The long-term negative impact of childhood stroke on language.

Objectives: This study aims to investigate the long-term language outcome in children with unilateral childhood stroke in comparison to those with perinatal strokes and typically developing individuals and to explore the impact of lesion-specific modifiers. Methods: We examined nine patients with childhood stroke, acquired between 0;2 and 16;1 years (CHILD; 3 female, median = 13.5 years, 6 left-sided), 23 patients with perinatal strokes (PERI; 11 female, median = 12.5 years, 16 left-sided), and 33 age-matched typically developing individuals (CONTROL; 15 female, median = 12.33 years). The language outcome was assessed using age-appropriate tasks of the Potsdam Illinois Test of Psycholinguistic Abilities (P-ITPA) or the Peabody Picture Vocabulary Test (PPVT). For group comparisons, study-specific language z-scores were calculated. Non-verbal intelligence was assessed using the Test of Non-verbal Intelligence (TONI-4), language lateralization with functional MRI, and lesion size with MRI-based volumetry. Results: All four patients with childhood stroke who initially presented with aphasic symptoms recovered from aphasia. Patients with childhood stroke showed significantly lower language scores than those in the control group, but their scores were similar to those of the patients with perinatal stroke, after adjusting for general intelligence (ANCOVA, language z-score CHILD = -0.30, PERI = -0.38, CONTROL = 0.42). Among the patients with childhood stroke, none of the possible modifying factors, including lesion side, correlated significantly with the language outcome. Conclusion: Childhood stroke, regardless of the affected hemisphere, can lead to chronic language deficits, even though affected children show a "full recovery." The rehabilitation of children and adolescents with childhood stroke should address language abilities, even after the usually quick resolution of clear aphasic symptoms.

Atypical language organization following perinatal infarctions of the left hemisphere is associated with structural changes in right-hemispheric grey matter.

AIM: To assess how atypical language organization after early left-hemispheric brain lesions affects grey matter in the contralesional hemisphere. METHOD: This was a cross-sectional study with between-group comparisons of 14 patients (six female, 8-26 years) with perinatal left-hemispheric brain lesions (two arterial ischemic strokes, 11 periventricular haemorrhagic infarctions, one without classification) and 14 typically developing age-matched controls (TDC) with functional magnetic resonance imaging (fMRI) documented left-hemispheric language organization (six female, 8-28 years). MRI data were analysed with SPM12, CAT12, and custom scripts. Language lateralization indices were determined by fMRI within a prefrontal mask and right-hemispheric grey matter group differences by voxel-based morphometry (VBM). RESULTS: FMRI revealed left-dominance in seven patients with typical language organization (TYP) and right-dominance in seven patients with atypical language organization (ATYP) of 14 patients. VBM analysis of all patients versus controls showed grey matter reductions in the middle temporal gyrus of patients. A comparison between the two patient subgroups revealed an increase of grey matter in the middle frontal gyrus in the ATYP group. Voxel-based regression analysis confirmed that grey matter increases in the middle frontal gyrus were correlated with atypical language organization. INTERPRETATION: Compatible with a non-specific lesion effect, we found areas of grey matter reduction in patients as compared to TDC. The grey matter increase in the middle frontal gyrus seems to reflect a specific compensatory effect in patients with atypical language organization. WHAT THIS PAPER ADDS: Perinatal stroke leads to decreased grey matter in the contralesional hemisphere. Atypical language organization is associated with grey matter increases in contralesional language areas.

High neutralizing antibody mismatch as a possible reason for vaccine failure in two children with severe tick-borne encephalitis.

We describe two adolescents (13 and 16 years old) with severe tick-borne encephalitis (TBE) and vaccination breakthrough (VBT). Both suffer from severe persistent neurologic sequelae. Both patients had high TBE-IgG-titers after vaccination at the beginning of the infection and a low or missing TBE-IgM response (Type 2 vaccine failure). Neutralization tests show low titers against the respective infecting TBE virus strain and higher titers against the vaccine strain at the beginning of the infection implying an individual weak or impaired immune response to the respective virus as possible cause of TBE vaccine failure. We do not know of any similar observation or explanation for the phenomenon and at the moment can only speculate of a severe course correlated to highly mismatched IgG. This constellation of high TBE IgGs, the lack of immune response and a severe course strongly resembles the severe TBE courses that occurred in the past after TBE immunoglobulin administration. To our knowledge differentiation between structural and functional antibodies by neutralization tests with a) the affecting TBE virus strain and b) the vaccine virus strain in TBE vaccine failures has never been described before. We conclude (1) to consider a TBE virus infection also in vaccinated children presenting with meningoencephalitis, (2) to perform a broad immunological work-up in severe TBE especially after VBT, (3) to further study if high mismatch IgG's are a possible reason for vaccine failure.

