Papers by Regina Trollmann
Journal of Neuromuscular Diseases
Background and objectives: Disease progression in patients with spinal muscular atrophy (SMA) has... more Background and objectives: Disease progression in patients with spinal muscular atrophy (SMA) has changed dramatically within the past years due to the approval of three different disease-modifying treatments. Nusinersen was the first drug to be approved for the treatment of SMA patients. Clinical trials provided data from infants with SMA type 1 and children with SMA type 2, but there is still insufficient evidence and only scarcely reported long-term experience for nusinersen treatment in ambulant patients. Here, we report data from the SMArtCARE registry of ambulant patients under nusinersen treatment with a follow-up period of up to 38 months. Methods: SMArtCARE is a disease-specific registry in Germany, Austria and Switzerland. Data are collected as real-world data during routine patient visits. Our analysis included all patients under treatment with nusinersen able to walk independently before start of treatment with focus on changes in motor function. Results: Data from 231 a...
Brain
5q-associated spinal muscular atrophy is a rare neuromuscular disorder with the leading symptom o... more 5q-associated spinal muscular atrophy is a rare neuromuscular disorder with the leading symptom of a proximal muscle weakness. Three different drugs have been approved by the European Medicines Agency and Food and Drug Administration for the treatment of spinal muscular atrophy patients, however, long-term experience is still scarce. In contrast to clinical trial data with restricted patient populations and short observation periods, we report here real-world evidence on a broad spectrum of patients with early-onset spinal muscular atrophy treated with nusinersen focusing on effects regarding motor milestones, and respiratory and bulbar insufficiency during the first years of treatment. Within the SMArtCARE registry, all patients under treatment with nusinersen who never had the ability to sit independently before the start of treatment were identified for data analysis. The primary outcome of this analysis was the change in motor function evaluated with the Children’s Hospital of P...
Orphanet Journal of Rare Diseases
Orphanet Journal of Rare Diseases
Background The development and approval of disease modifying treatments have dramatically changed... more Background The development and approval of disease modifying treatments have dramatically changed disease progression in patients with spinal muscular atrophy (SMA). Nusinersen was approved in Europe in 2017 for the treatment of SMA patients irrespective of age and disease severity. Most data on therapeutic efficacy are available for the infantile-onset SMA. For patients with SMA type 2 and type 3, there is still a lack of sufficient evidence and long-term experience for nusinersen treatment. Here, we report data from the SMArtCARE registry of non-ambulant children with SMA type 2 and typen 3 under nusinersen treatment with a follow-up period of up to 38 months. Methods SMArtCARE is a disease-specific registry with data on patients with SMA irrespective of age, treatment regime or disease severity. Data are collected during routine patient visits as real-world outcome data. This analysis included all non-ambulant patients with SMA type 2 or 3 below 18 years of age before initiation ...
Neurological Research and Practice
Background In Dravet syndrome (DS), a rare epileptic and developmental encephalopathy, the effect... more Background In Dravet syndrome (DS), a rare epileptic and developmental encephalopathy, the effectiveness of a new treatment is predominantly measured in terms of seizure frequency. However, this may not fully capture the impact of a treatment on the broader aspects of the syndrome and patients’ health-related quality of life (HRQoL). Using a previously published survey which collected data from DS patients and their carers on the broader manifestations of their syndrome, their HRQoL, and their experience of seizures, this study created composite measures of symptom severity to offer new perspectives on the multifaceted aspects of this rare condition. Methods Survey responses on the severity of physical and psychosocial symptoms were combined with independent assessments of disability and care need, to generate three composite symptom scores assessing the manifestations of DS (physical, psychosocial and care requirements). Variation in HRQoL was investigated in multiple regression an...
European Journal of Neurology, 2022
Background and purposeThe therapeutic landscape of spinal muscular atrophy (SMA) has changed dram... more Background and purposeThe therapeutic landscape of spinal muscular atrophy (SMA) has changed dramatically during the past 4 years, but treatment responses differ remarkably between individuals, and therapeutic decision‐making remains challenging, underlining the persistent need for validated biomarkers.MethodsWe applied untargeted proteomic analyses to determine biomarkers in cerebrospinal fluid (CSF) samples of SMA patients under treatment with nusinersen. Identified candidate proteins were validated in CSF samples of SMA patients by Western blot and enzyme‐linked immunosorbent assay. Furthermore, levels of peripheral neurofilament heavy and light chain were determined.ResultsUntargeted proteomic analysis of CSF samples of three SMA type 1 patients revealed the lysosomal protease cathepsin D as a candidate biomarker. Subsequent validation analysis in a larger cohort of 31 pediatric SMA patients (type 1, n = 12; type 2, n = 9; type 3, n = 6; presymptomatically treated, n = 4; age = ...
