Predicting motor outcome in preterm infants from very early brain diffusion MRI using a deep learning convolutional neural network (CNN) model.

BACKGROUND AND AIMS: Preterm birth imposes a high risk for developing neuromotor delay. Earlier prediction of adverse outcome in preterm infants is crucial for referral to earlier intervention. This study aimed to predict abnormal motor outcome at 2 years from early brain diffusion magnetic resonance imaging (MRI) acquired between 29 and 35 weeks postmenstrual age (PMA) using a deep learning convolutional neural network (CNN) model. METHODS: Seventy-seven very preterm infants (born <31 weeks gestational age (GA)) in a prospective longitudinal cohort underwent diffusion MR imaging (3T Siemens Trio; 64 directions, b â€‹= â€‹2000 â€‹s/mm2). Motor outcome at 2 years corrected age (CA) was measured by Neuro-Sensory Motor Developmental Assessment (NSMDA). Scores were dichotomised into normal (functional score: 0, normal; n â€‹= â€‹48) and abnormal scores (functional score: 1-5, mild-profound; n â€‹= â€‹29). MRIs were pre-processed to reduce artefacts, upsampled to 1.25 â€‹mm isotropic resolution and maps of fractional anisotropy (FA) were estimated. Patches extracted from each image were used as inputs to train a CNN, wherein each image patch predicted either normal or abnormal outcome. In a postprocessing step, an image was classified as predicting abnormal outcome if at least 27% (determined by a grid search to maximise the model performance) of its patches predicted abnormal outcome. Otherwise, it was considered as normal. Ten-fold cross-validation was used to estimate performance. Finally, heatmaps of model predictions for patches in abnormal scans were generated to explore the locations associated with abnormal outcome. RESULTS: For the identification of infants with abnormal motor outcome based on the FA data from early MRI, we achieved mean sensitivity 70% (standard deviation SD 19%), mean specificity 74% (SD 39%), mean AUC (area under the receiver operating characteristic curve) 72% (SD 14%), mean F1 score of 68% (SD 13%) and mean accuracy 73% (SD 19%) on an unseen test data set. Patch-based prediction heatmaps showed that the patches around the motor cortex and somatosensory regions were most frequently identified by the model with high precision (74%) as a location associated with abnormal outcome. Part of the cerebellum, and occipital and frontal lobes were also highly associated with abnormal NSMDA/motor outcome. DISCUSSION/CONCLUSION: This study established the potential of an early brain MRI-based deep learning CNN model to identify preterm infants at risk of a later motor impairment and to identify brain regions predictive of adverse outcome. Results suggest that predictions can be made from FA maps of diffusion MRIs well before term equivalent age (TEA) without any prior knowledge of which MRI features to extract and associated feature extraction steps. This method, therefore, is suitable for any case of brain condition/abnormality. Future studies should be conducted on a larger cohort to re-validate the robustness and effectiveness of these models.

Acute Diffusivity Biomarkers for Prediction of Motor and Language Outcome in Mild-to-Severe Stroke Patients.

Background and Purpose- Early severity of stroke symptoms-especially in mild-to-severe stroke patients-are imperfect predictors of long-term motor and aphasia outcome. Motor function and language processing heavily rely on the preservation of important white matter fasciculi in the brain. Axial diffusivity (AD) from the diffusion tensor imaging model has repeatedly shown to accurately reflect acute axonal damage and is thus optimal to probe the integrity of important white matter bundles and their relationship with long-term outcome. Our aim was to investigate the independent prognostic value of the AD of white matter tracts in the motor and language network evaluated at 24 hours poststroke for motor and aphasia outcome at 3 months poststroke. Methods- Seventeen (motor cohort) and 28 (aphasia cohort) thrombolyzed patients with initial mild-to-severe stroke underwent a diffusion tensor imaging sequence at 24 hours poststroke. Motor and language outcome were evaluated at 3 months poststroke with a composite motor score and the aphasia handicap scale. We first used stepwise regression to determine which classic (age, initial motor or aphasia severity, and lesion volume) and imaging (ratio of affected/unaffected AD of motor and language fasciculi) factors were related to outcome. Second, to determine the specificity of our a priori choices of fasciculi, we performed voxel-based analyses to determine if the same, additional, or altogether new regions were associated with long-term outcome. Results- The ratio of AD in the corticospinal tract was the sole predictor of long-term motor outcome, and the ratio of AD in the arcuate fasciculus-along with age and initial aphasia severity-was an independent predictor of 3-month aphasia outcome. White matter regions overlapping with these fasciculi naturally emerged in the corresponding voxel-based analyses. Conclusions- AD of the corticospinal tract and arcuate fasciculus are effective biomarkers of long-term motor and aphasia outcome, respectively.

