Bilateral Responses Research Articles

Impulsivity in amphetamine use disorder: Examination of sex differences.

This study aimed to test whether there are sex differences in the relationship between impulsivity and amphetamine use disorder (AMP). A naturalistic cross-sectional design was used. The Tulsa 1000 study was held in Tulsa, OK, USA. There were two groups in this study: AMP+ (29F, 20M) and AMP- (57F, 33M). This project focuses on data related to impulsivity: UPPS-P impulsive behavior scale and a stop signal task (SST) during functional magnetic resonance imaging (fMRI) recording. Group, sex and their interaction were compared for UPPS-P ratings and SST fMRI and behavioral responses. AMP+ reported higher UPPS-P positive and negative urgency scores (Ps< 0.001; r = 0.56 and 0.51) and displayed greater bilateral insula and amygdala responses across correct SST trials (Ps < 0.001, g range = 0.57-0.81) than AMP-. fMRI results indicated that AMP+ exhibited larger right anterior/middle insula, amygdala and nucleus accumbens signals during successful difficult stop trials than AMP- (Ps< 0.01; g = 0.63, 0.54 and 0.44, respectively). Crucially, two group × sex effects emerged: (a) within females, AMP+ reported larger UPPS-P lack of premeditation scores than AMP- (P < 0.001, r = 0.51), and (b) within males, AMP+ showed greater left middle insula signals than AMP- across correct SST trials (P = 0.01, g = 0.78). Both female and male amphetamine users appear to be characterized by rash action in the presence of positive and negative mood states as well as heightened recruitment of right hemisphere regions during behavioral inhibition. In contrast, planning ahead may be particularly difficult for female amphetamine users, whereas male amphetamine users may need to recruit additional left hemisphere resources during inhibitory processing.

Energy absorbing multilayered self-recovering metamaterials with chiral topology

A novel energy absorbing material is proposed for the design of shock absorbers and vibrational dampers. A layered architectured microstructure is put forward consisting of the repetition of plane lattices having hexachiral topology with alternate chirality, each being designed as a periodic assembly of rigid disks connected by elastic ligaments. Because of the chiral topology of the single layer, the rotation of the rigid disks takes place when in-plane stress states are applied so implying a relative rotation between the disks of adjacent lattices with opposite chirality. Pins passing through for each stacking of disks impose them the same in-plane displacement. Moreover, frictional dissipative mechanisms at the interface between adjacent disks according to two different compression modes orthogonal to the layers make the metamaterial suitable for either reusing or self-recovering the initial configuration. In the first case the pre-tensioning of the pins implies the compression of plane frictional interfaces. The frictional sliding compatible with the disk relative rotation implies an overall hysteretic bilinear response with remarkable energy dissipation. The metamaterial may be reused once the pins are relaxed and re-tensioned. In the latter case no pre-tension is applied to the pins and the compressive force between the disks is obtained through saw-tooth shaped interfaces between adjacent disks to get elastically constrained transverse dilation when the relative rotations at the interfaces take place. The overall response turns out to be highly dissipative and self-recovering, i.e. able to return to the initial configuration when removing the applied stresses. As shown in the examples the quasi-static behavior of the proposed metamaterial makes it a candidate as an efficient vibration damper and a shock absorber characterized by i) hysteretic response with remarkable energy dissipation under biaxial stress states; ii) reuse or self-recovering after the energy absorption event; iii) bilateral response, i.e. equal behavior under both tension and compression.

