BACKGROUND AND PURPOSE: Although "corpus callosum agenesis" is an umbrella term for multiple enti... more BACKGROUND AND PURPOSE: Although "corpus callosum agenesis" is an umbrella term for multiple entities, prenatal counseling is based reductively on the presence (associated) or absence (isolated) of additional abnormalities. Our aim was to test the applicability of a fetal MR neuroimaging score in a cohort of fetuses with prenatally diagnosed isolated corpus callosum agenesis and associated corpus callosum agenesis and correlate it with neurodevelopmental outcomes. MATERIALS AND METHODS: We performed a single-center retrospective analysis of a cohort of cases of consecutive corpus callosum agenesis collected between January 2011 and July 2019. Cases were scored by 2 raters, and interater agreement was calculated. Outcome was assessed by standardized testing (Bayley Scales of Infant and Toddler Development, Kaufman Assessment Battery for Children) or a structured telephone interview and correlated with scores using 2-way ANOVA. RESULTS: We included 137 cases (74 cases of isolated corpus callosum agenesis), imaged at a mean of 27 gestational weeks. Interrater agreement was excellent (0.98). Scores were higher in associated corpus callosum agenesis (P , .0001) without a significant score difference between complete and partial corpus callosum agenesis (P ¼ .38). Outcome was assessed in 42 children with isolated corpus callosum agenesis and 9 with associated corpus callosum agenesis (mean age, 3.1 years). MR imaging scores correctly predicted developmental outcome in 90.7% of patients with isolated corpus callosum agenesis, improving neurodevelopmental risk stratification in corpus callosum agenesis. CONCLUSIONS: The scoring system is very reproducible and can differentiate isolated corpus callosum agenesis and associated isolated corpus callosum agenesis (significantly higher scores) but not between partial and complete corpus callosum agenesis. Scores correlated with outcome in isolated corpus callosum agenesis, but there were too few associated postnatal cases of isolated corpus callosum agenesis to draw conclusions in this group. ABBREVIATIONS: aCCA ¼ associated corpus callosum agenesis; CC ¼ corpus callosum; CCA ¼ corpus callosum agenesis; DCC ¼ deleted in colorectal cancer; iCCA ¼ isolated corpus callosum agenesis; MCD ¼ malformations of cortical development; TOP ¼ termination of pregnancy C orpus callosum (CC) agenesis (CCA) is one of the most com
The present study is interested in the role of the corpus callosum in the development of the lang... more The present study is interested in the role of the corpus callosum in the development of the language network. We, therefore, investigated language abilities and the language network using task-based fMRI in three cases of complete agenesis of the corpus callosum (ACC), three cases of partial ACC and six controls. Although the children with complete ACC revealed impaired functions in specific language domains, no child with partial ACC showed a test score below average. As a group, ACC children performed significantly worse than healthy controls in verbal fluency and naming. Furthermore, whole-brain ROI-to-ROI connectivity analyses revealed reduced intrahemispheric and right intrahemispheric functional connectivity in ACC patients as compared to controls. In addition, stronger functional connectivity between left and right temporal areas was associated with better language abilities in the ACC group. In healthy controls, no association between language abilities and connectivity was...
In most humans, the superior temporal sulcus (STS) shows a rightward depth asymmetry. This asymme... more In most humans, the superior temporal sulcus (STS) shows a rightward depth asymmetry. This asymmetry can not only be observed in adults, but is already recognizable in the fetal brain. As the STS lies adjacent to brain areas important for language, STS depth asymmetry may represent an anatomical marker for language abilities. This study investigated the prognostic value of STS depth asymmetry in healthy fetuses for later language abilities, language localization, and language-related white matter tracts. Less right lateralization of the fetal STS depth was significantly associated with better verbal abilities, with fetal STS depth asymmetry explaining more than 40% of variance in verbal skills 6–13 years later. Furthermore, less right fetal STS depth asymmetry correlated with increased left language localization during childhood. We hypothesize that earlier and/or more localized fetal development of the left temporal cortex is accompanied by an earlier development of the left STS an...