High prevalence of congenital deafness on Reunion Island is due to a founder variant of LHFPL5.

Reunion Island is a French oversea department in the Indian Ocean with 1.6/1000, an estimated prevalence of deafness that is almost double as compared to the mainland France. Twelve children having isolated bilateral prelingual profound deafness along with motor delay attributed to vestibular areflexia were enrolled. Their mean walking age was 19 months. Electroretinography and temporal bone CT-scans were normal in all cases. A novel homozygous frameshift lipoma HMGIC fusion partner-like 5 (LHFPL5) variant c.185delT p.(Phe62Serfs*23) was identified using whole-exome sequencing. It was found in seven families. Four patients from two different families from both Reunion Island and mainland France, were compound heterozygous: c.185delT p.(Phe62Serfs*23) and c.472C > T p.(Arg158Trp). The phenotype observed in our patients completely mimics the hurry-scurry (hscy) murine Tmhs knock-out model. The recurrent occurrence of same LHFPL5 variant in Reunion Island is attributed to common ancestor couple born in 1693.

Antiphospholipid Antibodies: Cognitive and Motor Decline, Neuroimaging and Neuropathology.

BACKGROUND: Few data are available on associations of antiphospholipid (aPL) antibodies with cognitive and motor decline in aging, and cerebrovascular disease on in vivo neuroimaging and postmortem neuropathology. METHODS: This longitudinal, clinical-pathologic study (aPL antibodies, brain infarcts, and cognitive and motor decline in aging), was derived from 2 ongoing community-based cohort studies. A panel of 3 aPL antibodies was assayed in serum from 956 older individuals (mean age = 81.1 years; 72% women). Serum was also tested in a subset for markers of inflammation (C-reactive protein [CRP]) and blood-brain barrier breakdown (matrix metalloproteinases, MMPs). Annual clinical evaluations documented cognitive (17 neuropsychological tests) and motor function including parkinsonism. Cerebrovascular disease data were derived from in vivo neuroimaging and postmortem neuropathologic evaluations (699 individuals). We examined associations of aPL with cognitive and motor decline, other serum markers, neuroimaging, and neuropathology. RESULTS: Of 956 individuals, 197 (20.6%) had aPL positivity, defined as positivity on any of the assays, at the time of first measurement. During a mean follow-up of 6.6 years (SD 4), overall aPL positivity was not associated with change in global cognition (estimate = -0.005, SE 0.011; p = 0.622) or parkinsonian signs (estimate = -0.003, SE 0.017; p = 0.860). aPL were not associated with serum CRP or MMPs (both p > 0.268). aPL were not associated with in vivo brain magnetic resonance imaging white matter hyperintensities or infarcts (both p > 0.376). Among those autopsied, aPL were not associated with pathologically confirmed brain infarcts, or cerebral atherosclerosis or arteriolosclerosis (all p≥ 0.447). CONCLUSIONS: In older individuals followed longitudinally, aPL do not relate to cognitive or motor decline, inflammation, or cerebrovascular disease on in vivo neuroimaging or postmortem neuropathology.

Motor and language deficits correlate with resting state functional magnetic resonance imaging networks in patients with brain tumors.