Regional Coverage Differences With Single- and Multi-Area Burst Spinal Cord Stimulation for Treatment of Chronic Pain

IntroductionBurst spinal cord stimulation (SCS) has shown superior relief from overall pain and a reduction in back and leg pain compared with traditional tonic neurostimulation therapies. However, nearly 80% of patients have two or more noncontiguous pain areas. This can provide challenges in effectively programming stimulation and long-term therapy efficacy. Multiarea DeRidder Burst programming is a new option to treat multisite pain by delivering stimulation to multiple areas along the spinal cord. This study aimed to identify the effect of intraburst frequency, multiarea stimulation, and location of DeRidder Burst on the evoked electromyography (EMG) responses. Materials and MethodsNeuromonitoring was performed during permanent implant of SCS leads in nine patients diagnosed with chronic intractable back and/or leg pain. Each patient underwent the surgical placement of a Penta Paddle electrode via laminectomy at the T8–T10 spinal levels. Subdermal electrode needles were placed into lower extremity muscle groups, in addition to the rectus abdominis muscles, for EMG recording. Evoked responses were compared across multiple trials of burst stimulation in which the number of independent burst areas were varied. ResultsThe thresholds for EMG recruitment with DeRidder Burst differed across patients owing to anatomic and physiological variations. The average threshold to evoke a bilateral EMG response using single site DeRidder Burst was 3.2 mA. Multisite DeRidder Burst stimulation on up to four stimulation programs evoked a bilateral EMG response at a threshold of 2.5 mA (∼23% lower threshold). DeRidder Burst stimulation across four electrode pairs resulted in more proximal recruitment (vastus medialis and tibialis anterior) than did stimulation across two pairs. It also resulted in more focal coverage of areas across multiple sites. ConclusionsAcross all patients, multisite DeRidder Burst provided broader myotomal coverage than did traditional DeRidder Burst. Multisite DeRidder Burst stimulation provided focal recruitment and differential control of noncontiguous distal myotomes. Energy requirements were also lower when multisite DeRidder Burst was used.

Low-level language processing in brain-injured patients.

Assessing cognitive function-especially language processing-in severely brain-injured patients is critical for prognostication, care, and development of communication devices (e.g. brain-computer interfaces). In patients with diminished motor function, language processing has been probed using EEG measures of command-following in motor imagery tasks. While such tests eliminate the need for motor response, they require sustained attention. However, passive listening tasks, with an EEG response measure can reduce both motor and attentional demands. These considerations motivated the development of two assays of low-level language processing-identification of differential phoneme-class responses and tracking of the natural speech envelope. This cross-sectional study looks at a cohort of 26 severely brain-injured patient subjects and 10 healthy controls. Patients' level of function was assessed via the coma recovery scale-revised at the bedside. Patients were also tested for command-following via EEG and/or MRI assays of motor imagery. For the present investigation, EEG was recorded while presenting a 148 s audio clip of Alice in Wonderland. Time-locked EEG responses to phoneme classes were extracted and compared to determine a differential phoneme-class response. Tracking of the natural speech envelope was assessed from the same recordings by cross-correlating the EEG response with the speech envelope. In healthy controls, the dynamics of the two measures were temporally similar but spatially different: a central parieto-occipital component of differential phoneme-class response was absent in the natural speech envelope response. The differential phoneme-class response was present in all patient subjects, including the six classified as vegetative state/unresponsive wakefulness syndrome by behavioural assessment. However, patient subjects with evidence of language processing either by behavioural assessment or motor imagery tests had an early bilateral response in the first 50 ms that was lacking in patient subjects without any evidence of language processing. The natural speech envelope tracking response was also present in all patient subjects and responses in the first 100 ms distinguished patient subjects with evidence of language processing. Specifically, patient subjects with evidence of language processing had a more global response in the first 100 ms whereas those without evidence of language processing had a frontopolar response in that period. In summary, we developed two passive EEG-based methods to probe low-level language processing in severely brain-injured patients. In our cohort, both assays showed a difference between patient subjects with evidence of command-following and those with no evidence of command-following: a more prominent early bilateral response component.

