Evoked potentials after autologous hematopoietic stem cell transplantation for multiple sclerosis.

OBJECTIVE: To investigate the effect of autologous hematopoietic stem cell transplantation (AHSCT) on functional aspects of the nervous system assessed by visual (VEP), somatosensory (SEP), and motor (MEP) evoked potentials in patients with relapsing-remitting multiple sclerosis. BACKGROUND: Several studies have demonstrated the efficacy of AHSCT on inflammatory activity and disability progression in patients with multiple sclerosis. However, the impact of AHSCT on evoked potentials has not been evaluated before. METHODS: Twelve AHSCT-treated patients from Uppsala University Hospital were consecutively recruited. Evoked potentials (EP) were collected at baseline and two follow-up visits, 3 and 12 months post-AHSCT. We calculated a composite EP score for each participant and compared it between different time points. RESULTS: The median total EP score decreased from 5 at baseline, to 2.5 at 12 months post-ASHCT (p = 0.008). A significant improvement in tibial SEP (tSEP) latencies was observed (42.7 vs 41.5 ms, p < 0.001), with a similar trend for MEP latencies 12 months post-ASHCT. No significant changes in median SEP or VEP latencies were observed. CONCLUSIONS: Treatment with AHSCT was associated with improved transmission in some central nervous system pathways in multiple sclerosis patients.

GABAA Receptor Availability in Relation to Cortical Excitability in Depressed and Healthy: A Positron Emission Tomography and Transcranial Magnetic Stimulation Study.

INTRODUCTION: Gamma-aminobutyric acid (GABA) deficiency is suggested in depressive disorders, along with alterations in cortical excitability. However, whether these excitability changes are related to GABAA receptor availability is largely unknown. Our aim was to assess the correlation between these measures in depressed patients and healthy controls. METHODS: Twenty-eight patients with a major depressive episode, measured before and after participating in a clinical trial with repetitive transcranial magnetic stimulation (TMS), and 15 controls underwent [11C]flumazenil positron emission tomography to assess GABAA receptor availability and paired pulse TMS (ppTMS) to evaluate cortical excitability. Both whole-brain voxel-wise GABAA receptor availability and mean values from left hand motor cortex and left paracentral lobule were correlated to the ppTMS outcomes: short-interval intracortical inhibition reflecting GABAA receptor activity, long-interval intracortical inhibition representing GABAB receptor activity, intracortical facilitation reflecting glutamate N-methyl-D-aspartate-receptor activity, as well as the resting motor threshold (rMT), considered a global measure of corticospinal excitability. RESULTS: No significant differences in baseline GABAA receptor availability or cortical excitability were found between patients and controls. Additionally, no correlations were observed between baseline measurements of GABAA receptor availability and TMS outcomes. Changes in GABAA receptor availability in the hand motor cortex, between pre- and post-assessments, were inversely related to pre-post changes in hand rMT. CONCLUSION: We found that a change in GABAA receptor availability was inversely related to a change in rMT, suggesting a link between GABA deficiency and increased rMT previously observed in depressive episodes. The results highlight the complex mechanisms governing cortical excitability measures and offer new insight into their properties during the depressive state.

Continuous subcortical language mapping in awake glioma surgery.

Repetitive monopolar short-train stimulation (STS) delivered from a suction probe enables continuous mapping and distance assessment of corticospinal tracts during asleep glioma resection. In this study, we explored this stimulation technique in awake glioma surgery. Fourteen patients with glioma involving language-related tracts were prospectively included. Continuous (3-Hz) cathodal monopolar STS (five pulses, 250 Hz) was delivered via the tip of a suction probe throughout tumor resection while testing language performance. At 70 subcortical locations, surgery was paused to deliver STS in a steady suction probe position. Monopolar STS influence on language performance at different subcortical locations was separated into three groups. Group 1 represented locations where STS did not produce language disturbance. Groups 2 and 3 represented subcortical locations where STS produced language interference at different threshold intensities (≥7.5 and ≤5 mA, respectively). For validation, bipolar Penfield stimulation (PS; 60 Hz for 3 s) was used as a "gold standard" comparison method to detect close proximity to language-related tracts and classified as positive or negative regarding language interference. There was no language interference from STS in 28 locations (Group 1), and PS was negative for all sites. In Group 2 (STS threshold ≥ 7.5 mA; median, 10 mA), there was language interference at 18 locations, and PS (median, 4 mA) was positive in only one location. In Group 3 (STS threshold ≤ 5 mA; median, 5 mA), there was language interference at 24 locations, and positive PS (median 4 mA) was significantly (p < 0.01) more common (15 out of 24 locations) compared with Groups 1 and 2. Despite the continuous stimulation throughout tumor resection, there were no seizures in any of the patients. In five patients, temporary current spread to the facial nerve was observed. We conclude that continuous subcortical STS is feasibly also in awake glioma surgery and that no language interference from STS or interference at ≥7.5 mA seems to indicate safe distance to language tracts as judged by PS comparisons. STS language interference at STS ≤ 5 mA was not consistently confirmed by PS, which needs to be addressed.

