[Show abstract][Hide abstract] ABSTRACT: This non-interventional study was conducted to evaluate the efficacy and tolerability of intravenous lacosamide (LCM-iv) under routine conditions in daily clinical practice as a prospective registry.
[Show abstract][Hide abstract] ABSTRACT: Hintergrund
Der Status epilepticus (SE) im Kindesalter ist nicht häufig, aber lebensbedrohlich. Die Prognose hängt von Ursache und Dauer des SE ab, sodass die rasche Diagnostik und Therapie erforderlich sind.
Material und Methode
Es wurde eine Fragebogenerhebung zum aktuellen Management des SE in allen Kinderkliniken und -abteilungen Deutschlands durchgeführt.
Von 368 versandten Fragebogen wurden 30 (8 %) zurückgesendet. Der SE wird uneinheitlich definiert. Ein Therapiestandard existiert überwiegend (87 %). Enteral ist rektales Diazepam (87 %) Mittel der 1. Wahl, bukkales Lorazepam (40 %) Mittel der 2. Wahl. Mehr als 2 Dosen Benzodiazepine würden 31 % der Antwortenden geben. Parenteral werden Diazepam (50 %) und Lorazepam (47 %) bevorzugt. Phenobarbital (40 %) ist Mittel der 2. Wahl. Im Intervall von mehr als 5 min geben 57 % der Studienteilnehmer die Medikamente. Valproat und Levetiracetam werden unterschiedlich infundiert. Auf Intensivstationen ist Midazolam Mittel der 1. Wahl (83 %) und Thiopental Mittel der 2. Wahl (50 %). Primäre Behandlungsziele sind die klinische Anfallsfreiheit (83 %), keine elektrographischen Anfälle (33 %), „Burst-suppression“-Muster (16 %) oder komplette EEG-Suppression (6 %). Es behandeln 63 % der Kliniken den fokalen SE und den Absence-Status anders als den tonisch-klonischen SE. Zusätzlich zur Intensivtherapie werden enterale Antiepileptika oder Immuntherapie von 43 % angewendet. Die ketogene Diät ist in 53 % möglich. Auf 87 % der Intensivstationen wird der SE gemeinsam mit Neuropädiatern behandelt. Ein MRT steht überall, kontinuierliches Elektroenzephalogramm (cEEG) in 50 % und amplitudenintegriertes Elektroenzephalogramm (aEEG) in 66 % zur Verfügung. Neuronale Antikörper als mögliche Ursache eines SE sind 60 % der antwortenden Ärzte bekannt.
Die Rücklaufquote der Fragebogen war gering. Die Antworten zu Definition, Diagnostik und Therapie waren uneinheitlich. Deshalb sind multizentrische Studien und Änderungen des aktuellen Managements zur Verbesserung der Prognose des SE im Kindesalter dringend erforderlich.
No preview · Article · May 2014 · Zeitschrift für Epileptologie
[Show abstract][Hide abstract] ABSTRACT: Knowledge on pediatric herpes simplex virus encephalitis is limited. Here we summarize 6 neonates and 32 children diagnosed by polymerase chain reaction (n = 37) or serological studies (n = 1), respectively. Diagnosis was difficult, as only 15 patients presented neurologic symptoms. Moreover, cerebrospinal fluid glucose, protein, and leukocytes were normal in 6 patients. Subsequently, all but 2 showed neurologic symptoms. Diffusion-weighted neuroimaging was the most sensitive early imaging method. Despite acyclovir treatment, 8 patients experienced early relapses, showing movement abnormalities, impaired vigilance, and seizures. Diffuse white matter changes, found in 3 of 5 relapse patients on neuroimaging, and a negative cerebrospinal fluid herpes simplex virus polymerase chain reaction suggested inflammatory processes. All relapse patients were again treated with acyclovir, and 3 responded to additional corticosteroid treatment. Whereas outcome after relapses was poor, overall outcome was good. No child died; 14 were asymptomatic at discharge, and neuroimaging remained normal in 7 of 30 patients studied.
No preview · Article · Jan 2013 · Journal of child neurology
[Show abstract][Hide abstract] ABSTRACT: Aim Febrile infection-related epilepsy syndrome (FIRES) is an enigmatic seizure disorder in childhood with an innocuous febrile infection triggering severe and intractable multifocal epilepsy, mostly with status epilepticus. FIRES shares several phenotypic features with epilepsies seen in patients with protocadherin 19 (PCDH19), sodium channel protein type 1 subunit alpha (SCN1A), and DNA polymerase subunit gamma-1 (POLG) mutations. The aim of the study was the mutation analysis of these prime candidate genes in a cohort of patients with FIRES. Additionally, given that rare copy number variations (CNVs) have recently been established as important risk factors for epilepsies, we performed a genome-wide CNV analysis.
