[DIAGNOSIS AND TREATMENT OF A GIRL SUFFERING FROM DRUG RESISTANT EPILEPSY WITH AN INNOVATIVE MINIMALLY INVASIVE APPROACH].

INTRODUCTION: About one percent (over 81,000 patients) of the Israeli population suffer from epilepsy. The main treatment for this condition is medication, but about a third of the patients suffer from drug-resistant epilepsy (DRE). Each year about 5,000 new patients are diagnosed with epilepsy, of whom 3,000 are children. For these patients, an evaluation in designated centers is required in order to diagnose possible foci and propose neurosurgical treatment alternatives. BACKGROUND: A model for diagnosis and treatment of the epileptic network in a minimally invasive approach is presented through the description of a case study. Phase I: includes diagnosis of the semiology, neuropsychological assessment, video EEG recording and performing a PET-MRI-FMRI-EEG synchronized examination. Phase II: involves stereo-electroencephalography (SEEG) minimally invasive diagnosis to target the epileptic area and accurately map adjacent functional areas and assessment of cortical redundancy. Phase III: includes radiofrequency ablation of the foci without any further surgery. This procedure is performed under clinical monitoring (the patient is awake during treatment) and continuous EEG monitoring. CONCLUSIONS: This case study demonstrates the multi-dimensional model performed by a multidisciplinary team, combining innovative technologies. This model is essential for the precision of the diagnosis and treatment methods of focal epilepsy and allows preservation of function based, among other factors, on the identification of cortical redundancy. DISCUSSION: The preoperative assessment identified focal epilepsy adjacent to the motor area dominating the right hand. A combined PET-FMRI-MRI-EEG examination enabled detecting redundancy of motor functions beyond the epileptic focus. Based on this information, a targeted implantation of depth electrodes (SEEG) was performed, the epileptic foci were identified and targeted ablations were performed during clinical monitoring and continuous EEG. This resulted in the cessation of seizures in parallel with the disappearance of the pathological signal in the EEG, all while preserving the patient's hand function.

Cortical Reorganization following Injury Early in Life.

The brain has a remarkable capacity for reorganization following injury, especially during the first years of life. Knowledge of structural reorganization and its consequences following perinatal injury is sparse. Here we studied changes in brain tissue volume, morphology, perfusion, and integrity in children with hemiplegia compared to typically developing children, using MRI. Children with hemiplegia demonstrated reduced total cerebral volume, with increased cerebrospinal fluid (CSF) and reduced total white matter volumes, with no differences in total gray matter volume, compared to typically developing children. An increase in cortical thickness at the hemisphere contralateral to the lesion (CLH) was detected in motor and language areas, which may reflect compensation for the gray matter loss in the lesion area or retention of ipsilateral pathways. In addition, reduced cortical thickness, perfusion, and surface area were detected in limbic areas. Increased CSF volume and precentral cortical thickness and reduced white matter volume were correlated with worse motor performance. Brain reorganization of the gray matter within the CLH, while not necessarily indicating better outcome, is suggested as a response to neuronal deficits following injury early in life.

Brain Plasticity following Intensive Bimanual Therapy in Children with Hemiparesis: Preliminary Evidence.

Neuroplasticity studies examining children with hemiparesis (CH) have focused predominantly on unilateral interventions. CH also have bimanual coordination impairments with bimanual interventions showing benefits. We explored neuroplasticity following hand-arm bimanual intensive therapy (HABIT) of 60 hours in twelve CH (6 females, mean age 11 ± 3.6 y). Serial behavioral evaluations and MR imaging including diffusion tensor (DTI) and functional (fMRI) imaging were performed before, immediately after, and at 6-week follow-up. Manual skills were assessed repeatedly with the Assisting Hand Assessment, Children's Hand Experience Questionnaire, and Jebsen-Taylor Test of Hand Function. Beta values, indicating the level of activation, and lateralization index (LI), indicating the pattern of brain activation, were computed from fMRI. White matter integrity of major fibers was assessed using DTI. 11/12 children showed improvement after intervention in at least one measure, with 8/12 improving on two or more tests. Changes were retained in 6/8 children at follow-up. Beta activation in the affected hemisphere increased at follow-up, and LI increased both after intervention and at follow-up. Correlations between LI and motor function emerged after intervention. Increased white matter integrity was detected in the corpus callosum and corticospinal tract after intervention in about half of the participants. Results provide first evidence for neuroplasticity changes following bimanual intervention in CH.