A rare spinal reflex in brain death: Bilateral plantar flexion in nuchal rigidity examination

A 74-year-old female patient, who developed a hypoxic brain injury after cardiopulmonary arrest, was diagnosed with brain death on the 4th day of the clinical onset depending on the absence of brainstem reflexes and the intracranial blood circulation in magnetic resonance angiography, and positive apnea test. Bilateral plantar flexion response to the neck flexion was observed while lifting the head for the examination of oculocephalic reflex during the in-service nurse training. The plantar flexion response was observed every time the neck flexion was performed. This finding was interpreted primarily in favor of spinal reflex and the repeated brain death tests confirmed the diagnosis. Regarding the literature, spinal reflexes may emerge in patients with brain death and plantar flexion is among the most common reflexes. These reflexes are usually observed following painful stimuli, during the apnea test or when the patient is taken off the mechanical ventilation. Although the nuchal rigidity examination is not included in the routine diagnosis procedure of brain death, in this paper we report bilateral plantar flexion as a response to the neck flexion in a patient with brain death in the light of the studies found in the literature. We conclude that the introduction of the above-mentioned examination to the diagnosis of brain death will contribute to the improvement of the diagnosis procedure and prevent delays in the preparation of the potential donors.

Evolution of synchronous female bilateral breast cancers and response to treatment

Synchronous bilateral breast cancer (sBBC) occurs after both breasts have been affected by the same germline genetics and environmental exposures. Little evidence exists regarding immune infiltration and response to treatment in sBBCs. Here we show that the impact of the subtype of breast cancer on levels of tumor infiltrating lymphocytes (TILs, n = 277) and on pathologic complete response (pCR) rates (n = 140) differed according to the concordant or discordant subtype of breast cancer of the contralateral tumor: luminal breast tumors with a discordant contralateral tumor had higher TIL levels and higher pCR rates than those with a concordant contralateral tumor. Tumor sequencing revealed that left and right tumors (n = 20) were independent regarding somatic mutations, copy number alterations and clonal phylogeny, whereas primary tumor and residual disease were closely related both from the somatic mutation and from the transcriptomic point of view. Our study indicates that tumor-intrinsic characteristics may have a role in the association of tumor immunity and pCR and demonstrates that the characteristics of the contralateral tumor are also associated with immune infiltration and response to treatment.

Visible CCD Camera-Guided Photoacoustic Imaging System for Precise Navigation during Functional Rat Brain Imaging

In photoacoustic (PA) imaging, tissue absorbs specific wavelengths of light. The absorbed energy results in thermal expansion that generates ultrasound waves that are reconstructed into images. Existing commercial PA imaging systems for preclinical brain imaging are limited by imprecise positioning capabilities and inflexible user interfaces. We introduce a new visible charge-coupled device (CCD) camera-guided photoacoustic imaging (ViCPAI) system that integrates an ultrasound (US) transducer and a data acquisition platform with a CCD camera for positioning. The CCD camera accurately positions the US probe at the measurement location. The programmable MATLAB-based platform has an intuitive user interface. In vitro carbon fiber and in vivo animal experiments were performed to investigate the precise positioning and imaging capabilities of the ViCPAI system. We demonstrated real-time capturing of bilateral cerebral hemodynamic changes during (1) forelimb electrical stimulation under normal conditions, (2) forelimb stimulation after right brain focal photothrombotic ischemia (PTI) stroke, and (3) progression of KCl-induced cortical spreading depression (CSD). The ViCPAI system accurately located target areas and achieved reproducible positioning, which is crucial in animal and clinical experiments. In animal experiments, the ViCPAI system was used to investigate bilateral cerebral cortex responses to left forelimb electrical stimulation before and after stroke, showing that the CBV and SO2 in the right primary somatosensory cortex of the forelimb (S1FL) region were significantly changed by left forelimb electrical stimulation before stroke. No CBV or SO2 changes were observed in the bilateral cortex in the S1FL area in response to left forelimb electrical stimulation after stroke. While monitoring CSD progression, the ViCPAI system accurately locates the S1FL area and returns to the same position after the probe moves, demonstrating reproducible positioning and reducing positioning errors. The ViCPAI system utilizes the real-time precise positioning capability of CCD cameras to overcome various challenges in preclinical and clinical studies.

