Oliver Schwartz

University Hospital of Münster · Pediatric Neurology

Importance There is increasing evidence that early diagnosis and treatment are key for outcomes in infants with spinal muscular atrophy (SMA), and newborn screening programs have been implemented to detect the disease before onset of symptoms. However, data from controlled studies that reliably confirm the benefits of newborn screening are lacking....

Newborn screening for 5qSMA offers the potential for early, ideally pre-symptomatic, therapeutic intervention. However, limited data exist on the outcomes of individuals with 4 copies of SMN2, and there is no consensus within the SMA treatment community regarding early treatment initiation in this subgroup. To provide evidence-based insights into d...

Objective: Numerous studies have consistently found that reduced SMN protein expression does not severely affect cognitive function in SMA patients. However, the average intelligence quotient of SMA patients has ranged above to below average in different studies. The cognitive development of SMA patients identified through newborn screening remains...

Purpose: Primary ciliary dyskinesia (PCD) is a heterogeneous disorder including respiratory symptoms, laterality defects and infertility caused by dysfunction of motile cilia. Most PCD-causing variants result in abnormal outer dynein arms (ODAs), which provide the generative force for respiratory ciliary beating and proper mucociliary clearance....

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...

Now that targeted therapies for spinal muscular atrophy are available, attempts are being made worldwide to include screening for spinal muscular atrophy in general newborn screening. In Germany, after a pilot project from 2018–2021, it was included in the general newborn screening from October 2021. To ensure a smooth transition, criteria for foll...

The aim of this study was to assess the psychosocial burden in parents of children with spinal muscular atrophy (SMA), detected by newborn screening (NBS), for which first pilot projects started in January 2018 in Germany. The survey, performed 1–2 years after children’s diagnosis of SMA via NBS, included 3 parent-related questionnaires to evaluate...

Correction to: Orphanet Journal of Rare Diseases (2022) 17:276 https://doi.org/10.1186/s13023-022-02420-8

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-...

5q-associated spinal muscular atrophy (SMA) is a rare neuromuscular disorder with the leading symptom of a proximal muscle weakness. Three different drugs have been approved by EMA and FDA for the treatment of SMA patients, however long-term experience is still scarce. In contrast to clinical trial data with restricted patient populations and short...

Background: Early treatment after genetic newborn screening for SMA significantly improves outcomes in infantile SMA. However, there is no consensus in the SMA treatment community about early treatment initiation in patients with four copies of SMN2. Objective: Approach to a responsible treatment strategy for SMA patients with four SMN2 copies d...

Background: Prompt treatment after genetic NBS for SMA substantially improves outcome in infantile SMA. However, deficiency of SMN-protein can cause damage of motor neurons even prior to birth. Objective: To describe the neurological status at the time of NBS and the reversibility of neurological deficits in a cohort of patients with only two co...

Background: The therapeutic landscape of spinal muscular atrophy (SMA) has changed dramatically during the last 4 years but treatment responses differ remarkably between individuals and therapeutic decision-making remains challenging - underlining the persistent need for validated biomarkers. Methods: We applied untargeted proteomic analyses to...

Background: The NBS projects started in February 2018 in Germany. The aim of our study was to assess the psychosocial burden in parents of children with spinal muscular atrophy (SMA) detected by newborn screening (NBS). Follow-up a year on after diagnosis included 3 parent-related questionnaires to evaluate the psychosocial burden, quality of life...

Background Spinal muscular atrophy (SMA) is the most common neurodegenerative disease in childhood. Since motor neuron injury is usually not reversible, early diagnosis and treatment are essential to prevent major disability. Our objective was to assess the impact of genetic newborn screening for SMA on outcome. Methods We provided clinical data f...

Background The introduction of a comprehensive newborn screening program for spinal muscular atrophy (SMA), specifically for 5q-SMA, is planned for the end of 2021 in Germany. Several targeted treatment options have become available for all patients with SMA.Material and methodsNewborn screening for 5q-SMA is based on the detection of a homozygous...