Diffuse excessive high signal intensity in low-risk preterm infants at term-equivalent age does not predict outcome at 1 year: a prospective study.

INTRODUCTION: The outcome of premature infants with only diffuse excessive high signal intensity (DEHSI) is not clear. We explored the relationship between DEHSI, white matter (WM) diffusion characteristics, perinatal characteristics, and neurobehavioral outcome at 1 year in a homogenous group of preterm infants without major brain abnormalities. METHODS: Fifty-eight preterm infants, gestational age 29 ± 2.6 weeks, underwent an MRI at term-equivalent age (TEA). Griffiths Mental Developmental Scales, neurological assessment, and Parental Stress Index (PSI) were performed at 1 year corrected age. These measures were compared between preterm infants according to DEHSI classification (none, mild, moderate). Diffusion tensor imaging was used in major WM volumes of interest to objectively measure the degree of WM maturation. RESULTS: No significant differences were detected in the perinatal risk characteristics, neurobehavioral outcome, and PSI at 1 year between infants with different DEHSI classifications. In infants with DEHSI, increased axial and radial diffusivities were detected in the optic radiations, centrum semiovale, and posterior limb of the internal capsule, indicating less advanced maturation of the WM. Significant correlations were detected between the time interval from birth to MRI and the WM microstructure in infants without DEHSI. CONCLUSION: DEHSI in premature infants is neither a predictive measure for short-term adverse neurobehavioral outcome nor related to perinatal risk characteristics. Extrauterine exposure time had a differential effect on WM maturational trajectories in infants with DEHSI compared to those without. We suggest DEHSI may represent an alteration in WM maturational characteristics. Further follow-up studies may verify later consequences of DEHSI in premature infants.

One-Year Consistent Safety, Utilization, and Efficacy Assessment of Remote Electrical Neuromodulation (REN) for Migraine Treatment.

INTRODUCTION: Migraine is a chronic neurological disorder causing severe pain and disability in more than a billion people worldwide. Ideal treatment should provide long-term efficacy with minimal side effects. Previous studies indicate that remote electrical neuromodulation (REN) is an efficacious and safe treatment option for the acute treatment of migraine in clinical practice. This study examined long-term safety, utilization, and efficacy of REN during 12 consecutive usage months. METHODS: Data from patients with migraine across the USA using REN to treat their migraine attacks were electronically collected from the Nerivio® device. All patients who used REN during 12 consecutive months were included, and data were compared across months. Safety was assessed by the number and type of adverse events. Utilization was measured by the number of monthly treatments. Efficacy was evaluated as consistent change in headache pain intensity, functional disability, and disappearance of associated symptoms from baseline to 2 h post treatment. RESULTS: Data were analyzed from 409 people living with migraine who treated with REN for 12 consecutive months, performing a total of 39,531 treatments. The incidence of device-related adverse events (dAEs) was 1.96% (8/409), including two negligible (0.49%), five mild (1.22%), one moderate (0.24%), and no severe events. All patients continued treatment with REN despite dAEs. One-year average monthly utilization was 8.05 treatments (SD 1.15). Month-to-month utilization did not change during 12 months of consecutive use [F(4.895, 1997.204) = 2.014, p = 0.075, repeated-measures ANOVA]. One-year average efficacy showed 74.1% of users reported consistent 2-h pain relief, and 26.0% reported consistent pain freedom. Month-to-month pain relief and pain freedom did not change during 12 months of consecutive use [F(11, 1069) = 0.55, p = 0.873 and F(11, 1295) = 0.69, p = 0.750 respectively; generalized linear mixed model analysis]. CONCLUSION: REN is a safe and well-tolerated acute migraine treatment, with stable efficacy and utilization over 1 year, making it an advantageous non-drug option for the long-term management of this chronic disease. TRIAL REGISTRATION NUMBER: NCT05760638.

