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Papers by Thomas Schmitt-mechelke

Research paper thumbnail of Incidence and Outcomes of Symptomatic Neonatal Arterial Ischemic Stroke

Pediatrics, Jan 20, 2015

Neonatal arterial ischemic stroke (NAIS) is associated with considerable lifetime burdens such as... more Neonatal arterial ischemic stroke (NAIS) is associated with considerable lifetime burdens such as cerebral palsy, epilepsy, and cognitive impairment. Prospective epidemiologic studies that include outcome assessments are scarce. This study aimed to provide information on the epidemiology, clinical manifestations, infarct characteristics, associated clinical variables, treatment strategies, and outcomes of NAIS in a prospective, population-based cohort of Swiss children. This prospective study evaluated the epidemiology, clinical manifestations, vascular territories, associated clinical variables, and treatment of all full-term neonates diagnosed with NAIS and born in Switzerland between 2000 and 2010. Follow-up was performed 2 years (mean 23.3 months, SD 4.3 months) after birth. One hundred neonates (67 boys) had a diagnosis of NAIS. The NAIS incidence in Switzerland during this time was 13 (95% confidence interval [CI], 11-17) per 100 000 live births. Seizures were the most common ...

Research paper thumbnail of Outcome of extremely low gestational age newborns (ELGANs) following a pro-active treatment approach: A Swiss single centre experience over 10 years

Swiss Medical Weekly, 2014

To determine the impact of a pro-active treatment approach on outcome of extremely low gestationa... more To determine the impact of a pro-active treatment approach on outcome of extremely low gestational age neonates (ELGANs; gestational age [GA] <28 weeks) born at the perinatal centre of Lucerne, Switzerland. We assessed rates of survival, severe neonatal morbidity and neuro-developmental impairment (NDI) of all ELGANs born alive and treated at our centre between 2000 and 2009. The results were compared with published data from contemporary national and international cohorts. Over the 10-year study period, a total of 216 ELGANs were born alive at the perinatal centre of Lucerne. The survival rate was 74% for all live-born infants, and 81% for those admitted to the neonatal intensive care unit. Among the 160 survivors, 25% sustained at least one major neonatal morbidity; severe brain injury (i.e., periventricular/intraventricular haemorrhage grade 3 or 4 and/or cystic periventricular leukomalacia) affected 10%; moderate or severe bronchopulmonary dysplasia 16%; retinopathy of prematurity ≥ stage 3 1%; and necrotising enterocolitis 2%. Neuro-developmental outcome data at 18 to 24 months was available for 92% of all survivors: 88% had no or mild NDI, whereas moderate and severe NDI were present in 10% and 2%, respectively. When compared with published national or international data, our pro-active treatment approach to ELGANs was associated with higher or equal survival rates without increasing rates of severe neonatal morbidity or neuro-developmental impairment at the age of 18 to 24 months.

Research paper thumbnail of The First Three Years of the Swiss Neuropaediatric Stroke Registry (SNPSR): A Population-Based Study of Incidence, Symptoms and Risk Factors

Neuropediatrics, 2005

We report the results of three years of the population-based, prospective Swiss NeuroPaediatric S... more We report the results of three years of the population-based, prospective Swiss NeuroPaediatric Stroke Registry (SNPSR) of children (up to 16 years) with childhood arterial ischaemic stroke (AIS1), neonatal stroke (AIS2), or symptomatic sinus venous thrombosis (SVT). Data on risk factors (RF), presentation, diagnostic work-up, localisation, and short-term neurological outcome were collected. 80 children (54 males) have been included, 40 AIS1, 23 AIS2, and 17 SVT. The data presented will be concentrated on AIS. The presentation for AIS1 was hemiparesis in 77% and cerebellar symptoms and seizures in 20 %, respectively. AIS2 presented in 83% with seizures and in 38% with abnormality of muscle tone. Two or more RF were detected in 54%, one RF in 35%. The most prominent RF for AIS1 were infections (40%), followed by cardiopathies and coagulopathies (25% each). AIS2 were frequently related to birth problems. Neurological outcomes in AIS1 and AIS2 were moderate/severe in 45 % and 32%, respectively. The outcome correlated significantly with the size of infarction (p = 0.013) and age at stroke (p = 0.027). The overall mortality was 6%. Paediatric stroke is a multiple risk problem, which leads to important long-term sequelae.