Cognitive development after perinatal unilateral infarctions: No evidence for preferential sparing of verbal functions.

BACKGROUND: Even children with extensive perinatal left-sided lesions have been reported to show normal language functions based on right-hemispheric language reorganization. This reorganization can lead to deficits in originary right hemispheric functions ("crowding hypothesis"). In a previous study, however, we identified epilepsy (even when well-controlled), and not language reorganization, as the major risk factor for impaired nonverbal functions. Here, we asked whether verbal and nonverbal functions develop differently, and whether they share the same risk factors. METHODS: We investigated 23 patients (11f, Md = 12.56 years) with perinatal strokes (16 left-sided, 8 with epilepsy), and 23 healthy age-matched controls (8 f, Md = 12.42years). Language functions were assessed using the Potsdam Illinois Test of Psycholinguistic Abilities, nonverbal intelligence with the Test of Nonverbal Intelligence, language lateralization with functional MRI, and lesion size with MRI-based volumetry. RESULTS: We found no systematic difference between verbal and nonverbal skills in our patients or controls [median difference Z(PITPA)-Z(TONI): patients = -0.03, controls = -0.06]. Accordingly, verbal and nonverbal functions were strongly correlated in patients (r = 0.80) and in controls (r = 0.74). Language ability correlated significantly with epilepsy. Furthermore, in patients with epilepsies, verbal skills were significantly lower than in controls. CONCLUSION: In our cohort, we found no evidence for a differential effect of perinatal strokes on the development of verbal versus nonverbal functions, and, specifically, no evidence for a preferential sparing of verbal functions. Epilepsy, even when well-controlled, was confirmed as a single key risk factor for verbal functions.

Multilobar unilateral hypoplasia with emphasis on the posterior quadrant and severe epilepsy in children with FCD ILAE Type 1A.

OBJECTIVE: Focal cortical dysplasia (FCD) Type 1 and its three subtypes have yet not been fully characterized at the clinical, anatomopathological, and molecular level (International League Against Epilepsy [ILAE] FCD classification from 2011). We aimed to describe the clinical phenotype of patients with histopathologically confirmed FCD1A obtained from a single epilepsy center between 2002 and 2016. METHODS: Medical records were retrieved from the hospital's archive. Results from electroencephalography (EEG) video recordings, neuroimaging, and histopathology were reevaluated. Magnetic resonance imaging (MRI) post-processing was retrospectively performed in nine patients. DNA methylation studies were carried out from archival surgical brain tissue in 11 patients. RESULTS: Nineteen children with a histopathological diagnosis of FCD1A were included. The average onset of epilepsy was 0.9 years (range 0.2-10 years). All children had severe cognitive impairment and one third had mild motor deficits, yet fine finger movements were preserved in all patients. All patients had daily seizures, being drug resistant from disease onset. Interictal electroencephalography revealed bilateral multi-regional epileptiform discharges. Interictal status epilepticus was observed in 8 and countless subclinical seizures in 11 patients. Regional continuous irregular slow waves were of higher lateralizing and localizing yield than spikes. Posterior background rhythms were normal in 16 of 19 children. Neuroimaging showed unilateral multilobar hypoplasia and increased T2-FLAIR signals of the white matter in 18 of 19 patients. All children underwent tailored multilobar resections, with seizure freedom achieved in 47% (Engel class I). There was no case with frontal involvement without involvement of the posterior quadrant by MRI and histopathology. DNA methylation profiling distinguished FCD1A samples from all other epilepsy specimens and controls. SIGNIFICANCE: We identified a cohort of young children with drug resistance from seizure onset, bad EEG with posterior emphasis, lack of any focal neurological deficits but severe cognitive impairment, subtle hypoplasia of the epileptogenic area on MRI, and histopathologically defined and molecularly confirmed by DNA methylation analysis as FCD ILAE Type 1A.