Patterns of hemispheric asymmetry provide evidence dissociating the semantic and syntactic P600

To understand how neural networks in the left (LH) and right (RH) cerebral hemispheres contribute to different aspects of language comprehension, in two experiments we measured event-related potentials (ERPs) as right-handed participants read sentences, some of which contained morphosyntactic and thematic role violations. Replicating prior work (Kuperberg et al., 2006), in Experiment 1 thematic role violations elicited both an N400 and a (semantic) P600 effect. Morphosyntactic violations elicited effects that differed as a function of participants’ familial sinistrality (the presence [FS+] or absence [FS-] of a left-handed biological relative): FS+ participants showed a (syntactic) P600 effect whereas FS- participants showed a biphasic N400 and P600 response. To assess whether this difference reflects different underlying patterns of lateralization, in Experiment 2 target words were presented using visual half-field (VF) presentation. Indeed, for morphosyntactic violations, the FS- group elicited an asymmetric pattern, showing a P600 effect only with LH-biased presentation and an N400 effect in both VFs (cf. Lee and Federmeier, 2015). In contrast, FS+ participants showed a bilateral (N400-only) response pattern. This provides further evidence of FS-based differences in hemispheric contributions to syntactic processing. Strikingly, we found that, when lateralized, thematic role violations did not elicit a P600 effect, suggesting that this effect requires contributions from both hemispheres. The different response patterns for morphosyntactic and thematic role animacy violations across FS and VF also point to a processing difference in the comprehension mechanisms underlying the semantic and syntactic P600, which had heretofore been assumed to be variants of the same component.

Neuronal ceroid lipofuscinosis in a Border Collie: a case report

A 2-year-old spayed female Border Collie presented with visual deficits and behavioral changes. Neurological examination revealed bilateral menace response deficit with a normal pupil light reflex. Cerebral cortical thinning, cerebral sulci and cerebellar fissure widening, ventriculomegaly, and cerebral atrophy were observed on magnetic resonance imaging (MRI). Histopathology revealed fluorescent lipopigment accumulation in the cerebrum, and the dog was diagnosed with neuronal ceroid lipofuscinosis. This is the first case report describing the changes in clinical signs, MRI findings, and histopathologic changes in neuronal ceroid lipofuscinosis in Korea.

Neurochondrin Autoimmunity With Slow Saccades: A Case Report

Objective N/A. Background Neurochondrin is a cytoplasmic neuronal antigen that can be targeted by specific antibodies, resulting in an antigen-specific T-cell response and autoimmune cerebellar and brain stem degeneration.1 Previously reported cases of neurochondrin antibody positivity have been predominantly associated with rapidly-progressive rhombencephalitis, but various other neurological symptoms and signs may be present.1,2 Design/Methods N/A. Results 34-year-old woman presented with 2 years of constant numbness in her toes, gradually worsening to involve the entire lower and upper extremities. She also reported dysarthria, imbalance, and leg spasticity. Neurological examination showed a slow, wide-based gait, brisk reflexes bilaterally, and bilateral extensor plantar responses. MRI brain was normal and CSF analysis showed 7 oligoclonal bands. The patient was diagnosed with probable multiple sclerosis and steroids were initiated but resulted in no improvement of symptoms. Plasmapheresis was also ineffective. 3 months later, MRI showed subtly increased T2 signal of the central cord mainly involving the gray matter at the level of C5 and C6. CSF analysis showed 15 oligoclonal bands and an elevated IgG index of 1.39. VDRL was nonreactive. HTLV, ANCA, AQP4, CSF VZ PCR, HSV PCR, and HHV6 PCR were all negative. EMG showed mild length-dependent axonal sensory motor peripheral neuropathy. On neuro-ophthalmic examination, the patient showed slowed saccades with some preservation of optokinetic nystagmus (OKN) fast phases. Repeat MR showed abnormal T2 hyperintensity in the anterior horns of the gray matter from C1-2 to T1. Serum testing at that time showed a positive neurochondrin antibody. She was then started on cyclophosphamide and mycophenolate mofetil. 6 months after initiation of cyclophosphamide, dysarthria and upper limb mobility improved, and she had no further neurological deterioration at that time. Conclusions Neurochondrin IgG-related autoimmunity is rare and can result in a wide variety of neurological signs and symptoms. Ocular dysmotility, including slowed saccades, may be present.

