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Leucine aminoacyl tRNA-synthetase 1 (LARS1)-deficiency (infantile liver failure syndrome type 1 (ILFS1)) has a multisystemic phenotype including fever-associated acute liver failure (ALF), chronic neurologic abnormalities, and encephalopathic episodes. In order to better characterize encephalopathic episodes and MRI changes, 35 cranial MRIs from 13 individuals with LARS1 deficiency were systematically assessed and neurological phenotype was analyzed. All individuals had developmental delay and 10/13 had seizures. Encephalopathic episodes in 8/13 were typically associated with infections, presented with seizures and reduced consciousness, mostly accompanied by hepatic dysfunction, and recovery in 17/19 episodes. Encephalopathy without hepatic dysfunction occurred in one individual after liver transplantation. On MRI, 5/7 individuals with MRI during acute encephalopathy had deep gray matter and brainstem changes. Supratentorial cortex involvement (6/13) and cerebellar watershed injury (4/13) occurred with seizures and/or encephalopathy. Abnormal brainstem contour on sagittal images (8/13), atrophy (8/13), and myelination delay (8/13) were not clearly associated with encephalopathy. The pattern of deep gray matter and brainstem changes are apparently characteristic of encephalopathy in LARS1-deficiency, differing from patterns of hepatic encephalopathy or metabolic stroke in organic acidurias and mitochondrial diseases. While the pathomechanism remains unclear, fever and energy deficit during infections might be causative; thus, sufficient glucose and protein intake along with pro-active fever management is suggested. As severe episodes were observed during influenza infections, we strongly recommend seasonal vaccination.
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OBJECTIVE: The aim of the study was to assess whether children and adolescents with epilepsy are at higher risk of behavioral disturbances when they have concomitant cognitive disturbances. METHODS: Behavioral scores were generated using the Child Behavior Checklist (CBCL). Cognitive evaluation was applied by using different age appropriate versions of the Wechsler Intelligence Scale. CBCL scores (total, externalizing, internalizing) were compared between patients with and without intellectual disability (IQ score < 70 and ≥70, respectively). RESULTS: 144 (10.2 mean age, 6.0-17.9 range) patients were recruited for the study. Patients with mild to moderate intellectual disability (full-scale intelligence quotient (FSIQ) < 70) were not at higher risk of behavioral disturbances (total CBCL score ≥ 63) than patients without cognitive impairment. The mean total CBCL score was 62.0 ± 10.6 (range 42.0-83.5, 95% CI 57.9-62.0) and 59.3 ± 10.3 (range 38.0-80.0, CI 57.4-61.2) for patients with FSIQ < 70 and ≥70, respectively. There was no correlation between FSIQ and total CBCL scores. These findings were true for all IQ subcategories. SIGNIFICANCE: Behavioral disturbances among children and adolescents with epilepsy occur despite the presence or absence of intellectual dysfunction with respect to full-scale IQ.
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BACKGROUND: Magnetic resonance (MRI) imaging of the skeletal muscles (muscle MRI for short) is increasingly being used in clinical routine for diagnosis and longitudinal assessment of muscle disorders. However, cross-centre standards for measurement protocol and radiological assessment are still lacking. OBJECTIVES: The aim of this expert recommendation is to present standards for the application and interpretation of muscle MRI in hereditary and inflammatory muscle disorders. METHODS: This work was developed in collaboration between neurologists, neuroradiologists, radiologists, neuropaediatricians, neuroscientists and MR physicists from different university hospitals in Germany. The recommendations are based on expert knowledge and a focused literature search. RESULTS: The indications for muscle MRI are explained, including the detection and monitoring of structural tissue changes and oedema in the muscle, as well as the identification of a suitable biopsy site. Recommendations for the examination procedure and selection of appropriate MRI sequences are given. Finally, steps for a structured radiological assessment are presented. CONCLUSIONS: The present work provides concrete recommendations for the indication, implementation and interpretation of muscle MRI in muscle disorders. Furthermore, it provides a possible basis for the standardisation of the measurement protocols at all clinical centres in Germany.
