Pediatric neuroimaging at a university hospital in Rwanda: a pictorial essay.

Rwanda is a country of 12 million people with 41% of its population under the age of 14 years. Despite major improvements in health care since the 1994 genocide, pediatric neuroimaging in Rwanda remains challenging. Prenatal and advanced imaging techniques, such as magnetic resonance imaging (MRI), are not widespread. As a result, many children with neurological diseases present unexpectedly as newborns or are in advanced stages of disease at diagnosis. The goal of this essay is to describe some unique features of the practice of pediatric neuroradiology in Rwanda in 2018.

Deconstructing normal pressure hydrocephalus: Ventriculomegaly as early sign of neurodegeneration.

Idiopathic normal pressure hydrocephalus (NPH) remains both oversuspected on clinical grounds and underconfirmed when based on immediate and sustained response to cerebrospinal fluid diversion. Poor long-term postshunt benefits and findings of neurodegenerative pathology in most patients with adequate follow-up suggest that hydrocephalic disorders appearing in late adulthood may often result from initially unapparent parenchymal abnormalities. We critically review the NPH literature, highlighting the near universal lack of blinding and controls, absence of specific clinical, imaging, or pathological features, and ongoing dependence for diagnostic confirmation on variable cutoffs of gait response to bedside fluid-drainage testing. We also summarize our long-term institutional experience, in which postshunt benefits in patients with initial diagnosis of idiopathic NPH persist in only 32% of patients at 36 months, with known revised diagnosis in over 25% (Alzheimer's disease, dementia with Lewy bodies, and progressive supranuclear palsy). We postulate that previously reported NPH cases with "dual" pathology (ie, developing a "second" disorder) more likely represent ventriculomegalic presentations of selected neurodegenerative disorders in which benefits from shunting may be short-lived, with a consequently unfavorable risk-benefit ratio. Ann Neurol 2017;82:503-513.

Functional neurological disorders in Parkinson disease.

OBJECTIVE: To ascertain demographic and clinical features of Parkinson disease (PD) associated with functional neurological features. METHODS: A standardised form was used to extract data from electronic records of 53 PD patients with associated functional neurological disorders (PD-FND) across eight movement disorders centres in the USA, Canada and Europe. These subjects were matched for age, gender and disease duration to PD patients without functional features (PD-only). Logistic regression analysis was used to compare both groups after adjusting for clustering effect. RESULTS: Functional symptoms preceded or co-occurred with PD onset in 34% of cases, nearly always in the most affected body side. Compared with PD-only subjects, PD-FND were predominantly female (68%), had longer delay to PD diagnosis, greater prevalence of dyskinesia (42% vs 18%; P=0.023), worse depression and anxiety (P=0.033 and 0.025, respectively), higher levodopa-equivalent daily dose (972±701 vs 741±559 mg; P=0.029) and lower motor severity (P=0.019). These patients also exhibited greater healthcare resource utilisation, higher use of [(123)I]FP-CIT SPECT and were more likely to have had a pre-existing psychiatric disorder (P=0.008) and family history of PD (P=0.036). CONCLUSIONS: A subtype of PD with functional neurological features is familial in one-fourth of cases and associated with more psychiatric than motor disability and greater use of diagnostic and healthcare resources than those without functional features. Functional manifestations may be prodromal to PD in one-third of patients.

MFN2 deletion of exons 7 and 8: founder mutation in the UK population.