Challenging neurovascular coupling through complex and variable duration cognitive paradigms: A subcomponent analysis.

A similar pattern of cerebral blood velocity (CBv) response has been observed for neurovascular coupling (NVC) assessment with cognitive tasks of varying complexity and duration. This lack of specificity could result from parallel changes in arterial blood pressure (BP) and PaCO2, which could confound the estimates of NVC integrity. Healthy participants (n=16) underwent recordings at rest (5min sitting) and during randomized paradigms of different complexity (naming words (NW) beginning with P-, R-, V- words and serial subtractions (SS) of 100-2, 100-7, 1000-17, with durations of 5, 30 and 60s). Bilateral CBv (middle cerebral arteries, transcranial Doppler), end-tidal CO2 (EtCO2, capnography), blood pressure (BP, Finapres) and heart rate (HR, ECG) were recorded continuously. The bilateral CBv response to all paradigms was classified under objective criteria to select only responders, then the repeated data were averaged between visits. Bilateral CBv change to tasks was decomposed into the relative contributions (subcomponents) of arterial BP (VBP; neurogenic), critical closing pressure (VCrCP; metabolic) and resistance area product (VRAP; myogenic). A temporal effect was demonstrated in bilateral VBP and VRAP during all tasks (p<0.002), increased VBP early (between 0 and 10s) and followed by decreases of VRAP late (25-35s) in the response. VCrCP varied by complexity and duration (p<0.046). The main contributions to CBv responses to cognitive tasks of different complexity and duration were VBP and VRAP, whilst a smaller contribution from VCrCP would suggest sensitivity to metabolic demands. Further studies are needed to assess the influence of different paradigms, ageing and cerebrovascular conditions.

Emotional modulation of cortical activity during gum chewing: A functional near-infrared spectroscopy study.

Distinct brain regions are known to be associated with various emotional states. Cortical activity may be modulated by emotional states that are triggered by flavors during food intake. We examined cortical activity during chewing with different flavors and assessed the emotional modulation of cortical activity using multichannel near-infrared spectroscopy. Thirty-six right-handed volunteers participated in this crossover trial. The participants experienced positive and negative emotions from chewing flavorful (palatable) or less flavorful (unpalatable) gums, respectively for 5 min. Participants rated the taste, odor, and deliciousness of each gum using a visual analog scale. Bilateral hemodynamic responses in the frontal and parietal lobes, bilateral masseter muscle activation, and heart rate were measured during gum chewing. Changes in all measured data during gum chewing were also evaluated. The ratings of the tastes and odors of each gum significantly differed among the participants (P < 0.001). Hemodynamic response changes were significantly elevated in the bilateral primary sensorimotor cortex during gum-chewing, in comparison to resting. The difference in hemodynamic responses between palatable and unpalatable gum conditions was detected in the left frontopolar/dorsolateral prefrontal cortex. Muscle activation and heart rate were not significantly different between different gum types. Our findings indicate that differential processing in the left prefrontal cortex might be responsible for the emotional states caused by palatable and unpalatable foods.

Cortical Reorganization of Early Somatosensory Processing in Hemiparetic Stroke.

The cortical motor system can be reorganized following a stroke, with increased recruitment of the contralesional hemisphere. However, it is unknown whether a similar hemispheric shift occurs in the somatosensory system to adapt to this motor change, and whether this is related to movement impairments. This proof-of-concept study assessed somatosensory evoked potentials (SEPs), P50 and N100, in hemiparetic stroke participants and age-matched controls using high-density electroencephalograph (EEG) recordings during tactile finger stimulation. The laterality index was calculated to determine the hemispheric dominance of the SEP and re-confirmed with source localization. The study found that latencies of P50 and N100 were significantly delayed in stroke brains when stimulating the paretic hand. The amplitude of P50 in the contralateral (to stimulated hand) hemisphere was negatively correlated with the Fügl-Meyer upper extremity motor score in stroke. Bilateral cortical responses were detected in stroke, while only contralateral cortical responses were shown in controls, resulting in a significant difference in the laterality index. These results suggested that somatosensory reorganization after stroke involves increased recruitment of ipsilateral cortical regions, especially for the N100 SEP component. This reorganization delays the latency of somatosensory processing after a stroke. This research provided new insights related to the somatosensory reorganization after stroke, which could enrich future hypothesis-driven therapeutic rehabilitation strategies from a sensory or sensory-motor perspective.

