Peripheral neuropathy: detection with diffusion-tensor imaging.

PURPOSE: To investigate the ability of diffusion-tensor imaging (DTI) and T2 to help detect the mildest nerve lesion conceivable, that is, subclinical ulnar neuropathy at the elbow. MATERIALS AND METHODS: This prospective study was approved by the institutional ethics board. Written informed consent was obtained from all participants. Magnetic resonance neurography was performed at 3.0 T by using proton density- and T2-weighted relaxometry and DTI on elbows in 30 healthy subjects without clinical evidence of neuropathy. Quantitative analysis of ulnar nerve T2 and fractional anisotropy (FA) was performed, and T2 and FA values were correlated to electrical nerve conduction velocities (NCVs) with Pearson correlation analysis. Additional qualitative assessment of T2-weighted and FA images was performed by two readers, and sensitivity and specificity were calculated. RESULTS: Ten of the 30 subjects (33%) had NCV slowing across the elbow segment. Compared with subjects without NCV slowing, subjects with slowing had decreased FA values (0.51 ± 0.09 vs 0.41 ± 0.07, respectively; P = .006) and increased T2 values (64.2 msec ± 10.9 vs 76.2 msec ± 13.7, respectively; P = .01) in the proximal ulnar sulcus. FA values showed a significant correlation (P = .01) with NCV slowing over the sulcus as an electrophysiologic indicator of myelin sheath damage. Qualitative assessment of FA maps and T2-weighted images helped identify subjects with conduction slowing with a sensitivity of 80% and 55%, respectively, and a specificity of 83% and 63%. CONCLUSION: FA maps can accurately depict even mild peripheral neuropathy and perform better than the current standard of reference, T2-weighted images. DTI may therefore add diagnostic value as a highly sensitive technique for the detection of peripheral neuropathy.

Exposure to 16 h of normobaric hypoxia induces ionic edema in the healthy brain.

Following prolonged exposure to hypoxic conditions, for example, due to ascent to high altitude, stroke, or traumatic brain injury, cerebral edema can develop. The exact nature and genesis of hypoxia-induced edema in healthy individuals remain unresolved. We examined the effects of prolonged, normobaric hypoxia, induced by 16 h of exposure to simulated high altitude, on healthy brains using proton, dynamic contrast enhanced, and sodium MRI. This dual approach allowed us to directly measure key factors in the development of hypoxia-induced brain edema: (1) Sodium signals as a surrogate of the distribution of electrolytes within the cerebral tissue and (2) Ktrans as a marker of blood-brain-barrier integrity. The measurements point toward an accumulation of sodium ions in extra- but not in intracellular space in combination with an intact endothelium. Both findings in combination are indicative of ionic extracellular edema, a subtype of cerebral edema that was only recently specified as an intermittent, yet distinct stage between cytotoxic and vasogenic edemas. In sum, here a combination of imaging techniques demonstrates the development of ionic edemas following prolonged normobaric hypoxia in agreement with cascadic models of edema formation.

Dorsal root ganglia hypertrophy as in vivo correlate of oxaliplatin-induced polyneuropathy.

PURPOSE: To investigate in vivo morphological and functional correlates of oxaliplatin-induced peripheral neuropathy (OXA-PNP) by magnetic resonance neurography (MRN). METHODS: Twenty patients (7 female, 13 male, 58.9±10.0 years) with mild to moderate OXA-PNP and 20 matched controls (8 female, 12 male, 55.7±15.6 years) were prospectively enrolled. All patients underwent a detailed neurophysiological examination prior to neuroimaging. A standardized imaging protocol at 3.0 Tesla included the lumbosacral plexus and both sciatic nerves and their branches using T2-weighted fat-saturated sequences and diffusion tensor imaging. Quantitative assessment included volumetry of the dorsal root ganglia (DRG), sciatic nerve normalized T2 (nT2) signal and caliber, and fractional anisotropy (FA), mean diffusivity (MD), axial (AD) and radial diffusivity (RD). Additional qualitative evaluation of sciatic, peroneal, and tibial nerves evaluated the presence, degree, and distribution of nerve lesions. RESULTS: DRG hypertrophy in OXA-PNP patients (207.3±47.7mm3 vs. 153.0±47.1mm3 in controls, p = 0.001) was found as significant morphological correlate of the sensory neuronopathy. In contrast, peripheral nerves only exhibited minor morphological alterations qualitatively. Quantitatively, sciatic nerve caliber (27.3±6.7mm2 vs. 27.4±7.4mm2, p = 0.80) and nT2 signal were not significantly changed in patients (1.32±0.22 vs. 1.22±0.26, p = 0.16). AD, RD, and MD showed a non-significant decrease in patients, while FA was unchanged. CONCLUSION: OXA-PNP manifests with morphological and functional correlates that can be detected in vivo by MRN. We report hypertrophy of the DRG that stands in contrast to experimental and postmortem studies. DRG volume should be further investigated as a biomarker in other sensory peripheral neuropathies and ganglionopathies.

Diffusion Tensor Imaging Adds Diagnostic Accuracy in Magnetic Resonance Neurography.