Leitlinien Kinder- und Jugendmedizin, 2015
Der Nervenarzt, 2020
Zusammenfassung Hintergrund Die Muskeldystrophie Duchenne (DMD) ist die häufigste genetische neur... more Zusammenfassung Hintergrund Die Muskeldystrophie Duchenne (DMD) ist die häufigste genetische neuromuskuläre Krankheit im Kindesalter, bei der es meist im Alter von 9 bis 11 Jahren zum Verlust der Gehfähigkeit kommt. Ziel der Arbeit und Material und Methoden Auf der Grundlage aktueller Leitlinien und Studien erarbeiteten neuropädiatrische und neurologische Experten im Rahmen eines von der Firma PTC Therapeutics GmbH (Frankfurt am Main, Deutschland), die die Substanz Ataluren vertreibt, gesponserten Advisory Boards Empfehlungen zur Behandlung nichtgehfähiger Patienten mit DMD mit Schwerpunkt medikamentöse Therapien von Erwachsenen. Ergebnisse und Diskussion Der Verlust der Gehfähigkeit wird in Studien sehr unterschiedlich definiert und bezieht sich u. a. auf die Rollstuhlpflicht, das selbständige Gehen ohne Hilfsmittel oder die maximale Gehstrecke. Grundlage der Therapie von Patienten mit DMD in jedem Krankheitsstadium sind supportive und symptomatische Maßnahmen, die in der Regel auc...
Epilepsia, 2021
ObjectiveDravet syndrome (DS) is a rare but severe drug‐resistant epilepsy. Before the approval o... more ObjectiveDravet syndrome (DS) is a rare but severe drug‐resistant epilepsy. Before the approval of fenfluramine (FFA) for the treatment of seizures in DS, patients in Germany could receive treatment under a compassionate use program (CUP).MethodsWe conducted a multicenter, retrospective, observational study to describe the efficacy, tolerability, and retention of FFA within the CUP. Patients received add‐on therapy with oral FFA gradually titrated to a target dose between .13 and .7 mg/kg/day.ResultsOverall, 78 patients with DS (median age = 8.0 years, range = 2.1–46.0; 53% female, median concomitant antiseizure medications [ASMs] = 3) were treated with FFA for a median duration of 255.5 days (range = 31–572). Responder rates (a ≥50% reduction; n = 78) and seizure‐freedom rates at 3 months were 68% and 14% for total seizures, respectively, and 67% and 23% for generalized tonic–clonic seizures. Responder rates were consistent at 6 and 12 months (n = 66 and n = 43, respectively). Medi...
Journal of Neurodevelopmental Disorders, 2020
Background Tuberous sclerosis complex (TSC)-associated neuropsychiatric disorders (TAND) have uni... more Background Tuberous sclerosis complex (TSC)-associated neuropsychiatric disorders (TAND) have unique, individual patterns that pose significant challenges for diagnosis, psycho-education, and intervention planning. A recent study suggested that it may be feasible to use TAND Checklist data and data-driven methods to generate natural TAND clusters. However, the study had a small sample size and data from only two countries. Here, we investigated the replicability of identifying natural TAND clusters from a larger and more diverse sample from the TOSCA study. Methods As part of the TOSCA international TSC registry study, this embedded research project collected TAND Checklist data from individuals with TSC. Correlation coefficients were calculated for TAND variables to generate a correlation matrix. Hierarchical cluster and factor analysis methods were used for data reduction and identification of natural TAND clusters. Results A total of 85 individuals with TSC (female:male, 40:45) f...
European Journal of Paediatric Neurology, 2019
Objective: Screening for cognitive impairment (CI), fatigue and also Health-related quality of li... more Objective: Screening for cognitive impairment (CI), fatigue and also Health-related quality of life (HRQoL) in patients with pediatric-onset multiple sclerosis (POMS) is of utmost importance in clinical practice. The aim of this study was to establish a new and validated pediatric screening tool "MUSICADO" that is easy to use and time economical. Methods: 106 patients with POMS aged 12e18 years and 210 healthy controls (HCs) stratified for age and education underwent neuropsychological testing including a screening test "Multiple Sclerosis Inventory of Cognition" for adults and 8 standardized cognitive tests and established scales to assess fatigue and HRQoL. Results: The phonemic verbal fluency task (RWT "s-words"), the Trail Making Test A (TMT-A), and the Digit Span Forward discriminated significantly between patients and HCs (p ¼ 0.000, respectively) and showed the highest proportion of test failure in patients (24.5%, 17.9%; 15.1%, respectively). Therefore, they were put together to form the cognitive part of the "MUSICADO". After applying a scoring algorithm with balanced weighting of the
European Journal of Paediatric Neurology, 2015
