Tanveer S.,Pediatric Neurology |
Zecavati N.,Pediatric Neurology |
Delasobera E.B.,Pediatric Neurology |
Oyegbile T.O.,Pediatric Neurology
Pediatric Neurology | Year: 2017
Background: Studies have documented gender differences associated with concussion. The purpose of this study was to determine if these gender differences are also noted within a pediatric population. Methods: This prospective study analyzed 1971 patients who had completed preconcussion and postconcussion neuropsychological testing within the Washington, DC, area. Results: Our results showed that children and adolescents with concussion exhibit gender differences with respect to risk factors, recovery, and symptomatology. Females are more likely to present with a concussion (P < 0.001), experience more discomfort from a concussion (P < 0.001), and seek treatment for postconcussive headaches (P < 0.001). On the other hand, males are more likely to sustain a concussion from a contact sport (P < 0.001) and experience loss of consciousness, confusion, and amnesia with a concussion more frequently than females (P < 0.001). Postconcussive cognitive function also differs by gender. Both males and females exhibit a decline in cognitive testing compared with baseline (P < 0.001); however, visual memory (P = 0.02) is more affected in females than in males. These findings remain unchanged among pediatric patients aged ≥14 years; however, no gender differences were noted in individuals aged ≤13 years. Conclusion: It is important for health care providers, schools, athletic trainers, and coaches to be aware of these gender differences associated with concussion in order to provide adequate surveillance and appropriate monitoring and support during the recovery period. © 2017 Elsevier Inc.
News Article | December 5, 2016
EMERYVILLE, Calif., Dec. 05, 2016 (GLOBE NEWSWIRE) -- Zogenix, Inc. (NASDAQ:ZGNX), a pharmaceutical company developing therapies for the treatment of orphan and central nervous system (CNS) disorders, today announced new data demonstrating effectiveness and cardiovascular-related safety for patients treated with ZX008 (low-dose fenfluramine) as an adjunctive therapy for seizures associated with Lennox Gastaut Syndrome (LGS), and continued effectiveness and safety for the on-going open-label patients with Dravet syndrome. The data were presented at the 70th Annual American Epilepsy Society (AES) meeting, taking place this week in Houston, Texas (see study data here and here). The LGS data presented were from an interim analysis of the first 13 patients to have completed at least 12 weeks of a Phase 2 open-label, dose-finding investigator-initiated study, led by Lieven Lagae, M.D., Ph.D., Professor at the University of Leuven, Belgium, Head of the Pediatric Neurology Department and Director of the Childhood Epilepsy Program at the University of Leuven Hospitals. Patients enrolled in the study were 3-18 years of age diagnosed with LGS with at least four convulsive seizures and on at least two anti-epileptic drugs (AEDs) at stable doses in the four weeks prior to study initiation. Participants were treated with ZX008 as an add-on therapy for up to 20 weeks starting at 0.2mg/kg/day. The dose could be titrated at four-week intervals based on treatment response up to a maximum of 0.8 mg/kg/day (maximum daily dose in the trial could not exceed 30mg/day) if the patient did not reach at least a 50% reduction in major motor seizure frequency. It is important to note that, per protocol, dose escalation stopped when a patient’s major motor seizure frequency was reduced by ≥50% of baseline. The mean age of participants was 11.4 years (± 4.4) and they had failed a median of five antiepileptic therapies (range: 3-7) prior to this study. At study initiation, patients were receiving a median of four antiepileptic therapies. The median number of major motor seizures (defined as generalized tonic-clonic, tonic, atonic, and focal seizures with a motor component) during the four-week baseline period was 60 (range 21-1360). In the Intent-to-Treat (ITT) patient population (n=13), there was a median 50% reduction in seizure frequency over the entire treatment period compared to baseline (range: +74% to –90%), with seven patients (54%) to date achieving a ≥ 50% reduction (range: 50% to 90%) in the number of major motor seizures in this step dose study. There were no cardiovascular-related adverse events observed. The most common treatment-related adverse events were decreased appetite (n=3), decreased alertness/fatigue (n=3) and insomnia (n=2). Three patients withdrew due to adverse events (decreased alertness (n=2) and insomnia (n=1) and one patient withdrew due to lack of effect (the patient was initially a responder, but lost response after undergoing surgery during the trial). “These initial results for ZX008 in LGS are quite compelling for this refractory group of patients,” said Professor Lagae. “A significant unmet medical need currently exists in the treatment of LGS and these initial data indicate that ZX008 has the potential to be a safe and effective adjunctive treatment for this rare pediatric epilepsy condition. I look forward to continuing to evaluate ZX008 in this ongoing Phase 2 open-label study.” The Dravet syndrome data highlighted updated results from the ongoing prospective study in Belgium with the new patient cohort (n=9). All of these patients began add-on treatment with low-dose fenfluramine (5 mg to 20 mg per day) at various starting points between 2010 and January 2016. Median treatment duration was 2.1 years (range 0.8 to 5.6 years). During the 90-day run-in period prior to initiating low-dose fenfluramine treatment, the median frequency of major motor seizures (defined as tonic, clonic, tonic-clonic, atonic, and myoclonic seizures lasting >30 seconds) was 15.0 per month (range 0.4 to 39.7). Over the entire observation period, the median frequency of major motor seizures was reduced to 1.9 per month, and the median decrease was 76% (range 20-95%). Six of the nine patients (67%) had at least a 70% reduction in major motor seizures. In addition, regarding durability of effect, six of the nine patients (67%) experienced a ≥50% reduction in seizure frequency for at least 90% of the months they were being treated. Treatment with low-dose fenfluramine continues to be generally well-tolerated. The most common treatment-emergent adverse events were mild-to-moderate somnolence (n=5) and anorexia (n=4). No evidence of cardiac valvulopathy or pulmonary