Changes in Primary Somatosensory Cortex Following Allogeneic Hand Transplantation or Autogenic Hand Replantation.

Former amputees who undergo allogeneic hand transplantation or autogenic hand replantation (jointly, "hand restoration") present a unique opportunity to measure the range of post-deafferentation plastic changes in the nervous system, especially primary somatosensory cortex (S1). However, few such patients exist, and previous studies compared single cases to small groups of typical adults. Here, we studied 5 individuals (n = 8 sessions: a transplant with 2 sessions, a transplant with 3 sessions, and three replants with 1 session each). We used functional magnetic resonance imaging (fMRI) to measure S1 responsiveness to controlled pneumatic tactile stimulation delivered to each patient's left and right fingertips and lower face. These data were compared with responses acquired from typical adults (n = 29) and current unilateral amputees (n = 19). During stimulation of the affected hand, patients' affected S1 (contralateral to affected hand) responded to stimulation in a manner similar both to amputees and to typical adults. The presence of contralateral responses indicated grossly typical S1 function, but responses were universally at the low end of the range of typical variability. Patients' affected S1 showed substantial individual variability in responses to stimulation of the intact hand: while all patients fell within the range of typical adults, some patient sessions (4/8) had substantial ipsilateral responses similar to those exhibited by current amputees. Unlike hand restoration patients, current amputees exhibited substantial S1 reorganization compared to typical adults, including bilateral S1 responses to stimulation of the intact hand. In all three participant groups, we assessed tactile localization by measuring individuals' ability to identify the location of touch on the palm and fingers. Curiously, while transplant patients improved their tactile sensory localization over time, this was uncorrelated with changes in S1 responses to tactile stimuli. Overall, our results provide the first description of cortical responses to well-controlled tactile stimulation after hand restoration. Our case studies indicate that hand restoration patients show S1 function within the range of both typical adults and amputees, but with low-amplitude and individual-specific responses that indicate a wide range of potential cortical neurological changes following de-afferentation and re-afferentation.

Longitudinal Effects of Simultaneous and Sequential Bilateral Cochlear Implantation on Cortical Auditory-Evoked Potentials Recorded at Cz in a Large Cohort of Children.

Auditory development after bilateral cochlear implantation in children has been measured using source localization of multi-channel late latency responses. It is not clear, however, whether this development can be tracked using a more clinically feasible method of recording from one active recording electrode placed at mid-line center of the head (Cz). In this prospective cohort study, cortical auditory-evoked potential responses (CAEPs) were recorded from Cz referenced to each earlobe (Cz-CAEP) from 222 children with bilateral cochlear implant (CI); 128 (mean ± SD age: 2.78 ± 3.30 years) received both CIs in the same surgery (simultaneous group) and 94 (aged 7.72 ± 4.45 years) received a second CI after 4.21 ± 2.98 years of unilateral CI use. We sought to (1) identify cortical development over the first couple of years of bilateral CI use; (2) measure known asymmetries in auditory development between the CIs; and (3) detect the effects of bilateral rather than unilateral CI use. 4556 Cz-CAEPs were recorded across the cohort over 33.50 ± 7.67 months duration of bilateral CI use. Given concerns related to peak picking, amplitude areas were measured across two response time windows (50 to 199 ms and 200 to 400 ms). Results indicated that small response amplitudes occur at initial CI use and amplitudes increase in the negative or positive direction rapidly over the first months of CI use in both time windows. Asymmetries between Cz-CAEPs evoked by each CI were found in the sequential group and reduced with bilateral CI use, particularly in the first time window; these differences increased with longer inter-implant delay. Bilaterally evoked Cz-CAEPs were larger in amplitude than unilateral responses from either CI in the simultaneous group. In the sequential group, bilateral responses were similar to responses from the first implanted side but increased in relative amplitude with bilateral CI use. The Cz-CAEP measures were not able to predict asymmetries or bilateral benefits in speech perception measures. The Cz-CAEP was able to indicate cortical detection of CI input and showed gross morphological changes with bilateral CI use. Findings indicate Cz-CAEPs can be used to identify gross changes in auditory development in children with bilateral CIs, but they are less sensitive to tracking the remaining abnormalities that are measured by multi-channel CAEPs and speech perception testing.