BACKGROUND AND PURPOSE: Evidence of pre-operative resting state functional magnetic resonance (RS-fMRI) validation by correlating it with clinical pre-operative status in brain tumor patients is scarce. Our aim was to validate the functional relevance of RS-fMRI by investigating the association between RS-fMRI and pre-operative motor and language function performance in patients with brain tumor. MATERIALS AND METHODS: Sixty-nine patients with brain tumors were prospectively recruited. Patients with tumors near precentral gyrus (n = 49) underwent assessment for apparent (paresis) and subtle (finger tapping) deficits. Patients with left frontal tumors in the vicinity of the inferior frontal gyrus (n = 29) underwent assessment for gross (aphasia) and mild language (phonological verbal fluency) deficits. RS-fMRI results were extracted by spatial independent component analysis (ICA). RESULTS: Motor group: paretic patients showed significantly (P = 0.01) decreased BOLD signal in ipsilesional precentral gyrus when compared to contralesional one. Significantly (P < 0.01) lower BOLD signal was also observed in ipsilesional precentral gyrus of paretics when compared with the non-paretics. In asymptomatic patients, a strong positive correlation (r = 0.68, P < 0.01) between ipsilesional motor cortex BOLD signal and contralesional finger tapping performance was observed. Language group: patients with aphasia showed significantly (P = 0.01) decreased RS-fMRI BOLD signal in left BA 44 when compared with non- aphasics. In asymptomatic patients, a strong positive correlation (r = 0.72, P < 0.01) between BA 44 BOLD signal and phonological fluency performance was observed. CONCLUSIONS: Our results showed that RS-fMRI BOLD signal of motor and language networks were significantly affected by the tumors implying the usefulness of the method for assessment of the underlying functions in brain tumors patients.

Structural cerebellar correlates of cognitive and motor dysfunctions in cerebellar degeneration.

See King et al. (doi:10.1093/aww348) for a scientific commentary on this article.Detailed mapping of clinical dysfunctions to the cerebellar lobules in disease populations is necessary to establish the functional significance of lobules implicated in cognitive and motor functions in normal subjects. This study constitutes the first quantitative examination of the lobular correlates of a broad range of cognitive and motor phenomena in cerebellar disease. We analysed cross-sectional data from 72 cases with cerebellar disease and 36 controls without cerebellar disease. Cerebellar lobule volumes were derived from a graph-cut based segmentation algorithm. Sparse partial least squares, a variable selection approach, was used to identify lobules associated with motor function, language, executive function, memory, verbal learning, perceptual organization and visuomotor coordination. Motor dysfunctions were chiefly associated with the anterior lobe and posterior lobule HVI. Confrontation naming, noun fluency, recognition, and perceptual organization did not have cerebellar associations. Verb and phonemic fluency, working memory, cognitive flexibility, immediate and delayed recall, verbal learning, and visuomotor coordination were variably associated with HVI, Crus I, Crus II, HVII B and/or HIX. Immediate and delayed recall also showed associations with the anterior lobe. These findings provide preliminary anatomical evidence for a functional topography of the cerebellum first defined in task-based functional magnetic resonance imaging studies of normal subjects and support the hypotheses that (i) cerebellar efferents target frontal lobe neurons involved in forming action representations and new search strategies; (ii) there is greater involvement of the cerebellum when immediate recall tasks involve more complex verbal stimuli (e.g. longer words versus digits); and (iii) it is involved in spontaneous retrieval of long-term memory. More generally, they provide an anatomical background for studies that seek the mechanisms by which cognitive and motor dysfunctions arise from cerebellar degeneration. Beyond replicating these findings, future research should employ experimental tasks to probe the integrity of specific functions in cerebellar disease, and new imaging methods to quantitatively map atrophy across the cerebellum.

Supplementary motor area syndrome after surgery for parasagittal meningiomas.

BACKGROUND: Resection within the supplementary motor area (SMA) may be accompanied by dramatic motor deficits and speech arrest when the dominant hemisphere is involved, termed the SMA syndrome. Typically, the muscle tone of the paralyzed extremities is preserved, and in most cases, a complete or near complete recovery is seen within a few months. The SMA syndrome has not been recognized for extra-axial tumor surgery in approximation of the SMA. METHODS: We observed the SMA syndrome in a patient operated for a parasagittal meningioma in the posterior frontal region, and this observation intrigued us to prospectively collect similar cases. RESULTS: In the period from January 2010 to December 2015, we observed five patients who developed a partial SMA syndrome after surgery for frontal parasagittal meningiomas. The muscle tone was preserved in the affected extremities. All patients experienced improvement in motor function within a few days, and on follow-up, three out of five patients had recovered completely. Three of the patients had meningioma WHO grade II. CONCLUSIONS: Surgically induced SMA syndrome can easily be confused with pyramidal weakness. This series of cases demonstrate that the syndrome may also develop after removal of extra-axial tumors and is probably underdiagnosed and underreported. The good functional prognosis is helpful in the preoperative counseling and follow-up of these patients.