Migraine is a chronic disease leading to decades of significant disability, thus requiring safe, effective, and tolerable treatment for years. Remote electrical neuromodulation (REN) is a smartphone-controlled wearable device (Nerivio^®) indicated for the acute and/or preventive treatment of migraine in patients 12 years of age or older. It is a prescribed, self-administered device for use at the onset of migraine headache or aura for acute treatment, or every-other-day for preventive treatment. Treatments are automatically registered in the REN app and database, and users can prospectively report subjective migraine indicators and response to the treatment in the REN app, at treatment onset and again 2 h later. This study analyzed data from people who used REN for the acute treatment of their migraine attacks at least once per month, for at least 12 consecutive months. Data from 409 patients who met the study criteria and performed a total of 39,531 treatments was analyzed. Safety was measured by the incidence of device-related adverse events, which was 1.96%. Severe device-related adverse events were not reported, and all patients continued treating after the events. Efficacy over the year showed that 74.1% of the patients reported consistent pain relief, and 26.0% reported consistent pain freedom. Average monthly utilization over the year was 8.05 treatments. Month-to-month pain relief, pain freedom, and utilization did not differ between 12 months of consecutive use. These results show that REN is a safe and well-tolerated treatment, with stable efficacy and utilization over at least 1 year, making it an advantageous non-drug option for the long-term management of migraine.

Multi-metric predictors of radiofrequency-treated trigeminal neuralgias.

Evaluation of neurovascular compression-related trigeminal neuralgia (NVC-TN) and its resolution through microvascular decompression are demonstrable by MRI and intraoperatively [Leal et al. (Atrophic changes in the trigeminal nerves of patients with trigeminal neuralgia due to neurovascular compression and their association with the severity of compression and clinical outcomes: Clinical article. J Neurosurg. 2014;120(6):1484-1495)]. Non-NVC-TNs treated by radiofrequency (RF) lack such detectable features. Multimodal integration of pre-surgical diffusion tensor imaging (DTI) and volumetry (VOL) with intraoperative neurophysiology (ION) could improve understanding and performance of RF among non-NVC-TN. We hypothesized that DTI disturbances' localization (central relay versus peripherally) rather than their values bares the most significant predictive value upon outcome and that ION could quantitatively both localize and assist RF of affected branches. The first pre-surgical step evaluated the differences between affected and non-affected sides (by DTI and VOL). Four TN's segments were studied, from peripheral to central relay: Meckel's cave-trigeminal ganglion (MC-TGN), cisternal portion, root entry zone (REZ) and spinal tract [Lin et al. (Flatness of the Meckel cave may cause primary trigeminal neuralgia: A radiomics-based study. J Headache Pain. 2021;22(1):104)]. In the second intraoperative step, we used both ION and patient's testimonies to confirm the localization of the affected branch, evolving hypoesthesia, pain reduction and monitoring of adverse effects [Sindou (Neurophysiological navigation in the trigeminal nerve: Use of masticatory responses and facial motor responses evoked by electrical stimulation of the trigeminal rootlets for RF-thermorhizotomy guidance. Stereotact Funct Neurosurg. 1999;73(1-4):117-121); Sindou and Tatli (Traitement de la névralgie trigéminale par thermorhizotomie. Neurochirurgie. 2009;55(2):203-210)]. Last and postoperatively, each data set's features and correlation with short-term (3 months) and long-term outcomes (23.5 ± 6.7 months) were independently analysed and blind to each other. Finally, we designed a multimodal predictive model. Sixteen non-NVC-TN patients (mean 53.6 ± SD years old) with mean duration of 6.56 ± 4.1 years (75% right TN; 43.8% V3) were included. After 23.5 ± 6.7 months, 14/16 were good responders. Age, gender, TN duration and side/branch did not correlate with outcomes. Affected sides showed significant DTI disturbances in both peripheral (MC-TGNs) and central-relay (REZ) segments. However, worse outcome correlated only with REZ-located DTI disturbances (P = 0.04; r = 0.53). Concerning volumetry, affected MC-TGNs were abnormally flatter: lower volumes and surface area correlated with worse outcomes (both P = 0.033; r = 0.55 and 0.77, respectively). Intraoperatively, ION could not differ the affected from non-affected branch. However, the magnitude of ION's amplitude reduction (ION-Δ-Amplitude) had the most significant correlation with outcomes (r = 0.86; P < 0.00006). It was higher among responders [68.4% (50-82%)], and a <40% reduction characterized non-responders [36.7% (0-40%)]. Multiple regression showed that ION-Δ-Amplitude, centrally located only REZ DTI integrity and MC-TGN flatness explain 82.2% of the variance of post-RF visual analogue score. Integration of pre-surgical DTI-VOL with ION-Δ-Amplitude suggests a multi-metric predictive model of post-RF outcome in non-NVC-TN. In multiple regression, central-relay REZ DTI disturbances and insufficiently reduced excitability (<40%) predicted worse outcome. Quantitative fine-tuned ION tools should be sought for peri-operative evaluation of the affected branches.