TH-173. The bilateral R1 response of the electrically elicited laryngeal adductor reflex initiates airway closure in patients under general anesthesia

TH-173. The bilateral R1 response of the electrically elicited laryngeal adductor reflex initiates airway closure in patients under general anesthesia

Neurophysiological Correlates in Patients with Syringomyelia and Chiari Malformation: The Cortico-Diaphragmatic Involvement.

Purpose. Brainstem syndromes have frequently been reported in Chiari syndrome and in syringobulbia; previous studies have shown that determining the central motor conduction time (CMCT) along the circuit of the phrenic nerve makes the assessment of the voluntary control of the respiratory pathway possible. In our study, we evaluated the transcranial magnetic stimulation (TMS) of the phrenic nerve in patients affected by Chiari syndrome and/or syringomyelia (Syr) with the aim of identifying subclinical neurophysiological alterations. Methods. One hundred patients (75 females; average age: 51 ± 13.08 SD; range: 18–76) affected by Chiari syndrome and/or Syr without dyspnea were selected. The magnetic stimulation of the second motor neuron correlating with the phrenic nerve was performed using cervical magnetic stimulation (C5-MEP); the cortical MEP after magnetic stimulation (Cz-MEP) was recorded by magnetic stimulation of the motor cortex (areas corresponding to the diaphragm). The CMCT was calculated. The differences between the patients and controls were calculated (Student’s t test). Results. In 13% of the patients, the Cz-MEP were absent bilaterally, and the CMCT was not evaluable. In all these cases, bulbar/cervical Syr was present at MRI; in 10 of them, this was associated with CM1. A bilateral response was obtained in all the other patients (87%), and the CMCTs were normal. All the patients with alterations/absence of Cz-MEP presented bulbar/cervical Syr at MRI. The C5-MEP latency was prolonged or absent in 48%; of these, 84% presented bulbar/cervical Syr associated with CM1 at MRI. The C5-MEP latency values were significantly higher in the group of patients. Conclusions. Neurophysiological alterations of the diaphragmatic pathway were recorded in a group of Chiari syndrome and, particularly, in bulbar/cervical Syr. Future studies with larger cohorts of patients are needed to further assess the specific role of the TMS of the phrenic nerve in CM/Syr patients.

Comparative Use of Contralateral and Sham-Operated Controls Reveals Traces of a Bilateral Genetic Response in the Rat Brain after Focal Stroke.

Ischemic stroke is a multifactorial disease with a complex etiology and global consequences. Model animals are widely used in stroke studies. Various controls, either brain samples from sham-operated (SO) animals or symmetrically located brain samples from the opposite (contralateral) hemisphere (CH), are often used to analyze the processes in the damaged (ipsilateral) hemisphere (IH) after focal stroke. However, previously, it was shown that focal ischemia can lead to metabolic and transcriptomic changes not only in the IH but also in the CH. Here, using a transient middle cerebral artery occlusion (tMCAO) model and genome-wide RNA sequencing, we identified 1941 overlapping differentially expressed genes (DEGs) with a cutoff value >1.5 and Padj < 0.05 that reflected the general transcriptome response of IH subcortical cells at 24 h after tMCAO using both SO and CH controls. Concomitantly, 861 genes were differentially expressed in IH vs. SO, whereas they were not vs. the CH control. Furthermore, they were associated with apoptosis, the cell cycle, and neurotransmitter responses. In turn, we identified 221 DEGs in IH vs. CH, which were non-DEGs vs. the SO control. Moreover, they were predominantly associated with immune-related response. We believe that both sets of non-overlapping genes recorded transcriptome changes in IH cells associated with transhemispheric differences after focal cerebral ischemia. Thus, the specific response of the CH transcriptome should be considered when using it as a control in studies of target brain regions in diseases that induce a global bilateral genetic response, such as stroke.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) masquerading as CNS demyelination