Zusammenfassung Im Dezember 2020 hat der Gemeinsame Bundesausschuss beschlossen, dass das Screening auf spinale Muskelatrophie (SMA) in das allgemeine Neugeborenenscreening aufgenommen werden soll. Grundlage dieser Entscheidung war die Tatsache, dass inzwischen gezielte Behandlungsmöglichkeiten für die Patienten mit SMA zur Verfügung stehen und der...

MAN1B1‐CDG is a multisystem disorder caused by mutations in MAN1B1, encoding the endoplasmic reticulum mannosyl‐oligosaccharide alpha‐1,2‐mannnosidase. A defect leads to dysfunction within the degradation of misfolded glycoproteins. We present two additional patients with MAN1B1‐CDG and a resulting defect in endoplasmic reticulum‐associated protein...

Background: Clinicians have questioned whether any disorder involving seizures and neural antibodies should be called "(auto)immune epilepsy." The concept of "acute symptomatic seizures" may be more applicable in cases with antibodies against neural cell surface antigens. We aimed at determining the probability of achieving seizure-freedom, the us...

FUT8-CDG is a severe multisystem disorder caused by mutations in FUT8, encoding the α-1,6-fucosyltransferase. We report on dizygotic twins with FUT8-CDG presenting with dysmorphisms, failure to thrive, and respiratory abnormalities. Due to the severe phenotype, oral L-fucose supplementation was started. Glycosylation analysis using mass spectrometr...

Background: Spinal muscular atrophy (SMA) is the most common neurodegenerative disease in childhood. Since motor neuron injury is mostly not reversible, early diagnosis and treatment are essential to prevent major disability. The aim of this study was to assess the impact of newborn screening (NBS) for SMA on clinical outcome. Methods: The pilot pr...

Background Spinal muscular atrophy (SMA) is a severe, life-limiting neurodegenerative disease. A disease-modifying and approved therapy with nusinersen has been available in Germany since July 2017. Gene therapies offer another promising treatment option through a once in a lifetime administration. In May 2019 a gene replacement therapy for the tre...

Although the value of newborn screening (NBS) for early detection and treatment opportunity in SMA patients is generally accepted, there is still an ongoing discussion about the best strategy in children with 4 and more copies of the SMN2 gene. This gene is known to be the most important but not the only disease modifier.In our SMA-NBS pilot projec...

Hintergrund Die spinale Muskelatrophie (SMA) ist eine schwere, lebenslimitierende neurodegenerative Erkrankung. Seit Juli 2017 steht in Deutschland eine krankheitsmodifizierende und zugelassene Therapie mit Nusinersen zur Verfügung. Eine weitere vielversprechende Behandlungsmöglichkeit durch eine einmalige Applikation bieten konzeptionell Gentherap...

The natural history of patients with spinal muscular atrophy (SMA) has changed due to advances in standard care and development of targeted treatments. Nusinersen was the first drug approved for the treatment of all SMA patients. The transfer of clinical trial data into a real-life environment is challenging, especially regarding the advice of pati...

Objective: Spinal muscular atrophy (SMA) is the most common neurodegenerative disease in childhood. The study was conducted to assess the impact of early detection of SMA by newborn screening (NBS) on the clinical course of the disease. Methods: Screening was performed in two federal states of Germany, Bavaria and North Rhine Westphalia, between...

Objective: There is a high risk for a profound developmental disorder in West Syndrome. However, a prognostic biomarker for neurodevelopmental outcome does not exist. Hypsarrhythmia disturbs normal EEG sleep patterns and hence sleep spindles, which are thought to be important for memory consolidation and learning. We postulated that the early recu...

