ORCID Profile
0000-0002-1116-126X
Current Organisation
Mayo Clinic
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Publisher: SAGE Publications
Date: 31-03-2014
Abstract: Approximately one-third of those with pediatric-onset multiple sclerosis (MS) experience cognitive impairment. Less is known concerning their change in cognitive functioning over time. Changes in cognitive function over time were measured in the largest pediatric cohort to date through the US Network of Pediatric MS Centers. A total of 67 in iduals with pediatric MS ( n=62) or clinically isolated syndrome (CIS, n=5), ranging from 8–17 years of age (mean age±standard deviation (SD)=14.37±2.02) completed initial and follow-up neuropsychological testing after an average of 1.64±0.63 years apart. The nine tests administered measure general intellect, attention and working memory, verbal memory, visuomotor integration, language, and executive functioning. Rate of impairment (having one-third or more scores in the impaired range) was 37% at baseline and 33% at follow-up. Tests commonly impaired were measures of visuomotor integration, speeded processing, and attention. Most tested did not decline over two years. There was no clear pattern of change on any specific measure. Findings suggest that, over short timeframes, stable or even improved performances on measures of cognitive ability can occur. Pediatric MS may instead prevent expected age-related cognitive gains.
Publisher: Elsevier BV
Date: 04-2009
Publisher: SAGE Publications
Date: 11-2008
Abstract: In this study, we examine the long-term clinical outcome of children with symptomatic infantile spasm. The children between 2 and 18 years of age diagnosed with symptomatic infantile spasms were reviewed. Sixty-eight children (age range, 2-13 years mean, 4.5 years) met the inclusion criteria. Children who underwent epilepsy surgery were excluded. Age of onset for infantile spasms ranged from 1 to 24 months (mean, 7.1 months). Developmental delay was noted in all there was seizure freedom in 14 children (20.5%). Infantile spasms were reported as the only seizure type in 10 (14.5%) children older than age 2 years. During the follow-up symptomatic generalized epilepsy was diagnosed in 23 childern (34%) and focal epilepsy in 21 (31%). The long-term outcome of these children remains unchanged in the majority of the children with symptomatic infantile spasms. We could not establish any risk factor that might be related to favorable or adverse outcome.
Publisher: Wiley
Date: 21-12-2010
DOI: 10.1002/AJMG.B.30969
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-05-2010
Publisher: SAGE Publications
Date: 27-01-2011
Abstract: Abnormal copper metabolism has been linked with neurological disorders, such as Wilson and Menkes disease. Another disorder causing symptoms similar to copper metabolism disorder is Niemann-Pick type C. However, a definite pathophysiological connection between Niemann-Pick type C and copper metabolism disorders has never been established. The authors present an adolescent with an unusual presentation of copper deficiency—dysarthria, ataxia, and vertical gaze paresis, without significant cognitive degeneration or pathological magnetic resonance imaging (MRI). The patient was found to carry 2 mutations in the NPC1 gene. A possible link, explaining how copper deficiency might induce the Niemann-Pick phenotype might involve overproduction of cholesterol and inhibition of acid sphingomyelinase. We suggest that copper metabolism disorders be included in the differential diagnosis for ataxia and dysarthria, even in cases with unusual presentations. Moreover, should the connection between copper and Niemann-Pick be validated, screening for copper metabolism disorders may be advisable in Niemann-Pick type C patients and vice-versa.
Publisher: Elsevier BV
Date: 06-2006
Publisher: Elsevier BV
Date: 06-2009
Publisher: Elsevier BV
Date: 03-2010
Publisher: Wiley
Date: 21-06-2014
Publisher: Elsevier BV
Date: 05-2007
Publisher: Oxford University Press (OUP)
Date: 17-01-2008
Abstract: To determine whether elevated B-type natriuretic peptide (BNP) predicts left ventricular (LV) contractile dysfunction on exercise stress echocardiography in patients with severe mitral regurgitation (MR). Thirty three patients with moderate-to-severe or severe MR, a LV ejection fraction > or =60% and New York Heart Association Class I or II symptoms, and 12 controls underwent resting and exercise stress echocardiography. In 20 MR patients, BNP was within the normal range (mean +/- SD, 7.7 +/- 2.7 pmol/L), and in 13 MR patients, BNP was >12 pmol/L (19.6 +/- 7.6 pmol/L). LV end-systolic volume index after exercise was lower in controls than patients with MR (P 0.05). However, pulmonary artery systolic pressure (PAP) after exercise was higher in MR with high BNP (70 +/- 20 vs. 48 +/- 11 mmHg, <0.0001) and controls (38+/-11 mmHg). A two-fold increase in plasma BNP was associated with an average increase in resting PAP of 7.6 (95% CI 2.9, 12.2) mmHg, an increase in post-exercise PAP of 14.4 (95% CI 9.0, 19.9) mmHg and increase in left atrial area index of 2.1 (95% CI 0.5, 3.8) cm(2)/m(2). However, there was no significant association between the plasma level of BNP and any rest or post-exercise measure of LV systolic function (r 0.05 for all). The plasma level of BNP may be within the normal range in patients with moderate-to-severe or severe MR despite significant increases in LV end-systolic volume. Increase in BNP is associated with pulmonary artery hypertension on exercise and left atrial enlargement even when LV systolic function on exercise stress echocardiography is normal.