Clinical Speech fMRI in Children and Adolescents : Development of an Optimal Protocol and Analysis Algorithm.

PURPOSE: In patients with drug-resistant focal epilepsy, surgical resection is often the only treatment option to achieve long-term seizure control. Prior to brain surgery involving potential language areas, identification of hemispheric language dominance is crucial. Our group developed and validated a functional magnetic resonance imaging (fMRI) battery of four pediatric language tasks. The present study aimed at optimizing fMRI data acquisition and analysis using these tasks. METHODS: We retrospectively analyzed speech fMRI examinations of 114 neuropediatric patients (age range 5.8-17.8 years) who were examined prior to possible epilepsy surgery. In order to evaluate hemispheric language dominance, 1-4 language tasks (vowel identification task VIT, word-chain task WCT, beep-story task BST, synonym task SYT) were measured. RESULTS: Language dominance was classified using fMRI activation in the 13 validly lateralizing ROIs (VLR) in frontal, temporal and parietal lobes and cerebellum of the recent validation study from our group: 47/114 patients were classified as left-dominant, 34/114 as bilateral and 6/114 as right-dominant. In an attempt to enlarge the set of VLR, we then compared for each task agreement of these ROI activations with the classified language dominance. We found four additional task-specific ROIs showing concordant activation and activation in ≥ 10 sessions, which we termed validly lateralizing (VLRnew). The new VLRs were: for VIT the temporal language area and for SYT the middle frontal gyrus, the intraparietal sulcus and cerebellum. Finally, in order to find the optimal sequence of measuring the different tasks, we analyzed the success rates of single tasks and all possible task combinations. The sequence 1) VIT 2) WCT 3) BST 4) SYT was identified as the optimal sequence, yielding the highest chance to obtain reliable results even when the fMRI examination has to be stopped, e.g., due to lack of cooperation. CONCLUSION: Our suggested task order together with the enlarged set of VLRnew may contribute to optimize pediatric speech fMRI in a clinical setting.

[Hemispherotomy in pediatric epilepsy surgery-Surgical, epileptological and functional aspects]. / Hemisphärotomien in der pädiatrischen Epilepsiechirurgie ­ operative, epileptologische und funktionelle Aspekte.

Hemispherotomies represent a major part of surgical interventions for epilepsy in childhood (16-21%). The anatomical resection has been replaced by minimally invasive disconnection techniques with lower perioperative mortality and fewer postoperative complications. Today the procedure is not only carried out from the lateral aspect via the Sylvian fissure/insula but also via a vertical parasagittal approach. Depending on the publication, hemispherotomy leads to freedom from postoperative seizures in 60-90% of patients. Despite changes in the surgical technique, disturbances of the cerebrospinal fluid circulation continue to be the main complication in 5-15% of cases. Hemispheric epileptogenic lesions usually lead to early onset and difficult to treat epilepsy in childhood. These epilepsies are characterized by a high frequency of seizures and propagation of epileptic discharges to the healthy hemisphere. The aim of a hemispherotomy is, in addition to postoperative freedom from seizures, the complete disconnection of the affected hemisphere. When deciding on a hemispherotomy, the expected functional consequences play a major role in addition to epileptological aspects. In the case of deficits already present preoperatively (hemianopia, hemiparesis) or reorganization of functions in the contralesional hemisphere (language), no new deficits are to be expected from the operation. In terms of cognition, a hemispherotomy can improve function by releasing the neuroplastic potential of the healthy hemisphere. In order to keep the negative and often irreversible effects of epilepsy as low as possible and to be able to use as much potential for neuroplasticity of the healthy hemisphere as possible, surgery should be considered as early as possible.

Childhood Stroke: Long-Term Outcomes and Health-Related Quality of Life with a Special Focus on the Development of Epilepsy.