Research paper thumbnail of Neuroimaging in childhood arterial ischaemic stroke: evaluation of aetiologies and imaging modalities

Research paper thumbnail of Neuropsychological Problems after Paediatric Stroke: Two Year Follow-Up of Swiss Children

Neuropediatrics, 2006

The aim of this study was to obtain information about neurological and cognitive outcome for a po... more The aim of this study was to obtain information about neurological and cognitive outcome for a population-based group of children after paediatric ischaemic stroke. Data from the Swiss neuropaediatric stroke registry (SNPSR), from 1.1.2000 to 1.7.2002, including children (AIS 1) and neonates (AIS 2). At 18-24 months after a stroke, a follow-up examination was performed including a history, neurological and neuropsychological assessment. 33/48 children (22 AIS 1, 11 AIS 2) participated in the study. Neurological outcome was good in 16/33. After childhood stroke mean IQ levels were normal (94), but 6 children had IQ < 85 (50-82) and neuropsychological problems were present in 75%. Performance IQ (93) was reduced compared to verbal IQ (101, p = 0.121) due to problems in the domain of processing speed (89.5); auditory short-term memory was especially affected. Effects on school career were common. Outcome was worse in children after right-sided infarction. Children suffering from stroke in mid-childhood had the best prognosis. There was no clear relationship between outcome and localisation of the lesion. After neonatal stroke 7/11 children showed normal development and epilepsy indicated a worse prognosis in the remaining 4. After paediatric stroke neuropsychological problems are present in about 75% of children. Younger age at stroke as well as an emergence of epilepsy were predictors for worse prognosis.

Research paper thumbnail of Mutations in the cyclin family member FAM58A cause an X-linked dominant disorder characterized by syndactyly, telecanthus and anogenital and renal malformations

Research paper thumbnail of Pontocerebellar hypoplasia type 2: Variability in clinical and imaging findings

European Journal of Paediatric Neurology, 2007

We report 24 children (14 girls) who presented with the typical neuroimaging findings of pontocer... more We report 24 children (14 girls) who presented with the typical neuroimaging findings of pontocerebellar hypoplasia (PCH) to describe the clinical spectrum of type 2. Twenty-one presented with the classical form described by Barth; characteristic features (15/21) were breathing and/or sucking problems during neonatal period and early onset hyperkinetic movement disorder. Eighteen were normocephalic at birth, but all developed microcephaly during infancy. Development was severely affected with none of the children being capable of sitting, walking, or talking. Social contact and visual fixation were persistently poor. Dyskinetic movement disorder was present in all, in some together with mild spasticity. Seizures occurred in 14 (in 7 as neonates). Eight children died (age 1 day-6 years). Neuroimaging showed an absent or severely flattened pons, different degrees of vermian hypoplasia, with cerebellar hemispheres (wing-like structures) being equally or more affected. Three (all girls) were less severely affected clinically and did not develop the dyskinetic movement disorder, motor and cognitive development were somewhat better. Microcephaly was also a prominent sign. Severity of pontocerebellar neuroimaging findings did not differentiate between the typical and atypical clinical group and did not correlate with clinical outcome.