Publisher: Elsevier BV
Date: 09-1999
Publisher: Hindawi Limited
Date: 10-2003
DOI: 10.1002/HUMU.10255
Abstract: The two known complementation groups of Niemann-Pick Type C disease, NPC1 and NPC2, result from non-allelic protein defects. Both the NPC1 and NPC2 (HE1) gene products are intimately involved in cholesterol and glycolipid trafficking and/or transport. We describe mutation analysis on s les from 143 unrelated affected NPC patients using conformation sensitive gel electrophoresis and DNA sequencing as the primary mutation screening methods for NPC1 and NPC2, respectively. These methods are robust, sensitive, and do not require any specialized laboratory equipment. Analyses identified two NPC1 mutations for 115 (80.4%) patients, one NPC1 mutation for 10 (7.0%) patients, two NPC2 mutations for five (3.5%) patients, one NPC2 mutation for one (0.7%) patient, and no mutations for 12 (8.4%) patients. Thus, mutations were identified on 251 of 286 (88%) disease alleles, including 121 different mutations (114 in NPC1 and seven in NPC2), 58 of which are previously unreported. The most common NPC1 mutation, I1061T, was detected on 18% of NPC alleles. Other NPC1 mutations were mostly private, missense mutations located throughout the gene with clustering in the cysteine-rich luminal domain. Correlation with biochemical data suggests classification of several mutations as severe and others as moderate or variable. The region between amino acids 1038 and 1253, which shares 35% identity with Patched 1, appears to be a hot spot for mutations. Additionally, a high percentage of mutations were located at amino acids identical to the NPC1 homolog, NPC1L1. Biochemical complementation analysis of cases negative for mutations revealed a high percentage of equivocal results where the complementation group appeared to be non-NPC1 and non-NPC2. This raises the possibilities of an additional NPC complementation group(s) or non-specificity of the biochemical testing for NPC. These caveats must be considered when offering mutation testing as a clinical service.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-08-2009
Publisher: American Academy of Pediatrics (AAP)
Date: 03-2007
Abstract: The North American epidemic of overeating, combined with a sedentary lifestyle, has led to a growing prevalence of obesity, diabetes, and the “metabolic syndrome” in children. Excessive caloric intake does not imply adequate nutrition, and vitamin-deficiency syndromes still occur in some American children. Here we describe cases of scurvy and vitamin D deficiency in 2 children with cognitive disorders. Thorough dietary histories suggested the diagnosis in each patient and, had they been obtained at presentation, would likely have obviated invasive diagnostic workup, unnecessary stress to the patients and their families, and significant functional disability. Overnutrition and malnutrition may coexist, particularly among those with abnormal cognition or autistic spectrum disorders. Classic nutritional deficiencies must not be omitted from the differential diagnosis. A comprehensive dietary history and screening for vitamin deficiencies in at-risk children are important aspects of preventive health care and are essential for prompt diagnosis and treatment.
Publisher: Elsevier BV
Date: 05-1993
Publisher: Springer Science and Business Media LLC
Date: 2012
Publisher: Elsevier BV
Date: 11-2009
Publisher: Wiley
Date: 21-02-2013
DOI: 10.1002/AUR.1273
Abstract: Proton magnetic resonance spectroscopy ((1) H-MRS) is a safe, noninvasive way of quantifying in vivo biochemical and metabolite concentration levels in in iduals with Autism Spectrum Disorders (ASD). Findings to date suggest ASD is associated with widespread reduction in N-acetylaspartate (NAA), creatine plus phosphocreatine (Cr), choline-containing compounds (Cho), myo-inositol (mI), and glutamate plus glutamine plus gamma-Aminobutyric Acid (Glx) however, variable findings, and even substantial increases, are not uncommon depending on the study and/or region-of-interest. Widespread reduction of NAA, Cr, Cho, mI, and Glx in ASD likely reflects impaired neuronal function and/or metabolism related to abnormal neurodevelopmental processes. Future studies should attempt to relate (1) H-MRS findings to histological findings and control for variability in subject age and functioning level this would assist in evaluating the relationship between (1) H-MRS metabolic levels and neuronal and glial cell densities, as well as neurodevelopmental process associated with ASD. Furthermore, more longitudinal (1) H-MRS studies are needed in both control and ASD subjects to attempt to standardize metabolite levels across different developmental periods in well-defined endophenotypes. This will provide for a standard rubric for which metabolic aberrations (as well as treatment responses) can be measured. With higher magnetic field strengths and spectral-editing techniques capable of quantifying less-concentrated metabolites, (1) H-MRS will continue to be an important tool in ASD research.