[Spinal dural arteriovenous fistulas. A series of clinical cases and an analysis of the literature data]. / Dural'nye spinal'nye arteriovenoznye fistuly. Seriia sobstvennykh klinicheskikh nabliudenii i analiz dannykh literatury.

Spinal dural arteriovenous fistulas (SDAVFs) are the most common vascular malformation of the spinal cord, causing segmental lesions of the spinal cord due to venous ischemia. Functional outcomes of treatment in SDAVF patients are favorable, but the rate of improvement varies from 25 to 100%, which complicates prediction of the treatment outcome. AIM: the study aim was to identify a relationship between fistula localization and clinical manifestations and evaluate the effect of disease duration and severity of neurological impairments on immediate and long-term treatment outcomes, based on analysis of the literature and own data. MATERIAL AND METHODS: In September 2016, we performed a PubMed search for publications using keywords 'spinal arteriovenous fistula', 'treatment', and 'outcome'. We selected publications containing information on the patient's age, fistula location, disease duration, and evaluation of symptom severity (Aminoff-Logue scale) preoperatively, postoperatively, and at least 3 months after surgery. The analysis also included data on patients operated on at the clinic. A total of 187 patients were included in the analysis. RESULTS: The fistula was most often located at the T6, T7, and T9 level, with motor disorders being more severe for fistulas located at or below the T9 vertebra. Surgical isolation of the fistula improved the functional state of patients, with patients under the age of 60 years having a better prognosis for recovery of impaired functions. Motor disorders significantly regressed in the early postoperative period in all patients, but in the long-term period, there was worsening of motor disorders in patients with a better baseline functional state.

[Surgical treatment of eloquent brain area tumors using neurophysiological mapping of the speech and motor areas and conduction tracts]. / Khirurgicheskoe lechenie opukholei funktsional'no znachimykh zon golovnogo mozga s primeneniem metoda neirofiziologicheskogo kartirovaniya rechevykh, motornykh zon i provodyashchikh putei.

AIM: To evaluate the efficacy of intraoperative neurophysiological mapping in removing eloquent brain area tumors (EBATs). MATERIAL AND METHODS: Sixty five EBAT patients underwent surgical treatment using intraoperative neurophysiological mapping at the Pirogov National Medical and Surgical Center in the period from 2014 to 2015. On primary neurological examination, 46 (71%) patients were detected with motor deficits of varying severity. Speech disorders were diagnosed in 17 (26%) patients. Sixteen patients with concomitant or isolated lesions of the speech centers underwent awake surgery using the asleep-awake-asleep protocol. Standard neurophysiological monitoring included transcranial stimulation as well as motor and, if necessary, speech mapping. The motor and speech areas were mapped with allowance for the preoperative planning data (obtained with a navigation station) synchronized with functional MRI. In this case, a broader representation of the motor and speech centers was revealed in 12 (19%) patients. During speech mapping, no speech disorders were detected in 7 patients; in 9 patients, stimulation of the cerebral cortex in the intended surgical area induced motor (3 patients), sensory (4), and amnesic (2) aphasia. In the total group, we identified 11 patients in whom the tumor was located near the internal capsule. Upon mapping of the conduction tracts in the internal capsule area, the stimulus strength during tumor resection was gradually decreased from 10 mA to 5 mA. Tumor resection was stopped when responses retained at a stimulus strength of 5 mA, which, when compared to the navigation data, corresponded to a distance of about 5 mm to the internal capsule. Completeness of tumor resection was evaluated (contrast-enhanced MRI) in all patients on the first postoperative day. RESULTS: According to the control MRI data, the tumor was resected totally in 60% of patients, subtotally in 24% of patients, and partially in 16% of patients. In the early postoperative period, the development or aggravation of a motor neurological deficit was detected in 18 patients: worsening of paresis was observed in 11 patients, and worsening of speech disorders occurred in 7 patients. After 4 months, motor and speech disorders regressed in 10 patients. Therefore, a persistent neurological deficit developed after surgery in 8 (12%) patients (motor deficit in 5 cases; speech deficit in 3 cases). CONCLUSION: Resection of eloquent brain area tumors using intraoperative neurophysiological monitoring enables complete resection of the tumor at a low risk of persistent neurological deficits, which ultimately improves the patient's life prognosis.