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Imagen por Resonancia Magnética , Enfermedades Musculares , Imagen por Resonancia Magnética/métodos , Imagen por Resonancia Magnética/normas , Humanos , Enfermedades Musculares/diagnóstico por imagen , Alemania , Guías de Práctica Clínica como Asunto , Músculo Esquelético/diagnóstico por imagen , Músculo Esquelético/patologíaRESUMEN
BACKGROUND: Magnetic resonance (MRI) imaging of the skeletal muscles (muscle MRI for short) is increasingly being used in clinical routine for diagnosis and longitudinal assessment of muscle disorders. However, cross-centre standards for measurement protocol and radiological assessment are still lacking. OBJECTIVES: The aim of this expert recommendation is to present standards for the application and interpretation of muscle MRI in hereditary and inflammatory muscle disorders. METHODS: This work was developed in collaboration between neurologists, neuroradiologists, radiologists, neuropaediatricians, neuroscientists and MR physicists from different university hospitals in Germany. The recommendations are based on expert knowledge and a focused literature search. RESULTS: The indications for muscle MRI are explained, including the detection and monitoring of structural tissue changes and oedema in the muscle, as well as the identification of a suitable biopsy site. Recommendations for the examination procedure and selection of appropriate MRI sequences are given. Finally, steps for a structured radiological assessment are presented. CONCLUSIONS: The present work provides concrete recommendations for the indication, implementation and interpretation of muscle MRI in muscle disorders. Furthermore, it provides a possible basis for the standardisation of the measurement protocols at all clinical centres in Germany.
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Imagen por Resonancia Magnética , Músculo Esquelético , Imagen por Resonancia Magnética/normas , Imagen por Resonancia Magnética/métodos , Humanos , Alemania , Músculo Esquelético/diagnóstico por imagen , Músculo Esquelético/patología , Enfermedades Musculares/diagnóstico por imagen , Guías de Práctica Clínica como Asunto , Radiología/normas , Neurología/normasRESUMEN
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. Objective: To compare data obtained on patients with SMA diagnosed through newborn screening and those diagnosed after clinical symptom onset. Design, Setting, and Participants: This nonrandomized controlled trial used data from the SMARTCARE registry to evaluate all children born between January 2018 and September 2021 with genetically confirmed SMA and up to 3 SMN2 copies. The registry includes data from 70 participating centers in Germany, Austria, and Switzerland. Data analysis was performed in February 2023 so that all patients had a minimal follow-up of 18 months. Exposure: Patients born in 2 federal states in Germany underwent screening in a newborn screening pilot project. All other patients were diagnosed after clinical symptom onset. All patients received standard care within the same health care system. Main Outcomes: The primary end point was the achievement of motor milestones. Results: A total of 234 children (123 [52.6%] female) were identified who met inclusion criteria and were included in the analysis: 44 (18.8%) in the newborn screening cohort and 190 children (81.2%) in the clinical symptom onset cohort. The mean (SD) age at start of treatment with 1 of the approved disease-modifying drugs was 1.3 (2.2) months in the newborn screening cohort and 10.7 (9.1) months in the clinical symptom onset cohort. In the newborn screening cohort, 40 of 44 children (90.9%) gained the ability to sit independently vs 141 of 190 (74.2%) in the clinical symptom onset cohort. For independent ambulation, the ratio was 28 of 40 (63.6%) vs 28 of 190 (14.7%). Conclusions and Relevance: This nonrandomized controlled trial demonstrated effectiveness of newborn screening for infants with SMA in the real-world setting. Functional outcomes and thus the response to treatment were significantly better in the newborn screening cohort compared to the unscreened clinical symptom onset group. Trial Registration: German Clinical Trials Register: DRKS00012699.