hypertension was observed in any patient on any echocardiogram. There were no patient discontinuations. Two additional posters were also presented in the main exhibit hall at the AES meeting. One poster presented pre-clinical data suggesting that there may be a protective effect of fenfluramine in an accepted pre-clinical model of Sudden Unexpected Death in Epilepsy (SUDEP) (see study data here). In this SUDEP animal model, the administration of fenfluramine significantly (p<0.05) reduced the susceptibility of the mice to have seizure-induced respiratory arrest (S-IRA) 30 minutes post-dosing (20 or 30 mg/kg i.p.) and maintained significance through 24 hours. The prolonged effect of fenfluramine in the present study was not consistently observed with other serotonergic agents tested. These data provide the first evidence of a protective effect of fenfluramine in a mammalian model of SUDEP. The second poster highlighted the findings from roundtable discussions with parents and caregivers of children with Dravet syndrome that sought to identify those aspects of caregivers’ lives that are most impacted by caring for a child with Dravet syndrome (see study data here). These roundtable discussions identified significant impacts on the lives of these families in four overarching areas: physical, mental, social, and financial. Future work by this group will focus on developing a validated measure of caregiver burden in Dravet syndrome. “The Zogenix team is extremely pleased with all of the data presented at this year’s AES meeting,” said Stephen J. Farr, Ph.D., President and CEO. “Based on the strength of the LGS data generated, we are currently evaluating a move into a Phase 3 program of ZX008 in this indication. In Dravet syndrome, our confidence in the potential of ZX008 as a safe and effective treatment for seizures associated with Dravet syndrome continues to strengthen with the meaningful reduction in seizure frequency and sustained cardiovascular safety that remain consistent in the results observed in the new cohort of patients. Additionally, the preliminary data generated in the animal model of SUDEP, which suggests a protective effect of fenfluramine against seizure-induced respiratory arrest, is an interesting finding that we intend to explore further.” Zogenix also hosted a Scientific Exhibit Room at the AES meeting entitled, “Evolution of Low-Dose Fenfluramine in the Treatment of Epileptic Encephalopathies: New Understandings of the Mechanisms, Basic Science, and Clinical Data.” In this Scientific Exhibit Room, the Company highlighted important ZX008-related research conducted over the last year, including multiple scientific posters that were not presented in the main poster session of the AES meeting. These posters can be found here. Zogenix’s Phase 3 program for Dravet syndrome continues to enroll patients in the U.S. and internationally, and the Company expects the availability of Phase 3 top-line data in Dravet syndrome in the second quarter of 2017, and potential regulatory submissions for approval to occur by year-end 2017. ZX008 is designated as an orphan drug in both the U.S. and Europe, and also received Fast Track designation in the U.S., for the treatment of Dravet syndrome. About Zogenix Zogenix, Inc. (Nasdaq:ZGNX) is a pharmaceutical company committed to developing and commercializing CNS therapies that address specific clinical needs for people living with orphan and other CNS disorders who need innovative treatment alternatives to improve their daily functioning. Forward Looking Statements Zogenix cautions you that statements included in this press release that are not a description of historical facts are forward-looking statements. Words such as "believes," "anticipates," "plans," "expects," "indicates," "will," "intends," "potential," "suggests," "assuming," "designed" and similar expressions are intended to identify forward-looking statements. These statements are based on the company's current beliefs and expectations. These forward-looking statements include statements regarding ZX008’s potential as a treatment for seizures associated with Dravet syndrome or LGS and treatment for SUDEP; the enrollment of patients in the two on-going Phase 3 clinical trials of ZX008 for patients with Dravet syndrome; the continued evaluation of patients in the open-label Phase 2 clinical trial of ZX008 for patients with LGS and the potential to move into a Phase 3 program for LGS; the timing of any submission of a new drug application to the U.S. Food and Drug Administration or comparable market authorization filing in Europe; and the further exploration of fenfluramine in SUDEP. The inclusion of forward-looking statements should not be regarded as a representation by Zogenix that any of its plans will be achieved. Actual results may differ from those set forth in this release due to the risks and uncertainties inherent in Zogenix's business, including, without limitation: the uncertainties associated with the clinical development and regulatory approval of product candidates such as ZX008, including potential delays in the commencement, enrollment and completion of clinical trials; the potential that earlier clinical trials and studies may not be predictive of future results; Zogenix's reliance on third parties to conduct its clinical trials, enroll patients, manufacture its preclinical and clinical drug supplies and manufacture commercial supplies of its drug products, if approved; unexpected adverse side effects or inadequate therapeutic efficacy of ZX008 that could limit approval and/or commercialization, or that could result in recalls or product liability claims; Zogenix's ability to fully comply with numerous federal, state and local laws and regulatory requirements, as well as rules and regulations outside the United States, that apply to its product development activities; Fast Track designation may not result in an expedited regulatory review process; and other risks described in Zogenix's prior press releases as well as in public periodic filings with the Securities and Exchange Commission. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof, and Zogenix undertakes no obligation to revise or update this press release to reflect events or circumstances after the date hereof. All forward-looking statements are qualified in their entirety by this cautionary statement. This caution is made under the safe harbor provisions of Section 21E of the Private Securities Litigation Reform Act of 1995.