Permanent consequences in Langerhans cell histiocytosis (LCH) are irreversible late sequelae rela... more Permanent consequences in Langerhans cell histiocytosis (LCH) are irreversible late sequelae related to the disease that may severely impair the quality of life of survivors. The frequency and pattern of permanent consequences affecting the central nervous system (CNS) remains to be determined. In this single center study, 25 LCH patients observed for a median time of 10 years 3 months underwent a uniform thorough follow-up program including neuropsychological testing and electrophysiological evaluation. Overall permanent consequences were seen in 9 of 25 patients. Intracranial abnormalities were the most frequent including diabetes insipidus (DI) in seven patients, anterior pituitary deficiencies in five patients, and neurodegenerative CNS disease in five patients. No patient had overt neurological symptoms upon neurological evaluation, but psychological testing revealed subtle deficits in short-term auditory memory (STAM) in 14 patients. Brain stem evoked potentials showed abnormalities in four of nine tested patients, all of these four had neurodegeneration on MRI. Psychoneuroendocrine sequelae were found in an unexpectedly high number of patients in this single center study. Long-term follow-up focusing on such sequelae are important in LCH survivors, in order to detect early deficits, to monitor the evolution of the disease, and to provide specific support.
Headaches in children are a common, but unspecific symptom that can have many underlying causes, ... more Headaches in children are a common, but unspecific symptom that can have many underlying causes, ranging from unspecific tension headache through migraine and up to encephalitis and intracranial hypertension. We present the case of a 14-year-old boy who presented to our emergency department with headache, nausea as well as vomiting and developed seizures later on. The initial diagnosis was complicated by a magnetic resonance imaging which did not show any signs of inflammation, but was of limited informative value due to orthodontic appliances. Despite the unremarkable imaging, prophylactic antiviral and antibiotic treatment was started after lumbar puncture. Herpes simplex virus as well as human herpes virus 7 were confirmed in the cerebrospinal fluid. Although both viruses are ubiquitous, severe infections are a rare complication. Immunodeficiency syndromes are predisposing factors for serious complications and genetic analysis of UNC93B and TLR-3 might be helpful for decision-mak...
This systematic comparison between pre‐ and postnatal imaging findings and postnatal motor outcom... more This systematic comparison between pre‐ and postnatal imaging findings and postnatal motor outcome assesses the reliability of MRI accuracy in the prognostication of the future long‐term (mean, 11.4 years) ambulatory status in a historic group of postnatally repaired myelomeningocele (MMC) cases.
Abstract The specific role of the corpus callosum (CC) in language network organization remains u... more Abstract The specific role of the corpus callosum (CC) in language network organization remains unclear, two contrasting models have been proposed: inhibition of homotopic areas allowing for independent functioning of the hemispheres versus integration of information from both hemispheres. This study aimed to add to this discussion with the first investigation of language network connectivity in combination with CC volume measures. In 38 healthy children aged 6–12, we performed task‐based functional magnetic resonance imaging to measure language network connectivity, used structural magnetic resonance imaging to quantify CC subsection volumes, and administered various language tests to examine language abilities. We found an increase in left intrahemispheric and bilateral language network connectivity and a decrease in right intrahemispheric connectivity associated with larger volumes of the posterior, mid‐posterior, and central subsections of the CC. Consistent with that, larger volumes of the posterior parts of the CC were significantly associated with better verbal fluency and vocabulary, the anterior CC volume was positively correlated with verbal span. Thus, children with larger volumes of CC subsections showed increased interhemispheric language network connectivity and were better in different language domains. This study presents the first evidence that the CC is directly linked to language network connectivity and underlines the excitatory role of the CC in the integration of information from both hemispheres.