A multi-site study of functional outcomes following a themed approach to hand-arm bimanual intensive therapy for children with hemiplegia.

AIM: This study investigated the effects of a theme-based ('magic') variation of the hand-arm bimanual intensive therapy programme, in two different countries, in improving activity performance for children with hemiplegia, including those with severe movement restrictions. METHOD: Twenty-three children with spastic hemiplegia (13 males, 10 females; mean age 10y 7mo, range 7-15y; Manual Ability Classification System level I, two; level II, 13; level III, eight), participated in one of three, 2-week, summer camps. A within-participant experimental design was used with the Assisting Hand Assessment and Children's Hand Experience Questionnaire as primary outcome measures. Evaluations occurred immediately before the first day, on the last day, and 3 months after intervention. Two groups underwent additional assessments 2 weeks before the camp. RESULTS: Significant intervention effects were seen on the Assisting Hand Assessment (p=0.002) and on the Children's Hand Experience Questionnaire (p<0.001), the latter maintained at follow-up. The affected hand was reported to be used in 25% of bimanual activities before the camp, progressing to 93% after camp, and decreasing to 86% at follow-up. Severity of impairment did not influence progress. INTERPRETATION: This themed approach to intensive intervention showed positive results in bimanual use, with improvements in independence sustained at follow-up. Although children across camps and motor severity made progress, some questions remain about intensity and duration of intervention to optimize longer-term outcomes.

SEEG-RF for revealing and treating Geschwind syndrome's epileptic network: A case study.

Stereotypic neural networks are repeatedly activated in drug-refractory epilepsies (DRE), reinforcing the expression of certain psycho-affective traits. Geschwind syndrome (GS) can serve as a model for such phenomena among patients with temporal lobe DRE. We describe stereo-electroencephalogram (SEEG) exploration in a 34-year-old male with DRE and GS, and his treatment by SEEG-radiofrequency (SEEG-RF) ablation. We hypothesized that this approach could reveal the underlying epileptic network and map eloquent faculties adjacent to SEEG-RF targets, which can be further used to disintegrate the epileptic network. The patient underwent a multi-modal pre-surgical evaluation consisting of video EEG (VEEG), EEG source localization, 18-fluorodexyglucose-PET/MRI, neuropsychological and psychiatric assessments. Pre-surgical multi-modal analyses suggested a T4-centered seizure onset zone. SEEG further localized the SOZ within the right amygdalo-hippocampal region and temporal neocortex, with the right parieto-temporal region as the propagation zone. SEEG-RF ablation under awake conditions and continuous EEG monitoring confirmed the abolishment of epileptic activity. Follow-up at 20 months showed seizure suppression (Engel 1A/ILEA 1) and a significantly improved and stable psycho-affective state. To the best of our knowledge this is the first description of the intracranial biomarkers of GS and its further treatment through SEEG-RF ablation within the scope of DRE.