BACKGROUND: Childhood stroke is rare and can predispose to post-stroke epilepsy. The purpose of this study was to evaluate long-term quality of life (QoL) in patients with childhood stroke, focusing on epileptic aspects. METHOD: This involves a retrospective study of 98 patients with childhood stroke (pre- and neonatal strokes excluded), who had been inpatients between 1986 and 2003 for early rehabilitation. Data were obtained via interviews using a standardized questionnaire: QoL evaluation with KINDL, functional outcome with Barthel Index, and motor handicaps-assessment with modified Rankin Score. RESULTS: Forty-nine of 98 patients (31 males, mean follow-up 16 years, range 8-25 years) were included. Six patients passed away (three of sudden unexpected death in epilepsy). At least one epileptic seizure occurred in 27/49 patients (occurrence: 2 days-13 years.; mean 3.3 years.). Epilepsy manifested in 19/49 patients. No correlation was found between the development of epilepsy and the location or etiology of the stroke. The presence of functional independence was significantly higher in seizure-free patients and in patients without epilepsy. For the external assessment (filled in for the patient by the parent/caregiver), there was no significant difference in QoL in patients with and without epilepsy; however, in the in-person KINDL questionnaire a significantly lower QoL was noted in epilepsy patients compared with patients without epilepsy. CONCLUSION: One important finding in our study is that in the long-term course 39% of patients developed epilepsy after a childhood stroke. It occurred as late as 13 years after the acute episode and affected the QoL especially in cognitively less handicapped patients.

Non-verbal Intelligence in Unilateral Perinatal Stroke Patients With and Without Epilepsies.

Background: The risk factors for impaired cognitive development after unilateral perinatal stroke are poorly understood. Non-verbal intelligence seems to be at particular risk, since language can shift to the right hemisphere and may thereby reduce the capacity of the right hemisphere for its originary functions. Pharmaco-refractory epilepsies, a frequent complication of perinatal strokes, often lead to impaired intelligence. Yet, the role of well-controlled epilepsies is less well-understood. Here, we investigated whether well-controlled epilepsies, motor impairment, lesion size, lesion side, and lateralization of language functions influence non-verbal functions. Methods: We recruited 8 patients with well-controlled epilepsies (9-26 years), 15 patients without epilepsies (8-23 years), and 23 healthy controls (8-27 years). All underwent the Test of Non-verbal Intelligence, a motor-independent test, which excludes biased results due to motor impairment. Language lateralization was determined with functional MRI, lesion size with MRI-based volumetry, and hand motor impairment with the Jebson-Taylor Hand Function-Test. Results: Patients with epilepsies showed significantly impaired non-verbal intelligence [Md = 89.5, interquartile range (IQR) = 13.5] compared with controls (Md = 103, IQR = 17). In contrast, patients without epilepsies (Md = 97, IQR = 15.0) performed within the range of typically developing children. A multiple regression analysis revealed only epilepsy as a significant risk factor for impaired non-verbal functions. Conclusion: In patients with unilateral perinatal strokes without epilepsies, the neuroplastic potential of one healthy hemisphere is able to support the development of normal non-verbal cognitive abilities, regardless of lesion size, lesion side, or language lateralization. In contrast, epilepsy substantially reduces this neuroplastic potential; even seizure-free patients exhibit below-average non-verbal cognitive functions.

Deep Brain Stimulation in KMT2B-Related Dystonia: Case Report and Review of the Literature With Special Emphasis on Dysarthria and Speech.

Objective: KMT2B-related dystonia is a progressive childhood-onset movement disorder, evolving from lower-limb focal dystonia into generalized dystonia. With increasing age, children frequently show prominent laryngeal or facial dystonia manifesting in dysarthria. Bilateral deep brain stimulation of the globus pallidus internus (GPi-DBS) is reported to be an efficient therapeutic option. Especially improvement of dystonia and regaining of independent mobility is commonly described, but detailed information about the impact of GPi-DBS on dysarthria and speech is scarce. Methods: We report the 16-months outcome after bilateral GPi-DBS in an 8-year-old child with KMT2B-related dystonia caused by a de-novo c.3043C>T (p.Arg1015*) non-sense variant with special emphasis on dysarthria and speech. We compare the outcome of our patient with 59 patients identified through a PubMed literature search. Results: A remarkable improvement of voice, articulation, respiration and prosodic characteristics was seen 16 months after GPi-DBS. The patients' speech intelligibility improved. His speech became much more comprehensible not only for his parents, but also for others. Furthermore, his vocabulary and the possibility to express his feelings and wants expanded considerably. Conclusion: A positive outcome of GPi-DBS on speech and dysarthria is rarely described in the literature. This might be due to disease progression, non-effectiveness of DBS or due to inadvertent spreading of the electrical current to the corticobulbar tract causing stimulation induced dysarthria. This highlights the importance of optimal lead placement, the possibility of horizontal steering of the electrical field by applying directional stimulation with segmented leads as well as the use of the lowest possible effective stimulation intensity.