News Article | December 16, 2016
Basel, December 16, 2016 - Novartis today announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion for Votubia® (everolimus) dispersible tablets* as an adjunctive treatment of patients aged two years and older whose refractory partial-onset seizures, with or without secondary generalization, are associated with tuberous sclerosis complex (TSC). If approved by the European Commission (EC), Votubia would address an unmet need as currently there are no pharmacologic treatments approved specifically for the treatment of refractory seizures associated with TSC. "As refractory seizures are among the most debilitating manifestations of TSC, a new therapy that provides seizure control would be a meaningful advance for these patients in the EU," said Bruno Strigini, CEO, Novartis Oncology. "This CHMP opinion is an important milestone in our longstanding commitment to improving care for patients affected by TSC." The positive CHMP opinion was based on efficacy and safety data from a pivotal Phase III study (EXIST-3: amining everolimus n a tudy of SC), which found that when used as an adjunctive therapy, everolimus significantly reduced refractory partial-onset seizures associated with TSC compared to placebo. The youngest patient enrolled was two years of age and patients in all treatment arms received one to three anti-epileptic drugs (AEDs). Seizure response rate (>=50% reduction) was significantly greater with everolimus low exposure (LE) (28.2%, 95% CI 20.3 - 37.3; p=0.008) and high exposure (HE) (40.0%, 95% CI 31.5 - 49.0; p<0.001) vs placebo (15.1%, 95% CI 9.2 - 22.8). The median percentage reduction from baseline in seizure frequency was also significantly greater among patients randomized to everolimus LE (29.3%, 95% CI 18.8 - 41.9; p=0.003) and HE (39.6%, 95% CI 35.0 - 48.7; p<0.001) vs placebo (14.9%, 95% CI 0.1 - 21.7). The most common all-grade adverse events (AEs) of any cause reported during the core phase at frequencies 15% in everolimus LE/HE arms included stomatitis, diarrhea, pyrexia, nasopharyngitis, and upper respiratory tract infection. The EC typically adheres to the recommendation of the CHMP and usually delivers its final decision in two months or earlier. The decision will be applicable to all 28 European Union (EU) member states plus Iceland and Norway. In Europe, everolimus has orphan drug designation for TSC. Orphan drugs are those that treat a condition which affects no more than five in 10,000 people in the EU. Tuberous sclerosis complex is a rare genetic disorder affecting up to one million people worldwide. Approximately 85% of individuals with TSC are affected by epilepsy, and uncontrolled seizures associated with TSC can be debilitating for patients. Everolimus is the only approved non-surgical option indicated for treating non-cancerous brain and kidney tumors in certain patients with TSC. EXIST-3 is the first Phase III study to demonstrate the significant benefit of adjunctive everolimus in the treatment of refractory partial-onset seizures in patients with TSC,,. These data may be used to support regulatory filings in other countries. Everolimus works by inhibiting the mammalian target of rapamycin (mTOR), a protein that regulates multiple cellular functions. TSC is caused by mutations in the TSC1 or TSC2 genes, resulting in hyperactive signaling of the mTOR pathway which can lead to increased cellular growth and proliferation, neuronal hyper-excitability, abnormalities in cortical architecture and network function and impaired synaptic plasticity,. Pre-clinical research suggests that hyperactive mTOR activity may influence several mechanisms of epileptogenesis, the gradual process by which the brain develops epilepsy in TSC. About EXIST-3 (EXIST-3: EXamining everolimus In a Study of TSC) EXIST-3 is a Phase III, three-arm, randomized, double-blind, placebo-controlled study of the efficacy and safety of high and low exposure ranges of everolimus as adjunctive therapy in patients with TSC who have refractory partial-onset seizures, defined as seizures persisting despite the use of two anti-epileptic drugs (AEDs). The study enrolled male and female participants (ages 2.2-56.3 years) with clinically defined TSC, who were on stable doses of one to three AEDs for at least four weeks prior to a two-month, pre-randomization, evaluation period. The primary objective was to assess the effectiveness of adjunctive everolimus as compared to placebo in reducing refractory partial-onset seizures in patients with TSC who are taking one to three AEDs. Secondary objectives included the percentage of patients free from seizure during the maintenance period, change in seizure frequency, and safety. The most frequent (>=10%) all grade adverse events (AEs), of any cause, reported with everolimus LE/HE vs placebo included stomatitis (55.0%/64.0% vs 9.0%), diarrhea (17.1%/21.5% vs 5.0%), nasopharyngitis (13.7%/16.2% vs 16.0%), upper respiratory tract infection (12.8%/15.4% vs 12.6%), pyrexia (fever) (19.7%/13.8% vs 5.0%), vomiting (12.0%/10.0% vs 9.2%), cough (11.1%/10.0% vs 3.4%) and rash (6.0%/10.0% vs 2.5%). Grade 3 or 4 AEs occurred in 13 (11.0%) patients in the placebo group, 21 (18.0%) in the LE group, and 31 (24.0%) in the HE group. About tuberous sclerosis complex Tuberous sclerosis complex (TSC) may cause non-cancerous tumors to form in vital organs including the brain, kidney, heart, lungs, and skin, as well as resulting disorders such as epilepsy, autism, cognitive impairment, behavioral problems, and psychiatric disorders. Many people with TSC show evidence of the disease in the first year of life. However, because manifestations vary from person to person and can take years to develop, many children are not diagnosed until later in life, often with the onset of seizures, skin lesions or other significant symptoms, such as developmental delays. Because TSC is a lifelong condition, the latest professional diagnostic guidelines issued in 2012 advise that individuals be monitored by a doctor experienced with the disorder to ensure tumor growth or new symptoms are identified early,. About Votubia® (everolimus) In the European Union (EU), everolimus is approved as Votubia® tablets for the treatment of adult patients with renal angiomyolipoma associated with tuberous sclerosis complex (TSC) who are at risk of complications (based on factors such as tumor size or presence of aneurysm, or presence of multiple or bilateral tumors) but who do not require immediate surgery. The evidence is based on analysis in sum of angiomyolipoma volume. Votubia® tablets and dispersible tablets are also indicated in the EU for the treatment of patients with subependymal giant cell astrocytoma (SEGA) associated with TSC who require therapeutic intervention but are not amenable to surgery. The evidence is based on analysis of change in SEGA volume. Further clinical benefit, such as improvement in disease-related symptoms, has not been demonstrated. In the United States (US), everolimus is approved as Afinitor® tablets for the treatment of adult patients with renal angiomyolipoma and TSC, not requiring immediate surgery. Afinitor® tablets and Afinitor Disperz(TM) (dispersible tablets) are also indicated in the US in pediatric and adult patients with TSC for the treatment of SEGA that requires therapeutic intervention but cannot be curatively resected. Additionally, Afinitor tablets is approved in >110 countries, including the US and throughout the EU, for locally advanced, metastatic or unresectable progressive neuroendocrine tumors (NET) of pancreatic origin and in the US and EU for the treatment of adult patients with progressive, well-differentiated (Grade 1 or 2), nonfunctional NET of gastrointestinal (GI) or lung origin that are unresectable, locally advanced or metastatic. It is also approved in >120 countries including the US and EU for advanced renal cell carcinoma following progression on or after vascular endothelial growth factor (VEGF)-targeted therapy (in the US, specifically following sunitinib and sorafenib). Afinitor is also approved in 115 countries including the US and EU for advanced HR+/HER2- breast cancer in combination with exemestane, after prior endocrine therapy. Everolimus is also available from Novartis under the brand names Afinitor®, Certican® and Zortress® for use in oncology and transplant patient populations and is exclusively licensed to Abbott and sublicensed to Boston Scientific for use in drug-eluting stents. Indications vary by country and not all indications are available in every country. The safety and efficacy profile of everolimus has not yet been established outside the approved indications. Because of the uncertainty of clinical trials, there is no guarantee that everolimus will become commercially available for additional indications anywhere else in the world. Important safety information Votubia/Afinitor can cause serious side effects including lung or breathing problems, infections (including sepsis), and kidney failure, which can lead to death. Patients taking concomitant angiotensin-converting enzyme (ACE) inhibitors may be at an increased risk for angioedema. Mouth ulcers and mouth sores are common side effects. Votubia/Afinitor can affect blood cell counts, kidney and liver function, and blood sugar, cholesterol, and triglyceride levels. Votubia/Afinitor may cause fetal harm in pregnant women. Highly effective contraception is recommended for women of child-bearing potential while receiving Votubia/Afinitor and for up to eight weeks after ending treatment. Women taking Votubia/Afinitor should not breast feed. Fertility in women and men may be affected by treatment with Votubia/Afinitor. The most common adverse drug reactions (incidence >=10 percent) are infections (including sore throat and runny nose, upper respiratory tract infection, pneumonia, sinusitis, and urinary tract infection), mouth ulcers, skin rash, feeling tired, diarrhea, fever, vomiting, nausea, cough, decreased appetite, low level of red blood cells, headache, abnormal taste, absence of menstrual periods, acne, inflammation of lung tissue, irregular menstrual periods, swelling of extremities or other parts of the body, high level of blood sugar, feeling weak, itching, weight loss, high levels of cholesterol, and nose bleeds. The most common Grade 3-4 adverse drug reactions (incidence >=2 percent) are mouth