Publisher: Elsevier BV
Date: 2016
Publisher: SAGE Publications
Date: 30-09-2015
Abstract: Multiple sclerosis and other demyelinating diseases in the pediatric population have received an increasing level of attention by clinicians and researchers. The low incidence of these diseases in children creates a need for the involvement of multiple clinical centers in research efforts. The Network of Pediatric Multiple Sclerosis Centers was created initially in 2006 to improve the diagnosis and care of children with demyelinating diseases. In 2010, the Network shifted its focus to multicenter research while continuing to advance the care of patients. The Network has obtained support from the National Multiple Sclerosis Society, the Guthy-Jackson Charitable Foundation, and the National Institutes of Health. The Network will continue to serve as a platform for conducting impactful research in pediatric demyelinating diseases of the central nervous system. This article provides a description of the history and development, organization, mission, research priorities, current studies, and future plans of the Network.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 19-10-2011
Publisher: Cold Spring Harbor Laboratory
Date: 13-11-2020
DOI: 10.1101/2020.11.12.379701
Abstract: N-acetyl-DL-leucine is an analogue of the alpha amino acid leucine with a chiral stereocenter. The active L-enantiomer of the racemate is currently under development for rare neurological disorders. Here we present evidence that a selective recognition of N-acetyl-L-leucine versus L-leucine by different uptake transporters significantly contributes to the therapeutic effects of N-acetyl-L-leucine. A previous study of the pharmacokinetics of racemic N-acetyl-DL-leucine and N-acetyl-L-leucine revealed D-L enantiomer competition and saturation kinetics, best explained by carrier-mediated uptake. The strategy we used was to first analyze the physicochemical properties associated with good oral bioavailable drugs and how these are alerted by N-acetylation by comparing N-acetyl-L-leucine with L-leucine. Using in silico computational chemistry we found that N-acetylation has a profound impact on certain physicochemical properties that can rationalize why N-acetyl-L-leucine is drug-like compared to L-leucine. Our calculations show that at physiological pH, L-leucine is a zwitterion, whereas N-acetyl-L-leucine is present as mainly an anion. Specifically, N-acetylation removes a charge from the nitrogen at physiological pH and N-acetyl-L-leucine is an anion that is then a substrate for the organic anion transporters. We examined N-acetyl-L-leucine uptake in human embryonic kidney cells overexpression candidate organic anion transporters (OAT) and pharmacological inhibitors. We found that N-acetyl-L-leucine is a translocated substrate for OAT1 and OAT3 with low affinity (Km ~10 mM). In contrast, L-leucine is known to be transported by the L-type Amino Acid Transporter (LAT) with high affinity (Km ~0.2 mM) and low capacity. The clinical consequence is that L-leucine uptake becomes saturated at 50-fold lower concentration than N-acetyl-L-leucine. These results demonstrate a mechanism of action that explains why N-acetyl-L-leucine is effective as a drug and L-leucine itself is not.
Publisher: Springer Science and Business Media LLC
Date: 08-03-2011
Publisher: Elsevier BV
Date: 04-2015
Publisher: Elsevier BV
Date: 04-2015
Publisher: Elsevier BV
Date: 04-2015
DOI: 10.1016/J.YMGME.2014.12.433
Abstract: Leukodystrophies are inherited disorders whose primary pathophysiology consists of abnormal deposition or progressive disruption of brain myelin. Leukodystrophy patients manifest many of the same symptoms and medical complications despite the wide spectrum of genetic origins. Although no definitive cures exist, all of these conditions are treatable. This report provides the first expert consensus on the recognition and treatment of medical and psychosocial complications associated with leukodystrophies. We include a discussion of serious and potentially preventable medical complications and propose several preventive care strategies. We also outline the need for future research to prioritize clinical needs and subsequently develop, validate, and optimize specific care strategies.
Publisher: Annual Reviews
Date: 08-07-2015
DOI: 10.1146/ANNUREV-NEURO-071714-034019
Abstract: This review presents principles of glycosylation, describes the relevant glycosylation pathways and their related disorders, and highlights some of the neurological aspects and issues that continue to challenge researchers. More than 100 rare human genetic disorders that result from deficiencies in the different glycosylation pathways are known today. Most of these disorders impact the central and/or peripheral nervous systems. Patients typically have developmental delays/intellectual disabilities, hypotonia, seizures, neuropathy, and metabolic abnormalities in multiple organ systems. Among these disorders there is great clinical ersity because all cell types differentially glycosylate proteins and lipids. The patients have hundreds of misglycosylated products, which afflict a myriad of processes, including cell signaling, cell-cell interaction, and cell migration. This vast complexity in glycan composition and function, along with the limited availability of analytic tools, has impeded the identification of key glycosylated molecules that cause pathologies. To date, few critical target proteins have been pinpointed.