HighlightsHealthy children and adolescents exhibit mesial temporal lobe activations during semant... more HighlightsHealthy children and adolescents exhibit mesial temporal lobe activations during semantic language processing.Bilateral mesial temporal lobe involvement is advantageous for vocabulary skills in healthy, right‐handed children and adolescents.Thus, the mesial temporal lobes of both hemispheres play an important role in language functioning in right‐handed children and adolescents. Abstract This study considered the involvement of the mesial temporal lobe (MTL) in language and verbal memory functions in healthy children and adolescents. We investigated 30 healthy, right‐handed children and adolescents, aged 7–16, with a fMRI language paradigm and a comprehensive cognitive test battery. We found significant MTL activations during language fMRI in all participants; 63% of them had left lateralized MTL activations, 20% exhibited right MTL lateralization, and 17% showed bilateral MTL involvement during the fMRI language paradigm. Group analyses demonstrated a strong negative correlation between the lateralization of MTL activations and language functions. Specifically, children with less lateralized MTL activation showed significantly better vocabulary skills. These findings suggest that the mesial temporal lobes of both hemispheres play an important role in language functioning, even in right‐handers. Our results furthermore show that bilateral mesial temporal lobe involvement is advantageous for vocabulary skills in healthy, right‐handed children and adolescents.
B cell depletion with the anti-CD20-antibody rituximab is widely considered treatment of choice f... more B cell depletion with the anti-CD20-antibody rituximab is widely considered treatment of choice for long-term immunotherapy in aquaporin-4 (AQP4)-antibody positive neuromyelitis optica spectrum disorder (NMOSD). However, up to 30% of patients suffer from relapses despite complete B cell depletion. In these cases, the IL6 (interleukin-6)-receptor blocking antibody tocilizumab has been suggested as an alternative. We report two female adolescents with AQP4-antibody positive NMOSD who relapsed under rituximab treatment and clinically stabilized after switching to monthly administrations of tocilizumab. Our data suggest that early escalation of therapy with tocilizumab may lead to stabilization of disease activity in pediatric NMOSD patients who relapse under B cell depletion.
B cell depletion with the anti-CD20-antibody rituximab is widely considered treatment of choice f... more B cell depletion with the anti-CD20-antibody rituximab is widely considered treatment of choice for long-term immunotherapy in aquaporin-4 (AQP4)-antibody positive neuromyelitis optica spectrum disorder (NMOSD). However, up to 30% of patients suffer from relapses despite complete B cell depletion. In these cases, the IL6 (interleukin-6)-receptor blocking antibody tocilizumab has been suggested as an alternative. We report two female adolescents with AQP4-antibody positive NMOSD who relapsed under rituximab treatment and clinically stabilized after switching to monthly administrations of tocilizumab. Our data suggest that early escalation of therapy with tocilizumab may lead to stabilization of disease activity in pediatric NMOSD patients who relapse under B cell depletion.
The diagnosis of multiple sclerosis (MS) both in children and adults is based on clinical and mag... more The diagnosis of multiple sclerosis (MS) both in children and adults is based on clinical and magnetic resonance imaging (MRI) features according to the McDonald criteria. Little is known about differences in the presentation between pre-pubertal children, adolescents, and adult patients at disease onset. To compare (1) the clinical, cerebrospinal fluid (CSF), and MRI characteristics, and (2) the diagnostic performance of the 2010 McDonald criteria between pre-pubertal, adolescent, and adult patients with a clinically isolated syndrome (CIS). We performed a retrospective analysis of the initial brain and spinal cord MRI scans from 11 pre-pubertal children, 46 adolescents, and 56 adults with a CIS. Furthermore, clinical, CSF characteristics, and the performance of the 2010 McDonald criteria were compared. The first inter-attack interval tended to increase with age. With respect to MRI presentation, significantly fewer pre-pubertal children presented with juxtacortical and callosal lesions. We found no significant differences in the fulfillment of the 2010 McDonald criteria between the groups. In this retrospective series, subtle differences between children, adolescents, and adults with a CIS were noted. Larger samples are required in order to establish distinct features of the different age groups.