ulcers, infections (including pneumonia), low level of red blood cells, high level of blood sugar, feeling tired, absence of menstrual periods, diarrhea, low white blood cells, inflammation of lung tissue, feeling weak, fever, and spontaneous bleeding or bruising. Cases of hepatitis B reactivation, blood clots in the lung or legs, and pneumocystis jirovecii pneumonia (PJP) have been reported. Abnormalities were observed in hematology and clinical chemistry laboratory tests. Disclaimer The foregoing release contains forward-looking statements that can be identified by words such as "recommended," "would," "positive opinion," "CHMP opinion," "commitment," "recommendation," "will," "may," "suggests," "yet," or similar terms, or by express or implied discussions regarding potential new indications or labeling for Votubia, or regarding potential future revenues from Votubia. You should not place undue reliance on these statements. Such forward-looking statements are based on the current beliefs and expectations of management regarding future events, and are subject to significant known and unknown risks and uncertainties. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those set forth in the forward-looking statements. There can be no guarantee that Votubia will be submitted or approved for any additional indications or labeling in any market, or at any particular time. Nor can there be any guarantee that Votubia will be commercially successful in the future. In particular, management's expectations regarding Votubia could be affected by, among other things, the uncertainties inherent in research and development, including unexpected clinical trial results and additional analysis of existing clinical data; unexpected regulatory actions or delays or government regulation generally; the company's ability to obtain or maintain proprietary intellectual property protection; general economic and industry conditions; global trends toward health care cost containment, including ongoing pricing pressures; unexpected safety, quality or manufacturing issues, and other risks and factors referred to in Novartis AG's current Form 20-F on file with the US Securities and Exchange Commission. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise. About Novartis Novartis provides innovative healthcare solutions that address the evolving needs of patients and societies. Headquartered in Basel, Switzerland, Novartis offers a diversified portfolio to best meet these needs: innovative medicines, eye care and cost-saving generic pharmaceuticals. Novartis is the only global company with leading positions in these areas. In 2015, the Group achieved net sales of USD 49.4 billion, while R&D throughout the Group amounted to approximately USD 8.9 billion (USD 8.7 billion excluding impairment and amortization charges). Novartis Group companies employ approximately 118,000 full-time-equivalent associates. Novartis products are available in more than 180 countries around the world. For more information, please visit http://www.novartis.com. Novartis is on Twitter. Sign up to follow @Novartis at http://twitter.com/novartis and @NovartisCancer at http://twitter.com/novartiscancer For Novartis multimedia content, please visit www.novartis.com/news/media-library For questions about the site or required registration, please contact firstname.lastname@example.org *Known as Afinitor® (everolimus) tablets for certain patients with SEGA and renal angiomyolipoma associated with TSC in the US and other countries. References  French. J.A., et al. Adjunctive everolimus therapy for treatment-resistant focal-onset seizures associated with tuberous sclerosis (EXIST-3): a phase 3, randomised, double-blind, placebo-controlled study. Lancet. Available at http://dx.doi.org/10.1016/S0140-6736(16)31419-2. Accessed December 2016.  Chu-Shore C.J., et al. The natural history of epilepsy in tuberous sclerosis complex. Epilepsia. 2010: 51(7): 1236-1241.  European Medicines Agency. Orphan drugs and rare diseases at a glance. Available at http://www.ema.europa.eu/docs/en_GB/document_library/Other/2010/01/WC500069805.pdf. Accessed December 2016.  Budde, K. and Gaedeke, J. Tuberous sclerosis complex-associated angiomyolipomas: focus on mTOR inhibition. American Journal of Kidney Diseases. 2012:276-283.  Afinitor (everolimus) Prescribing information. East Hanover, New Jersey, USA: Novartis Pharmaceuticals Corporation; February 2016.  Votubia (everolimus): EU Summary of Product Characteristics. Novartis; December 2015.  National Institute of Neurological Disorders and Stroke fact sheet. 2010. Wong, M. Mammalian target of rapamycin (mTOR) pathways in neurological diseases. Biomed Journal. 2013; 36(2): 1-17.  Ostendorf, A. and Wong, M. mTOR inhibition in epilepsy: rationale and clinical perspectives. CNS Drugs. 2015:91-99.  Northrup, H. et al. Tuberous sclerosis complex diagnostic criteria update: recommendations of the 2012 international tuberous sclerosis complex consensus conference. Pediatric Neurology. 2013; 49: 243-254
Kaplan P.,Children's Hospital of Philadelphia |
Baris H.,Tel Aviv University |
De Meirleir L.,Pediatric Neurology |
Di Rocco M.,Gaslini Institute |
And 7 more authors.
