Patterson, Marc C.

Background: 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. Objective: Changes in cognitive function over time were measured in the largest pediatric cohort to date through the US Network of Pediatric MS Centers. Methods: A total of 67 individuals 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. Results: 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. Conclusion: 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.

AbstractObjectiveThe Suspicion Index (SI) screening tool was developed to identify patients suspected of having Niemann‐Pick disease type C (NP‐C). The SI provides a risk prediction score (RPS) based on NP‐C manifestations within and across domains (visceral, neurological, and psychiatric). The aim of these subanalyses was to further examine the discriminatory power of the SI by age and manifestation–associations by NP‐C suspicion‐level and leading manifestations.MethodsThe original retrospectively collected data were split into three patient age groups, where NP‐C‐positive cases were >16 years (n = 30), 4–16 years (n = 18), and <4 years (n = 23), and patients’ RPS were analyzed by logistic regression. Co‐occurrence of manifestations within groups of suspicion level (low, medium, high) and leading manifestations (presence/absence of ataxia, cognitive decline, psychosis, and splenomegaly) were analyzed descriptively.ResultsNP‐C‐positive cases versus controls showed strong discriminatory power of RPS. Area under the receiver operating characteristic curve was 0.964 (>16 years) and 0.981 (4–16 years) but weaker 0.562 for infants (<4 years). Patients with RPS <70 were characterized by a lack of psychiatric manifestations and low levels of neurological involvement, suggestive of a preneurological phase of the disease. In patients >4 years, prominent leading manifestation–associations were ataxia with dystonia, dysarthria/dysphagia, and cognitive decline. Psychosis was associated with dysarthria/dysphagia but also with cognitive decline and treatment‐resistant psychiatric symptoms.ConclusionsThe SI tool maintains strong discriminatory power in patients >4 years but is not as useful for infants <4 years. The SI is also informative regarding the association and co‐occurrence of manifestations in patients with NP‐C.

Proton magnetic resonance spectroscopy (1H‐MRS) is a safe, noninvasive way of quantifying in vivo biochemical and metabolite concentration levels in individuals withAutismSpectrumDisorders (ASD). Findings to date suggestASDis associated with widespread reduction inN‐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 ofNAA,Cr,Cho,mI, andGlxinASDlikely reflects impaired neuronal function and/or metabolism related to abnormal neurodevelopmental processes. Future studies should attempt to relate1H‐MRSfindings to histological findings and control for variability in subject age and functioning level; this would assist in evaluating the relationship between1H‐MRSmetabolic levels and neuronal and glial cell densities, as well as neurodevelopmental process associated withASD. Furthermore, more longitudinal1H‐MRSstudies are needed in both control andASDsubjects 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,1H‐MRSwill continue to be an important tool inASDresearch.Autism Res2013, 6: 119–133.© 2013 International Society for Autism Research, Wiley Periodicals, Inc.

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 sample 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.

AbstractPosterior 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.

In the largest sample 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.