10.0 ms and NCV <34.4 m/s for ulnar nerve. M, motor; S, sensory; NCS, nerve conduction study; NNN-SNCS, near-nerve needle sensory nerve conduction study. NP-NCV, negative peak nerve con-duction velocity.
sensory neuropathy involving the feet. In these patients the study documented demyelination. In 2 patients with predominant sensory symptoms in the arms and sensory neuropathy in the ulnar and median nerves in the routine study, NNN-SNCS in the ulnar and/or median nerve documented demyelination. Thus, we conclude that NNN-SNCS played an essential role in diagnosis of sensory IDP in these patients.
The diagnosis of IDP was also supported by nerve biopsy, CSF findings, and response to immu-notherapy. In 10 of 11 immunotherapy-treated patients, the clinical outcome was either stable or improved: 10 had partial or complete recovery but 1 progressed despite treatment.
There have been 3 studies on the NNN-SNCS of the plantar nerve in distal sensory polyneurop-athy with normal routine NCS, with abnormal find-ings in NNN-SNCS in plantar nerves seen in 37%–
65% of patients.7,14,15
Oh et al. developed a new technique for NCS using needle electrodes placed on the exposed nerve during the sural nerve biopsy and termed this method the on-nerve needle (ONN)
tech-nique.16 Needle electrodes are used with both
ONN-NCS and NNN-SNCS. There are many fea-tures common to the 2 techniques in recorded SNAPs. The ONN-NCS was able to record a SNAP in 15% of cases with polyneuropathy in which the
surface electrode NCS could not record a SNAP.16
The ONN-NCS showed a significantly better con-cordance with the nerve biopsy findings, especially in demyelinating neuropathies. Currently, this is the best available technique for the electrophysio-logical–histopathological correlation of the biop-sied sural nerve, but it is unlikely this technique will be widely used in practice because of technical
limitations.16 In recent years, ultrasound-guided
needle positioning near the nerve has been
intro-duced.17 This technique permits insertion of the
needle as close as 1 mm from the nerve, which is the nearest approximation of ONN-NCS without skin incision. Potentially, this ultrasound-guided NNN-SNCS will make the NNN-SNCS much easier and more reliable than in the past.
We believe that the diagnosis of sensory IDP is important because it helps the clinician to plan pos-sible immunotherapies, such as those administered in our patients. NNN-SNC provides useful and unequivocal evidence in identifying sensory IDP, which is a treatable disorder. Our study has shown that NNN-SNCS can confirm the diagnosis in patients who are clinically suspected of having sen-sory IDP but whose diagnosis is not confirmed by routine NCS.
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