Harnessing historical data to derive reference limits - A comparison of e-norms to traditionally derived reference limits.

Objective: Nerve conduction studies (NCS) require valid reference limits for meaningful interpretation. We aimed to further develop the extrapolated norms (e-norms) method for obtaining NCS reference limits from historical laboratory datasets for children and adults, and to validate it against traditionally derived reference limits. Methods: We compared reference limits obtained by applying a further developed e-norms with reference limits from healthy controls for the age strata's 9-18, 20-44 and 45-60 years old. The control data consisted of 65 healthy children and 578 healthy adults, matched with 1294 and 5628 patients respectively. Five commonly investigated nerves were chosen: The tibial and peroneal motor nerves (amplitudes, conduction velocities, F-waves), and the sural, superficial peroneal and medial plantar sensory nerves (amplitudes, conduction velocities). The datasets were matched by hospital to ensure identical equipment and protocols. The e-norms method was adapted, and reference limit calculation using both ±2 SD (original method) and ±2.5 SD (to compensate for predicted underestimation of population SD by the e-norms method) was compared to control data using ±2 SD. Percentage agreement between e-norms and the traditional method was calculated. Results: On average, the e-norms method (mean ±2 SD) produced slightly stricter reference limits compared to the traditional method. Increasing the e-norms range to mean ±2.5 SD improved the results in children while slightly overcorrecting in the adult group. The average agreement between the two methods was 95 % (±2 SD) and 96 % (±2.5 SD). Conclusions: The e-norms method yielded slightly stricter reference limits overall than ones obtained through traditional methods; However, much of the difference can be attributed to a few outlying plots where the raters found it difficult to apply e-norms correctly. The two methods disagreed on classification of 4-5% of cases. Our e-norms software is suited to analyze large amounts of raw NCS data; it should further reduce bias and facilitate more accurate ratings. Significance: With small adaptations, the e-norms method adequately replicates traditionally derived reference limits, and is a viable method to produce reference limits from historical datasets.

Experimental sleep restriction increases latency jitter in pain elicited cortical responses.

OBJECTIVE: Previous studies have shown increased pain scores to painful stimulation after experimental sleep restriction, but reduced or unchanged magnitude of the event related potentials (ERPs) when averaged in the time-domain. However, some studies found increased response magnitude when averaging in the time-frequency domain. The aim of this study was to determine whether ERP-latency jitter may contribute to this discrepancy. METHODS: Ninety painful electrical stimuli were given to 21 volunteers after two nights of 50% sleep restriction and after two nights of habitual sleep. ERPs were analyzed in the time-domain (N2-and P2-peaks) and time-frequency domain (power spectral density). We quantified latency jitter by the mean consecutive difference (MCD) between single-trial peak latencies and by phase locking value (PLV) across trials. RESULTS: P2-MCD increased from 20.4 ± 2.1 ms after habitual sleep to 24.3 ± 2.2 ms after sleep restriction (19%, p = 0.038) and PLV decreased from 0.582 ± 0.015 after habitual sleep to 0.536 ± 0.015 after sleep restriction (7.9%, p = 0.009). We found no difference for N2-MCD. CONCLUSIONS: Our results indicate that partial sleep restriction increase latency jitter in cortical responses to experimental pain. SIGNIFICANCE: Latency jitter may contribute to the discrepancies between ERP-responses in the time-frequency domain and time-domain. Latency jitter should be considered when ERPs are analyzed.

Reduced motor cortical inhibition in migraine: A blinded transcranial magnetic stimulation study.

OBJECTIVE: To investigate motor cortical excitability, inhibition, and facilitation with navigated transcranial magnetic stimulation (TMS) in migraine in a blinded cross-sectional study. METHODS: Resting motor threshold (RMT), cortical silent period (CSP), short-interval intracortical inhibition (SICI), and intracortical facilitation (ICF) were compared in 27 interictal migraineurs and 33 controls. 24 female interictal migraineurs and 27 female controls were compared in subgroup analyses. Seven preictal migraineurs were also compared to the interictal group in a hypothesis-generating analysis. Investigators were blinded for diagnosis during recording and analysis of data. RESULTS: SICI was decreased in interictal migraineurs when compared to healthy controls (p=0.013), CSP was shortened in female interictal migraineurs (p=0.041). ICF was decreased in preictal compared to interictal migraineurs (p=0.023). RMT and ICF were not different between interictal migraineurs and controls. CONCLUSION: Cortical inhibition was decreased in migraineurs between attacks, primarily in a female subgroup, indicating an importance of altered cortical inhibition in migraine. SIGNIFICANCE: Previous studies on motor cortical excitability in migraineurs have yielded varying results. This relatively large and blinded study provides support for altered cortical inhibition in migraine. Measuring intracortical facilitation in the period preceding migraine attacks may be of interest for future studies.

Non-invasive cortical modulation of experimental pain in migraine.

OBJECTIVE: To test the hypothesis that secondary somatosensory cortex (S2) is involved in the migraine pathogenesis, by exploring the effect of navigated repetitive transcranial magnetic stimulation (rTMS) to S2 on thermal perception and pain. METHODS: In this blinded sham-controlled case-control study of 26 interictal migraineurs and 31 controls, we measured thermal detection and pain thresholds on the hand and forehead, and pain ratings to heat stimulation on the forearm and temple, after real and sham 10Hz rTMS. RESULTS: rTMS increased cold and heat pain thresholds in controls as compared to interictal migraineurs (p<0.026). rTMS decreased forehead and arm pain ratings (p<0.005) and increased hand cool detection thresholds (p<0.005) in both interictal migraineurs and controls. CONCLUSIONS: The effects of rTMS to S2 on thermal pain measures differed significantly between migraine and control subjects, although the effects were generally low in magnitude and not present in pain ratings. However, the lack of cold and heat pain threshold increase in migraineurs may reflect a hypofunction of inhibitory pain modulation mechanisms. SIGNIFICANCE: The expected rTMS-induced cold and heat hypoalgesia was not found among migraineurs, possibly a reflection of reduced intracortical inhibition.