Method We analysed the protein coding region, including splice sites of the three candidate genes in 15 patients (eight males, seven females) with FIRES (age at onset 3–15y, median 6) using Sanger sequencing. Inclusion criteria were a status epilepticus without identifiable cause and a preceding febrile infection in previously healthy children. In addition, we performed genome-wide human single-nucleotide polymorphism 6.0 arrays in a subset of 10 patients to identify pathological CNVs.
Results We could not identify the most likely pathogenic mutations or CNVs in FIRES.
Interpretation Mutations in PCDH19, SCN1A, POLG, or CNVs are not responsible for FIRES.
Full-text · Article · Oct 2012 · Developmental Medicine & Child Neurology
[Show abstract][Hide abstract] ABSTRACT: Background
Acute cerebellitis (AC) is characterized by cerebellar symptoms and magnetic resonance imaging (MRI) changes primarily confined to the cerebellum. Objective
To analyze the neurological and cognitive long-term outcome of children with AC. Methods
Children with AC diagnosed by typical clinical features and MRI findings were included in this retrospective study. Medical charts were reviewed and neurological deficits were assessed by neurological examination or by the expanded disability status scale telephone interview. Cognitive outcome was evaluated with a parental questionnaire (Kognitive Probleme bei Kindern und Jugendlichen). ResultsA total of 11 children (6 boys, 5 girls; age range: 3 years to 14 years and 10 months) were included. Of them, six children had a severe disease manifestation including mental status changes and neurological symptoms. Of the rest, two children had a moderate and three children had a mild form of AC. MRI of the cerebellum was obtained in the acute phase revealing signal alterations with different patterns. The average follow-up period was 4 years and 4 months. A complete recovery was observed in five children. Neurological sequelae were reported in five children ranging from ataxia to mild tremor. Cognitive deficits were found in six patients. The affected areas of cognition did include spatial visualization ability, language skills, and concentration. Conclusion
Neurological and cognitive sequelae are common in children with AC and underline the role of the cerebellum in cognition.
[Show abstract][Hide abstract] ABSTRACT: Febrile infection-related epilepsy syndrome (FIRES) is a severe postinfectious epileptic encephalopathy in previously healthy children and has three phases: the initial phase with a simple febrile infection, a few days later the acute phase characterized by a peracute onset of highly recurrent seizures or refractory status epilepticus often with no more fever and generally without additional neurological features (the classical pure seizure phenotype), and last, the chronic phase with a drug-resistant epilepsy and neuropsychological impairments. FIRES seems to be sporadic and very rare: we estimated the annual incidence in children and adolescents by a prospective hospital-based German-wide surveillance as 1 in 1,000,000. Because of the preceding infection and lacking evidence of infectious encephalitis, an immune-mediated pathomechanism and, therefore, a response to immunotherapies may be involved. To test the hypothesis that antibodies against neuronal structures cause FIRES, we analyzed sera of 12 patients aged 2 to 12 years (median 6 years) and cerebral spinal fluids (CSFs) of 3 of these 12 patients with acute or chronic FIRES. We studied six patients (two including CSF) 1 to 14 weeks (median 3 weeks) and six patients 1 to 6 years (median 3.5 years) after seizure onset. All samples were analyzed for antibodies against glutamate receptors of type N-methyl-D-aspartate (NMDA) and type α-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA), gamma-aminobutyric acid (GABA)B-receptors, voltage-gated potassium channel (VGKC)-associated proteins leucin-rich glioma inactivated 1 (LGI1) and contactin-associated protein like 2 (CASPR2), and glutamic acid decarboxylase (GAD) by a multiparametric recombinant immunofluorescence assay employing human embryonic kidney (HEK) cells transfected with cDNAs for the antigens. In addition, indirect immunohistochemistry using rat whole-brain sections was done in three patients. Finally, sera of 10 patients were tested for VGKC complex antibodies by radioimmunoprecipitation assay (RIA). None of the antibody tests were positive in any of the patients. Moreover, steroids, immunoglobulins, and plasmapheresis had no clear effect in the seven patients receiving immunotherapy. The failure of antibody-detection against the known neuronal antigens as well as the ineffectiveness of immunotherapy questions a role for autoantibodies in the epileptogenesis of classical FIRES. As we discuss, other underlying causes need to be considered including the possibility of a mitochondrial encephalopathy.
