Electrophysiological Responsiveness to Long-Term Therapy in Chronic Inflammatory Demyelinating Polyneuropathy: Case Report

Electrophysiological studies are essential for the diagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP), but the utility of nerve conduction studies in monitoring outcomes in individual CIDP patients is controversial. Electrophysiological improvements after short-term treatment have been described in large cohorts of CIDP patients, but the magnitude of the changes is small and might be obscured in individual patients due to the variation inherent in nerve conduction testing. We present the case of a CIDP patient treated successfully with immunosuppression and followed for 31 years with serial standardized clinical and electrophysiological evaluations. Improvement in electrophysiological parameters lagged clinical changes for up to 2 years, but all motor parameters improved (distal motor and F wave latencies, conduction velocities, and compound muscle action potential amplitudes) even with evidence of initial axonal damage. Worsening of electrophysiological parameters, specifically increasing F wave latencies, heralded clinical relapse by as much as a year. Electrophysiological parameters do improve with treatment in CIDP patients, although the changes can take up to 2 years, and also worsening electrophysiological parameters can herald clinical relapse and might help guide therapeutic decisions

Duration and temporal dispersion measurements in CIDP subjects from the Polyneuropathy And Treatment with Hizentra (PATH) study

Abstract: Introduction: Distal compound muscle action potential (dCMAP) duration and temporal dispersion (TD) are electrophysiological hallmarks of demyelination and important for the diagnosis of CIDP. While the impact of CIDP treatment on other nerve conduction parameters has been examined, the effects on dCMAP and TD remain unexplored. The aim of the study was to examine the impact of withdrawal of immunoglobulin treatment on dCMAP duration and TD, and also the influence of the measurement technique on dCMAP duration and TD. Methods: Nerve conduction studies were analyzed from the PATH (Polyneuropathy And Treatment with Hizentra) study which randomized patients with CIDP to two doses of IgPro 20 and placebo. Distal CMAP duration and TD were obtained by two methods of measurements (D1 and D2, TD1 and TD2) from the median and peroneal nerves.   Results: The dCMAP and TD were obtained from 389 tracings. While the two methods of measurement showed differences in D1 and D2 with D2 longer than D1 in all the three groups, there was no difference between the TD1 and TD2. There was no difference at baseline in dCMAP duration or TD among the three groups. At the end of treatment, patients in the placebo arm had no worsening of dCMAP and TD compared to baseline or the treated groups. Conclusion: dCMAP duration and TD did not show a difference between treated and placebo groups, and may be less sensitive measures than other nerve conduction parameters when evaluating changes in treatment. The method of dCMAP duration measurement does not affect TD as long as a consistent method is followed. &nbsp

Identification and prediction of diabetic sensorimotor polyneuropathy using individual and simple combinations of nerve conduction study parameters.

OBJECTIVE: Evaluation of diabetic sensorimotor polyneuropathy (DSP) is hindered by the need for complex nerve conduction study (NCS) protocols and lack of predictive biomarkers. We aimed to determine the performance of single and simple combinations of NCS parameters for identification and future prediction of DSP. MATERIALS AND METHODS: 406 participants (61 with type 1 diabetes and 345 with type 2 diabetes) with a broad spectrum of neuropathy, from none to severe, underwent NCS to determine presence or absence of DSP for cross-sectional (concurrent validity) analysis. The 109 participants without baseline DSP were re-evaluated for its future onset (predictive validity). Performance of NCS parameters was compared by area under the receiver operating characteristic curve (AROC). RESULTS: At baseline there were 246 (60%) Prevalent Cases. After 3.9 years mean follow-up, 25 (23%) of the 109 Prevalent Controls that were followed became Incident DSP Cases. Threshold values for peroneal conduction velocity and sural amplitude potential best identified Prevalent Cases (AROC 0.90 and 0.83, sensitivity 80 and 83%, specificity 89 and 72%, respectively). Baseline tibial F-wave latency, peroneal conduction velocity and the sum of three lower limb nerve conduction velocities (sural, peroneal, and tibial) best predicted 4-year incidence (AROC 0.79, 0.79, and 0.85; sensitivity 79, 70, and 81%; specificity 63, 74 and 77%, respectively). DISCUSSION: Individual NCS parameters or their simple combinations are valid measures for identification and future prediction of DSP. Further research into the predictive roles of tibial F-wave latencies, peroneal conduction velocity, and sum of conduction velocities as markers of incipient nerve injury is needed to risk-stratify individuals for clinical and research protocols

Measurement of cooling detection thresholds for identification of diabetic sensorimotor polyneuropathy in type 1 diabetes.

OBJECTIVE: Compared to recently-studied novel morphological measures, conventional small nerve fiber functional tests have not been systematically studied for identification of diabetic sensorimotor polyneuropathy (DSP). We aimed to determine and compare the diagnostic performance of cooling detection thresholds (CDT) in a cross-sectional type 1 diabetes cohort. RESEARCH DESIGN AND METHODS: 136 subjects with type 1 diabetes and 52 healthy volunteers underwent clinical and electrophysiological examination for DSP classification concomitantly with the Toronto Clinical Neuropathy Score (TCNS) and three small fiber function tests: CDT, heart rate variability (HRV), and laser doppler imaging of axon-mediated neurogenic flare responses to cutaneous heating (LDIFLARE). Area under the curve (AUC) and optimal thresholds were determined by receiver operating characteristic (ROC) curves in the type 1 diabetes cohort. RESULTS: Type 1 diabetes subjects were 42±17 years of age with mean HbA1c 7.9±1.7%. Fifty-nine (45%) met the case definition for DSP. CDT values were lowest in cases with DSP (18.3±8.4°C) compared to controls without DSP (28.4±3.5°C) and to healthy volunteers (29.6±1.8°C; p-value for both comparisons<0.0001). AUCCDT was 0.863 which was similar to AUCTCNS (0.858, p = 0.24) and AUCHRV (0.788, p = 0.05), but exceeded AUCLDIFLARE (0.750, p = 0.001). The threshold of <25.1°C was equivalent to the lower bound of the healthy volunteer 95% distribution [25.1, 30.8°C] and performed with 83% sensitivity and 82% specificity. CONCLUSIONS: Akin to novel small fiber morphological measures, CDT is a functional test that identifies DSP with very good diagnostic performance. These findings support further research that revisits the role of CDT in early DSP detection