Superoxide dismutase 1 (SOD1) is the principal cytoplasmic superoxide dismutase in humans and plays a major role in redox potential regulation. It catalyses the transformation of the superoxide anion (O2•-) into hydrogen peroxide. Heterozygous variants in SOD1 are a common cause of familial amyotrophic lateral sclerosis. In this study we describe t...

The heterooctameric mitochondrial trifunctional protein (MTP), composed of four α- and β-subunits harbours three enzymes that each perform a different function in mitochondrial fatty acid β-oxidation. Pathogenic variants in the MTP genes (HADHA and HADHB) cause MTP deficiency, a rare autosomal recessive metabolic disorder characterized by phenotypi...

Aims To define the neurological and neuropathological alterations caused by SYNE1 mutations. Methods We describe 5 patients (3 males, 2 females; age 3–24 years) from 3 families. The diagnostic work-up included three muscle biopsies and two nerve biopsies in three of the cases. Results Three different phenotypes were discerned. Two patients showed...

Background: Spinal muscular atrophy (SMA) is a neuromuscular disorder characterized by muscle weakness and muscle atrophy. Nusinersen acts as a splicing modifier and has recently been approved for intrathecal treatment of SMA. Objective: Prior to approval, nusinersen was provided to patients with SMA type 1 in Germany within an Expanded Access P...

Background/Purpose: West syndrome (WS) is associated with a high risk for developmental delay. There is no prognostic biomarker for neurodevelopment in these patients. Hypsarrhythmia is the characteristic EEG-pattern in WS and mostly leads to disturbed physiological sleep architecture, for example, absence of sleep spindles. There is growing eviden...

Isolated optic neuritis in adults (ON) is the most common initial manifestation of multiple sclerosis (MS). Conversion to MS after childhood ON is not well determined. We aimed to identify risk factors predicting MS following ON and to develop risk profiles with adjusted clinical follow-up based on current diagnostic tools. Medical records of 42 ca...

Zusammenfassung Die kognitive Entwicklung von Kindern nach einem Fieberkrampf wird insbesondere von deren Eltern aus Angst vor negativen Auswirkungen auf die mentalen Bereiche mit großer Sorge gesehen. Populationsbasierte und erste klinikbasierte Studien können belegen, dass diese Angst unberechtigt ist. Kinder nach Fieberkrämpfen besuchen ebenso h...

Introduction Primary Ciliary Dyskiensia (PCD) describes a clinically and genetically heterogeneous group of hereditary disorders characterized by chronic mucopurulent infections of the airways caused by dysfunction of multiple motile cilia. Mutations in > 30 genes have been described to cause PCD. We present a new genetic PCD-variant caused by defe...

Multiciliated epithelial cells protect the upper and lower airways from chronic bacterial infections by moving mucus and debris outward. Congenital disorders of ciliary beating, referred to as primary ciliary dyskinesia (PCD), are characterized by deficient mucociliary clearance and severe, recurrent respiratory infections. Numerous genetic defects...

Hintergrund: Unter dem Charcot-Marie-Tooth-Syndrom (CMT) werden erblich bedingte periphere Neuropathien zusammengefasst. Es werden demyelinisierende (CMT1), axonale (CMT2), frühkind- lich beginnend/schwer verlaufende (CMT3 oder Déjerine-Sottas-Syndrom [DSS]), autosomal-rezes- siv (CMT4) oder X-chromosomal (CMTX) vererbte und komplexe Sonderformen u...

Hintergrund: Wir präsentieren den Fall eines 22-jährigen Patienten, der im Kindesalter Zeichen einer schweren Polyneuropathie, sensorineuralen Schwerhörigkeit und bilateralen Optikusatrophie bot. Es erfolgte der molekulargenetische Ausschluß von Mutationen im PMP22-, Cx32-, MPZ-, MFN2- und GDAP-Gen. Im Krankheitsverlauf traten zunehmend bulbäre Sym...