Research paper thumbnail of Tracking the source of cerebellar epilepsy: Hemifacial seizures associated with cerebellar cortical dysplasia

Epilepsy Research, 2013

Please cite this article in press as: Lascano, A.M., et al., Tracking the source of cerebellar ep... more Please cite this article in press as: Lascano, A.M., et al., Tracking the source of cerebellar epilepsy: Hemifacial seizures associated with cerebellar cortical dysplasia. Epilepsy Res. (2013), http://dx.Summary Traditionally, subcortical structures such as the cerebellum are supposed to exert a modulatory effect on epileptic seizures, rather than being the primary seizure generator. We report a 14-month old girl presenting, since birth, with seizures symptomatic of a right cerebellar dysplasia, manifested as paroxystic contralateral hemifacial spasm and ipsilateral facial weakness. Multimodal imaging was used to investigate both anatomical landmarks related to the cerebellar lesion and mechanisms underlying seizure generation. Electric source imaging (ESI) supported the hypothesis of a right cerebellar epileptogenic generator in concordance with nuclear imaging findings; subsequently validated by intra-operative intralesional recordings. Diffusion spectrum imaging-related tractography (DSI) showed severe cerebellar structural abnormalities confirmed by histological examination. We suggest that hemispheric cerebellar lesions in cases like this are likely to cause epilepsy via an effect on the facial nuclei through ipsilateral and contralateral aberrant connections.

Research paper thumbnail of Vigabatrin therapy in infantile spasms: Solving one problem and inducing another?

Research paper thumbnail of Cerebral sinus venous thrombosis in Swiss children

Developmental Medicine & Child Neurology, 2010

AIM To describe the characteristics of paediatric cerebral sinus venous thrombosis (CSVT) in Swit... more AIM To describe the characteristics of paediatric cerebral sinus venous thrombosis (CSVT) in Switzerland.

Research paper thumbnail of Basilar artery stroke in childhood

Developmental Medicine & Child Neurology, 2013

Research paper thumbnail of Infection-Triggered Familial or Recurrent Cases of Acute Necrotizing Encephalopathy Caused by Mutations in a Component of the Nuclear Pore, RANBP2

The American Journal of Human Genetics, 2009

Acute necrotizing encephalopathy (ANE) is a rapidly progressive encephalopathy that can occur in ... more Acute necrotizing encephalopathy (ANE) is a rapidly progressive encephalopathy that can occur in otherwise healthy children after common viral infections such as influenza and parainfluenza. Most ANE is sporadic and nonrecurrent (isolated ANE). However, we identified a 7 Mb interval containing a susceptibility locus (ANE1) in a family segregating recurrent ANE as an incompletely penetrant, autosomal-dominant trait. We now report that all affected individuals and obligate carriers in this family are heterozygous for a missense mutation (c.1880C/T, p.Thr585Met) in the gene encoding the nuclear pore protein Ran Binding Protein 2 (RANBP2). To determine whether this mutation is the susceptibility allele, we screened controls and other patients with ANE who are unrelated to the index family. Patients from 9 of 15 additional kindreds with familial or recurrent ANE had the identical mutation. It arose de novo in two families and independently in several other families. Two other patients with familial ANE had different RANBP2 missense mutations that altered conserved residues. None of the three RANBP2 missense mutations were found in 19 patients with isolated ANE or in unaffected controls. We conclude that missense mutations in RANBP2 are susceptibility alleles for familial and recurrent cases of ANE. Neurology,

Research paper thumbnail of Neuroimaging in childhood arterial ischaemic stroke: evaluation of imaging modalities and aetiologies

Developmental Medicine & Child Neurology, 2010

ACA Anterior cerebral artery AIS Acute ischaemic stroke DWI Diffusion-weighted imaging MCA Middle... more ACA Anterior cerebral artery AIS Acute ischaemic stroke DWI Diffusion-weighted imaging MCA Middle cerebral artery MRA Magnetic resonance angiography AIM The aim of this study was to describe neuroimaging patterns associated with arterial ischaemic stroke (AIS) in childhood and to differentiate them according to stroke aetiology. METHOD Clinical and neuroimaging (acute and follow-up) findings were analysed prospectively in 79 children (48 males, 31 females) aged 2 months to 15 years 8 months (median 5y 3mo) at the time of stroke by the Swiss Neuropaediatric Stroke Registry from 2000 to 2006.