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Tamizaje Neonatal , Humanos , Tamizaje Neonatal/métodos , Recién Nacido , Femenino , Masculino , Lactante , Alemania , Sistema de Registros , Atrofia Muscular Espinal/diagnóstico , Proyectos Piloto , Diagnóstico PrecozRESUMEN
BACKGROUND: Spinal muscular atrophy is a progressive neuromuscular disorder and among the most frequent genetic causes of infant mortality. While recent advancements in gene therapy provide the potential to ameliorate the disease severity, there is currently no modality in clinical use to visualize dynamic pathophysiological changes in disease progression and regression after therapy. METHODS: In this prospective diagnostic clinical study, ten pediatric patients with spinal muscular atrophy and ten age- and sex-matched controls have been examined with three-dimensional optoacoustic imaging and clinical standard examinations to compare the spectral profile of muscle tissue and correlate it with motor function (ClinicalTrials.gov: NCT04115475). FINDINGS: We observed a reduced optoacoustic signal in muscle tissue of pediatric patients with spinal muscular atrophy. The reduction in signal intensity correlated with disease severity as assessed by grayscale ultrasound and standard motor function tests. In a cohort of patients who received disease-modifying therapy prior to the study, the optoacoustic signal intensity was similar to healthy controls. CONCLUSIONS: This translational study provides early evidence that three-dimensional optoacoustic imaging could have clinical implications in monitoring disease activity in spinal muscular atrophy. By visualizing and quantifying molecular changes in muscle tissue, disease progression and effects of gene therapy can be assessed in real time. FUNDING: The project was funded by ELAN Fonds (P055) at the University Hospital of the Friedrich-Alexander-Universität (FAU) Erlangen-Nurnberg to A.P.R.
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Imagenología Tridimensional , Atrofia Muscular Espinal , Técnicas Fotoacústicas , Humanos , Femenino , Masculino , Estudios Prospectivos , Preescolar , Imagenología Tridimensional/métodos , Técnicas Fotoacústicas/métodos , Niño , Atrofia Muscular Espinal/genética , Atrofia Muscular Espinal/diagnóstico por imagen , Atrofia Muscular Espinal/terapia , Lactante , Progresión de la Enfermedad , Estudios de Casos y Controles , Músculo Esquelético/diagnóstico por imagen , Músculo Esquelético/patología , Adolescente , Atrofias Musculares Espinales de la Infancia/diagnóstico por imagen , Atrofias Musculares Espinales de la Infancia/genética , Atrofias Musculares Espinales de la Infancia/terapia , Atrofias Musculares Espinales de la Infancia/fisiopatología , Atrofias Musculares Espinales de la Infancia/diagnósticoRESUMEN
This data analysis aimed to systematically analyze a pediatric patient population with a life-limiting disease who were administered cannabinoids. It was a retrospective single-center analysis of patients under supervision of the specialized outpatient pediatric palliative care (SOPPC) team at the Department of Pediatrics and Adolescent Medicine of the Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU). Thirty-one patients with a primary diagnosis of neuropediatric, oncologic, metabolic, and cardiologic categories were included. The indications we identified were spasticity, pain, restlessness, anxiety, loss of appetite, epilepsy, and paresis. Certain aspects of quality of life were improved for 20 of 31 patients (64.5%). For nine patients (29%), no improvement was detected. No conclusions could be drawn for two patients (6.5%). Adverse events were reported for six of the thirty-one patients (19.4%). These were graded as mild, including symptoms such as restlessness, nausea, and behavioral issues. We detected no clinically relevant interactions with other medications. We collected fundamental data on the use of cannabinoids by pediatric palliative patients. Cannabinoids are now frequently administered in pediatric palliative care. They seem to be safe to use and should be considered an add-on therapy for other drug regimens.
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Peripheral arterial disease (PAD) leads to chronic vascular occlusion and results in end organ damage in critically perfused limbs. There are currently no clinical methods available to determine the muscular damage induced by chronic mal-perfusion. This monocentric prospective cross-sectional study investigated n = 193 adults, healthy to severe PAD, in order to quantify the degree of calf muscle degeneration caused by PAD using a non-invasive hybrid ultrasound and single wavelength optoacoustic imaging (US/SWL-OAI) approach. While US provides morphologic information, SWL-OAI visualizes the absorption of pulsed laser light and the resulting sound waves from molecules undergoing thermoelastic expansion. US/SWL-OAI was compared to multispectral data, clinical disease severity, angiographic findings, phantom experiments, and histological examinations from calf muscle biopsies. We were able to show that synergistic use of US/SWL-OAI is most likely to map clinical degeneration of the muscle and progressive PAD.