Mitofusin 2 (MFN2) mutations are the most common cause of axonal Charcot-Marie-Tooth disease (CMT2). The majority are inherited in an autosomal dominant manner but recessive and semi-dominant kindreds have also been described. We previously reported a deletion of exons 7 and 8 resulting in nonsense-mediated decay, segregating with disease when present in trans with another pathogenic MFN2 mutation. Detailed clinical and electrophysiological data on a series of five affected patients from four kindreds and, when available, their parents and relatives were collected. MFN2 Sanger sequencing, multiplex ligation probe amplification, and haplotype analysis were performed. A severe early-onset CMT phenotype was seen in all cases: progressive distal weakness, wasting, and sensory loss from infancy or early childhood. Optic atrophy (four of five) and wheelchair dependency in childhood were common (four of five). All were compound heterozygous for a deletion of exons 7 and 8 in MFN2 with another previously reported pathogenic mutation (Phe216Ser, Thr362Met, and Arg707Trp). Carrier parents and relatives were unaffected (age range: 24-82 years). Haplotype analysis confirmed that the deletion had a common founder in all families.

How do authors' perceptions of their papers compare with co-authors' perceptions and peer-review decisions?

How do author perceptions match up to the outcomes of the peer-review process and perceptions of others? In a top-tier computer science conference (NeurIPS 2021) with more than 23,000 submitting authors and 9,000 submitted papers, we surveyed the authors on three questions: (i) their predicted probability of acceptance for each of their papers, (ii) their perceived ranking of their own papers based on scientific contribution, and (iii) the change in their perception about their own papers after seeing the reviews. The salient results are: (1) Authors had roughly a three-fold overestimate of the acceptance probability of their papers: The median prediction was 70% for an approximately 25% acceptance rate. (2) Female authors exhibited a marginally higher (statistically significant) miscalibration than male authors; predictions of authors invited to serve as meta-reviewers or reviewers were similarly calibrated, but better than authors who were not invited to review. (3) Authors' relative ranking of scientific contribution of two submissions they made generally agreed with their predicted acceptance probabilities (93% agreement), but there was a notable 7% responses where authors predicted a worse outcome for their better paper. (4) The author-provided rankings disagreed with the peer-review decisions about a third of the time; when co-authors ranked their jointly authored papers, co-authors disagreed at a similar rate-about a third of the time. (5) At least 30% of respondents of both accepted and rejected papers said that their perception of their own paper improved after the review process. The stakeholders in peer review should take these findings into account in setting their expectations from peer review.

Differential response of speed, amplitude, and rhythm to dopaminergic medications in Parkinson's disease.

Although movement impairment in Parkinson's disease includes slowness (bradykinesia), decreased amplitude (hypokinesia), and dysrhythmia, clinicians are instructed to rate them in a combined 0-4 severity scale using the Unified Parkinson's Disease Rating Scale motor subscale. The objective was to evaluate whether bradykinesia, hypokinesia, and dysrhythmia are associated with differential motor impairment and response to dopaminergic medications in patients with Parkinson's disease. Eighty five Parkinson's disease patients performed finger-tapping (item 23), hand-grasping (item 24), and pronation-supination (item 25) tasks OFF and ON medication while wearing motion sensors on the most affected hand. Speed, amplitude, and rhythm were rated using the Modified Bradykinesia Rating Scale. Quantitative variables representing speed (root mean square angular velocity), amplitude (excursion angle), and rhythm (coefficient of variation) were extracted from kinematic data. Fatigue was measured as decrements in speed and amplitude during the last 5 seconds compared with the first 5 seconds of movement. Amplitude impairments were worse and more prevalent than speed or rhythm impairments across all tasks (P < .001); however, in the ON state, speed scores improved exclusively by clinical (P < 10(-6) ) and predominantly by quantitative (P < .05) measures. Motor scores from OFF to ON improved in subjects who were strictly bradykinetic (P < .01) and both bradykinetic and hypokinetic (P < 10(-6) ), but not in those strictly hypokinetic. Fatigue in speed and amplitude was not improved by medication. Hypokinesia is more prevalent than bradykinesia, but dopaminergic medications predominantly improve the latter. Parkinson's disease patients may show different degrees of impairment in these movement components, which deserve separate measurement in research studies. © 2011 Movement Disorder Society.

TRPV6 is not required for 1alpha,25-dihydroxyvitamin D3-induced intestinal calcium absorption in vivo.