[Show abstract][Hide abstract] ABSTRACT: Mutations affecting the mitochondrial DNA-polymerase gamma 1 (POLG1) gene have been shown to cause Alpers-Huttenlocher disease. Ultrastructural data on brain and muscle tissue are rare. We report on ultrastructural changes in brain and muscle tissue of two sisters who were compound heterozygous for the c.2243G>C and c.1879C>T POLG1 mutations. Patient 1 (16 years) presented with epilepsia partialis continua that did not respond to antiepileptic treatment. Neuroimaging showed right occipital and bithalamic changes. Light microscopy from a brain biopsy performed after 3 weeks suggested chronic encephalitis showing astro- and microgliosis as well as perivascular CD8-positive T-cells. However, immunosuppressive therapy failed to improve her condition. When her 17-year-old sister (patient 2) also developed epilepsy, an intensified search for metabolic diseases led to the diagnosis. On electron microscopy mitochondrial abnormalities mainly affecting neurons were detected in the brain biopsy of patient 1, including an increase in number and size, structural changes and globoid inclusions. In patient 2, light and electron microscopy on a muscle biopsy confirmed a mitochondrial myopathy, also revealing an increase in mitochondrial size and number, as well as globoid inclusions. Neurons may be the primary target of mitochondrial dysfunction in brains of patients with Alpers disease related to POLG1 mutations. During early disease stages, brain histopathology may be misleading, showing reactive inflammatory changes.
[Show abstract][Hide abstract] ABSTRACT: We conducted a retrospective multicenter study on children who had been included in eight studies published between November 2001 and July 2010 to explore the correlations between burst-suppression coma (BSC) with outcome in febrile infection-related epilepsy syndrome (FIRES). The 77 enrolled patients presented with prolonged refractory status epilepticus. BSC was induced in 46 patients. Cognitive levels at follow-up were significantly associated with duration of a BSC (p=0.005). The outcome of FIRES is poor. Treatment by inducing a prolonged BSC was associated with a worse cognitive outcome.
[Show abstract][Hide abstract] ABSTRACT: To explore the correlations between treatment modalities and selected disease parameters with outcome in febrile infection-related epilepsy syndrome (FIRES), a catastrophic epileptic encephalopathy with a yet undefined etiology.
We conducted a retrospective multicenter study on children who had been included in eight studies published between November 2001 and July 2010. Additional data were retrieved from six of the eight participating centers.
The 77 enrolled patients presented with prolonged refractory status epilepticus. A preceding febrile infection had been reported in 96% of them. Treatment modalities included antiepileptic drugs (a median of six), intravenous immunoglobulin (IVIG, 30 patients), steroids (29 patients), burst-suppression coma (BSC, 46 patients), and other less conventional agents. There was no evidence of efficacy for those treatment modalities except for IVIG (two patients), a ketogenic diet (one patient), and a prolonged cycle of barbiturate anesthesia coma (one patient). Nine patients (11.7%) died during the acute phase of FIRES. Only 12 of the 68 surviving patients (18%) retained normal cognitive level, but most of them had learning disabilities. Sixty-three patients (93%) had refractory epilepsy at follow-up. Cognitive levels at follow-up were significantly associated with duration of BSC (p = 0.005) and younger age at FIRES onset (p = 0.02).
The outcome of FIRES is poor. No therapeutic agent was efficacious in shortening the acute phase, with the possible exception of a ketogenic diet. Treatment by inducing a prolonged BSC was associated with a worse cognitive outcome.
[Show abstract][Hide abstract] ABSTRACT: Cases of severe childhood epilepsies in temporal association with vaccination have great impact on the acceptance of vaccination programs by parents and health care providers. However, little is known about the type and frequency of seizures and epilepsy syndromes following vaccination. This study aims to describe the clinical features of children presenting with seizures after vaccination using a register-based cohort.
We surveyed the national German database of adverse events following immunization (AEFI) for reported seizures and epilepsies in children aged 0-6 years. All cases reported in 2006-2008 were analyzed retrospectively; available clinical information was reevaluated and classified by seizure type and epilepsy syndrome.
In total, 328 cases reported between 2006 and 2008 were included. Data supportive of seizures or epilepsy were present in 247 (75.3%) of 328 patients with a mean interval between the vaccination and the epileptic event of 24 h and 7.5 days for inactivated and attenuated vaccines, respectively. Fifty-one (15.5%) of 328 patients presented with syncope, hypotonic-hyporesponsive episodes, or other nonepileptic events. Information was insufficient for classification into epileptic versus nonepileptic events in 30 (11.3%) of 328 patients. For cases with confirmed seizures, febrile seizures were present in 121 (49%) of 247 cases, and 38 (15.4%) of 247 patients had single afebrile seizures. Status epilepticus was described in 21 (8.5%) of 247 patients. Thirty-one (12.6%) of 247 patients presented with various pediatric epilepsy syndromes. Severe childhood epilepsies (Dravet syndrome, West syndrome, Lennox-Gastaut syndrome, or Doose syndrome) were diagnosed in 29 (11.7%) of 247 patients, with the vaccination-associated event being the first documented seizure in 15 (51.7%) of 29 patients.