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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 disease progression, we performed a retrospective analysis of 268 patients with 4 copies of SMN2 from the SMArtCARE registry in Germany, Austria and Switzerland. Inclusion criteria required comprehensive baseline data and diagnosis outside of newborn screening. Only data prior to initiation of disease-modifying treatment were included. The median age at disease onset was 3.0 years, with a mean of 6.4 years. Significantly, 55% of patients experienced symptoms before the age of 36 months. 3% never learned to sit unaided, a further 13% never gained the ability to walk independently and 33% of ambulatory patients lost this ability during the course of the disease. 43% developed scoliosis, 6.3% required non-invasive ventilation and 1.1% required tube feeding. In conclusion, our study, in line with previous observations, highlights the substantial phenotypic heterogeneity in SMA. Importantly, this study provides novel insights: the median age of disease onset in patients with 4 SMN2 copies typically occurs before school age, and in half of the patients even before the age of three years. These findings support a proactive approach, particularly early treatment initiation, in this subset of SMA patients diagnosed pre-symptomatically. However, it is important to recognize that the register will not include asymptomatic individuals.
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Atrofia Muscular Espinal , Proteína 2 para la Supervivencia de la Neurona Motora , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Edad de Inicio , Austria/epidemiología , Progresión de la Enfermedad , Alemania , Atrofia Muscular Espinal/genética , Atrofia Muscular Espinal/diagnóstico , Tamizaje Neonatal , Sistema de Registros , Estudios Retrospectivos , Proteína 2 para la Supervivencia de la Neurona Motora/genética , SuizaRESUMEN
BACKGROUND AND OBJECTIVES: GM2 gangliosidoses, a group of autosomal-recessive neurodegenerative lysosomal storage disorders, result from ß-hexosaminidase (HEX) deficiency with GM2 ganglioside as its main substrate. Historically, GM2 gangliosidoses have been classified into infantile, juvenile, and late-onset forms. With disease-modifying treatment trials now on the horizon, a more fine-grained understanding of the disease course is needed. METHODS: We aimed to map and stratify the clinical course of GM2 gangliosidoses in a multicenter cohort of pediatric and adult patients. Patients were stratified according to age at onset and age at diagnosis. The 2 resulting GM2 disease clusters were characterized in-depth for respective disease features (detailed standardized clinical, laboratory, and MRI assessments) and disease evolution. RESULTS: In 21 patients with GM2 gangliosidosis (17 Tay-Sachs, 2 GM2 activator deficiency, 2 Sandhoff disease), 2 disease clusters were discriminated: an early-onset and early diagnosis cluster (type I; n = 8, including activator deficiency and Sandhoff disease) and a cluster with very variable onset and long interval until diagnosis (type II; n = 13 patients). In type I, rapid onset of developmental stagnation and regression, spasticity, and seizures dominated the clinical picture. Cherry red spot, startle reactions, and elevated AST were only seen in this cluster. In type II, problems with balance or gait, muscle weakness, dysarthria, and psychiatric symptoms were specific and frequent symptoms. Ocular signs were common, including supranuclear vertical gaze palsy in 30%. MRI involvement of basal ganglia and peritrigonal hyperintensity was seen only in type I, whereas predominant infratentorial atrophy (or normal MRI) was characteristic in type II. These types were, at least in part, associated with certain genetic variants. DISCUSSION: Age at onset alone seems not sufficient to adequately predict different disease courses in GM2 gangliosidosis, as required for upcoming trial planning. We propose an alternative classification based on age at disease onset and dynamics, predicted by clinical features and biomarkers, into type I-an early-onset, rapid progression cluster-and type II-a variable onset, slow progression cluster. Specific diagnostic workup, including GM2 gangliosidosis, should be performed in patients with combined ataxia plus lower motor neuron weakness to identify type II patients.