BackgroundCADASIL is the most common single-gene disorder causing ischemic stroke. CADASIL has been linked to mutations in NOTCH3 gene, due to heterozygous missense mutations. The disease is of insidious onset, presenting with initial clinical features in third and fourth decade of life. However, it is now being increasingly acknowledged that individual clinical presentation, age, time of onset as well as disease severity are quite varied among patients with CADASIL most likely leading to under- or mis-diagnosis. The authors thereby report a genetically confirmed case of CADASIL with atypical clinical course and findings.Case presentationA 48-year-old woman presented with complaints of episodic headache, relapsing–remitting neurological illness, progressive cognitive impairment, and acute-onset loss of speech and ambulation. She was earlier being treated as a case of CNS demyelination for 10 years. On examination, vital parameters were within normal limits. Neurological examination revealed that the patient was drowsy, not verbalizing, not obeying commands, with movement of all four limbs on painful stimuli, hypertonia of all limbs, grade 3 + deep tendon reflexes, bilateral striatal toe and extensor plantar response. Magnetic resonance imaging of brain showed involvement of anterior temporal lobe and external capsule along with multiple acute infarcts. Cerebrospinal fluid analysis was found to be normal. Exome sequencing revealed heterozygous missense mutation in exon 2 of NOTCH3 gene. A definite diagnosis of CADASIL was made and patient was started on fluoxetine and aspirin, following which there was significant improvement over 4–6 weeks. Patient is able to carry out daily activities independently although continues to have mild persistent cognitive impairment with excessive talking and over familiarity.ConclusionsAs CADASIL has a relapsing and partially remitting course with frequently observed varied clinical presentation, patients may receive treatment for demyelination which may not be necessary. Hence, detailed family history along with knowledge of characteristic magnetic resonance imaging findings seen in CADASIL can help discern the diagnosis.

Exposed and Sequestered Antigens in Testes and Their Protection by Regulatory T Cell-Dependent Systemic Tolerance.

Continuous exposure of tissue antigen (Ag) to the autoantigen-specific regulatory T cells (Treg) is required to maintain Treg-dependent systemic tolerance. Thus, testis autoantigens, previously considered as sequestered, may not be protected by systemic tolerance. We now document that the complete testis antigen sequestration is not valid. The haploid sperm Ag lactate dehydrogenase 3 (LDH3) is continuously exposed and not sequestered. It enters the residual body (RB) to egress from the seminiferous tubules and interact with circulating antibody (Ab). Some LDH3 also remains inside the sperm cytoplasmic droplets (CD). Treg-depletion in the DEREG mice that express diphtheria toxin receptor on the Foxp3 promoter results in spontaneous experimental autoimmune orchitis (EAO) and Ab to LDH3. Unlike the wild-type male mice, mice deficient in LDH3 (wild-type female or LDH3 NULL males) respond vigorously to LDH3 immunization. However, partial Treg depletion elevated the wild-type male LDH3 responses to the level of normal females. In contrast to LDH3, zonadhesin (ZAN) in the sperm acrosome displays properties of a sequestered Ag. However, when ZAN and other sperm Ag are exposed by vasectomy, they rapidly induce testis Ag-specific tolerance, which is terminated by partial Treg-depletion, leading to bilateral EAO and ZAN Ab response. We conclude that some testis/sperm Ag are normally exposed because of the unique testicular anatomy and physiology. The exposed Ag: 1) maintain normal Treg-dependent systemic tolerance, and 2) are pathogenic and serve as target Ag to initiate EAO. Unexpectedly, the sequestered Ags, normally non-tolerogenic, can orchestrate de novo Treg-dependent, systemic tolerance when exposed in vasectomy.