FIRDA, refractory epilepsy, and SEEG-guided RF: A case report.

OBJECTIVES: We will demonstrate that FIRDA (frontal intermittent rhythmic delta activity)-otherwise related to systemic disorders and encephalopathy-has a role as an epileptic biomarker of deep-seated midline SOZ. Its abolishment following SEEG-guided radiofrequency of such SOZ correlates with clinical improvement suggesting its role as a noninvasive biomarker of otherwise inaccessible SOZs. METHODS: We report the case of AK who was admitted with "psychiatric and gastrointestinal complaints." AK's complaints were further associated with FIRDA during VEEG. His previous refractoriness to AEDs, the clinico-electroencephalographic correlation, MRI showing bilateral hippocampal atrophy (more to the left) and severe memory deficits, prompted us to suggest a left temporo-mesial SOZ, for which SEEG was done. Dual SEEG and scalp electrodes were used primarily for diagnostic purposes but taking into account an option for a therapeutic action by RF ablation. RESULTS: The dual array demonstrated a clear association between left hippocampal high voltage spikes and HFOs on SEEG recordings with FIRDA on concomitant scalp EEG parallel to behavioral changes, as suspected in our preliminary hypothesis. A further RF ablation eliminated the epileptiform activity (Spikes, HFOs, and FIRDA) followed by clinical improvement. SIGNIFICANCE: This is the first report showing the clinical significance of FIRDA associated with behavioral changes as a marker for latent refractory mesial epilepsy. SEEG exploration has the potential to uncover deep sources, which are manifested as FIRDA on scalp EEG. These abnormalities and clinical symptoms can be eliminated by RF ablation.

Abnormal white matter integrity in young children with autism.

This study investigated white matter integrity in young children with autism using diffusion tensor imaging (DTI). Twenty-two children with autism, mean age 3:2 years, and 32 controls, mean age 3:4 years, participated in the study. Tract-based spatial statistics (TBSS) revealed white matter abnormalities in several distinct clusters within the genu and body of the corpus callosum (CC), left superior longitudinal fasciculus (SLF) and right and left cingulum (Cg). TBSS-VOIs analysis was performed in the clusters where differences in fractional anisotropy (FA) were detected to investigate the relationship between changes in FA and diffusivity indices. In all VOIs, increase in FA was caused by a decrease in radial diffusivity (Dr), while no changes in axial diffusivity (Da) or mean diffusivity (MD) were observed. Tractography analysis was applied to further study the CC, SLF, and Cg. Witelson parcellation scheme was used for the CC. Significant increase in FA was seen in children with autism in the mid-body of the CC as well as in the left Cg. It is suggested that such abnormal white matter integrity in young children with autism may adversely affect connectivity between different brain regions and may be linked to some of the behavioral impairments apparent in autism.

Understanding the relationship between brain and upper limb function in children with unilateral motor impairments: A multimodal approach.