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Gangliosidosis GM2 , Enfermedad de Sandhoff , Adulto , Humanos , Niño , Enfermedad de Sandhoff/diagnóstico por imagen , Enfermedad de Sandhoff/genética , Gangliosidosis GM2/diagnóstico por imagen , Gangliosidosis GM2/genética , Diagnóstico por Imagen , Ataxia , Progresión de la EnfermedadRESUMEN
Recently, the importance of post-COVID-19 in children has been recognized in surveys and retrospective chart analysis. However, objective data in the form of cardiopulmonary exercise test as performed in adults suffering from this condition are still lacking. This study aimed to investigate the cardiopulmonary effects of post-COVID-19 on children and adolescents. In this cross-sectional study (the FASCINATE study), children fulfilling the criteria of post-COVID-19 and an age- and sex-matched control group underwent cardiopulmonary exercise testing on a treadmill and completed a questionnaire with regard to physical activity before, during and after the infection with SARS-CoV-2. We were able to recruit 20 children suffering from post-COVID-19 (mean age 12.8 ± 2.4 years, 60% females) and 28 control children (mean age 11.7 ± 3.5 years, 50% females). All participants completed a maximal treadmill test with a significantly lower V Ë O 2 peak in the post-COVID-19 group (37.4 ± 8.8 ml/kg/min vs. 43.0 ± 6.7 ml/kg/min. p = 0.019). This significance did not persist when comparing the achieved percentage of predicted V Ë O 2 peak . There were no significant differences for oxygen pulse, heart rate, minute ventilation or breathing frequency. Conclusion: This is the first study to investigate post-COVID-19 in children using the cardiopulmonary exercise test. Although there was a significantly reduced V Ë O 2 peak in the post-COVID-19 group, this was not true for the percent of predicted values. No pathological findings with respect to cardiac or pulmonary functions could be discerned. Deconditioning was the most plausible cause for the experienced symptoms. Trial registration: clinicaltrials.gov, NCT054445531, Low-field Magnetic Resonance Imaging in Pediatric Post Covid-19-Full Text View-ClinicalTrials.gov. What is Known: ⢠The persistence of symptoms after an infection with SARS-CoV 2, so-called post-COVID-19 exists also in children. ⢠So far little research has been conducted to analyze this entity in the pediatric population. What is New: ⢠This is the first study proving a significantly lower cardiopulmonary function in pediatric patients suffering from post-COVID-19 symptoms. ⢠The cardiac and pulmonary function appear similar between children suffering from post-COVID-19 and those who don't, but the peripheral muscles seem affected.
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COVID-19 , Adulto , Femenino , Adolescente , Humanos , Niño , Masculino , Estudios Retrospectivos , Estudios Transversales , SARS-CoV-2 , Pulmón , Prueba de Esfuerzo/métodosRESUMEN
OBJECTIVE: The aim was to investigate the monitoring, interventions, and occurrence of critical, potentially life-threatening incidents in patients with Dravet syndrome (DS) and caregivers' knowledge about sudden unexpected death in epilepsy (SUDEP). METHODS: This multicenter, cross-sectional study of patients with DS and their caregivers in Germany consisted of a questionnaire and prospective diary querying the disease characteristics and demographic data of patients and caregivers. RESULTS: Our analysis included 108 questionnaires and 82 diaries. Patients with DS were 49.1% male (n = 53), with a mean age of 13.5 (SD ± 10.0 years) and primary caregivers were 92.6% (n = 100) female, with a mean age of 44.7 (SD ± 10.6 years). Monitoring devices were used regularly by 75.9% (n = 82) of caregivers, and most monitored daily/nightly. Frequently used devices were pulse oximeters (64.6%), baby monitors (64.6%), thermometers (24.1%), and Epi-Care (26.8%). Younger caregiver and patient age and history of status epilepticus were associated with increased use of monitoring, and 81% of monitor users reported having avoided a critical incident with nocturnal monitoring. The need for resuscitation due to cardiac or respiratory arrest was reported by 22 caregivers (20.4%), and most cases (72.7%) were associated with a seizure. Caregivers reported frequently performing interventions at night, including oropharyngeal suction, oxygenation, personal hygiene, and change of body position. Most caregivers were well informed about SUDEP (n = 102; 94%) and monitored for a lateral or supine body position; however, only 39.8% reported receiving resuscitation training, whereas 52.8% (n = 57) knew what to do in case the child's breathing or heart activity failed. SIGNIFICANCE: Critical incidents and the need for resuscitation are reported frequently by caregivers and may be related to high mortality and SUDEP rates in DS. Resuscitation training is welcomed by caregivers and should be continuously provided. Oxygen monitoring devices are frequently used and considered useful by caregivers.