Research paper thumbnail of Incidence and Outcomes of Symptomatic Neonatal Arterial Ischemic Stroke

Pediatrics, Jan 20, 2015

Neonatal arterial ischemic stroke (NAIS) is associated with considerable lifetime burdens such as... more Neonatal arterial ischemic stroke (NAIS) is associated with considerable lifetime burdens such as cerebral palsy, epilepsy, and cognitive impairment. Prospective epidemiologic studies that include outcome assessments are scarce. This study aimed to provide information on the epidemiology, clinical manifestations, infarct characteristics, associated clinical variables, treatment strategies, and outcomes of NAIS in a prospective, population-based cohort of Swiss children. This prospective study evaluated the epidemiology, clinical manifestations, vascular territories, associated clinical variables, and treatment of all full-term neonates diagnosed with NAIS and born in Switzerland between 2000 and 2010. Follow-up was performed 2 years (mean 23.3 months, SD 4.3 months) after birth. One hundred neonates (67 boys) had a diagnosis of NAIS. The NAIS incidence in Switzerland during this time was 13 (95% confidence interval [CI], 11-17) per 100 000 live births. Seizures were the most common ...

Research paper thumbnail of Outcome of extremely low gestational age newborns (ELGANs) following a pro-active treatment approach: A Swiss single centre experience over 10 years

Swiss Medical Weekly, 2014

To determine the impact of a pro-active treatment approach on outcome of extremely low gestationa... more To determine the impact of a pro-active treatment approach on outcome of extremely low gestational age neonates (ELGANs; gestational age [GA] <28 weeks) born at the perinatal centre of Lucerne, Switzerland. We assessed rates of survival, severe neonatal morbidity and neuro-developmental impairment (NDI) of all ELGANs born alive and treated at our centre between 2000 and 2009. The results were compared with published data from contemporary national and international cohorts. Over the 10-year study period, a total of 216 ELGANs were born alive at the perinatal centre of Lucerne. The survival rate was 74% for all live-born infants, and 81% for those admitted to the neonatal intensive care unit. Among the 160 survivors, 25% sustained at least one major neonatal morbidity; severe brain injury (i.e., periventricular/intraventricular haemorrhage grade 3 or 4 and/or cystic periventricular leukomalacia) affected 10%; moderate or severe bronchopulmonary dysplasia 16%; retinopathy of prematurity ≥ stage 3 1%; and necrotising enterocolitis 2%. Neuro-developmental outcome data at 18 to 24 months was available for 92% of all survivors: 88% had no or mild NDI, whereas moderate and severe NDI were present in 10% and 2%, respectively. When compared with published national or international data, our pro-active treatment approach to ELGANs was associated with higher or equal survival rates without increasing rates of severe neonatal morbidity or neuro-developmental impairment at the age of 18 to 24 months.

Research paper thumbnail of The First Three Years of the Swiss Neuropaediatric Stroke Registry (SNPSR): A Population-Based Study of Incidence, Symptoms and Risk Factors

Neuropediatrics, 2005

We report the results of three years of the population-based, prospective Swiss NeuroPaediatric S... more We report the results of three years of the population-based, prospective Swiss NeuroPaediatric Stroke Registry (SNPSR) of children (up to 16 years) with childhood arterial ischaemic stroke (AIS1), neonatal stroke (AIS2), or symptomatic sinus venous thrombosis (SVT). Data on risk factors (RF), presentation, diagnostic work-up, localisation, and short-term neurological outcome were collected. 80 children (54 males) have been included, 40 AIS1, 23 AIS2, and 17 SVT. The data presented will be concentrated on AIS. The presentation for AIS1 was hemiparesis in 77% and cerebellar symptoms and seizures in 20 %, respectively. AIS2 presented in 83% with seizures and in 38% with abnormality of muscle tone. Two or more RF were detected in 54%, one RF in 35%. The most prominent RF for AIS1 were infections (40%), followed by cardiopathies and coagulopathies (25% each). AIS2 were frequently related to birth problems. Neurological outcomes in AIS1 and AIS2 were moderate/severe in 45 % and 32%, respectively. The outcome correlated significantly with the size of infarction (p = 0.013) and age at stroke (p = 0.027). The overall mortality was 6%. Paediatric stroke is a multiple risk problem, which leads to important long-term sequelae.