Brain disorders associated with corticotropin-releasing hormone expression in the placenta among children born before the 28th week of gestation.

AIM: To evaluate the relationship between placenta corticotropin-releasing hormone (CRH) expression and brain structure and function abnormalities in extremely preterm newborns. METHODS: In a sample of 1243 infants born before the 28th week of gestation, we evaluated the relationship between CRH expression in the placenta and the risk of brain ultrasound scan abnormalities identified while these infants were in the intensive care nursery, low scores on the Bayley Scales of Infant Development-II of 900 of these children at age two years and head circumference measurements then more than one and two standard deviations below the mean. RESULTS: Infants who had a low placenta CRH messenger ribonucleic acid (mRNA) concentration were at increased risk of ventriculomegaly on an ultrasound scan. An elevated placenta CRH mRNA concentration was associated with increased risk of an inability to walk at age two years, and a Bayley Motor Scale 3 standard deviations below the mean. CONCLUSION: Placenta CRH mRNA concentration appears to convey information about the risk of brain damage in the infant born at an extremely low gestational age.

Diagnosis of cognitive and motor disorders levels in stroke patients through explainable machine learning based on MRI.

BACKGROUND: Globally, stroke is the third most significant cause of disability. A stroke may produce motor, sensory, perceptual, or cognitive disorders that result in disability and affect the likelihood of recovery, affecting a person's ability to function. Evaluation post-stroke is critical for optimal stroke care. PURPOSE: Traditional methods for classifying the clinical disorders of cognitive and motor in stroke patients use assessment and interrogative measures, which are time-consuming, complex, and labor-intensive. In response to the current situation, this study develops an algorithm to automatically classify motor and cognitive disorders in stroke patients by 3D brain MRI to assist physicians in diagnosis. METHODS: First, radiomics and fusion features are extracted from the OAx T2 Propeller of 3D brain MRI. Then, we use 14 machine learning models and one model ensemble method to predict Fugl-Meyer and MMSE levels of stroke patients. Next, we evaluate the models using accuracy, recall, f1-score, and area under the curve (AUC). Finally, we employ SHAP to explain the output of the model. RESULTS: The best predictive models come from Random Forest (RF) Classifier with fusion features in cognitive classification and Linear Discriminant Analysis (LDA) with radiomics features in motor classification. The highest accuracies are 92.0 and 82.5% for cognitive and motor disorders. CONCLUSIONS: MRI brain maps can classify the cognitive and motor disorders of stroke patients. Radiomics features demonstrate its merits. The proposed algorithms with MRI images can efficiently assist physicians in diagnosing the cognitive and motor disorders of stroke patients in clinical practice. Additionally, this lessens labor costs, improves diagnostic effectiveness, and avoids the subjective difference that comes with manual assessment.

Using Neonatal Magnetic Resonance Imaging to Predict Gross Motor Disability at Four Years in Term-Born Children With Neonatal Encephalopathy.

BACKGROUND: Children with neonatal encephalopathy (NE) are at risk for basal ganglia/thalamus (BG/T) and watershed patterns of brain injury. Children with BG/T injury are at high risk for motor impairment in infancy, but the predictive validity of a published rating scale for outcome at age four years is not known. We examined a cohort of children with NE and magnetic resonance imaging (MRI) to examine the relationship between BG/T injury and severity of cerebral palsy (CP) in childhood. METHODS: Term-born neonates at risk for brain injury due to NE were enrolled from 1993 to 2014 and received MRI within two weeks of birth. Brain injury was scored by a pediatric neuroradiologist. The Gross Motor Function Classification System (GMFCS) level was determined at four years. The relationship between BG/T injury and dichotomized GMFCS (no CP or GMFCS I to II = none/mild versus III to V = moderate/severe CP) was evaluated with logistic regression, and predictive performance was assessed by cross-validated area under the receiver operating characteristic curve (AUROC). RESULTS: Among 174 children, higher BG/T scores were associated with more severe GMFCS level. Clinical predictors had a low AUROC (0.599), compared with that of MRI (0.895). Risk of moderate to severe CP was low (<20%) in all patterns of brain injury except BG/T = 4, which carried a 67% probability (95% confidence interval 36% to 98%) of moderate to severe CP. CONCLUSIONS: The BG/T injury score can be used to predict the risk and severity of CP at age four years and thereby inform early developmental interventions.