European Journal of Pediatrics | Year: 2013
Gaucher disease is an inherited pan-ethnic disorder that commonly begins in childhood and is caused by deficient activity of the lysosomal enzyme glucocerebrosidase. Two major phenotypes are recognized: nonneuropathic (type 1) and neuropathic (types 2 and 3). Symptomatic children are severely affected and manifest growth retardation, delayed puberty, early-onset osteopenia, significant splenomegaly, hepatomegaly, thrombocytopenia, anemia, severe bone pain, acute bone crises, and fractures. Symptomatic children with types 1 or 3 should receive enzyme replacement therapy, which will prevent debilitating and often irreversible disease progression and allow those with non-neuropathic disease to lead normal healthy lives. Children should be monitored every 6 months (physical exam including growth, spleen and liver volume, neurologic exam, hematologic indices) and have one to two yearly skeletal assessments (bone density and imaging, preferably with magnetic resonance, of lumbar vertebrae and lower limbs), with specialized cardiovascular monitoring for some type 3 patients. Response to treatment will determine the frequency of monitoring and optimal dose of enzyme replacement. Treatment of children with type 2 (most severe) neuropathic Gaucher disease is supportive. Pre-symptomatic children, usually with type 1 Gaucher, increasingly are being detected because of affected siblings and screening in high-prevalence communities. In this group, annual examinations (including bone density) are recommended. However, monitoring of asymptomatic children with affected siblings should be guided by the age and severity of manifestations in the first affected sibling. Treatment is necessary only if signs and symptoms develop. Conclusion: Early detection and treatment of symptomatic types 1 and 3 Gaucher disease with regular monitoring will optimize outcome. Pre-symptomatic children require regular monitoring. Genetic counseling is important. © Springer-Verlag 2012.
Datta A.N.,University of Basel |
Oser N.,University of Basel |
Bauder F.,Childrens Hospital |
Maier O.,Ostschweizer Childrens Hospital |
And 5 more authors.
Epilepsia | Year: 2013
Summary Purpose Benign epilepsy with centrotemporal spikes (BECTS) is associated with mild cognitive deficits, especially language impairment. This study aimed to clarify whether children with BECTS with left- or right-hemispheric, or bilateral focus have specific neuropsychological language deficits when compared to healthy controls, whether these deficits correlate functionally with language network organization (typical vs. atypical), and whether cofactors such as duration, handedness, and medication have a relevant impact on language reorganization processes. Methods Twenty-seven patients and 19 healthy controls were examined with several neuropsychological tests (German version of the Wechsler Intelligence Scale for Children [WISC-IV], Regensburger verbal fluency test [RWT], Corsiblock forward and backward and Hand-Dominanz-Test [HDT]) and with two language paradigms on functional magnetic resonance imaging (fMRI): silent reading of word-pairs and silent generation of simple sentences. Key Findings Although neuropsychological test results only differed by trend between BECTS patients and controls, language laterality indices (LIs) in fMRI were significantly lower in patients than in controls. In particular, the anterior language network with Broca's area and the supplementary motor area (SMA) revealed the lowest LIs and showed the most bilateral or right hemispheric activations in the sentence generation task. Medication and duration of epilepsy did not have any significant effect on language reorganization and patients' performances. Significance Language reorganization in BECTS patients takes place in bilateral or right hemispheric language networks, with a strong focus in anterior language regions. These functional changes can be interpreted as important compensatory strategies of the central nervous system (CNS) to stabilize cognitive, especially language performance. © Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.
News Article | November 7, 2016
The report firstly introduced Global Pediatric Neurology Devices including classification, application and industry chain overview; Then we deeply analyzed global growth forecast indicators by the as well as the regional market conditions that including the product price, profit, utilization, supply, demand and industry growth rate etc. In the end, the report introduced medical suction device market SWOT analysis, PEST analysis, market share analysis and competitive landscape, company profiles by analyzing the major players. It is a depth research study on Global Pediatric Neurology Devices. Taste the market data and market information presented through more than 100 market data tables and figures spread in 120 numbers of pages of the project report. Avail the in-depth table of content TOC & market synopsis on “Global Pediatric Neurology Devices Market (North America, Europe, Asia, Rest of the World) – Forecast to 2021" We are thankful for the support and assistance from Global Pediatric Neurology Devices . Industry chain related technical experts and marketing experts during Research Team survey and interviews. The report for Pediatric Neurology Devices Market of Market Research Future comprises of extensive primary research along with the detailed analysis of qualitative as well as quantitative aspects by various industry experts, key opinion leaders to gain the deeper insight of the market and industry performance. The report gives the clear picture of current market scenario which includes historical and projected market size in terms of value and volume, technological advancement, macro economical and governing factors in the market. The report provides details information and strategies of the top key players in the industry. The report also gives a broad study of the different market segments and regions. APAC Infectious Disease Diagnosis & Treatment Market Information, by applications (Tuberculosis (TB), Aids, Hepatitis B, Hepatitis C and others), by treatment (Antibiotics, antivirals, antifungals, anti-parasitic, alternative medicine and others) by end users (hospitals, clinics, reference labs and others) - Forecast to 2027 At Market Research Future (MRFR), we enable our customers to unravel the complexity of various industries through our Cooked Research Report (CRR), Half-Cooked Research Reports (HCRR), Raw Research Reports (3R), Continuous-Feed Research (CFR), and Market Research & Consulting Services. MRFR team have supreme objective to provide the optimum quality market research and intelligence services to our clients. Our market research studies by products, services, technologies, applications, end users, and market players for global, regional, and country level market segments, enable our clients to see more, know more, and do more, which help to answer all their most important questions.