Research paper thumbnail of Neuroimaging in childhood arterial ischaemic stroke: evaluation of aetiologies and imaging modalities

Research paper thumbnail of Neuropsychological Problems after Paediatric Stroke: Two Year Follow-Up of Swiss Children

Neuropediatrics, 2006

The aim of this study was to obtain information about neurological and cognitive outcome for a po... more The aim of this study was to obtain information about neurological and cognitive outcome for a population-based group of children after paediatric ischaemic stroke. Data from the Swiss neuropaediatric stroke registry (SNPSR), from 1.1.2000 to 1.7.2002, including children (AIS 1) and neonates (AIS 2). At 18-24 months after a stroke, a follow-up examination was performed including a history, neurological and neuropsychological assessment. 33/48 children (22 AIS 1, 11 AIS 2) participated in the study. Neurological outcome was good in 16/33. After childhood stroke mean IQ levels were normal (94), but 6 children had IQ < 85 (50-82) and neuropsychological problems were present in 75%. Performance IQ (93) was reduced compared to verbal IQ (101, p = 0.121) due to problems in the domain of processing speed (89.5); auditory short-term memory was especially affected. Effects on school career were common. Outcome was worse in children after right-sided infarction. Children suffering from stroke in mid-childhood had the best prognosis. There was no clear relationship between outcome and localisation of the lesion. After neonatal stroke 7/11 children showed normal development and epilepsy indicated a worse prognosis in the remaining 4. After paediatric stroke neuropsychological problems are present in about 75% of children. Younger age at stroke as well as an emergence of epilepsy were predictors for worse prognosis.

Research paper thumbnail of Mutations in the cyclin family member FAM58A cause an X-linked dominant disorder characterized by syndactyly, telecanthus and anogenital and renal malformations

Research paper thumbnail of Pontocerebellar hypoplasia type 2: Variability in clinical and imaging findings

European Journal of Paediatric Neurology, 2007

We report 24 children (14 girls) who presented with the typical neuroimaging findings of pontocer... more We report 24 children (14 girls) who presented with the typical neuroimaging findings of pontocerebellar hypoplasia (PCH) to describe the clinical spectrum of type 2. Twenty-one presented with the classical form described by Barth; characteristic features (15/21) were breathing and/or sucking problems during neonatal period and early onset hyperkinetic movement disorder. Eighteen were normocephalic at birth, but all developed microcephaly during infancy. Development was severely affected with none of the children being capable of sitting, walking, or talking. Social contact and visual fixation were persistently poor. Dyskinetic movement disorder was present in all, in some together with mild spasticity. Seizures occurred in 14 (in 7 as neonates). Eight children died (age 1 day-6 years). Neuroimaging showed an absent or severely flattened pons, different degrees of vermian hypoplasia, with cerebellar hemispheres (wing-like structures) being equally or more affected. Three (all girls) were less severely affected clinically and did not develop the dyskinetic movement disorder, motor and cognitive development were somewhat better. Microcephaly was also a prominent sign. Severity of pontocerebellar neuroimaging findings did not differentiate between the typical and atypical clinical group and did not correlate with clinical outcome.