Concurrent validity ROC curves for sural, peroneal, tibial and summative parameters.

<p>See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0058783#pone-0058783-t002" target="_blank">Table 2</a> for estimates of AROC for each parameter. Peroneal conduction velocity and sural amplitude potential had the highest AROC (AROC 0.90 and 0.83, respectively). Dashed lines represent amplitude potentials. Solid lines represent conduction velocities. Dotted lines represent F-wave latencies.</p

Baseline Characteristics of the 251 Prevalent DSP Cases and the 107 Prevalent Controls According to the 4-Year Incidence of DSP.

<p>Data are means ± standard deviations or <i>n</i> (%). For comparisons between two groups, p values reported are χ² test statistics for categorical variables and T-tests for continuous variables. For comparisons between three groups, p values reported are χ² test statistics for categorical variables and ANOVA for continuous variables. Normal values for individual NCS are as follows. Sural amp≥7.2 µV for age ≤65 and ≥5.5 µV for age >65, sural CV≥40 m/s, peroneal amp≥5 µV for age ≤65 and ≥3 for age >65, peroneal CV≥40 m/s, peroneal F wave ≤59 ms for height ≥182.9 cm and ≤58 ms for height ≤182.9 cm, tibial amp≥10 µV, tibial CV≥40 m/s, tibial F wave ≤55 ms.</p>*<p>p-value for ANOVA between Prevalent Cases, Incident DSP Cases and Incident DSP Controls.</p>†<p>By subject self-report.</p>‡<p>HbA1C, glycated hemoglobin A1C.</p>§<p>Summative parameters are composed of the following: sum amplitude = sural+tibial, sum conduction velocity = sural+peroneal +tibial, sum F-wave latency = peroneal+tibial.</p>¶<p>Summed amplitude potentials are expressed in arbitrary units since sural amplitude potential is measured in microvolts and tibial amplitude potential is measured in millivolts.</p>∥<p>Statistical tests for the NCS parameters applied a Bonferroni correction for multiple comparisons for significance such that p-values <0.0045 (0.05/11) were considered significant. All p-values except for two indicated by this symbol, met significance criteria.</p><p> <b>TCNS, Toronto Clinical Neuropathy Score. Amp, amplitude potential. CV, conduction velocity. F-wave, F-wave latency.</b></p

Comparison of Area Under the Receiver Operating Characteristic Curve (AROC) Between Individual and Summative NCS Parameters for the Cross-Cectional (Concurrent Validity) Analysis and the Longitudinal (Predictive Validity) Analysis.

<p>Normal values for individual NCS are as follows. Sural amp≥7.2 µV for age ≤65 and ≥5.5 µV for age >65, sural CV≥40 m/s, peroneal amp≥5 µV for age ≤65 and ≥3 for age >65, peroneal CV≥40 m/s, peroneal F wave ≤59 ms for height ≥182.9 cm and ≤58 ms for height ≤182.9 cm, tibial amp≥10 µV, tibial CV≥40 m/s, tibial F wave ≤55 ms.</p>*<p>Two tailed p value for comparison with the AROC for the parameters with the highest AROC in concurrent and predictive analyses.</p>†<p>Established by the distribution in healthy control subects <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0058783#pone.0058783-Oh1" target="_blank">[23]</a>.</p>‡<p>Summative parameters are composed of the following: sum amplitude = sural+tibial, sum conduction velocity = sural+peroneal +tibial, sum F-wave latency = peroneal+tibial. Summed amplitude potentials are expressed in arbitrary units since sural amplitude potential is measured in microvolts and tibial amplitude potential is measured in millivolts.</p><p> <b>Amp, amplitude potential. CV, conduction velocity. F-wave, F-wave latency.</b></p

Predictive validity ROC curves for sural, peroneal, tibial and summative parameters.

<p>See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0058783#pone-0058783-t002" target="_blank">Table 2</a> for estimates of AROC for each parameter. Tibial F-wave latency and the sum of sural, peroneal, and tibial conduction velocities had the highest AROC (0.80 and 0.83, respectively). Dashed lines represent amplitude potentials. Solid lines represent conduction velocities. Dotted lines represent F-wave latencies.</p

ROC curves for functional small fiber measures and the TCNS in the identification of clinical DSP in 136 Subjects with type 1 diabetes.

<p>Clinical DSP was defined as having a nerve conduction abnormality in both the sural sensory nerve and peroneal motor nerve, in addition to at least one clinical sign or symptom. AUCs for CDT, TCNS, HRV, and LDI were 0.863, 0.858, 0.788, and 0.745, respectively. The optimal threshold for CDT (*) was 25.1°C (83% sensitivity, 82% specificity).</p