Role of Preoperative Assessment in Predicting Tumor-Induced Plasticity in Patients with Diffuse Gliomas.

When diffuse gliomas (DG) affect the brain's potential to reorganize functional networks, patients can exhibit seizures and/or language/cognitive impairment. The tumor-brain interaction and the individual connectomic organization cannot be predicted preoperatively. We aimed to, first, investigate the relationship between preoperative assessment and intraoperative findings of eloquent tumors in 36 DG operated with awake surgery. Second, we also studied possible mechanisms of tumor-induced brain reorganization in these patients. FLAIR-MRI sequences were used for tumor volume segmentation and the Brain-Grid system (BG) was used as an overlay for infiltration analysis. Neuropsychological (NPS) and/or language assessments were performed in all patients. The distance between eloquent spots and tumor margins was measured. All variables were used for correlation and logistic regression analyses. Eloquent tumors were detected in 75% of the patients with no single variable able to predict this finding. Impaired NPS functions correlated with invasive tumors, crucial location (A4C2S2/A3C2S2-voxels, left opercular-insular/sub-insular region) and higher risk of eloquent tumors. Epilepsy was correlated with larger tumor volumes and infiltrated A4C2S2/A3C2S2 voxels. Language impairment was correlated with infiltrated A3C2S2 voxel. Peritumoral cortical eloquent spots reflected an early compensative mechanism with age as possible influencing factor. Preoperative NPS impairment is linked with high risk of eloquent tumors. A systematic integration of extensive cognitive assessment and advanced neuroimaging can improve our comprehension of the connectomic brain organization at the individual scale and lead to a better oncological/functional balance.

Equalization and Participation for All: Swedish Disability Policy at a Crossroads.

The political line in Swedish disability policy advocates the use of generalized solutions in order to fit potential needs of the largest possible group of people and, where needed, special solutions to bridge the remaining gap between the generalized level of accessibility and additional individual needs. This is referred to as the disability perspective (DP). The DP has embraced two tracks: one that pertains to generalized solutions that promote an overall high level of accessibility and usability, and another one that pertains to different types of individual support for people with disabilities. The present study is a self-reflective inquiry on key issues for the development of future disability policies. Five experts entered a discussion about the pros and cons concerning the DP. This confirmed or refuted assumptions, dilemmas, themes as well as reoccurring patterns in the political viva voce procedure that has formed the contemporary disability policy. Over the course of time, the experts believed that the DP had nurtured a belief that there is a dichotomy. This may have created an imbalance in the relation between the DP and policies such as those concerning healthcare and social care. With a clearer focus on interdependence, the experts saw synergies between needs for assistive technology, assistive products and the requirements for the built environment.

Stochastic anomaly detection in eye-tracking data for quantification of motor symptoms in Parkinson's disease.

Two methods for distinguishing between healthy controls and patients diagnosed with Parkinson's disease by means of recorded smooth pursuit eye movements are presented and evaluated. Both methods are based on the principles of stochastic anomaly detection and make use of orthogonal series approximation for probability distribution estimation. The first method relies on the identification of a Wiener model of the smooth pursuit system and attempts to find statistically significant differences between the estimated parameters in healthy controls and patients with Parkinson's disease. The second method applies the same statistical method to distinguish between the gaze trajectories of healthy and Parkinson subjects tracking visual stimuli. Both methods show promising results, where healthy controls and patients with Parkinson's disease are effectively separated in terms of the considered metric. The results are preliminary because of the small number of participating test subjects, but they are indicative of the potential of the presented methods as diagnosing or staging tools for Parkinson's disease.