Research paper thumbnail of Tracking the source of cerebellar epilepsy: Hemifacial seizures associated with cerebellar cortical dysplasia

Epilepsy Research, 2013

Please cite this article in press as: Lascano, A.M., et al., Tracking the source of cerebellar ep... more Please cite this article in press as: Lascano, A.M., et al., Tracking the source of cerebellar epilepsy: Hemifacial seizures associated with cerebellar cortical dysplasia. Epilepsy Res. (2013), http://dx.Summary Traditionally, subcortical structures such as the cerebellum are supposed to exert a modulatory effect on epileptic seizures, rather than being the primary seizure generator. We report a 14-month old girl presenting, since birth, with seizures symptomatic of a right cerebellar dysplasia, manifested as paroxystic contralateral hemifacial spasm and ipsilateral facial weakness. Multimodal imaging was used to investigate both anatomical landmarks related to the cerebellar lesion and mechanisms underlying seizure generation. Electric source imaging (ESI) supported the hypothesis of a right cerebellar epileptogenic generator in concordance with nuclear imaging findings; subsequently validated by intra-operative intralesional recordings. Diffusion spectrum imaging-related tractography (DSI) showed severe cerebellar structural abnormalities confirmed by histological examination. We suggest that hemispheric cerebellar lesions in cases like this are likely to cause epilepsy via an effect on the facial nuclei through ipsilateral and contralateral aberrant connections.

Research paper thumbnail of Vigabatrin therapy in infantile spasms: Solving one problem and inducing another?

Research paper thumbnail of Cerebral sinus venous thrombosis in Swiss children

Developmental Medicine & Child Neurology, 2010

AIM To describe the characteristics of paediatric cerebral sinus venous thrombosis (CSVT) in Swit... more AIM To describe the characteristics of paediatric cerebral sinus venous thrombosis (CSVT) in Switzerland.

Research paper thumbnail of Basilar artery stroke in childhood

Developmental Medicine & Child Neurology, 2013

Research paper thumbnail of Infection-Triggered Familial or Recurrent Cases of Acute Necrotizing Encephalopathy Caused by Mutations in a Component of the Nuclear Pore, RANBP2

The American Journal of Human Genetics, 2009

Acute necrotizing encephalopathy (ANE) is a rapidly progressive encephalopathy that can occur in ... more Acute necrotizing encephalopathy (ANE) is a rapidly progressive encephalopathy that can occur in otherwise healthy children after common viral infections such as influenza and parainfluenza. Most ANE is sporadic and nonrecurrent (isolated ANE). However, we identified a 7 Mb interval containing a susceptibility locus (ANE1) in a family segregating recurrent ANE as an incompletely penetrant, autosomal-dominant trait. We now report that all affected individuals and obligate carriers in this family are heterozygous for a missense mutation (c.1880C/T, p.Thr585Met) in the gene encoding the nuclear pore protein Ran Binding Protein 2 (RANBP2). To determine whether this mutation is the susceptibility allele, we screened controls and other patients with ANE who are unrelated to the index family. Patients from 9 of 15 additional kindreds with familial or recurrent ANE had the identical mutation. It arose de novo in two families and independently in several other families. Two other patients with familial ANE had different RANBP2 missense mutations that altered conserved residues. None of the three RANBP2 missense mutations were found in 19 patients with isolated ANE or in unaffected controls. We conclude that missense mutations in RANBP2 are susceptibility alleles for familial and recurrent cases of ANE. Neurology,

Research paper thumbnail of Neuroimaging in childhood arterial ischaemic stroke: evaluation of imaging modalities and aetiologies

Developmental Medicine & Child Neurology, 2010

ACA Anterior cerebral artery AIS Acute ischaemic stroke DWI Diffusion-weighted imaging MCA Middle... more ACA Anterior cerebral artery AIS Acute ischaemic stroke DWI Diffusion-weighted imaging MCA Middle cerebral artery MRA Magnetic resonance angiography AIM The aim of this study was to describe neuroimaging patterns associated with arterial ischaemic stroke (AIS) in childhood and to differentiate them according to stroke aetiology. METHOD Clinical and neuroimaging (acute and follow-up) findings were analysed prospectively in 79 children (48 males, 31 females) aged 2 months to 15 years 8 months (median 5y 3mo) at the time of stroke by the Swiss Neuropaediatric Stroke Registry from 2000 to 2006.