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Epilepsias Mioclónicas , Muerte Súbita e Inesperada en la Epilepsia , Niño , Humanos , Masculino , Femenino , Adolescente , Adulto , Cuidadores , Estudios Prospectivos , Estudios Transversales , Muerte Súbita/epidemiología , Muerte Súbita/etiología , Epilepsias Mioclónicas/terapia , Alemania/epidemiologíaRESUMEN
Background: Spinal muscular atrophy (SMA) is a genetic neurodegenerative disease leading to muscular weakness and premature death. Three therapeutic options are currently available including gene replacement therapy (GRT), which is potentially cardiotoxic. High-sensitive cardiac troponin I (hs-cTnI) is widely used to monitor potential cardiac contraindications or side effects of GRT, but reference data in healthy newborns are limited and lacking in neonates with SMA. The aim of this study is to determine the range of pre-therapeutic hs-cTnI concentrations in neonates with SMA and to provide guidance for the assessment of these values. Methods: Hs-cTnI levels, genetic and clinical data of 30 newborns (age range 2-26 days) with SMA were retrospectively collected from 6 German neuromuscular centers. In addition, hs-cTnI levels were measured in 16 neonates without SMA. Results: The median hs-cTnI concentration in neonates with SMA was 39.5â ng/L (range: 4-1205). In 16 newborns with SMA, hs-cTnI levels were above the test-specific upper reference limit (URL). Exploratory statistical analysis revealed no relevant correlation between hs-cTnI levels and gender, gestational age, mode of delivery, SMN2 copy number, symptoms of SMA or abnormal cardiac findings. Discussion: Our results suggest higher hs-cTnI plasma levels in newborns with and without SMA compared to assay-specific reference values generated in adults. Given the wide range of hs-cTnI values in neonates with SMA, hs-cTnI levels must be determined before treatment in each patient and post-treatment elevations should be interpreted in the context of the course rather than as individual values.
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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 TSC manifestations included structural brain lesions (cortical tubers, 91.4%; subependymal nodules, 82.9%), epilepsy (85.7%), and cardiac rhabdomyomas (62.9%). Mean age at seizure onset was 1.5 ± 2.3 years, with onset in 80.0% of patients within the first two years of life. Infantile spasms, which were the first seizure type in 23.3% of the patients, developed earlier (0.6 ± 0.4 years) than focal seizures (1.8 ± 2.5 years). Refractory epilepsy was present in 21 (70.0%) patients, mild or severe intellectual impairment in 66.6%, and autism spectrum disorders in 11.4%. Severe cognitive impairment (33.3%) was significantly associated with epilepsy type and age at seizure onset (p < 0.05). CONCLUSIONS: The results emphasized the phenotypic variability of pediatric-onset TSC and the high rate of neurological and neuropsychiatric morbidity. Early-onset refractory epilepsy was associated with impaired cognitive development. Children of all ages with TSC require multidisciplinary long-term care and individual early-intervention programs.