Since the first postmortem lesion studies of patients with aphasia, we know that the left hemisph... more Since the first postmortem lesion studies of patients with aphasia, we know that the left hemisphere carries many language functions (Broca, 1861; Wernicke, 1874). Modern neuroimaging methods demonstrate that in about 90%-96% of adult right-handers, language is localized predominantly in the left hemisphere (Berl,
We investigated the predictive value of prenatal superior temporal sulcus (STS) depth asymmetry i... more We investigated the predictive value of prenatal superior temporal sulcus (STS) depth asymmetry in a special case of a female dizygotic twin that showed inverted prenatal asymmetry of this structure. For this purpose, we performed a follow-up investigation in this former fetus at the age of seven, where we assessed the functional language lateralization using task-based and resting-state functional magnetic resonance imaging (fMRI). As control group we employed her twin brother, who showed a typical folding pattern prenatally, as well as a complementary set of four age-matched children that had fetal MRI of their brains and typical STS depth asymmetry. We could show that the twin with the atypical fetal asymmetry of the STS also showed significantly differing rightward language lateralization in the frontal and temporal lobes. Additionally, resting-state data suggest a stronger connectivity between inferior frontal gyri in this case. The twin showed normal cognitive development. Thi...
Prenatal detection of abnormal white matter tracts might serve as a structural marker for altered... more Prenatal detection of abnormal white matter tracts might serve as a structural marker for altered neurodevelopment. As a result of many technical and patient-related challenges, the accuracy of prenatal tractography remains unknown. We hypothesized that characteristics of prenatal tractography of the corpus callosum and corticospinal tracts derived from fetal diffusion tensor imaging (DTI) data are accurate and predictive of the integrity of these tracts postnatally. We compared callosal and corticospinal tracts of 12 subjects with paired prenatal (age: 23-35 gestational weeks) and postnatal (age: 1 day to 2 years) DTI examinations (b values of 0 s/mmand 700 s/mm, 16 gradient encoding directions) using deterministic tractography. Evaluation for the presence of callosal segments and corticospinal tracts showed moderate degrees of accuracy (67-75%) for the four segments of the corpus callosum and moderate to high degrees of accuracy (75-92%) for the corticospinal tracts. Positive pred...
Situs inversus totalis is a rare condition where the visceral organs are organized as a mirror im... more Situs inversus totalis is a rare condition where the visceral organs are organized as a mirror image of default organ position. In this study we picture the co-development between brain and visceral organs in a case of situs inversus totalis from a fetal stage to adolescence and compare our findings to an age-, gender-, and education-matched control with normal position of thoracic and abdominal organs. We show that in this case of situs inversus, functional and structural brain lateralization do not coincide with visceral organ situs. Furthermore, cognitive development in situs inversus is normal. To our knowledge, this is the first report of antenatal cerebral origins of structural and functional brain asymmetry in a case of situs inversus totalis.
Mutations in genes encoding enzymes responsible for the biosynthesis and structural diversity of ... more Mutations in genes encoding enzymes responsible for the biosynthesis and structural diversity of glycosaminoglycans (GAGs) cause a variety of disorders affecting bone and connective tissues, including Desbuquois dysplasia (DD). In an infant with prenatal-onset disproportionate short stature, joint laxity, and radiographic findings typical for DD compound-heterozygosity for a large intragenic deletion, and a p.Pro384Arg missense mutation in CSGALNACT1 was found. CSGALNACT1 encodes chondroitin sulfate N-acetylgalactosaminyltransferase-1 (CSGalNAcT-1, ChGn-1), which initiates chondroitin sulfate (CS) chain biosynthesis on the so-called GAG-protein linker region tetrasaccharide. Biochemical studies revealed a reduced GalNAc-transferase activity of the Arg-384 mutant protein, whereas no differences in proteoglycan synthesis in fibroblasts and the GAG content in the urine were found between patient and controls. This is the first description of bi-allelic loss-of-function mutations in CSGALNACT1 that produce a skeletal dysplasia reminiscent of the skeletal dysplasia of Csgalnact1(-/-) mice, and adds to the genetic heterogeneity of DD.