Trigeminal nerve stimulation does not acutely affect cortical excitability in healthy subjects.

BACKGROUND: Trigeminal nerve stimulation (TNS) has recently emerged as a new therapeutic option for patients with drug-resistant epilepsy but its potential mechanisms of action are not known. Since other antiepileptic treatments have been shown to alter cortical excitability, thereby reducing the liability to seizures, it has been suggested that cranial nerve stimulation such as TNS may act in the same way. OBJECTIVE: To study whether TNS has the potential to alter cortical excitability in healthy subjects. METHODS: An adaptive paired-pulse transcranial magnetic stimulation protocol stimulating the dominant hand motor area was used to measure resting motor threshold (rMT), short-interval intracortical inhibition (SICI), intracortical facilitation (ICF) and long-interval intracortical inhibition (LICI) before, during, and after 40 min of 120 Hz bilateral external continuous trigeminal nerve stimulation. Neuronavigation was used for guidance. RESULTS: TNS was well tolerated by all subjects. No significant changes were seen in the parameters studied. CONCLUSION: Unlike for example anti-epileptic drugs and the ketogenic diet, trigeminal nerve stimulation does not seem to alter cortical excitability in healthy subjects. This is the first study on cortical excitability in relation to continuous trigeminal nerve stimulation. It still remains to be proven that TNS has the prerequisites to effectively counteract epileptic events in humans.

Physiological and structural anorectal abnormalities in patients with systemic sclerosis and fecal incontinence.

OBJECTIVE: Fecal incontinence is common in systemic sclerosis (SSc), but the underlying mechanisms are not fully understood. The objectives of this study were to characterize anorectal physiological and morphological defects in SSc patients and to correlate the results with incontinence symptoms. MATERIALS AND METHODS: Twenty-five SSc patients underwent anorectal neurophysiological investigations, anal manometry, and ultrasound. RESULTS: Eleven patients (44%) reported incontinence to solid or liquid feces, but no patient reported diarrhea. Increased fiber density (FD) was recorded in 78% of patients with and in 86% of patients without fecal incontinence not significant (NS). Incontinent patients had lower squeeze pressure (SP; median 49.5 mm Hg) in the high-pressure zone (HPZ) than continent patients (median 72 mm Hg; p = 0.01). In two of the incontinent patients, sonographic abnormalities of the internal anal sphincter (IAS) and the external anal sphincter (EAS) were present, whereas in another two patients isolated IAS abnormalities were seen. These four individuals had lower resting pressure at 1 cm and in the HPZ, and lower SP at 2 cm than patients with normal anorectal sonographic findings (p < 0.05). CONCLUSION: Lower voluntary SP in incontinent patients and EAS sonographic abnormalities only in patients with incontinence suggest that the EAS is more important in maintaining fecal continence in SSc patients than has previously been reported. The finding of increased FD in most patients further supports involvement of the EAS function in SSc and could indicate previous nerve injury with consequent incomplete reinnervation.

Hemispheric lateralization of motor thresholds in relation to stuttering.

Stuttering is a complex speech disorder. Previous studies indicate a tendency towards elevated motor threshold for the left hemisphere, as measured using transcranial magnetic stimulation (TMS). This may reflect a monohemispheric motor system impairment. The purpose of the study was to investigate the relative side-to-side difference (asymmetry) and the absolute levels of motor threshold for the hand area, using TMS in adults who stutter (n = 15) and in controls (n = 15). In accordance with the hypothesis, the groups differed significantly regarding the relative side-to-side difference of finger motor threshold (p = 0.0026), with the stuttering group showing higher motor threshold of the left hemisphere in relation to the right. Also the absolute level of the finger motor threshold for the left hemisphere differed between the groups (p = 0.049). The obtained results, together with previous investigations, provide support for the hypothesis that stuttering tends to be related to left hemisphere motor impairment, and possibly to a dysfunctional state of bilateral speech motor control.

Intraoperative cavernous nerve stimulation and Laser-Doppler flowmetry during radical prostatectomy.