News Article | November 7, 2016
— The report firstly introduced Global Pediatric Neurology Devices including classification, application and industry chain overview; Then we deeply analyzed global growth forecast indicators by the as well as the regional market conditions that including the product price, profit, utilization, supply, demand and industry growth rate etc. In the end, the report introduced medical suction device market SWOT analysis, PEST analysis, market share analysis and competitive landscape, company profiles by analyzing the major players. It is a depth research study on Global Pediatric Neurology Devices. • To provide detailed analysis of the market structure along with forecast for the next 6 years of the various segments and sub-segments of the Pediatric Neurology Devices Market • provide insights about factors affecting the market growth • To Analyze the Pediatric Neurology Devices Market based on various factors- price analysis, supply chain analysis, porters five force analysis etc. • To provide historical and forecast revenue of the market segments and sub-segments with respect to four main geographies and their countries- North America, Europe, Asia, and Rest of the World (ROW) • To provide country level analysis of the market with respect to the current market size and future prospective • To provide country level analysis of the market for segment by Form, by End-users, and by Application. • To provide strategic profiling of key players in the market, comprehensively analyzing their core competencies, and drawing a competitive landscape for the market • To track and analyze competitive developments such as joint ventures, strategic alliances, mergers and acquisitions, new product developments, and research and developments in the Pediatric Neurology Devices Market Taste the market data and market information presented through more than 100 market data tables and figures spread in 120 numbers of pages of the project report. Avail the in-depth table of content TOC & market synopsis on “Global Pediatric Neurology Devices Market (North America, Europe, Asia, Rest of the World) – Forecast to 2021" We are thankful for the support and assistance from Global Pediatric Neurology Devices . Industry chain related technical experts and marketing experts during Research Team survey and interviews. 7 Global Pediatric Neurology Devices Market, By Region 7.1 Introduction 7.2 North America 7.3 Europe 7.4 Asia 7.5 Rest of The World The report for Pediatric Neurology Devices Market of Market Research Future comprises of extensive primary research along with the detailed analysis of qualitative as well as quantitative aspects by various industry experts, key opinion leaders to gain the deeper insight of the market and industry performance. The report gives the clear picture of current market scenario which includes historical and projected market size in terms of value and volume, technological advancement, macro economical and governing factors in the market. The report provides details information and strategies of the top key players in the industry. The report also gives a broad study of the different market segments and regions. APAC Infectious Disease Diagnosis & Treatment Market Information, by applications (Tuberculosis (TB), Aids, Hepatitis B, Hepatitis C and others), by treatment (Antibiotics, antivirals, antifungals, anti-parasitic, alternative medicine and others) by end users (hospitals, clinics, reference labs and others) - Forecast to 2027 At Market Research Future (MRFR), we enable our customers to unravel the complexity of various industries through our Cooked Research Report (CRR), Half-Cooked Research Reports (HCRR), Raw Research Reports (3R), Continuous-Feed Research (CFR), and Market Research & Consulting Services. MRFR team have supreme objective to provide the optimum quality market research and intelligence services to our clients. Our market research studies by products, services, technologies, applications, end users, and market players for global, regional, and country level market segments, enable our clients to see more, know more, and do more, which help to answer all their most important questions. For more information, please visit https://www.marketresearchfuture.com
Datta A.N.,University of Basel |
Oser N.,University of Basel |
Ramelli G.P.,Pediatric Neurology |
Gobbin N.Z.,Pediatric Neurology |
And 3 more authors.