Predicting Language Outcome After Left Hemispherotomy: A Systematic Literature Review.

OBJECTIVE: Hemidecortication is a therapeutic option in patients with drug-resistant structural epilepsy. If surgery is performed early enough in left-hemispheric pathology, the plasticity of the developing brain may enable the right hemisphere to take over language-if this has not occurred before surgery. A systematic overview of potential predictors of language outcome after left hemidecortication in children is warranted. METHODS: In a systematic literature review, we analyzed 58 studies on language lateralization after congenital or postneonatally acquired left-hemispheric pathology, and on language outcome after left-sided hemidisconnection, such as hemispherotomy. Single-subject data were pooled to determine the distribution of lateralization across etiologies in congenital lesions and across age groups in acute postneonatal lesions. A hierarchical linear regression assessed the influence of age at surgery, lesion type, age at seizure onset, and presurgery language function on language outcome after left hemidecortication. RESULTS: In acute postneonatal lesions, younger age at injury was significantly associated with right-sided language lateralization (Cramér V = 0.458; p = 0.039). In patients with hemidecortication, age at surgery was not significantly associated with language outcome (Cramér V = -0.056; p = 0.584). Presurgical language function was the most powerful predictor for postsurgical language outcome (F 4,47 = 7.35, p < 0.0001), with good presurgical language bearing the risk of postsurgical deterioration. In congenital pathology, right-sided language lateralization was most frequent in pre-/perinatal stroke (Cramér V = 0.357; p < 0.0001). CONCLUSIONS: We propose a presurgical decision algorithm with age, presurgical language function, language lateralization, and left-hemispheric structural pathology as decision points regarding surgery.

Sacrificing one visual hemifield during pediatric epilepsy surgery: Effects on visual search.

OBJECTIVES: To investigate early and late effects of planned surgically acquired homonymous hemianopias on visual search in children and adolescents. METHODS: This prospective study included five patients (5y 5 m-18y 0 m; 2 girls) with pharmaco-refractory epilepsies in whom one visual hemifield was sacrificed as part of the surgical strategy, and, as controls, seven patients (5y 11 m-18y 0 m; 6 girls) undergoing epilepsy surgeries not affecting the visual fields. Visual search was studied using the "Table Test", which is an everyday life-like visual search test. General processing speed was studied using a standard IQ subtest. RESULTS: All five patients with newly acquired homonymous hemianopias showed a relative disadvantage of visual search times for objects in their newly blind hemifields immediately after the surgery. Six months later, this relative disadvantage had recovered completely in all patients. Nevertheless, compared with the preoperative situation, overall search times were still prolonged in the hemianopic patients, but this effect could be mitigated or even overcompensated by improvements in processing speed. CONCLUSIONS: Children with homonymous hemianopias inflicted by epilepsy surgery develop effective compensation strategies to minimize the relative disadvantage of visual search in their blind hemifields. For changes in overall visual search times between the preoperative and the six-month follow-up examination, we could demonstrate overlapping effects of (a) deterioration by hemianopia and (b) amelioration by improved processing speed as part of the cognitive improvements achieved by amelioration of the epilepsy.

Correlates of intellectual development before and after hemispherotomy: an analysis of 75 children and adolescents.