INTRODUCTION: Erectile dysfunction is a common side effect following radical prostatectomy mainly due to damage of the pelvic autonomic nerve fibers (cavernous nerves). Intraoperative electrical stimulation of the cavernous nerves while measuring changes in penile girth has previously been shown to provide the surgeon with feedback of nerve integrity. AIM: To test the feasibility of recording changes in glans penis blood flow by Laser Doppler flowmetry from cavernous nerve stimulation. METHODS: Fifteen patients with localized prostate cancer undergoing radical prostatectomy had electrical stimulation of the proximal and distal parts of the neurovascular bundles after prostate removal. The stimulation consisted of 30-40 seconds biphasic constant current (10-30 mA) with 0.5 millisecond pulse duration. MAIN OUTCOME MEASURES: Stimulus induced changes in penile blood flow was recorded from a Laser Doppler probe attached to the glans penis. Changes in penile girth were simultaneously recorded from a mercury-in rubber strain gauge. Erectile function was evaluated three months after surgery. RESULTS: Ten patients had stimulus induced increase in Laser Doppler flow unilaterally (N=7) or bilaterally (N=3). Out of 10 patients, 6 reported some preserved erectile function postoperatively at 3 months follow-up (indicating 6 true and 4 false positives). Three patients had no Doppler response from stimulation and had no postoperative erectile function postoperatively (indicating three true negatives). Two patients were excluded from the study due to bad signal quality in the Laser Doppler signal. In the majority of patients, stimulation produced increase in penile girth sensed by the strain gauge. CONCLUSION: This preliminary report provides evidence that Laser Doppler Flowmetry is able to detect increased penile blood flow from intraoperative electrical stimulation of the neurovascular bundles. However, further improvement in the recording technique is required. Laser Doppler Flowmetry may also be feasible to confirm autonomic nerve sparing in women undergoing pelvic surgery.

Plasticity of the contralateral motor cortex following focal traumatic brain injury in the rat.

PURPOSE: Recovery is limited following traumatic brain injury (TBI) since injured axons regenerate poorly and replacement of lost cells is minimal. Behavioral improvements could instead be due to plasticity of uninjured brain regions. We hypothesized that plasticity of the uninjured hemisphere occurs contralateral to a focal TBI in the adult rat. Thus, we performed cortical mapping of the cortex contralateral to the TBI using intracortical microstimulation (ICMS). METHODS: A focal TBI was induced using the weight-drop technique (n = 5) and sham-injured animals were used as controls (n = 4). At five weeks post-injury, ICMS was used to map the motor area contralateral to the injury. Motor responses were detected by visual inspection and electromyography (EMG). RESULTS: In sham- and brain-injured animals, numerous fore- and hindlimb motor responses contralateral to the stimulation (ipsilateral to the injury) were obtained. Compared to sham-injured controls, there was a markedly increased (p < 0.05) number of fore- and hindlimb responses ipsilateral to the stimulation after TBI. CONCLUSION: Following focal TBI in the rat, our data suggest reorganization of cortical and/or subcortical regions in the uninjured hemisphere contralateral to a focal TBI leading to an altered responsiveness to ICMS. Although we cannot exclude that these changes are maladaptive, it is plausible that this plasticity process positively influences motor recovery after TBI.

Compound motor action potential interexaminer variability in photoguided placement of the recording electrodes.

Interpretation of neurographic data in follow-up studies of patients with neuromuscular disease is sometimes challenging because of the expected variability in repeated tests. In this study, we explored whether the interexaminer variability of the compound motor action potential (CMAP) amplitude is reduced if the examiner is guided by the previously taken photographs of the position of the recording electrodes. The CMAPs were recorded from 20 subjects by unilateral distal stimulation of the median, ulnar, peroneal, and tibial nerve by 4 different technicians. All the subjects were examined on 2 occasions (∼1 week apart). On the first occasion, the technicians recorded the CMAP values according to routine protocols. On the second occasion, the technicians had additional guidance from photographs displaying the recording electrode positions from the first study. The CMAP coefficient of variation (CoV) was calculated for each nerve examined by the four technicians. Differences in CoV between the two types of tests (i.e., with or without photographs) were evaluated. When the examiners were guided by the photographs during electrode application, the CMAP CoV for the tibial innervated abductor hallucis (AH) muscle was reduced (P = 0.02) from 18.5% to 13%. There were, however, no significant reductions in CoV for the abductor pollicis brevis (APB, P = 0.23, median nerve), abductor digiti minimi (P = 0.37, ulnar nerve), or extensor digitorum brevis (EDB, P = 0.15, peroneal nerve) muscles. Photographic documentation of the CMAP recording electrodes seems to have a limited overall effect on interexaminer variability in a subsequent study.