BACKGROUND AND PURPOSE: Although "corpus callosum agenesis" is an umbrella term for multiple enti... more BACKGROUND AND PURPOSE: Although "corpus callosum agenesis" is an umbrella term for multiple entities, prenatal counseling is based reductively on the presence (associated) or absence (isolated) of additional abnormalities. Our aim was to test the applicability of a fetal MR neuroimaging score in a cohort of fetuses with prenatally diagnosed isolated corpus callosum agenesis and associated corpus callosum agenesis and correlate it with neurodevelopmental outcomes. MATERIALS AND METHODS: We performed a single-center retrospective analysis of a cohort of cases of consecutive corpus callosum agenesis collected between January 2011 and July 2019. Cases were scored by 2 raters, and interater agreement was calculated. Outcome was assessed by standardized testing (Bayley Scales of Infant and Toddler Development, Kaufman Assessment Battery for Children) or a structured telephone interview and correlated with scores using 2-way ANOVA. RESULTS: We included 137 cases (74 cases of isolated corpus callosum agenesis), imaged at a mean of 27 gestational weeks. Interrater agreement was excellent (0.98). Scores were higher in associated corpus callosum agenesis (P , .0001) without a significant score difference between complete and partial corpus callosum agenesis (P ¼ .38). Outcome was assessed in 42 children with isolated corpus callosum agenesis and 9 with associated corpus callosum agenesis (mean age, 3.1 years). MR imaging scores correctly predicted developmental outcome in 90.7% of patients with isolated corpus callosum agenesis, improving neurodevelopmental risk stratification in corpus callosum agenesis. CONCLUSIONS: The scoring system is very reproducible and can differentiate isolated corpus callosum agenesis and associated isolated corpus callosum agenesis (significantly higher scores) but not between partial and complete corpus callosum agenesis. Scores correlated with outcome in isolated corpus callosum agenesis, but there were too few associated postnatal cases of isolated corpus callosum agenesis to draw conclusions in this group. ABBREVIATIONS: aCCA ¼ associated corpus callosum agenesis; CC ¼ corpus callosum; CCA ¼ corpus callosum agenesis; DCC ¼ deleted in colorectal cancer; iCCA ¼ isolated corpus callosum agenesis; MCD ¼ malformations of cortical development; TOP ¼ termination of pregnancy C orpus callosum (CC) agenesis (CCA) is one of the most com
The present study is interested in the role of the corpus callosum in the development of the lang... more The present study is interested in the role of the corpus callosum in the development of the language network. We, therefore, investigated language abilities and the language network using task-based fMRI in three cases of complete agenesis of the corpus callosum (ACC), three cases of partial ACC and six controls. Although the children with complete ACC revealed impaired functions in specific language domains, no child with partial ACC showed a test score below average. As a group, ACC children performed significantly worse than healthy controls in verbal fluency and naming. Furthermore, whole-brain ROI-to-ROI connectivity analyses revealed reduced intrahemispheric and right intrahemispheric functional connectivity in ACC patients as compared to controls. In addition, stronger functional connectivity between left and right temporal areas was associated with better language abilities in the ACC group. In healthy controls, no association between language abilities and connectivity was...
In most humans, the superior temporal sulcus (STS) shows a rightward depth asymmetry. This asymme... more In most humans, the superior temporal sulcus (STS) shows a rightward depth asymmetry. This asymmetry can not only be observed in adults, but is already recognizable in the fetal brain. As the STS lies adjacent to brain areas important for language, STS depth asymmetry may represent an anatomical marker for language abilities. This study investigated the prognostic value of STS depth asymmetry in healthy fetuses for later language abilities, language localization, and language-related white matter tracts. Less right lateralization of the fetal STS depth was significantly associated with better verbal abilities, with fetal STS depth asymmetry explaining more than 40% of variance in verbal skills 6–13 years later. Furthermore, less right fetal STS depth asymmetry correlated with increased left language localization during childhood. We hypothesize that earlier and/or more localized fetal development of the left temporal cortex is accompanied by an earlier development of the left STS an...