Fragestellung: Wie verlässlich sind die Diagnosekriterien der Hämophagozytischen Lymphohistiozytose (HLH)? Methode: Case-Report über einen Jungen, der im Rahmen einer Gastroenteritis im Alter von 8 LM mit wechselnder Vigilanz, beidseitiger Abduzensparese und Hepatosplenomegalie auffiel. Auch traten über wenige Tage anhaltende, rezidivierende Fiebe...

Die Erstsymptome des Morbus Wilson können vielfältig sein; neurologisch, hepatisch oder psychiatrisch. Das Erkrankungsalter liegt typischerweise in der 2. und 3. Lebensdekade. Wir berichten über die Neudiagnose eines Morbus Wilson bei einem 15-Jahre alten Jungen. Er wurde wegen einer akuten Exazerbation seiner bekannten, aber bisher nicht eingeordn...

Costello syndrome is rare, it is thought likely that there is a high number of unreported cases. To date, just more than 200 people with Costello syndrome have been described in the literature. It is characterized by mutations in the HRAS gene and belongs to the clinically defined group of RASopathies with an increased risk of malignant tumorous di...

The sphenoethmoidal cell (Onodi cell) is a quite posterior ethmoid cell with more cranial and dorsal extension which leads to dorsal displacement of sphenoidal sinus. Onodi cell shows very close proximity (medial, cranial, and caudal) to the optic canal respectively to the optic nerve. We present the case of a 5-year-old boy with right rhinogenic o...

Optic neuritis [ON] is generally identified as the most frequent potential risk factor associated with future development of multiple sclerosis [ms]. Whereas coherency in case of the adult disease is proved, findings concerning ms after childhood ON could not be demonstrated so far. The aim of this study consists of the identification of risk facto...

We present the case of a 14-year old girl with progressive toe walking and great difficulties in climbing stairs. The neurological exam was remarkable for weakness of the shoulder girdle musculature with bilateral scapula alata, positive Gower's sign, hyperlordosis upon climbing stairs, inability to walk on heels and positive Trendelenburg's sign w...

Globoid cell leukodystrophy (Morbus Krabbe) is a rare autosomal recessive disorder involving a deficiency of galactocerebrosidase which causes progressive demyelination and consecutive proliferation of glial cells with globoid cell clusters at the affected sites. The infantile form is clinically distinguished from the late infantile, juvenile and a...

Die kognitive Entwicklung von Kindern nach einem Fieberkrampf wird insbesondere von deren Eltern aus Angst vor negativen Auswirkungen auf die mentalen Bereiche mit großer Sorge gesehen. Populationsbasierte und erste klinikbasierte Studien können belegen, dass diese Angst unberechtigt ist. Kinder nach Fieberkrämpfen besuchen ebenso häufig ein Gymnas...

Die Inzidenz der akuten Neuritis nervi optici (ON) im Kindesalter betragt 4/100.000/a. Die ON ist generell der haufigste Risikofaktor fur die Entwicklung einer Multiplen Sklerose [MS] Wahrend dieser Zusammenhang fur das Auftreten der ON im Erwachsenenalter empirisch bestatigt wurde, konnte dieser Zusammenhang im Falle einer Erkrankung im Kindesalte...

Purpose of the study: Since Desmoteplase (DSPA) differs from recombinant tissue plasminogen activator (rtPA) in its higher fibrinogen affinity and absence of excitotoxicity, we regarded it as a key candidate for local fibrinolysis of experimental intracerebral hemorrhages. Methods used: In 17 pigs with a body weight of 30-35 kg, a balloon was infla...

In der vorliegenden Arbeit wurde die rekombinant hergestellte Desmoteplase zur Lyse intrazerebraler Blutungen in einem etablierten Großtiermodell untersucht. Dabei ging es neben dem fibrinolytischen Potential im Besonderen um den Einfluß auf das verspätete Ödem, das ungefähr um den dritten bis fünften Tag postläsionell am stärksten ausgeprägt ist....