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Epilepsia Refractaria , Epilepsia , Rabdomioma , Esclerosis Tuberosa , Niño , Humanos , Lactante , Preescolar , Esclerosis Tuberosa/complicaciones , Esclerosis Tuberosa/genética , Epilepsia Refractaria/complicaciones , Estudios Transversales , Epilepsia/genética , Convulsiones/genéticaRESUMEN
Age at onset of epilepsy is an important predictor of deterioration in naming ability following epilepsy surgery. In 141 patients with left hemispheric epilepsy and language dominance who received epilepsy surgery at the Epilepsy Centre Erlangen, naming of objects (Boston naming test, BNT) was assessed preoperatively and 6 months postoperatively. Surgical lesions were plotted on postoperative MRI and normalized for statistical analysis using voxel-based lesion-symptom mapping (VBLSM). The correlation between lesion and presence of postoperative naming deterioration was examined varying the considered age range of epilepsy onsets. The VBLSM analysis showed that volumes of cortex areas in the left temporal lobe, which were associated with postoperative decline of naming, increased with each year of later epilepsy onset. In patients with later onset, an increasing left posterior temporobasal area was significantly associated with a postoperative deficit when included in the resection. For late epilepsy onset, the temporomesial expansion also included the left hippocampus. The results underline that early onset of epilepsy is a good prognostic factor for unchanged postoperative naming ability following epilepsy surgery. For later age of epilepsy onset, the extent of the area at risk of postoperative naming deficit at 6 months after surgery included an increasing left temporobasal area which finally also comprised the hippocampus.
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Epilepsia , Neocórtex , Humanos , Lactante , Hipocampo , Lóbulo Temporal , Epilepsia/diagnóstico por imagen , Epilepsia/cirugía , LenguajeRESUMEN
Real-time imaging and functional assessment of the intestinal tract and its transit pose a significant challenge to conventional clinical diagnostic methods. Multispectral optoacoustic tomography (MSOT), a molecular-sensitive imaging technology, offers the potential to visualize endogenous and exogenous chromophores in deep tissue. Herein, a novel approach using the orally administered clinical-approved fluorescent dye indocyanine green (ICG) for bedside, non-ionizing evaluation of gastrointestinal passage is presented. The authors are able to show the detectability and stability of ICG in phantom experiments. Furthermore, ten healthy subjects underwent MSOT imaging at multiple time points over eight hours after ingestion of a standardized meal with and without ICG. ICG signals can be visualized and quantified in different intestinal segments, while its excretion is confirmed by fluorescent imaging of stool samples. These findings indicate that contrast-enhanced MSOT (CE-MSOT) provides a translatable real-time imaging approach for functional assessment of the gastrointestinal tract.
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Verde de Indocianina , Tomografía Computarizada por Rayos X , Humanos , Colorantes Fluorescentes , Fantasmas de Imagen , Tracto Gastrointestinal/diagnóstico por imagenRESUMEN
BACKGROUND: One of the most critical steps in the medication process on pediatric wards is the medical prescription. This study aims to investigate the impact of a computerized physician order entry (CPOE) system on Adverse Drug Events (ADEs) and potentially harmful ADEs (pot ADEs) in comparison with paper-based documentation in a general pediatric ward at a German University hospital. METHODS: A prospective pre-post study was conducted. All patients aged 17 years or younger were observed during the study periods (5 months pre- and postimplementation). Issues Regarding Medication (IRM) were identified by intensive chart review. Events were assessed regarding causality (WHO), severity (WHO; Dean & Barber for MEs), and preventability (Shumock) and classified into (pot) ADEs, (pot) Medication errors (ME), Adverse drug Reactions (ADR), and Other incidents (OI) accordingly. RESULTS: Total of 333 patients with medication were included in the paper-based prescribing cohort (phase I) and 320 patients with medication in the electronic prescribing cohort (phase II). In each cohort, patients received a median number of four different drugs (IQR 5 and IQR 4). A total of 3966 IRM was observed. During the hospitalization, 2.7% (n = 9) patients in phase I and 2.8% (n = 9) in phase II experienced an ADE. Potentially harmful MEs were less often observed in the cohort with electronic prescribing (n = 228 vs. n = 562). The mean number per patient significantly decreased from 1.69 to 0.71 (p < .01). CONCLUSION: The implementation of a CPOE system resulted in a reduction of issues regarding medication, particularly MEs with the potential to harm patients decreased significantly.