This study describes the intellectual development of 75 children and adolescents who underwent hemispherotomy. Furthermore, we aimed to reveal predicting factors on pre- and postsurgical development with a focus on the role of aetiology. We analysed presurgical and six-month postsurgical developmental and intellectual data of 75 patients (age range: 0.87-19.78 years) and divided them into two groups: a not severely impaired group in which outcome of intellectual functioning was reported based on FSIQ score, and a severely impaired group (not testable by IQ tests) in which intellectual developmental outcome was described based on developmental quotients instead. In the not severely impaired group (n = 31), the preoperative level of intellectual functioning was a strong predictor of postoperative intellectual outcome; for 22/31 (71%) patients, postoperative FSIQ and its subscales were similar to preoperative levels. Improvements were observed for FSIQ in five patients, only for Verbal IQ in one patient and only for Performance IQ in one further patient; significant losses occurred in two patients, only for Performance IQ in both. In the severely impaired group, 30/40 (75%) patients showed further development after surgery, nine (23%) patients had the same results as before surgery, and one (2%) patient showed regression. Longer duration of presurgical epilepsy was related to a marginally lower presurgical developmental level, and good seizure outcome was a predictor of better postoperative development. For all patients, early age at seizure onset and early lesion origin correlated with poorer presurgical intellectual development. Although an entire hemisphere was disconnected, most patients exhibited ongoing development after hemispherotomy or had at least the same preoperative intellectual status; deterioration was rare.

Dog-Assisted Therapy in Neurorehabilitation of Children with Severe Neurological Impairment: An Explorative Study.

BACKGROUND: Dog-assisted therapy (DAT) is increasingly applied in neurorehabilitation of patients with severe neurological impairments. To date, there are only anecdotal reports investigating its effects. OBJECTIVES: This study was aimed to evaluate the potential of DAT in pediatric inpatient neurorehabilitation for severely neurologically impaired children and adolescents, to identify characteristics of patients receiving this therapy, characteristics of the therapy sessions, and to evaluate feasibility and extent of goal achievement. METHODS: We retrospectively analyzed 850 DAT sessions performed between 2010 and 2017 at an inpatient neurorehabilitation center. The dataset included 196 children and adolescents (Md = 5.50, 0.58-20.33 years) suffering from severe neurological impairments (disorders of consciousness in 37 patients) of various etiologies. We extracted information regarding patient and session characteristics, analyzed the predefined goals with content analysis, and examined to what extent the goals were met during DAT. Data were analyzed using descriptive statistics. RESULTS: Patients received an average of 4.34 therapy sessions. A total of 247 of 392 predefined goals (63%) were reached during DAT. The most frequently achieved goal was "enhancing fun" (83%), followed by "establishing contact and communication" (81%), and "relaxation" (71%). Only one critical incident regarding the dogs' safety occurred. CONCLUSION: DAT is a feasible approach and appears to facilitate emotional, social, and psychological goals in children and adolescents with severe neurological impairment.

Presurgical Language fMRI in Children, Adolescents and Young Adults : A Validation Study.

PURPOSE: To validate four established, child-friendly functional magnetic resonance imaging (fMRI) language tasks (word chain task [WCT], vowel identification task [VIT], synonym task [SYT] and beep story task [BST]) in a predominantly pediatric cohort. METHODS: Intracarotid amobarbital procedures (IAP) (n = 17) and unchanged language after hemispherotomy (n = 6) were used as gold standards. The fMRI activations of nine regions of interest (ROI) in the frontal, temporal and parietal lobes as well as in the cerebellum were visually assessed in 23 fMRI examinations (in total 117 fMRI task sessions) of 23 patients (age range 10.0-23.0 years) with drug-refractory epilepsies. RESULTS: The ROIs were considered valid when they showed activation in more than 25% of all sessions for the respective task and never showed false lateralization (in comparison to gold standards). Thus, 13 valid, task-specific ROIs were identified: 5 ROIs for the WCT (frontal operculum, inferior frontal gyrus, middle frontal gyrus, intraparietal sulcus, cerebellum), 3 ROIs for the VIT (frontal operculum, inferior frontal gyrus, middle frontal gyrus), 3 ROIs for the SYT (frontal operculum, inferior frontal gyrus, temporal language area) and 2 ROIs for the BST (inferior frontal gyrus, middle frontal gyrus). CONCLUSION: Clinical fMRI using the battery of four tasks is a valid tool for lateralizing language in children, adolescents and young adults. Each task proved to be specifically useful, which confirms that applying different tasks increases the probability of diagnosing language dominance in presurgical candidates.

Uncovering homonymous visual field defects in candidates for pediatric epilepsy surgery.