Acute Imaging Findings Predict Recovery of Cognitive and Motor Function after Inpatient Rehabilitation for Pediatric Traumatic Brain Injury: A Pediatric Brain Injury Consortium Study.

Traumatic brain injury (TBI) is a major cause of morbidity and mortality in children; survivors experience long-term cognitive and motor deficits. To date, studies predicting outcome following pediatric TBI have primarily focused on acute behavioral responses and proxy measures of injury severity; unsurprisingly, these measures explain very little of the variance following heterogenous injury. In adults, certain acute imaging biomarkers help predict cognitive and motor recovery following moderate to severe TBI. This multi-center, retrospective study, characterizes the day-of-injury computed tomographic (CT) reports of pediatric, adolescent, and young adult patients (2 months to 21 years old) who received inpatient rehabilitation services for TBI (n = 247). The study also determines the prognostic utility of CT findings for cognitive and motor outcomes assessed by the Pediatric Functional Independence Measure, converted to age-appropriate developmental functional quotient (DFQ), at discharge from rehabilitation. Subdural hematomas (66%), contusions (63%), and subarachnoid hemorrhages (59%) were the most common lesions; the majority of subjects had less severe Rotterdam CT scores (88%, ≤ 3). After controlling for age, gender, mechanism of injury, length of acute hospital stay, and admission DFQ in multivariate regression analyses, the highest Rotterdam score (ß = -25.2, p < 0.01) and complete cisternal effacement (ß = -19.4, p < 0.05) were associated with lower motor DFQ, and intraventricular hemorrhage was associated with lower motor (ß = -3.7, p < 0.05) and cognitive DFQ (ß = -4.9, p < 0.05). These results suggest that direct detection of intracranial injury provides valuable information to aid in prediction of recovery after pediatric TBI, and needs to be accounted for in future studies of prognosis and intervention.

Mobile Brain/Body Imaging of cognitive-motor impairment in multiple sclerosis: Deriving EEG-based neuro-markers during a dual-task walking study.

OBJECTIVE: Individuals with a diagnosis of multiple sclerosis (MS) often present with cognitive and motor deficits, and thus the ability to perform tasks that rely on both domains may be particularly impaired. Yet, dual-task walking studies yield mixed results. Individual variance in the ability to cope with brain insult and mobilize additional brain resources may contribute to mixed findings. METHODS: To test this hypothesis, we acquired event-related potentials (ERP) in individuals with MS and healthy controls (HCs) performing a Go/NoGo task while sitting (i.e., single task) or walking (i.e., dual-task) and looked at the relationship between task related modulation of the brain response and performance. RESULTS: On the Go/NoGo task the MS group showed dual-task costs when walking, whereas HCs showed a dual-task benefit. Further, whereas the HC group showed modulation of the brain response as a function of task load, this was not the case in the MS group. Analysis for the pooled sample revealed a positive correlation between load-related ERP effects and dual-task performance. CONCLUSIONS: These data suggest a neurophysiological marker of cognitive-motor dysfunction in MS. SIGNIFICANCE: Understanding neural processes underlying dual-task walking will help identify objective brain measurements of real-world issues and may improve assessment of MS.

Motor impairments in transient ischemic attack increase the odds of a positive diffusion-weighted imaging: A meta-analysis.