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Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Sistemas de Entrada de Órdenes Médicas , Humanos , Niño , Estudios Prospectivos , Hospitalización , Hospitales UniversitariosRESUMEN
BACKGROUND: This study measured sleep quality among caregivers of patients with Dravet syndrome (DS) and assessed the impacts of mental health problems and caregiver burden on sleep quality. METHODS: This multicenter, cross-sectional study of patients with DS and their caregivers throughout Germany consisted of a questionnaire and a prospective 4-week diary querying disease characteristics, demographic data, living conditions, nocturnal supervision, and caregivers' work situations. Sleep quality was assessed using the Pittsburgh Sleeping Quality Index (PSQI). The Hospital Anxiety and Depression Scale (HADS) and the Burden Scale for Family Caregivers (BSFC) were used to measure anxiety, symptoms of depression, and caregiver burden. RESULTS: Our analysis included 108 questionnaires and 82 four-week diaries. Patients with DS were 49.1% male (n = 53), with a mean age of 13.5 ± 10.0 years. Caregivers were 92.6% (n = 100) female, with a mean age of 44.7 ± 10.6 years. The overall mean PSQI score was 8.7 ± 3.5, with 76.9% of participants (n = 83) scoring 6 or higher, indicating abnormal sleep quality. The HADS for anxiety and depression had overall mean scores of 9.3 ± 4.3 and 7.9 ± 3.7, respectively; 61.8% and 50.9% of participants scored above the cutoff value of 8 for anxiety and depression, respectively. Statistical analyses revealed caregiver anxiety levels and patients' sleep disturbances as major factors influencing PSQI scores. The overall mean BSFC score of 41.7 ± 11.7 indicates a moderate burden, with 45.3% of caregivers scoring 42 or higher. CONCLUSIONS: Sleep quality is severely affected among caregivers of patients with DS, correlating with anxiety, comorbidities, and patients' sleep disturbances. A holistic therapeutic approach should be implemented for patients with DS and their caregivers, focusing on the sleep quality and mental health of caregivers. TRIAL REGISTRATION: German Clinical Trials Register (DRKS), DRKS00016967. Registered 27 May 2019, http://www.drks.de/DRKS00016967.
Asunto(s)
Epilepsias Mioclónicas , Trastornos del Sueño-Vigilia , Humanos , Masculino , Femenino , Preescolar , Niño , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Calidad de Vida/psicología , Carga del Cuidador , Calidad del Sueño , Depresión/psicología , Estudios Transversales , Estudios Prospectivos , Ansiedad , Cuidadores/psicología , Encuestas y Cuestionarios , Alemania , Atención al PacienteRESUMEN
BACKGROUND AND PURPOSE: Novel light- and sound-based technologies like multispectral optoacoustic tomography (MSOT) with co-registered reflected-ultrasound computed tomography (RUCT) could add additional value to conventional ultrasound (US) for disease phenotyping in pediatric spinal muscular atrophy (SMA). The aim of this study was to investigate the quality of RUCT compared to US for qualitative and quantitative assessment of imaging neuromuscular disorders. METHODS: Subanalyzing the MSOT SMA study, 288 RUCT and 276 US images from 10 SMA patients (mean age 9.0 ± 3.7) and 10 gender- and age-matched healthy volunteers (HV; mean age 8.7 ± 4.3) were analyzed for quantitative (grayscale levels [GSLs]) and qualitative (echogenicity, distribution pattern, Heckmatt scale, and muscle texture) muscle changes. RUCT and US measures were further correlated with clinical standard motor outcomes. RESULTS: Quantitative agreement using GSLs revealed significantly higher GSLs in muscles of SMA patients compared to healthy muscles in both techniques (US mean GSL [SD] SMA vs. HV: 110.70 [27.8] vs. 68.85 [19.2], p < .0001; RUCT mean GSL [SD] SMA vs. HV: 91.81 [21.8] vs. 59.86 [8.2], p < .0001) with good correlation with motor outcome tests, respectively. Qualitative agreement between methods for muscle composition was excellent for differentiation of pathological versus healthy muscles, echogenicity, and distribution pattern, moderate for Heckmatt scale, and poor for muscle texture. CONCLUSIONS: The data suggest that RUCT may allow the assessment of basic qualitative and quantitative measures for muscular diseases with comparable results to conventional US.