Atypical brain development and early brain injury have profound and long lasting impact on the development, skill acquisition, and subsequent independence of a child. Heterogeneity is present at the brain level and at the motor level; particularly with respect to phenomena of bilateral activation and mirrored movements (MMs). In this multiple case study we consider the feasibility of using several modalities to explore the relationship between brain structure and/or activity and hand function: Electroencephalography (EEG), both structural and functional Magnetic Resonance Imaging (sMRI, fMRI), diffusion tensor imaging (DTI), transcranial magnetic stimulation (TMS), Electromyography (EMG) and hand function assessments. METHODS: 15 children with unilateral CP (ages: 9.4 ± 2.5 years) undertook hand function assessments and at least two additional neuroimaging and/or neurophysiological procedures: MRI/DTI/fMRI (n = 13), TMS (n = 11), and/or EEG/EMG (n = 8). During the fMRI scans and EEG measurements, a motor task was performed to study cortical motor control activity during simple hand movements. DTI tractography analysis was used to study the corpus-callosum (CC) and cortico-spinal tracts (CST). TMS was used to study cortico-spinal connectivity pattern. RESULTS: Type and range of severity of brain injury was evident across all levels of manual ability with the highest radiological scores corresponded to children poorer manual ability. Evidence of MMs was found in 7 children, mostly detected when moving the affected hand, and not necessarily corresponding to bilateral brain activation. When moving the affected hand, bilateral brain activation was seen in 6/11 children while 3/11 demonstrated unilateral activation in the contralateral hemisphere, and one child demonstrated motor activation predominantly in the supplementary motor area (SMA). TMS revealed three types of connectivity patterns from the cortex to the affected hand: a contralateral (n = 3), an ipsilateral (n = 4) and a mixed (n = 1) connectivity pattern; again without clear association with MMs. No differences were found between children with and without MMs in lesion scores, motor fMRI laterality indices, CST diffusivity values, and upper limb function. In the genu, midbody, and splenium of the CC, higher fractional anisotropy values were found in children with MMs compared to children without MMs. The EEG data indicated a stronger mu-restoration above the contralateral hemisphere in 6/8 children and above the ipsilateral hemisphere in 2/8 children. CONCLUSION: The current results demonstrate benefits from the use of different modalities when studying upper-limb function in children with CP; not least to accommodate to the variations in tolerance and feasibility of implementation of the differing methods. These exposed multiple individual brain-reorganization patterns corresponding to different functional motor abilities. Additional research is warranted to understand the transactional influences of early brain injury, neuroplasticity and developmental and environmental factors on hand function in order to develop targeted interventions.

The motor and visual networks in preterm infants: An fMRI and DTI study.

Knowledge regarding the association between functional connectivity and white-matter (WM) maturation of motor and visual networks in preterm infants at term equivalent age (TEA) and their association with behavioral outcome is currently limited. Thirty-two preterm infants born <34 weeks gestational-age without major brain abnormalities were included in this study, underwent resting-state fMRI at TEA. Thirteen infants also underwent diffusion tensor imaging (DTI). Neurobehavioral assessments were performed at one and two years corrected age using the Griffiths Mental Developmental Scales. Functional connectivity between homolog motor and visual regions were detected, which may reflect that a level of organization in these domains is present already at TEA. DTI parameters of WM tracts at TEA demonstrated spatial-temporal variability, with the splenium of the corpus-callosum (CC) found to be the most mature fiber bundle. Correlations between DTI parameters, functional connectivity and behavioral outcome were detected, yet did not show the same pattern of diffusivity changes in the different networks. Visual functional connectivity was negatively correlated with radial-diffusivity (RD) in the optic radiation, while motor functional connectivity was positively correlated with RD in the splenium. In addition, axial-diffusivity (AD) and RD in the genu and midbody of the CC were positively correlated with neurobehavioral outcome at one and 2 years of age. This study highlights the importance of understanding the spatial-temporal changes occurring during this sensitive period of development and the potential effect of extrauterine exposure on the microstructural changes as measured by DTI; their correlation with functional connectivity; and their long term relationship with neuro-behavioral development.

Imaging Predictors of Improvement From a Motor Learning-Based Intervention for Children With Unilateral Cerebral Palsy.