Permanent consequences in Langerhans cell histiocytosis (LCH) are irreversible late sequelae rela... more Permanent consequences in Langerhans cell histiocytosis (LCH) are irreversible late sequelae related to the disease that may severely impair the quality of life of survivors. The frequency and pattern of permanent consequences affecting the central nervous system (CNS) remains to be determined. In this single center study, 25 LCH patients observed for a median time of 10 years 3 months underwent a uniform thorough follow-up program including neuropsychological testing and electrophysiological evaluation. Overall permanent consequences were seen in 9 of 25 patients. Intracranial abnormalities were the most frequent including diabetes insipidus (DI) in seven patients, anterior pituitary deficiencies in five patients, and neurodegenerative CNS disease in five patients. No patient had overt neurological symptoms upon neurological evaluation, but psychological testing revealed subtle deficits in short-term auditory memory (STAM) in 14 patients. Brain stem evoked potentials showed abnormalities in four of nine tested patients, all of these four had neurodegeneration on MRI. Psychoneuroendocrine sequelae were found in an unexpectedly high number of patients in this single center study. Long-term follow-up focusing on such sequelae are important in LCH survivors, in order to detect early deficits, to monitor the evolution of the disease, and to provide specific support.
Headaches in children are a common, but unspecific symptom that can have many underlying causes, ... more Headaches in children are a common, but unspecific symptom that can have many underlying causes, ranging from unspecific tension headache through migraine and up to encephalitis and intracranial hypertension. We present the case of a 14-year-old boy who presented to our emergency department with headache, nausea as well as vomiting and developed seizures later on. The initial diagnosis was complicated by a magnetic resonance imaging which did not show any signs of inflammation, but was of limited informative value due to orthodontic appliances. Despite the unremarkable imaging, prophylactic antiviral and antibiotic treatment was started after lumbar puncture. Herpes simplex virus as well as human herpes virus 7 were confirmed in the cerebrospinal fluid. Although both viruses are ubiquitous, severe infections are a rare complication. Immunodeficiency syndromes are predisposing factors for serious complications and genetic analysis of UNC93B and TLR-3 might be helpful for decision-mak...
This systematic comparison between pre‐ and postnatal imaging findings and postnatal motor outcom... more This systematic comparison between pre‐ and postnatal imaging findings and postnatal motor outcome assesses the reliability of MRI accuracy in the prognostication of the future long‐term (mean, 11.4 years) ambulatory status in a historic group of postnatally repaired myelomeningocele (MMC) cases.
Abstract The specific role of the corpus callosum (CC) in language network organization remains u... more Abstract The specific role of the corpus callosum (CC) in language network organization remains unclear, two contrasting models have been proposed: inhibition of homotopic areas allowing for independent functioning of the hemispheres versus integration of information from both hemispheres. This study aimed to add to this discussion with the first investigation of language network connectivity in combination with CC volume measures. In 38 healthy children aged 6–12, we performed task‐based functional magnetic resonance imaging to measure language network connectivity, used structural magnetic resonance imaging to quantify CC subsection volumes, and administered various language tests to examine language abilities. We found an increase in left intrahemispheric and bilateral language network connectivity and a decrease in right intrahemispheric connectivity associated with larger volumes of the posterior, mid‐posterior, and central subsections of the CC. Consistent with that, larger volumes of the posterior parts of the CC were significantly associated with better verbal fluency and vocabulary, the anterior CC volume was positively correlated with verbal span. Thus, children with larger volumes of CC subsections showed increased interhemispheric language network connectivity and were better in different language domains. This study presents the first evidence that the CC is directly linked to language network connectivity and underlines the excitatory role of the CC in the integration of information from both hemispheres.