BACKGROUND: Unilateral motor impairment is a key symptom used in the diagnosis of transient ischemic attack (TIA). Diffusion-weighted imaging (DWI) is a promising diagnostic tool for detecting ischemic lesions. While both motor impairments and DWI abnormalities are linked to the diagnosis of TIA, the association between these prognostic factors is not well understood. OBJECTIVE: To examine the association between unilateral motor impairments and the odds of a positive DWI in TIA. Further, to determine whether the time between symptom onset and neuroimaging (delay to scan) influences the odds of a positive DWI. METHODS: We used PRISMA guidelines to conduct a systematic search from 1989 to 2018. We included studies that reported number of individuals with/without unilateral motor symptoms and a positive/negative DWI. RESULTS: Twenty-four studies from North America, Australia, Asia, and Europe were submitted to a meta-analysis. A pooled odds ratio of 1.80 (95% CI, 1.45-2.24, p = 0.00; I2 = 57.38) suggested that the odds of a positive DWI are greater in TIA individuals who experience motor symptoms as compared with those who experience no motor symptoms. Further, increasing the time delay to scan from the symptom onset (>2 days) did not influence the odds of a positive DWI as compared with an earlier scan (≤2 days). CONCLUSIONS: The current meta-analysis provides cumulative evidence from 6710 individuals with TIA that the presence of motor symptoms increases the odds of a positive DWI by two-folds. These findings transform the clinical perception into evidence-based knowledge that motor impairments elevate the risk for brain tissue damage. Unilateral motor impairments in a cerebrovascular event should increase a physician's suspicion of detecting brain infarctions. These findings may influence the clinical management of TIA by generating faster response to motor impairments in TIA and accelerating referral to specialized stroke clinic.

Associations between neuroanatomical abnormality and motor symptoms in paroxysmal kinesigenic dyskinesia.

INTRODUCTION: The pathophysiologic mechanism of paroxysmal kinesigenic dyskinesia (PKD) is largely unclear. Basal ganglia-thalamo-cortical circuit involvement is thought to underlie PKD pathophysiology. However, microstructural alternations in the motor circuit of PKD require further elucidation. METHODS: Diffusion tensor imaging and high-resolution T1-weighted imaging were performed on 30 PKD patients (15 PRRT2 carriers, 15 PRRT2 non-carriers) and 15 matched healthy controls. Tract-based spatial statistics were conducted on diffusion indices to examine microstructural integrity of white matter. Voxel-based morphometry analysis was used to examine volumetric changes of gray matter. Multiple regression was employed to test the contribution of demography, disease duration, and PRRT2 status to pathological changes in brain structure. RESULTS: Six (including two novel) PRRT2 mutations were identified in PKD patients who exhibited significantly reduced mean diffusivity mainly along the left corticospinal tract, and reduced gray matter volume in pre-supplementary motor area (preSMA) and right opercular part of inferior frontal gyrus (IFGoperc), compared to healthy controls. Both gray matter volume reductions in preSMA and diffusion indices of abnormal white matter negatively correlated with disease duration. Genotype-phenotype analysis revealed that PRRT2 mutation carriers had earlier onset age, longer attacks, and a larger proportion of bilateral symptoms than non-carriers. CONCLUSIONS: We observed that PRRT2 mutations were associated with disease severity, while neuroanatomical abnormality was associated with disease duration in patients with PKD. Aberrant microstructural changes in preSMA and IFG areas, independent of mutation status, point to dysregulated motor inhibition in patients and provide new insights into neurobiological mechanisms underlying motor symptoms of PKD.

Predictive value of electroencephalography connectivity measures for motor training outcome in multiple sclerosis: an observational longitudinal study.