OBJECTIVES: Perimetry in children can be challenging due to low cooperation and short attention span. Especially during the pre-surgical work-up of children with pharmaco-refractory epilepsies, however, diagnosing homonymous visual field defects (HVFDs) can be crucial for planning surgical strategies. Here, we evaluated "campimetry" for visual field testing in children. Furthermore, we analyzed strabismus and anomalous head posture as clinical signs for HVFDs. METHODS: Campimetry and a standard orthoptic examination were performed in 18 patients (age range: 3 y 2 m-18 y) who underwent epilepsy surgeries in our center during the study period, and in 11 additional patients (age range: 2 y 10 m-22 y 10 m) with suspected or confirmed HVFDs. RESULTS: In 16/18 patients of our unselected surgery cohort, pre- and postoperative campimetry was successfully completed. Of these, only 7/16 patients had intact visual fields pre- and postoperatively, while 5/16 patients already showed preoperative HVFDs and 4/16 patients suffered newly acquired HVFDs as calculated consequences of the surgery. Regarding clinical signs, strabismus (mostly esotropia) and anomalous head posture were specific indicators of HVFDs (strabismus: 6/12 with HVFDs vs 1/18 without; anomalous head posture: 8/12 with HVFDs vs 0/18 without). CONCLUSIONS: For perimetry in children with limited cooperation, we suggest campimetry as it allows early detection and fast delineation of HVFDs. This is particularly important in pediatric epilepsy surgery patients, who display a surprisingly high proportion of HVFDs (9/16). Both, strabismus and anomalous head posture can indicate such HVFDs. Therefore, clinicians should pay attention to these clinical signs, especially in the context of epilepsy surgery.

Structural brain anomalies in patients with FOXG1 syndrome and in Foxg1+/- mice.

OBJECTIVE: FOXG1 syndrome is a rare neurodevelopmental disorder associated with heterozygous FOXG1 variants or chromosomal microaberrations in 14q12. The study aimed at assessing the scope of structural cerebral anomalies revealed by neuroimaging to delineate the genotype and neuroimaging phenotype associations. METHODS: We compiled 34 patients with a heterozygous (likely) pathogenic FOXG1 variant. Qualitative assessment of cerebral anomalies was performed by standardized re-analysis of all 34 MRI data sets. Statistical analysis of genetic, clinical and neuroimaging data were performed. We quantified clinical and neuroimaging phenotypes using severity scores. Telencephalic phenotypes of adult Foxg1+/- mice were examined using immunohistological stainings followed by quantitative evaluation of structural anomalies. RESULTS: Characteristic neuroimaging features included corpus callosum anomalies (82%), thickening of the fornix (74%), simplified gyral pattern (56%), enlargement of inner CSF spaces (44%), hypoplasia of basal ganglia (38%), and hypoplasia of frontal lobes (29%). We observed a marked, filiform thinning of the rostrum as recurrent highly typical pattern of corpus callosum anomaly in combination with distinct thickening of the fornix as a characteristic feature. Thickening of the fornices was not reported previously in FOXG1 syndrome. Simplified gyral pattern occurred significantly more frequently in patients with early truncating variants. Higher clinical severity scores were significantly associated with higher neuroimaging severity scores. Modeling of Foxg1 heterozygosity in mouse brain recapitulated the associated abnormal cerebral morphology phenotypes, including the striking enlargement of the fornix. INTERPRETATION: Combination of specific corpus callosum anomalies with simplified gyral pattern and hyperplasia of the fornices is highly characteristic for FOXG1 syndrome.

Learning to cope with mirror movements in unilateral spastic cerebral palsy: a brief report.

PURPOSE: Mirror movements (MM) in unilateral spastic cerebral palsy (USCP) interfere with many bimanual activities of daily living. METHODS: Here, we developed a specific bimanual therapeutic regimen, focusing on asymmetric simultaneous movements of the two hands. Twelve children (6-17 years old; complete data available in ten children) with USCP and MM were included. RESULTS: After three weeks of inpatient rehabilitation, we observed significant improvements for two self-defined bimanual goal activities (Goal Attainment Scaling, Canadian Occupational Performance Measure) and for bimanual performance in general (Assisting Hand Assessment). These improvements were still present 6 months later. In contrast, even immediately after therapy, the severity of MM had not changed. CONCLUSIONS: Hence, targeted bimanual therapy improved bimanual performance, but did not lead to a reduction of MM. The results of this pilot study might suggest that children with MM benefit more from acquiring strategies to cope with MM than by an active training which aimed to reduce MM.