HighlightsHealthy children and adolescents exhibit mesial temporal lobe activations during semant... more HighlightsHealthy children and adolescents exhibit mesial temporal lobe activations during semantic language processing.Bilateral mesial temporal lobe involvement is advantageous for vocabulary skills in healthy, right‐handed children and adolescents.Thus, the mesial temporal lobes of both hemispheres play an important role in language functioning in right‐handed children and adolescents. Abstract This study considered the involvement of the mesial temporal lobe (MTL) in language and verbal memory functions in healthy children and adolescents. We investigated 30 healthy, right‐handed children and adolescents, aged 7–16, with a fMRI language paradigm and a comprehensive cognitive test battery. We found significant MTL activations during language fMRI in all participants; 63% of them had left lateralized MTL activations, 20% exhibited right MTL lateralization, and 17% showed bilateral MTL involvement during the fMRI language paradigm. Group analyses demonstrated a strong negative correlation between the lateralization of MTL activations and language functions. Specifically, children with less lateralized MTL activation showed significantly better vocabulary skills. These findings suggest that the mesial temporal lobes of both hemispheres play an important role in language functioning, even in right‐handers. Our results furthermore show that bilateral mesial temporal lobe involvement is advantageous for vocabulary skills in healthy, right‐handed children and adolescents.
B cell depletion with the anti-CD20-antibody rituximab is widely considered treatment of choice f... more B cell depletion with the anti-CD20-antibody rituximab is widely considered treatment of choice for long-term immunotherapy in aquaporin-4 (AQP4)-antibody positive neuromyelitis optica spectrum disorder (NMOSD). However, up to 30% of patients suffer from relapses despite complete B cell depletion. In these cases, the IL6 (interleukin-6)-receptor blocking antibody tocilizumab has been suggested as an alternative. We report two female adolescents with AQP4-antibody positive NMOSD who relapsed under rituximab treatment and clinically stabilized after switching to monthly administrations of tocilizumab. Our data suggest that early escalation of therapy with tocilizumab may lead to stabilization of disease activity in pediatric NMOSD patients who relapse under B cell depletion.
B cell depletion with the anti-CD20-antibody rituximab is widely considered treatment of choice f... more B cell depletion with the anti-CD20-antibody rituximab is widely considered treatment of choice for long-term immunotherapy in aquaporin-4 (AQP4)-antibody positive neuromyelitis optica spectrum disorder (NMOSD). However, up to 30% of patients suffer from relapses despite complete B cell depletion. In these cases, the IL6 (interleukin-6)-receptor blocking antibody tocilizumab has been suggested as an alternative. We report two female adolescents with AQP4-antibody positive NMOSD who relapsed under rituximab treatment and clinically stabilized after switching to monthly administrations of tocilizumab. Our data suggest that early escalation of therapy with tocilizumab may lead to stabilization of disease activity in pediatric NMOSD patients who relapse under B cell depletion.
The diagnosis of multiple sclerosis (MS) both in children and adults is based on clinical and mag... more The diagnosis of multiple sclerosis (MS) both in children and adults is based on clinical and magnetic resonance imaging (MRI) features according to the McDonald criteria. Little is known about differences in the presentation between pre-pubertal children, adolescents, and adult patients at disease onset. To compare (1) the clinical, cerebrospinal fluid (CSF), and MRI characteristics, and (2) the diagnostic performance of the 2010 McDonald criteria between pre-pubertal, adolescent, and adult patients with a clinically isolated syndrome (CIS). We performed a retrospective analysis of the initial brain and spinal cord MRI scans from 11 pre-pubertal children, 46 adolescents, and 56 adults with a CIS. Furthermore, clinical, CSF characteristics, and the performance of the 2010 McDonald criteria were compared. The first inter-attack interval tended to increase with age. With respect to MRI presentation, significantly fewer pre-pubertal children presented with juxtacortical and callosal lesions. We found no significant differences in the fulfillment of the 2010 McDonald criteria between the groups. In this retrospective series, subtle differences between children, adolescents, and adults with a CIS were noted. Larger samples are required in order to establish distinct features of the different age groups.