Publisher: Wiley
Date: 31-08-2014
DOI: 10.1002/CCD.25134
Abstract: The aim of this study was to compare the long-term outcomes of transcoronary ablation of septal hypertrophy (TASH) with open surgical myomectomy (SM) in patients with symptomatic hypertrophic obstructive cardiomyopathy (HOCM). We reviewed patients who underwent either procedure at our institution. The demographics, clinical outcomes, echocardiographic parameters, and complications were compared. Seventy patients with HOCM were treated with either TASH (n = 47, 26 male) or SM (n = 23, 10 male). Compared to those treated with SM, patients undergoing TASH were older (57+/- 14.7 years versus 47 +/- 20.6 years, P = 0.021) and more symptomatic. A higher proportion of patients had syncope as a presenting feature in the TASH group compared to the SM group (57.5% vs. 17.4%, P = 0.002) respectively. They were also more likely to be in New York Heart Association (NYHA) class III/IV compared to the patients who underwent SM (85.1% vs. 39.1% P < 0.001). Patients were followed for a mean period of 43 months (TASH) and 46 months (SM). Repeat procedures were more common in the TASH group (17% vs. 0%, P = 0.04) but mitral valve replacement was more common in the SM group (0% vs. 8.7%, P = 0.105). Symptom improvement, the rate of complications and all cause mortality rates were similar in both groups. TASH compares favorably with surgical myectomy with regard to symptom resolution, rate of complications and mortality in a tertiary referral centre and should be seen as an attractive alternative to surgical myectomy in the appropriate patient population.
Publisher: Wiley
Date: 05-2000
DOI: 10.1002/1531-8257(200005)15:3<570::AID-MDS1022>3.0.CO;2-F
Publisher: Wiley
Date: 16-11-2009
DOI: 10.1002/AJMG.A.33108
Publisher: Elsevier BV
Date: 07-2006
Publisher: Wiley
Date: 11-08-2009
DOI: 10.1002/MDS.22744
Publisher: Wiley
Date: 08-05-2023
DOI: 10.1002/JIMD.12620
Publisher: Wiley
Date: 05-06-2009
DOI: 10.1111/J.1469-8749.2008.03217.X
Abstract: A variety of autoantibodies have been identified with complex neurological disorders including limbic encephalitis. The underlying trigger for the immune-mediated process and the role of autoantibodies in the pathogenesis of limbic encephalitis remain to be clarified. Here, we report a 16-year-old female who was diagnosed with acute-onset non-neoplastic limbic encephalitis. The initial treatment with pulse doses of i.v. methylprednisolone improved the neurological symptoms. During the next 12 months, progressive decline was reported in her academic functioning and seizure control. Additional diagnostic evaluation revealed no evidence of malignancy or central nervous system infection but circulating anti-GAD antibodies were present in the serum and cerebrospinal fluid. Intravenous gammaglobulin infusion was initiated and continued monthly. Intravenous and oral steroids were added to the intravenous immunoglobulin treatment because of the worsening course and seizures, despite treatment with antiepileptic medications. Screening for quantitative immunoglobulins demonstrated hypogammaglobulinaemia with low immunoglobulin M and G in addition to low immunoglobulin A levels. There was a lack of protective pneumococcal antibody titers before and after immunization. Therefore, common variable immunodeficiency was suspected despite there being no history of recurrent infections. To our knowledge, this is the first report describing a possible link between immune-mediated limbic encephalitis and immune deficiency.
Publisher: Elsevier BV
Date: 06-2011
DOI: 10.1016/J.SPEN.2011.06.016
Abstract: Inborn errors of metabolism (IEMs) are in idually rare, but collectively common, and impose a burden on affected in iduals, their families and society that is disproportionate to their in idual incidence and prevalence. Child neurologists should be able to recognize the possibility of an IEM as the cause of their patients' symptoms and signs, and utilize online and print resources to initiate an appropriate work up and referrals. The foundation of this knowledge is an understanding of the mechanisms of IEMs, coupled with a practical classification of the relevant diseases, and knowledge of the resources available to make diagnoses and devise treatment plans. They should also be prepared to manage affected children as part of a multidisciplinary team that draws on the skills of other professionals and community organizations. Because of rapid advances in diagnostic technology and the improving survival of children with IEMs, all child neurologists should anticipate caring for children and families with IEMs, and must acquire the ability to diagnose and manage these disorders as part of their residency training, recognizing that maintenance of this competence requires a commitment to life-long learning.