Objective: 0-3 years children seem to be at increased risk for speech and language disorders. Met... more Objective: 0-3 years children seem to be at increased risk for speech and language disorders. Methods: Parents of 202 children within age 0-3 years (141 male, 61 female) completed screening questionnaires and the child was evaluated on the language scale. The screening battery included the Risk Factor Assessment Questionnaire for socio demographic profile, Home Screening Questionnaire (HSQ) and LEST. Children with disabilities were excluded. Results: Twelve children (5.9%) screened positive for LEST delay. Among them 10 children (83.3%) had negative home environment while 2 children (16.7%) had positive environment on Home Screening Questionnaires. Of the 12 children who showed LEST delay 8 (66.7%) were boys and 4 (33.3%) were girls. LEST total delay showed a similar trend on the basis of religion as 8 (66.7%) were Hindus and 4 (33.3%) were Muslims. The overall socio economic status of majority of families was 73 (38.4%) lower middle class with 7 (58.3%) showing LEST delay. The mean age of mother in case of LEST delay was 23.42 (SD 2.234) and mean age of father in case of LEST delay was 26.42 (SD 2.644). The average birth weight noticed was 3158.33 grams (SD 511.163) with P value 0.047. There was no significant relation with gestational age and the LEST delay as 11 (91.7%) of the children were born at term and 1 (8.3%) was born preterm. There was relation in LEST delay and place of residence as 10 (83.3%) were urban dwellers and 2 (18.7%) were from rural background. Conclusion: Our results indicate a higher prevalence of speech and language delay in children with negative home environment compared to the general population prevalence. The speech and language delay was associated with male child. There was more so prevalence in urban children without any relation to the preterm gestation. Our findings support the simultaneous use of more than one screening tests in order to increase screening sensitivity PP02.13-2983 Human neural stem cells improve water maze learning after rat pup moderate ischemic injury without affecting injury volume
Neuropediatrics, 2012
Pyruvate dehydrogenase complex (PDHc) deficiency is an inborn error of carbohydrate metabolism th... more Pyruvate dehydrogenase complex (PDHc) deficiency is an inborn error of carbohydrate metabolism that is heterogeneous in its presentation and clinical course. Most cases of PDHc deficiency are attributable to mutations in the X-chromosomal PDHA1 gene which encodes the E1α subunit. We report the case of a girl with first symptoms at age 4 months including muscular hypotonia, lactic acidosis and microcephaly. Brain MRI revealed an incomplete corpus callosum and a pronounced generalized cortical atrophy. Muscle biopsy performed for clinically suspected mitochondriopathy revealed normal respiratory chain enzymes. Functional investigation of intact mitochondria from unfrozen muscle tissue showed a deficiency of pyruvate oxidation. Sequencing of PDHA1 gene revealed a heterogeneous mutation c.523G>A resulting in a predicted alanine to threonine substitution at amino acid 175. To the best of our knowledge, this mutation has not yet been reported. However, another mutation in the same codon has been described in a girl with PDHc-deficiency resulting in an amino acid substitution of alanine to proline. The fact that alanine 175 is highly conserved suggests that this substitution is the causative mutation.
Orphanet Journal of Rare Diseases
Background Tuberous sclerosis complex (TSC) is a rare multisystem disorder caused by mutations in... more Background Tuberous sclerosis complex (TSC) is a rare multisystem disorder caused by mutations in the TSC1 or TSC2 gene. More than 90% of patients with TSC develop neurological and/or neuropsychiatric manifestations. The aim of the present study was to determine the developmental and cognitive long-term outcomes of pediatric TSC patients. Methods This cross-sectional, monocenter study included pediatric TSC patients who received multidisciplinary long-term care with a last visit between 2005 and 2019. Neurological manifestations and cognitive development (BSID, K-ABC) were analyzed in relation to age and type of mutation. Results Thirty-five patients aged 13.5 ± 7.8 years were included in the study. Diagnosis was confirmed genetically in 65.7% of patients (TSC1, 26.1%; TSC2, 65.2%; NMI, 8.7%). Mean age at diagnosis was 1.3 ± 3.5 years; 74.3% of the patients had been diagnosed within the first year of life due to seizures (62.9%) or/and cardiac rhabdomyomas (28.6%). The most common T...
Frauenheilkunde up2date, 2012
Kurzlehrbuch Pädiatrie, 2012
Orphanet Journal of Rare Diseases
Background The oral, selective SMN2-splicing modifier risdiplam obtained European approval in Mar... more Background The oral, selective SMN2-splicing modifier risdiplam obtained European approval in March 2021 for the treatment of patients ≥ 2 months old with a clinical diagnosis of 5q-associated spinal muscular atrophy (SMA) 1/2/3 or with 1–4 SMN2 gene copies. For the preceding 12 months, this compassionate use program (CUP) made risdiplam available to patients with SMA1/2 in Germany who could not receive any approved SMA therapy. Patients and methods Patients with SMA1/2, aged ≥ 2 months at enrollment, could be included if they were not eligible for, no longer responsive to, or not able to tolerate nusinersen or not able to receive onasemnogene abeparvovec. Oral risdiplam dosing ranged from 0.2 mg/kg to 5 mg depending on age and weight. All treatment decisions were made by the attending physicians, who were required to report all adverse events (AEs). Results Between March 12, 2020 and March 30, 2021, 36 patients with SMA1 and 98 patients with SMA2 were enrolled, with 31 patients and...
Abstracts of the 45th Annual Meeting of the Society for Neuropediatrics, 2019
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Papers by Regina Trollmann