Background Motor-learning interventions may improve hand function in children with unilateral cerebral palsy (UCP) but with inconsistent outcomes across participants. Objective To examine if pre-intervention brain imaging predicts benefit from bimanual intervention. Method Twenty children with UCP with Manual Ability Classification System levels I to III, aged 7-16 years, participated in an intensive bimanual intervention. Assessments included the Assisting Hand Assessment (AHA), Jebsen Taylor Test of Hand Function (JTTHF) and Children's Hand Experience Questionnaire (CHEQ) at baseline (T1), completion (T2) and 8-10 weeks post-intervention (T3). Imaging at baseline included conventional structural (radiological score), functional (fMRI) and diffusion tensor imaging (DTI). Results Improvements were seen across assessments; AHA (P = 0.04), JTTHF (P < .001) and CHEQ (P < 0.001). Radiological score significantly correlated with improvement at T2; AHA (r = .475) and CHEQ (r = .632), but negatively with improvement on unimanual measures at T3 (JTTFH r = -.514). fMRI showed negative correlations between contralesional brain activation when moving the affected hand and AHA improvements (T2: r = -.562, T3: r = -0.479). Fractional Anisotropy in the affected posterior limb of the internal capsule correlated negatively with increased bimanual use on CHEQ at T2 (r = -547) and AHA at T3 (r = -.656). Conclusions Children with greater structural, functional and connective brain damage showed enhanced responses to bimanual intervention. Baseline imaging may identify parameters predicting response to intervention in children with UCP.

Neonatal neuropsychology: emerging relations of neonatal sensory-motor responses to white matter integrity.

The neonatal period is considered to be essential for neurodevelopment and wellbeing throughout the life span, yet little is known about brain-behavior relationships in the neonatal period. The aim of this study was to evaluate the association between neonatal sensory-motor regulation and white-matter (WM) integrity of major fiber tracts in the neonatal period. We hypothesized that WM integrity of sensory-motor systems would predict neurobehavioral maturation during the first month of life. Forty-nine premature neonates underwent magnetic-resonance-imaging at term. Diffusion-tensor-imaging analysis was performed in major WM tracts along with repeated neonatal neurobehavioral evaluations assessing sensory reactivity and motor regulation. Difficulties in one or more behavioral sub-category, mostly in auditory and visual attention, hypotonicity and jitteriness, were documented in 78.3% infants at term. Sixty-six percent of infants experienced difficulties, mostly in auditory attention, head-neck control, hypotonicity and motor asymmetry, at 44 weeks. Attention difficulties were associated with reduced integrity of cerebral and superior cerebellar peduncles; while tonicity was associated with reduced integrity of the corpus-callosum and inferior-posterior tracts. Overall, results showed that early maturing tracts were related with the degree of typicality of sensory reactivity status while late maturing tracts were related with the degree of typicality of tonic regulation. WM integrity and maturation factors explained 40.2% of the variance in neurobehavior at 44 weeks. This study suggests that in preterm neonates, deviant sensory-motor reactivity can be detected very early in development in manners that are related to lower integrity/maturational level of early and late maturing fiber tracts.

Interhemispheric and intrahemispheric connectivity and manual skills in children with unilateral cerebral palsy.

This study investigated patterns of motor brain activation, white matter (WM) integrity of inter- and intrahemispheric connectivity and their associations with hand function in children with unilateral cerebral palsy (CP-U). Fourteen CP-U (mean age 10.6 ± 2.7 years) and 14 typically developing children (TDC) underwent magnetic resonance imaging. CP-U underwent extensive motor evaluation. Pattern of brain activation during a motor task was studied in 12 CP-U and six TDC, by calculating laterality index (LI) and percent activation in the sensorimotor areas (around the central sulcus), and quantifying the activation in the supplementary motor area (SMA). Diffusivity parameters were measured in CP-U and eight other TDC for the corpus callosum (CC), affected and less affected cortico-spinal tracts (CST), and posterior limb of the internal capsule (PLIC). Abnormal patterns of brain activation were detected in areas around the central sulcus in 9/12 CP-U, with bilateral activation and/or reduced percent activation. More activation in areas around the central sulcus of the affected hemisphere was associated with better hand function. CP-U demonstrated more activation in the SMA when moving the affected hand compared to the less affected hand. CP-U displayed reduced WM integrity compared to TDC, in the midbody and splenium of the CC, affected CST and affected PLIC. WM integrity in these tracts was correlated with hand function. While abnormal pattern of brain activation was detected mainly when moving the affected hand, the integrity of the CC was correlated with function of both hands and bimanual skills. This study highlights the importance of interhemispheric connectivity for hand function in CP-U, which may have clinical implications regarding prognosis and management.