Vaccination-associated seizures present in the setting of various epilepsy syndromes, including severe childhood epilepsies in >10% of cases. Early diagnosis of the corresponding epilepsy syndromes and confirmation of an underlying etiology is important for treatment decisions, genetic counseling, and public health evaluation of vaccine safety.
[Show abstract][Hide abstract] ABSTRACT: IH can alter the configuration of anatomic structures of the central nervous system. We determined the sensitivity and specificity of MR imaging to detect these changes in patients with secondary IH.
Patients (n = 36) with IH were prospectively investigated with MR imaging and were matched to 36 controls. MR images were evaluated for elongation and edema of the optic nerves, protrusion of the optic disc, flattening of the posterior sclera, height of the pituitary gland, and width of the optic nerve sheath. On MRV, we recorded venous sinus abnormalities and measured the luminal width of the superior ophthalmic veins. A grading score was introduced to define cranial venous outflow obstruction.
Cranial venous outflow obstruction and ONS hydrops were the most valid signs indicating IH with a sensitivity of 94% and 92% and a specificity of 100% and 89%, respectively. Sensitivities and specificities were 56% and 97% for reduced pituitary height, 64% and 78% for flattening of the posterior sclera, 31% and 97% for widening of the superior ophthalmic veins, 33% and 100% for optic disc protrusion, 14% and 100% for optic nerve edema, and 6% and 100% for elongation of the optic nerve. At least 2 MR imaging findings could be demonstrated in each patient but in none of the controls. The number of positive MR imaging findings correlated with CSF pressure (r = 0.62, P = .01).
The combination of cranial and orbital MR imaging and MRV can be highly sensitive and specific in the diagnosis of patients with IH.
Preview · Article · Jun 2011 · American Journal of Neuroradiology
[Show abstract][Hide abstract] ABSTRACT: Ein Horner-Syndrom (einseitige Miosis, Ptosis, Enophthalmus) wird durch eine Irritation bzw. Schädigung des Ganglion stellatum
ausgelöst. Im vorliegenden Fall kam es nach Resektion einer Aortenisthmusstenose und Anlage einer linksseitigen Thoraxdrainage
am 3. postoperativen Tag zur Ausbildung eines Horner-Syndroms. Thoraxdrainagen sind als sehr seltene Ursache hierfür beschrieben,
bei Auftreten einer Horner-Trias sollte die Lage des Pleurakatheters kontrolliert und ggf. korrigiert werden.
Horner’s syndrome (miosis, ptosis, enophthalmus) is caused by an irritation or damage of the stellate ganglion. After correction
of coarctation of the aorta followed by a left-sided chest tube, a toddler developed Horner’s syndrome on the third day after
surgery. Chest tubes causing Horner’s syndrome are rarely described in the literature. In cases of sudden appearance the position
of the chest tube should be examined immediately and corrected if necessary.
SchlüsselwörterHorner-Syndrom–Ganglion stellatum–Thoraxdrainage–Horner-Trias –Herzchirurgie
KeywordsHorner’s syndrome–Stellate ganglion–Chest tube–Horner’s triad–Heart surgery
No preview · Article · Apr 2011 · Monatsschrift Kinderheilkunde
[Show abstract][Hide abstract] ABSTRACT: The objective of this study was to explore the volumetric alterations of dural sinuses in patients with idiopathic intracranial hypertension (IIH).
Standardized cranial magnetic resonance imaging (MRI) was used in 17 patients prior to and following treatment of IIH and in seven controls. Magnetic resonance venographies (MRV) were employed for (a) judgement of circumscript dural sinus stenoses and (b) computation of sinus volumes. Cross-sectional areas (CSA) of the superior sagittal sinuses (SSS) were measured on T2-weighted images. Results of the initial MRIs were compared to those on follow-up MRIs and to results of controls.
Stenoses of the transverse sinuses (TS) resulting in cranial venous outflow obstruction (CVOO) were present in 15/17 (88%) patients, normalizing in 7/15 cases (47%) after treatment of IIH. CVOO was not detected in the control group. Segmentation of MRV revealed decreased dural sinus volumes in patients with IIH as compared to controls (P = 0.018). Sinus volumes increased significantly with normalization of intracranial pressure independent from disappearing of TS stenoses (P = 0.007). The CSA of the SSS were normal on the initial MRIs of patients with IIH and increased on follow-up after treatment (P < 0.001). However, volumetries displayed overlap in patients and controls.
Patients with IIH not only exhibit bilateral stenoses of the TS as has been reported, but volume changes of their entire dural sinus system also occur. The potential etiopathological and diagnostic roles of these changes are discussed.