Publisher: Springer Science and Business Media LLC
Date: 26-07-2011
DOI: 10.1007/S10554-011-9926-Y
Abstract: Exclusion of ischemia is important in patients with newly diagnosed systolic heart failure (HF). We prospectively compared standard-of-care invasive catheter angiography (iCA) and echocardiography to a novel non-invasive strategy of both Coronary Computed Tomographic Angiography (CCTA) and Cardiovascular MRI (CMR) to determine the etiology of myocardial dysfunction Prospective data were collected from consecutive patients referred for iCA to investigate echocardiographically-confirmed new onset HF. CMR (1.5T GE) and dual source CCTA were performed within 2-7 days of iCA. Results were blinded and separately analyzed by expert readers. 426 coronary segments from 28 prospectively enrolled patients were analyzed by CCTA and quantitative iCA. The per-patient sensitivity and specificity of CCTA was 100% and 90%, respectively, negative predictive value (NPV) 100%, positive predictive value (PPV) 78%. Mean ejection fraction by CMR was 24%. Presence of ischemic-type LGE on CMR conferred a 67% sensitivity, 100% specificity, 90% NPV and 100% PPV. Combining CCTA with CMR conferred 100% specificity, 100% sensitivity, 100% PPV and 100% NPV for detection or exclusion of coronary disease. In patients with negative CCTA all invasive angiograms could have been avoided. In addition, two patients with no ischemic LGE by CMR had severe coronary disease on both CCTA and iCA, indicating global hibernation. This is a noteworthy finding in contrast to previous reports which suggested that absence of LGE rules out significant CAD. CCTA with CMR in newly-diagnosed HF enables non-invasive assessment of coronary artery disease, the severity and etiology of myocardial dysfunction and defines suitability for revascularization. Absence of ischemic-type LGE at CMR does not exclude CAD as a cause of LV dysfunction. A first-line strategy of functional and anatomic imaging with CMR and CCTA appears appropriate in newly diagnosed HF.
Publisher: SAGE Publications
Date: 12-10-2010
Abstract: Niemann-Pick disease type C is a rare, genetic disease associated with impaired intracellular lipid trafficking and progressive neurological symptoms. Miglustat slowed disease progression in a 12-month randomized trial in juveniles and adults with Niemann-Pick disease type C, and in a parallel, noncontrolled study in affected children. Here, the authors report the open-label extension to the pediatric study. Patients aged 4 to 12 years received open-label miglustat (dose adjusted for body surface area) for an initial 12 months, during a further 12-month extension, and a long-term, continued extension phase. Efficacy assessments included horizontal saccadic eye movement, swallowing, and ambulation. Ten children completed 24 months’ treatment. Horizontal saccadic eye movement, ambulation, and swallowing were stabilized at 24 months. Analysis of key parameters of disease progression showed disease stability in 8 of 10 patients (80%). Miglustat stabilized neurological disease progression in pediatric patients with Niemann-Pick disease type C, with comparable safety and tolerability to that observed in adults and juveniles.
Publisher: Elsevier BV
Date: 04-2015
Publisher: Wiley
Date: 12-10-1998
DOI: 10.1002/(SICI)1096-8628(19981012)79:5<383::AID-AJMG10>3.0.CO;2-N
Publisher: Elsevier BV
Date: 09-2012
Publisher: Springer Science and Business Media LLC
Date: 2013
Publisher: Elsevier BV
Date: 06-2014
Publisher: Elsevier BV
Date: 04-1999
Publisher: Wiley
Date: 29-09-2015
Publisher: Elsevier BV
Date: 04-2012
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 20-10-2008
DOI: 10.1212/01.WNL.0000327680.74910.93
Abstract: Histiocytosis, both Langerhans and non-Langerhans cell type, can be associated with cerebellar white matter abnormalities, thought to be paraneoplastic. The associated clinical picture consists of ataxia, spasticity, and cognitive decline. Hormonal dysfunction is frequent. MRI shows cerebellar white matter abnormalities, as well as brainstem and basal ganglia abnormalities. This so-called "neurodegenerative syndrome" may occur years before or during manifest histiocytosis and also years after cure. We discovered similar MRI abnormalities in 13 patients and wondered whether they could have the same syndrome. We reviewed the clinical and laboratory information of these 13 patients and evaluated their brain MRIs. Seven patients underwent spinal cord MRI. All patients were isolated cases 10 were male. They had signs of cerebellar and pyramidal dysfunction, behavioral problems, and cognitive decline. MRI showed abnormalities of the cerebellar white matter, brainstem, basal ganglia, and, to a lesser extent, cerebral white matter. Three patients had spinal cord lesions. Three patients had laboratory evidence of hormonal dysfunction. No evidence was found of an underlying metabolic defect. In two patients biopsy of nodular brain lesions revealed histiocytic infiltrates. Considering the striking clinical and MRI similarities between our patients and the patients with this neurodegenerative syndrome in the context of proven histiocytosis, it is likely that they share the same paraneoplastic syndrome, although we cannot exclude a genetic disorder with certainty. The fact that we found histiocytic lesions in two patients substantiates our conclusion. Patients with cerebellar white matter abnormalities should be monitored for histiocytosis.