Since the first postmortem lesion studies of patients with aphasia, we know that the left hemisph... more Since the first postmortem lesion studies of patients with aphasia, we know that the left hemisphere carries many language functions (Broca, 1861; Wernicke, 1874). Modern neuroimaging methods demonstrate that in about 90%-96% of adult right-handers, language is localized predominantly in the left hemisphere (Berl,
We investigated the predictive value of prenatal superior temporal sulcus (STS) depth asymmetry i... more We investigated the predictive value of prenatal superior temporal sulcus (STS) depth asymmetry in a special case of a female dizygotic twin that showed inverted prenatal asymmetry of this structure. For this purpose, we performed a follow-up investigation in this former fetus at the age of seven, where we assessed the functional language lateralization using task-based and resting-state functional magnetic resonance imaging (fMRI). As control group we employed her twin brother, who showed a typical folding pattern prenatally, as well as a complementary set of four age-matched children that had fetal MRI of their brains and typical STS depth asymmetry. We could show that the twin with the atypical fetal asymmetry of the STS also showed significantly differing rightward language lateralization in the frontal and temporal lobes. Additionally, resting-state data suggest a stronger connectivity between inferior frontal gyri in this case. The twin showed normal cognitive development. Thi...
Prenatal detection of abnormal white matter tracts might serve as a structural marker for altered... more Prenatal detection of abnormal white matter tracts might serve as a structural marker for altered neurodevelopment. As a result of many technical and patient-related challenges, the accuracy of prenatal tractography remains unknown. We hypothesized that characteristics of prenatal tractography of the corpus callosum and corticospinal tracts derived from fetal diffusion tensor imaging (DTI) data are accurate and predictive of the integrity of these tracts postnatally. We compared callosal and corticospinal tracts of 12 subjects with paired prenatal (age: 23-35 gestational weeks) and postnatal (age: 1 day to 2 years) DTI examinations (b values of 0 s/mmand 700 s/mm, 16 gradient encoding directions) using deterministic tractography. Evaluation for the presence of callosal segments and corticospinal tracts showed moderate degrees of accuracy (67-75%) for the four segments of the corpus callosum and moderate to high degrees of accuracy (75-92%) for the corticospinal tracts. Positive pred...
Situs inversus totalis is a rare condition where the visceral organs are organized as a mirror im... more Situs inversus totalis is a rare condition where the visceral organs are organized as a mirror image of default organ position. In this study we picture the co-development between brain and visceral organs in a case of situs inversus totalis from a fetal stage to adolescence and compare our findings to an age-, gender-, and education-matched control with normal position of thoracic and abdominal organs. We show that in this case of situs inversus, functional and structural brain lateralization do not coincide with visceral organ situs. Furthermore, cognitive development in situs inversus is normal. To our knowledge, this is the first report of antenatal cerebral origins of structural and functional brain asymmetry in a case of situs inversus totalis.
Mutations in genes encoding enzymes responsible for the biosynthesis and structural diversity of ... more Mutations in genes encoding enzymes responsible for the biosynthesis and structural diversity of glycosaminoglycans (GAGs) cause a variety of disorders affecting bone and connective tissues, including Desbuquois dysplasia (DD). In an infant with prenatal-onset disproportionate short stature, joint laxity, and radiographic findings typical for DD compound-heterozygosity for a large intragenic deletion, and a p.Pro384Arg missense mutation in CSGALNACT1 was found. CSGALNACT1 encodes chondroitin sulfate N-acetylgalactosaminyltransferase-1 (CSGalNAcT-1, ChGn-1), which initiates chondroitin sulfate (CS) chain biosynthesis on the so-called GAG-protein linker region tetrasaccharide. Biochemical studies revealed a reduced GalNAc-transferase activity of the Arg-384 mutant protein, whereas no differences in proteoglycan synthesis in fibroblasts and the GAG content in the urine were found between patient and controls. This is the first description of bi-allelic loss-of-function mutations in CSGALNACT1 that produce a skeletal dysplasia reminiscent of the skeletal dysplasia of Csgalnact1(-/-) mice, and adds to the genetic heterogeneity of DD.
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Papers by Rainer Seidl