OBJECTIVE: The aim of this study was to determine whether quantitative diffusion tensor imaging (DTI) adds diagnostic accuracy in magnetic resonance neurography. MATERIALS AND METHODS: This prospective study was approved by the institutional review board. We enrolled 16 patients with peripheral polyneuropathy of various etiologies involving the upper arm and 30 healthy controls. Magnetic resonance neurography was performed at 3 T using transverse T2-weighted (T2-w) turbo spin echo and spin echo planar imaging diffusion-weighted sequences. T2-weighted normalized signal (nT2), fractional anisotropy (FA), apparent diffusion coefficient (ADC), radial diffusivity (RD), and axial diffusivity (AD) of the median, ulnar, and radial nerves were quantified after manual segmentation. Diagnostic performance of each separate parameter and combinations of parameters was assessed using the area under the receiver operating characteristic curve (AUC). Bootstrap validation was used to adjust for potential overfitting. RESULTS: Average nT2, ADC, RD, and AD values of the median, ulnar, and radial nerve were significantly increased in neuropathy patients compared with that in healthy controls (nT2, 1.49 ± 0.05 vs 1.05 ± 0.05; ADC, 1.4 × 10(-3) ± 2.8 × 10(-5) mm(2)/s vs 1.1 × 10(-3) ± 1.3 × 10(-5) mm(2)/s; RD, 9.5 × 10(-4) ± 2.9 × 10(-5) mm(2)/s vs 7.2 × 10(-4) ± 1.3 × 10(-5) mm(2)/s; AD, 2.3 × 10(-3) ± 3.7 × 10(-5) mm(2)/s vs 2.0 × 10(-3) ± 2.2 × 10(-5) mm(2)/s; P < 0.001 for all comparisons). Fractional anisotropy values were significantly decreased in patients (0.51 ± 0.01 vs 0.59 ± 0.01; P < 0.001). T2-weighted normalized signal and DTI parameters had comparable diagnostic accuracy (adjusted AUC: T2-w, 0.92; FA, 0.88; ADC, 0.89; AD, 0.84; RD, 0.86). Combining DTI parameters significantly improved the diagnostic accuracy over single-parameter analysis. In addition, the combination of nT2 with DTI parameters yielded excellent adjusted AUCs up to 0.97 (nT2 + FA). CONCLUSIONS: Diffusion tensor imaging has high diagnostic accuracy in peripheral neuropathy. Combining DTI with T2 can outperform T2-w imaging alone and provides added value in magnetic resonance neurography.

The effect of transcutaneous vagus nerve stimulation on pain perception--an experimental study.

BACKGROUND: Recent preclinical work strongly suggests that vagus nerve stimulation efficiently modulates nociception and pain processing in humans. Most recently, a medical device has offered a transcutaneous electrical stimulation of the auricular branch of the vagus nerve (t-VNS) without any surgery. OBJECTIVE: Our study investigates whether t-VNS may have the potential to alter pain processing using a controlled design. METHODS: Different submodalities of the somatosensory system were assessed with quantitative sensory testing (QST) including a tonic heat pain paradigm in 48 healthy volunteers. Each subject participated in two experimental sessions with active t-VNS (stimulation) or sham t-VNS (no stimulation) on different days in a randomized order (crossed-over). One session consisted of two QST measurements on the ipsi- and contralateral hand, each before and during 1 h of a continuous t-VNS on the left ear using rectangular pulses (250 µS, 25 Hz). RESULTS: We found an increase of mechanical and pressure pain threshold and a reduction of mechanical pain sensitivity. Moreover, active t-VNS significantly reduced pain ratings during sustained application of painful heat for 5 min compared to sham condition. No relevant alterations of cardiac or breathing activity or clinical relevant side effects were observed during t-VNS. CONCLUSIONS: Our findings of a reduced sensitivity of mechanically evoked pain and an inhibition of temporal summation of noxious tonic heat in healthy volunteers may pave the way for future studies on patients with chronic pain addressing the potential analgesic effects of t-VNS under clinical conditions.

Aversive faces activate pain responsive regions in the brain.

Recent evidence points to an overlap in the neural systems processing pain and social distress. In this functional MRI study we focus on the possible interplay between the processing of a psychosocial stressor and somatic pain within pain responsive brain regions, the latter being identified in an independent localizer experiment. A paradigm based on emotional induction (Hariri et al., 2000, Neuroreport 11(1):43-48) was combined with moderate heat pain to yield a factorial design with factor 'pain' as somatic stressor and factor 'faces' as nonpainful psychosocial stressor. Pain responsive regions of interest in the insula, SII cortex, and thalamus were activated by the factor 'faces' to a various extent. The hemodynamic response to both factors tends to aggregate in a compressive manner in these regions.

A motion illusion reveals mechanisms of perceptual stabilization.

Visual illusions are valuable tools for the scientific examination of the mechanisms underlying perception. In the peripheral drift illusion special drift patterns appear to move although they are static. During fixation small involuntary eye movements generate retinal image slips which need to be suppressed for stable perception. Here we show that the peripheral drift illusion reveals the mechanisms of perceptual stabilization associated with these micromovements. In a series of experiments we found that illusory motion was only observed in the peripheral visual field. The strength of illusory motion varied with the degree of micromovements. However, drift patterns presented in the central (but not the peripheral) visual field modulated the strength of illusory peripheral motion. Moreover, although central drift patterns were not perceived as moving, they elicited illusory motion of neutral peripheral patterns. Central drift patterns modulated illusory peripheral motion even when micromovements remained constant. Interestingly, perceptual stabilization was only affected by static drift patterns, but not by real motion signals. Our findings suggest that perceptual instabilities caused by fixational eye movements are corrected by a mechanism that relies on visual rather than extraretinal (proprioceptive or motor) signals, and that drift patterns systematically bias this compensatory mechanism. These mechanisms may be revealed by utilizing static visual patterns that give rise to the peripheral drift illusion, but remain undetected with other patterns. Accordingly, the peripheral drift illusion is of unique value for examining processes of perceptual stabilization.