Publisher: Hindawi Limited
Date: 2000
DOI: 10.1002/1098-1004(200009)16:3<247::AID-HUMU7>3.0.CO;2-A
Publisher: Elsevier BV
Date: 04-1997
Publisher: Wiley
Date: 13-06-1997
DOI: 10.1002/(SICI)1096-8628(19970613)70:3<261::AID-AJMG9>3.0.CO;2-Z
Publisher: Elsevier BV
Date: 06-2014
Publisher: Elsevier BV
Date: 04-1994
Publisher: Wiley
Date: 17-01-2013
DOI: 10.1111/PETR.12039
Abstract: Posterior reversible encephalopathy syndrome (PRES) is a disorder characterized by gray and white matter abnormalities in the temporal, parietal, and occipital lobes of the brain. Its etiology has been attributed to renal failure, immunosuppressive drugs such as cyclosporine and tacrolimus, and other potential entities leading to acute hypertension. Clinical findings include headaches, altered mental status, seizures, visual changes, and focal neurologic deficits. We report the case of a child who developed PRES with intracerebral and subarachnoid hemorrhages associated with tacrolimus exposure 10 days after heart transplantation for restrictive cardiomyopathy. The patient initially presented with complex partial seizures, headache, agitation, and hypertension. Head MRI was suggestive of PRES along with intracerebral and subarachnoid hemorrhages. Tacrolimus was discontinued and blood pressure was controlled. The patient's encephalopathy resolved, but he has had ongoing neurologic symptoms secondary to hemorrhage. Generally, PRES is less common in children than in the adult population and is a rare complication of calcineurin inhibitors (CNI). Presentation with secondary hemorrhage also can occur. In children receiving CNIs presenting with new neurologic symptoms, PRES should be considered as prompt discontinuation of the offending agent can induce resolution of symptoms. Children can develop hemorrhage in the context of PRES, leading to increased morbidity.
Publisher: Elsevier BV
Date: 2015
Publisher: Elsevier BV
Date: 05-2012
Publisher: Elsevier BV
Date: 06-2014
Publisher: Wiley
Date: 03-1982
Publisher: Elsevier BV
Date: 06-2001
DOI: 10.1086/320599
Publisher: Hindawi Limited
Date: 2013
DOI: 10.1155/2013/595838
Abstract: The use of microspheres for the determination of regional microvascular blood flow (RMBF) has previously used different approaches. This study presents for the first time the intracardiac injection of microspheres using transeptal puncture under intracardiac echocardiography guidance. Five Merino sheep were instrumented and cardiovascularly supported according to local guidelines. Two catheter sheaths into the internal jugular vein facilitated the introduction of an intracardiac probe and transeptal catheter, respectively. Five million colour coded microspheres were injected into the left atrium via this catheter. After euthanasia the brain was used as proof of principle and the endpoint for determination of microcirculation at different time points. Homogeneous allocation of microspheres to different regions of the brain was found over time. Alternate slices from both hemispheres showed the following flow ranges: for slice 02 0.57–1.02 mL/min/g, slice 04 0.45–1.42 mL/min/g, slice 06 0.35–1.87 mL/min/g, slice 08 0.46–1.77 mL/min/g, slice 10 0.34–1.28 mL/min/g. A mixed effect regression model demonstrated that the confidence interval did include zero suggesting that the apparent variability intra- and intersubject was not statistically significant, supporting the stability and reproducibility of the injection technique. This study demonstrates the feasibility of the transeptal injection of microspheres, showing a homogeneous distribution of blood flow through the brain unchanged over time and has established a new interventional model for the measurement of RMBF in ovine models.
Publisher: Wiley
Date: 08-05-2020
DOI: 10.1002/JIMD.12245
Abstract: Miglustat has been indicated for the treatment of Niemann‐Pick disease type C (NP‐C) since 2009. The aim of this observational study was to assess the effect of miglustat on long‐term survival of patients with NP‐C. Data for 789 patients from five large national cohorts and from the NPC Registry were collected and combined. Miglustat‐treated and untreated patients overall and within sub‐groups according to age‐at‐neurological‐onset, that is, early infantile‐onset ( years), late infantile‐onset (2 to years), juvenile‐onset (6 to years), and adolescent/adult‐onset (≥15 years) were analysed and compared. Survival was analysed from the time of first neurological manifestation (Neurological onset group, comprising 669 patients) and from diagnosis (Diagnosis group, comprising 590 patients) using a Cox proportional hazard model adjusted for various covariates. Overall, 384 (57.4%) patients in the Neurological onset group and 329 (55.8%) in the Diagnosis group were treated with miglustat. Miglustat treatment was associated with a significant reduction in risk of mortality in both groups (entire Neurological onset group, Hazard ratio [HR] = 0.51 entire Diagnosis group, HR = 0.44 both P .001). The effect was observed consistently in all age‐at‐neurological‐onset sub‐groups (HRs = 0.3 to 0.7) and was statistically significant for late infantile‐onset patients in both groups (Neurological onset group, HR = 0.36, P .05 Diagnosis group, HR = 0.32, P .01), and juvenile‐onset patients in the Diagnosis group only (HR = 0.30, P .05). Despite the limitations of the data that urge cautious interpretation, the findings are consistent with a beneficial effect of miglustat on survival in patients with NP‐C.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-05-2012