BACKGROUND: Neurophysiological investigations represent powerful tools to shed light on brain plasticity in multiple sclerosis (MS) patients. AIM: We investigated the relationship between electroencephalography (EEG)-based connectivity, the extent of brain lesions and changes in motor performance after an intensive task-oriented circuit training (TOCT). DESIGN: Observational longitudinal study. SETTING: Outpatients training program. POPULATION: Sixteen MS patients (10F; mean age =51.4 years; range: 27-67; mean disease duration =15.1 years; range: 2-26; mean Expanded Disability Status Scale 4.4; range: 3.5-5.5), were included in our study. METHODS: MS patients with mild gait impairment were evaluated through functional scales and submitted to TOCT. Resting-state EEG was performed before (T0) and after (T1) rehabilitation. Alpha-band weighted Phase Lag Index (wPLI) and broadband weighted Symbolic Mutual Information (wSMI) connectivity analyses were performed. White matter lesion load was measured using MRI prior to the TOCT. Neurophysiological and structural parameters were then related to behavioral changes. RESULTS: Dynamic Gait Index significantly improved after TOCT (F(1,14) =13.10, P=0.003). Moreover, the interaction between TOCT and age was observed for changes in Timed Up and Go (TUG) performance (F(1,14) = 7.75, P=0.015), indicating that older patients only benefited in this measure. Regarding the relationship between EEG connectivity and TOCT outcome, we observed positive correlations between changes in TUG and strength (P=0.017) and efficiency (Pone-tail =0.029) of alpha-band wPLI connectivity at T0. Such correlation was mainly driven by antero-posterior regional interactions (P=0.038), rather than by inter-hemispheric connectivity (P=0.089). Moreover, we observed a positive correlation between performance improvements and wSMI connectivity at T1 (P=0.001) as well as the difference between T0 and T1 (P=0.005). Lesion load percentage was not related to functional improvement after TOCT (Pone-tail=0.137). CONCLUSIONS: Results of the current study demonstrated that baseline alpha-band wPLI connectivity predicts TOCT outcome in MS patients. Moreover, broadband wSMI tracks neural changes that accompany treatment-related variations in motor performance. CLINICAL REHABILITATION IMPACT: Our findings suggest that EEG-based connectivity measures may represent a potential tool for customizing rehabilitative management of the disease.

Altered activation and functional asymmetry of exner's area but not the visual word form area in a child with sudden-onset, persistent mirror writing.

Mirror writing is often produced by healthy children during early acquisition of literacy, and has been observed in adults following neurological disorders or insults. The neural mechanisms responsible for involuntary mirror writing remain debated, but in healthy children, it is typically attributed to the delayed development of a process of overcoming mirror invariance while learning to read and write. We present an unusual case of sudden-onset, persistent mirror writing in a previously typical seven-year-old girl. Using her dominant right hand only, she copied and spontaneously produced all letters, words and sentences, as well as some numbers and objects, in mirror image. Additionally, she frequently misidentified letter orientations in perceptual assessments. Clinical, neuropsychological, and functional neuroimaging studies were carried out over sixteen months. Neurologic and ophthalmologic examinations and a standard clinical MRI scan of the head were normal. Neuropsychological testing revealed average scores on most tests of intellectual function, language function, verbal learning and memory. Visual perception and visual reasoning were average, with the exception of below average form constancy, and mild difficulties on some visual memory tests. Activation and functional connectivity of the reading and writing network was assessed with fMRI. During a reading task, the VWFA showed a strong response to words in mirror but not in normal letter orientation - similar to what has been observed in typically developing children previously - but activation was atypically reduced in right primary visual cortex and Exner's Area. Resting-state connectivity within the reading and writing network was similar to that of age-matched controls, but hemispheric asymmetry between the balance of motor-to-visual input was found for Exner's Area. In summary, this unusual case suggests that a disruption to visual-motor integration rather than to the VWFA can contribute to sudden-onset, persistent mirror writing in the absence of clinically detectable neurological insult.

Identifying motor functional neurological disorder using resting-state functional connectivity.

BACKGROUND: Motor functional neurological disorder (mFND) is a clinical diagnosis with reliable features; however, patients are reluctant to accept the diagnosis and physicians themselves bear doubts on potential misdiagnoses. The identification of a positive biomarker could help limiting unnecessary costs of multiple referrals and investigations, thus promoting early diagnosis and allowing early engagement in appropriate therapy. OBJECTIVES: To test whether resting-state (RS) functional magnetic resonance imaging could discriminate patients suffering from mFND from healthy controls. METHODS: We classified 23 mFND patients and 25 age- and gender-matched healthy controls based on whole-brain RS functional connectivity (FC) data, using a support vector machine classifier and the standard Automated Anatomic Labeling (AAL) atlas, as well as two additional atlases for validation. RESULTS: Accuracy, specificity and sensitivity were over 68% (p = 0.004) to discriminate between mFND patients and controls, with consistent findings between the three tested atlases. The most discriminative connections comprised the right caudate, amygdala, prefrontal and sensorimotor regions. Post-hoc seed connectivity analyses showed that these regions were hyperconnected in patients compared to controls. CONCLUSIONS: The good accuracy to discriminate patients from controls suggests that RS FC could be used as a biomarker with high diagnostic value in future clinical practice to identify mFND patients at the individual level.