Brain diffusivity in infants with hypoxic-ischemic encephalopathy following whole body hypothermia: preliminary results.

Hypoxic-ischemic encephalopathy is an important cause of neuropsychological deficits. Little is known about brain diffusivity in these infants following cooling and its potential in predicting outcome. Diffusion tensor imaging was applied to 3 groups: (1) three infants with hypoxic-ischemic encephalopathy: cooled; (2) three infants with hypoxic-ischemic encephalopathy: noncooled; and (3) four controls. Diffusivity values at the corticospinal tract, thalamus, and putamen were correlated with Apgar scores and early neurodevelopmental outcome. While cooled infants exhibited lower Apgar scores than noncooled infants, their developmental scores at a mean age of 8 months were higher. All groups differed in their diffusivity values with the cooled infants showing better values compared with the noncooled, correlating with early neurodevelopmental outcome. These preliminary results indicate that diffusion tensor imaging performed at an early age in infants with hypoxic-ischemic encephalopathy may forecast clinical outcome and support the neuroprotective effect of hypothermia treatment.

Intraoperative mapping and monitoring of the corticospinal tracts with neurophysiological assessment and 3-dimensional ultrasonography-based navigation. Clinical article.

OBJECT: Preserving motor function is a major challenge in surgery for intraaxial brain tumors. Navigation systems are unreliable in predicting the location of the corticospinal tracts (CSTs) because of brain shift and the inability of current intraoperative systems to produce reliable diffusion tensor imaging data. The authors describe their experience with elaborate neurophysiological assessment and tractography-based navigation, corrected in real time by 3D intraoperative ultrasonography (IOUS) to identify motor pathways during subcortical tumor resection. METHODS: A retrospective analysis was conducted in 55 patients undergoing resection of tumors located within or in proximity to the CSTs at the authors' institution between November 2007 and June 2009. Corticospinal tract tractography was coregistered to surgical navigation-derived images in 42 patients. Direct cortical-stimulated motor evoked potentials (dcMEPs) and subcortical-stimulated MEPs (scrtMEPs) were recorded intraoperatively to assess function and estimate the distance from the CSTs. Intraoperative ultrasonography updated the navigation imaging and estimated resection proximity to the CSTs. Preoperative clinical motor function was compared with postoperative outcome at several time points and correlated with incidences of intraoperative dcMEP alarm and low scrtMEP values. RESULTS: The threshold level needed to elicit scrtMEPs was plotted against the distance to the CSTs based on diffusion tensor imaging tractography after brain shift compensation with 3D IOUS, generating a trend line that demonstrated a linear order between these variables, and a relationship of 0.97 mA for every 1 mm of brain tissue distance from the CSTs. Clinically, 39 (71%) of 55 patients had no postoperative deficits, and 9 of the remaining 16 improved to baseline function within 1 month. Seven patients had varying degrees of permanent motor deficits. Subcortical stimulation was applied in 45 of the procedures. The status of 32 patients did not deteriorate postoperatively (stable or improved motor status): 27 of them (84%) displayed minimum scrtMEP thresholds > 7 mA. Six patients who experienced postoperative deterioration quickly recovered (within 5 days) and displayed minimum scrtMEP thresholds > 6.8 mA. Five of the 7 patients who had late (> 5 days postoperatively) or no recovery had minimal scrtMEP thresholds < 3 mA. An scrtMEP threshold of 3 mA was found to be the cutoff point below which irreversible disruption of CST integrity may be anticipated (sensitivity 83%, specificity 95%). CONCLUSIONS: Combining elaborate neurophysiological assessment, tractography-based neuronavigation, and updated IOUS images provided accurate localization of the CSTs and enabled the safe resection of tumors approximating these tracts. This is the first attempt to evaluate the distance from the CSTs using the threshold of subcortical monopolar stimulation with real-time IOUS for the correction of brain shift. The linear correlation between the distance to the CSTs and the threshold of subcortical stimulation producing a motor response provides an intraoperative technique to better preserve motor function.