Publisher: Wiley
Date: 02-2012
Publisher: Springer Science and Business Media LLC
Date: 2013
Publisher: Wiley
Date: 06-2009
Publisher: Elsevier
Date: 2014
Publisher: Springer Science and Business Media LLC
Date: 28-05-2015
Publisher: Elsevier BV
Date: 10-2008
Publisher: Elsevier BV
Date: 10-2004
Publisher: Cold Spring Harbor Laboratory
Date: 16-03-2020
DOI: 10.1101/2020.03.11.20034256
Abstract: The lack of approved treatments for the majority of rare diseases is reflective of the unique challenges of orphan drug development. Novel methodologies, including new functionally relevant endpoints, are needed to render the development process more feasible and appropriate for these rare populations, and thereby expedite the approval of promising treatments to address patients’ high unmet medical need. Here, we describe the development of an innovative master protocol and primary outcome assessment to investigate the modified amino acid N-acetyl-L-leucine (Sponsor Code: IB1001) in three seperate, multinational, phase II trials for three ultra-rare, autosomal-recessive, neurodegenerative disorders: Niemann-Pick disease type C (NPC), GM2 Gangliosidoses (Tay-Sachs and Sandhoff disease “GM2”), and Ataxia Telangiectasia (A-T). The innovative IB1001 master protocol and novel CI-CS primary endpoints were developed through a close collaboration between the Industry Sponsor, Key Opinion Leaders, representatives of the Patient Communities, and National Regulatory Authorities. As a result, the open-label, rater-blinded study design is considerate of the practical limitations of recruitment and retention of subjects in these ultra-orphan populations. The novel primary endpoint, the Clinical Impression of Change in Severity © (CI-CS), accommodates the heterogenous clinical presentation of NPC, GM2, and A-T: at screening, the Principal Investigator appoints for each patient a primary anchor test (either the 8 Meter Walk Test (8MWT) or 9 Hole Peg Test of the Dominant Hand (9HPT-D)) based on his/her unique clinical symptoms. The anchor tests are videoed in a standardized manner at each visit to capture all aspects related to the patient’s functional performance. The CI-CS assessment is ultimately performed by independent, blinded raters who compare videos of the primary anchor test from three periods: baseline, the end of treatment, and the end of a post-treatment washout. Blinded to the timepoint of each video, the raters make an objective comparison scored on a 7-point Likert scale of the change in the severity of the patient’s neurological signs and symptoms from Video A to Video B. To investigate both the symptomatic and disease-modifying effects of treatment, N-acetyl-L-leucine is assessed during two treatment sequences: a 6-week parent study, and one-year extension phase. The novel CI-CS assessment, developed through a collaboration of all stakeholders, is advantageous in that it better ensures the primary endpoint is functionally relevant for each patient, is able to capture small but meaningful clinical changes critical to the patients’ quality of life (fine-motor skills gait), and blinds the primary outcome assessment. The results of these three trials will inform whether N-acetyl-L-leucine is an effective treatment for NPC, GM2, and A-T, and can also serve as a new therapeutic paradigm for the development of future treatments for other orphan diseases. The three trials (IB1001-201 for Niemann-Pick disease type C (NPC) IB1001-202 for GM2 Gangliosidoses (Tay-Sachs and Sandhoff) IB1001-203 for Ataxia-Telangiectasia (A-T)) have been registered at www.clinicaltrials.gov ( NCT03759639 NCT03759665 NCT03759678 ), www.clinicaltrialsregister.eu (EudraCT: 2018-004331-71 2018-004406-25 2018-004407-39) and www.germanctr.de (DR KS-ID: DRKS00016567 DRKS00017539 DRKS00020511).
Publisher: Elsevier BV
Date: 10-2004
Publisher: SAGE Publications
Date: 28-01-2013
Abstract: We surveyed child neurologists first certified in “Neurology with Special Qualification in Child Neurology” by the American Board of Psychiatry and Neurology (ABPN) between 2001 and 2010 using a 24-item questionnaire. Respondents (n = 204, 54% response rate) were between the ages of 30 and 59 years (54% male), and 68% completed adult neurology training in a 10- to 12-month, primarily inpatient block. Sixty-two percent of the s le completed subspecialty fellowship training and 82% currently reported practicing within a hospital or hospital-based/owned clinic. Current practice data showed just 3% provide general neurology services to adults. A majority reported using adult neurology residency training “less than weekly” and believed the ideal model for residency training in diagnosis and management of both common and rare neurologic conditions would involve less time in adult neurology and more time (mean 6 months) in child neurology, most prominently in genetics and developmental and behavioral areas.