Epilepsy and Behavior | Year: 2013
By means of a longitudinal case study, we demonstrated the course of cerebral reorganization of language representation due to epilepsy in a child with benign epilepsy with centro-temporal spikes (BECTS) evolving to Landau-Kleffner Syndrome (LKS) and returning to BECTS.The child underwent the following procedures at the ages of 8.2, 8.6, and 9.3. years: 3D source EEG imaging, language fMRI (sentence generation and reading), and neuropsychological testing. He had a follow-up testing at the age of 10.8. years. Further, 24-h EEGs were regularly performed.At the age of around 8. years, the child was diagnosed initially with left-hemispheric BECTS, which evolved to LKS with continuous bilateral discharges. In addition, 3D source imaging data revealed a left anterior temporal focus with a spreading to the right parietal and left centro-parietal areas. The patient had verbal agnosia with poor verbal yet good performance indices. Functional magnetic resonance imaging (fMRI) showed a left-hemispheric reading network but sentence generation was impossible to perform. After initiation of adequate treatment, continuous discharges disappeared, and only very rare left-hemispheric centro-temporal spikes remained. Verbal IQ and performance IQ increased at the age of 8.6. years. Functional magnetic resonance imaging showed, at this time, a right-hemispheric language activation pattern for sentence generation and reading. At the ages of 9.3 and 10.8. years, language tasks remained right-hemispheric and verbal IQ remained stable, but right-hemispheric non-verbal functions decreased due to possible crowding-out mechanisms. © 2013 Elsevier Inc.
Gillick B.T.,University of Minnesota |
Feyma T.,Pediatric Neurology |
Menk J.,Clinical Translational Science Institute |
Usset M.,University of Minnesota |
And 4 more authors.
Physical Therapy | Year: 2015
Background. Transcranial direct current stimulation (tDCS) is a form of noninvasive brain stimulation that has shown improved adult stroke outcomes. Applying tDCS in children with congenital hemiparesis has not yet been explored. Objective. The primary objective of this study was to explore the safety and feasibility of single-session tDCS through an adverse events profile and symptom assessment within a double-blind, randomized placebo-controlled preliminary study in children with congenital hemiparesis. A secondary objective was to assess the stability of hand and cognitive function. Design. A double-blind, randomized placebo-controlled pretest/posttest?follow-up study was conducted. Setting. The study was conducted in a university pediatric research laboratory. Participants. Thirteen children, ages 7 to 18 years, with congenital hemiparesis participated. Measurements. Adverse events/safety assessment and hand function were measured. Intervention. Participants were randomly assigned to either an intervention group or a control group, with safety and functional assessments at pretest, at posttest on the same day, and at a 1-week follow-up session. An intervention of 10 minutes of 0.7 mA tDCS was applied to bilateral primary motor cortices. The tDCS intervention was considered safe if there was no individual decline of 25% or group decline of 2 standard deviations for motor evoked potentials (MEPs) and behavioral data and no report of adverse events. Results. No major adverse events were found, including no seizures. Two participants did not complete the study due to lack of MEP and discomfort. For the 11 participants who completed the study, group differences in MEPs and behavioral data did not exceed 2 standard deviations in those who received the tDCS (n=5) and those in the control group (n=6). The study was completed without the need for stopping per medical monitor and biostatisticial analysis. Limitations. A limitation of the study was the small sample size, with data available for 11 participants. Conclusions. Based on the results of this study, tDCS appears to be safe, feasible, and well tolerated in most children with hemiparesis. Future investigations of serial sessions of tDCS in conjunction with rehabilitation in pediatric hemiparesis are indicated to explore the benefit of a synergistic approach to improving hand function. © 2015 American Physical Therapy Association.
Koehl B.,University of Paris Descartes |
Boyer O.,University of Paris Descartes |
Biebuyck-Gouge N.,University of Paris Descartes |
Kossorotoff M.,Pediatric Neurology |
And 3 more authors.
Pediatric Nephrology | Year: 2010
We report the case of a 4-year-old boy, diagnosed with atypical hemolytic uremic syndrome (HUS) due to a hybrid factor H. He progressed to end-stage renal failure despite plasmatherapy and underwent bilateral nephrectomy because of uncontrolled hypertension. Three days after, he had partial complex seizures with normal blood pressure, normal blood count and normal magnetic resonance imaging (MRI), which recurred 1 month later. Eight months later, he had a third episode of seizures, with hemoglobin of 10 g/dl without schizocytes, low haptoglobin of 0.18 g/l, and moderate thrombocytopenia (platelets 98 × 109/l). He remained hypertensive and deeply confused for 2 days. The third MRI showed bilateral symmetrical hyperintensities of the cerebral pedunculas, caudate nuclei, putamens, thalami, hippocampi, and insulae suggesting thrombotic microangiopathy secondary to a relapse of HUS rather than reversible posterior leukoencephalopathy syndrome (RPLS), usually occipital and asymmetrical. Plasmatherapy led to a complete neurological recovery within 2 days although hypertension had remained uncontrolled. The fourth MRI 10 weeks after, on maintenance plasmatherapy, was normal and clinical examination remained normal, except for high blood pressure. In conclusion, brain MRI allows differentiating thrombotic microangiopathy lesions from RPLS in atypical HUS, which is crucial since lesions may be reversible with plasmatherapy. © 2010 IPNA.