Simplified evaluation of the paradoxical puborectalis contraction with surface electrodes.

PURPOSE: Paradoxical puborectalis contraction during defecation is one possible explanation for constipation. The degree of paradoxical contraction can be evaluated by intramuscular electromyography from the puborectalis and external anal sphincter muscles. This study aimed to determine whether a noninvasive technique with surface electrodes placed over the subcutaneous part of the external anal sphincter is feasible in the evaluation of paradoxical activity. METHODS: Twenty-five patients with constipation were studied. Sphincter muscle activity during strain and squeeze maneuvers was recorded using surface electrodes placed 1 cm from the anal verge. In addition, intramuscular recordings were made simultaneously from the external anal sphincter and puborectalis muscles. The degree of paradoxical activation was calculated as a strain/squeeze index. The patients were examined either in the left lateral position or sitting on a commode. RESULTS: The study revealed significant (P < .01) correlations between indices obtained from the surface anal sphincter recordings and the intramuscular recordings (from the external anal sphincter and the puborectalis muscles). CONCLUSION: Surface recordings from the external anal sphincter seem to be an equally reliable, less time consuming, and less painful alternative to invasive measurements of paradoxical activity. In a few patients, however, invasive recordings may still be required.

Successful localization of the Broca area with short-train pulses instead of 'Penfield' stimulation.

Direct electrical stimulation of functional cortical areas is a standard procedure in epilepsy and glioma surgery. Many previous studies support that stimulation of the motor cortex with short-train pulses is a less epileptogenic alternative to the 50-60Hz 'Penfield' technique. However, whether the short-train stimulation is useful also in mapping of speech areas is unclear. In this case report we present a patient with oligodendroglioma near the Broca area. Extraoperative electrical stimulation via a subdural grid electrode was primarily performed to locate the speech area. The cortex was stimulated with short-train pulses (5 pulses, 0.5 pulse duration and 3ms interpulse interval) in addition to 1-3s 50Hz stimulation. The patient had speech arrest from both types of stimulation techniques during a naming task. It was however critical that the short (14.5ms) train stimulation was synchronized with the presentation of the naming objects. If not, there was no speech arrest. Despite this possible pitfall, this case has encouraged us to further try short-train stimulation in attempts to reduce stimulus-triggered seizures during mapping of eloquent areas.

Successful repeated treatment with high dose cyclophosphamide and autologous blood stem cell transplantation in CIDP.

Chronic inflammatory demyelinating polyneuropathy (CIDP) is characterised by the occurrence of symmetrical weakness and sensory impairment in arms and legs. The course is relapsing or chronic and progressing. CIDP is considered to be an autoimmune disease, which is supported by the beneficial response to immunomodulating therapies in most patients. We report on a patient with CIDP who has been in remission for more than 3 years after treatment with high dose cyclophosphamide and autologous blood stem cell transplantation in CIDP on two occasions.

Microdialysis and electromyography of experimental muscle fatigue in healthy volunteers and patients with mitochondrial myopathy.

Consecutive 60-min microdialysis samples were taken from the tibial anterior muscle in 11 healthy subjects and 4 patients with mitochondrial myopathy before (2-3 samples) and after (3-4 samples, 2 controls and 1 patient excluded) sustained isometric foot dorsiflexions. Before exercise, mean concentrations of lactate, pyruvate, hypoxanthine, urate, aspartate, and glutamate did not significantly differ between controls and patients. After exercise, the controls showed significantly increased concentrations of lactate, pyruvate, and urate, decreased hypoxanthine, and no change in aspartate and glutamate. Similar findings were observed in the patients. Plasma lactate was unchanged. Exercise-induced increase in integrated electromyogram amplitude and rated subjective fatigue were correlated to increased post-exercise lactate concentrations, with no obvious difference between the groups. Microdialysis of skeletal muscle allows the detection and monitoring of biochemical changes in the interstitial space. With the exercise protocol used, however, it was not possible to demonstrate any biochemical difference between healthy controls and patients with mitochondrial myopathy.