Publisher: S. Karger AG
Date: 03-02-2015
DOI: 10.1159/000371598
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 31-08-2011
Publisher: Wiley
Date: 10-1997
Publisher: Oxford University Press (OUP)
Date: 16-06-2013
DOI: 10.1093/HMG/DDT284
Publisher: SAGE Publications
Date: 05-01-2014
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 18-04-2012
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-06-2010
Publisher: Elsevier BV
Date: 05-2006
Publisher: Elsevier BV
Date: 10-2009
Publisher: Elsevier BV
Date: 03-2011
Publisher: SAGE Publications
Date: 15-11-2013
Abstract: In the largest s le studied to date, we measured cognitive functioning in children and adolescents with pediatric multiple sclerosis (n = 187) as well as those with clinically isolated syndrome (n = 44). Participants were consecutively enrolled from six United States Pediatric Multiple Sclerosis Centers of Excellence. Participants had a mean of 14.8 ± 2.6 years of age and an average disease duration of 1.9 ± 2.2 years. A total of 65 (35%) children with multiple sclerosis and 8 (18%) with clinically isolated syndrome met criteria for cognitive impairment. The most frequent areas involved were fine motor coordination (54%), visuomotor integration (50%), and speeded information processing (35%). A diagnosis of multiple sclerosis (odds ratio = 3.60, confidence interval = 1.07, 12.36, P = .04) and overall neurologic disability (odds ratio = 1.47, confidence interval = 1.10, 2.10, P = .03) were the only independent predictors of cognitive impairment. Cognitive impairment may occur early in these patients, and prompt recognition is critical for their care.
Publisher: Elsevier BV
Date: 04-2010
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-01-2010
Publisher: Elsevier BV
Date: 07-2012
Publisher: Elsevier BV
Date: 11-2014
DOI: 10.1016/J.CARREV.2014.10.004
Abstract: Patients with degenerated surgical bioprosthetic valves may be at high risk for further surgery because of age, comorbidities and the difficulties of repeat procedures. Percutaneous valve-in-valve implantation offers what may be a simpler and safer procedure. From May 2009 to March 2014 at the Prince Charles Hospital 1625 patients underwent surgical aortic valve replacement while 262 underwent transcatheter aortic valve implantation. Twelve patients had valve-in-valve implants for degenerated bioprosthetic aortic valves. These implants were deployed successfully without major valvular or paravalvular regurgitation. There were no periprocedural deaths, myocardial infarcts, neurological events or major vascular complications. Two patients died after 1624 and 1319days. Median survival for the remainder is 581days they are stable with New York Heart Association class I/II functional status although 4 have a degree of patient-prosthesis mismatch, one has moderate aortic regurgitation and one required surgery for a late aortic dissection. Transcatheter valve-in-valve implantation is safe and effective treatment for patients with failed bioprosthetic aortic valves for whom reoperation is considered to be hazardous.
Publisher: SAGE Publications
Date: 28-02-2012
Abstract: Seizures are often the first manifestation of central nervous system dysfunction and are common in many inborn errors of metabolism, especially in neonates, infants, and children. A high index of suspicion is required to diagnose inborn errors of metabolism as the cause of seizures. It is also important to recognize these metabolic disorders early, as specific disease-modifying treatments are available for some with favorable long-term outcomes. This review discusses the classification of metabolic disorders as a cause of seizures based on pathogenesis and age and proposes a tiered approach for cost-effective diagnosis of metabolic disorders.
Publisher: Elsevier BV
Date: 09-2007
Publisher: Elsevier BV
Date: 05-2003
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2003
Publisher: Elsevier BV
Date: 04-2013
Publisher: Springer Science and Business Media LLC
Date: 1986
DOI: 10.1007/BF00606655
Publisher: Wiley
Date: 15-11-2012
Publisher: American Association for the Advancement of Science (AAAS)
Date: 11-07-1997
DOI: 10.1126/SCIENCE.277.5323.228
Abstract: Niemann-Pick type C (NP-C) disease, a fatal neurovisceral disorder, is characterized by lysosomal accumulation of low density lipoprotein (LDL)–derived cholesterol. By positional cloning methods, a gene ( NPC1) with insertion, deletion, and missense mutations has been identified in NP-C patients. Transfection of NP-C fibroblasts with wild-type NPC1 cDNA resulted in correction of their excessive lysosomal storage of LDL cholesterol, thereby defining the critical role of NPC1 in regulation of intracellular cholesterol trafficking. The 1278–amino acid NPC1 protein has sequence similarity to the morphogen receptor PATCHED and the putative sterol-sensing regions of SREBP cleavage-activating protein (SCAP) and 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase.
Publisher: Elsevier BV
Date: 09-2009
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-10-2010
Publisher: Elsevier
Date: 2014
Publisher: Wiley
Date: 11-12-2015
Publisher: Wiley
Date: 09-05-2002
DOI: 10.1002/AJMG.10467
Publisher: Elsevier BV
Date: 09-2005
Publisher: Elsevier BV
Date: 09-2018
Publisher: Elsevier BV
Date: 09-2005
DOI: 10.1016/J.SPEN.2005.10.002
Abstract: N-linked glycosylation is essential for normal cellular function. Defects have now been described in eighteen genes that participate in the process. All give rise to complex multisystem diseases which, with a few exceptions, primarily involve the nervous system. Frequent features of these disorders include developmental delay, ataxia, seizures, stroke-like episodes, recurrent infections, coagulopathy and dysmorphism. Most cases can be detected by screening carbohydrate-deficient transferrin, but definitive diagnosis requires enzymatic and molecular confirmation, frequently in collaboration with a research glycobiologist.
Location: United States of America
Location: United States of America
Location: United States of America
No related grants have been discovered for Marc Patterson.