The requirement for TRPV6 for vitamin D-dependent intestinal calcium absorption in vivo has been examined by using vitamin D-deficient TRPV6 null mice and littermate wild-type mice. Each of the vitamin D-deficient animals received each day for 4 days 50 ng of 1,25-dihydroyvitamin D(3) in 0.1 ml of 95% propylene glycol:5% ethanol vehicle or vehicle only. Both the wild-type and TRPV6 null mice responded equally well to 1,25-dihydroxyvitamin D(3) in increasing intestinal calcium absorption. These results, along with our microarray data, demonstrate that TRPV6 is not required for vitamin D-induced intestinal calcium absorption and may not carry out a significant role in this process. These and previous results using calbindin D9k null mutant mice illustrate that molecular events in the intestinal calcium absorption process in response to the active form of vitamin D remain to be defined.

Early versus delayed bilateral subthalamic deep brain stimulation for parkinson's disease: a decision analysis.

The long-term benefits of subthalamic nucleus deep brain stimulation (STN DBS) applied earlier in the disease course, before significant disability accumulates, remain to be determined. We developed a Markov state transition decision analytic model to compare effectiveness in quality-adjusted life years (QALYs) of STN DBS applied to patients with PD at an "early" ("off time" 10-20%) versus "delayed" stage ("off time" >40%). A lifelong time horizon and societal perspective were assumed. Probabilities and rates were obtained from literature review; utilities were derived using the time trade-off technique and a computer-assisted utility assessment software tool applied to a cohort of 22 STN-DBS and 21 non-STN-DBS PD patients. Uncertainty was assessed through one- and two-way sensitivity analyses and probabilistic sensitivity analysis using second-order Monte Carlo simulations. Early STN DBS was preferred with a quality-adjusted life expectancy of 22.3 QALYs, a gain of 2.5 QALYs over those with delayed surgery (19.8 QALYs). Early STN DBS was preferred in 69% of 5,000 Monte Carlo simulations. Early surgery was robustly favored through most sensitivity analyses. Delayed STN DBS afforded greater QALYs when using utility estimates exclusively from non-STN-DBS patients and, for the entire group, if the rate of motor progression were to exceed 25% per year. Although decision modeling requires assumptions and simplifications, our exploratory analysis suggests that STN DBS performed in early PD may convey greater quality-adjusted life expectancy when compared to a delayed procedure. These findings support further evaluation of early STN DBS in a controlled clinical trial.

Growth and body composition of human milk-fed premature infants provided with extra energy and nutrients early after hospital discharge: 1-year follow-up.

OBJECTIVES: Human milk (HM) is the optimal source of nutrition for premature infants; however, it is unclear whether HM alone is sufficient to meet their elevated nutritional requirements early after hospital discharge. We previously reported that premature infants (750-1800 g birth weight) fed HM containing extra nutrients for 12 weeks after discharge had dietary intakes closer to recommended levels and grew more rapidly than those fed HM alone. The objectives of the present article are to examine the impact of this intervention on bone mineralization, body composition, and HM use up to 1 year. Data are also presented on general developmental level at 18-month corrected age (CA). PATIENTS AND METHODS: At discharge, predominantly HM-fed infants were randomized to receive for 12 weeks either approximately half of their feedings containing a multinutrient fortifier (intervention, n=19) or all of their feedings as HM alone (control, n=20). RESULTS: Intervention infants remained longer (P<0.001) and had greater whole-body bone mineral content (P=0.02) until 12-month CA compared with controls. Intervention infants born less than or equal to 1250 g continued to have a larger mean head circumference throughout the first year of life (P<0.0001). Human milk feeding (mL.kg(-1).day(-1)) differed between groups at 6- (P=0.035), but not 12-month CA. No statistically significant differences were found between groups in the mental, motor, or behavior rating scale scores of the Bayley II at 18-month CA. CONCLUSIONS: Adding a multinutrient fortifier to HM provided to predominantly HM-fed premature infants early after discharge results in sustained differences in weight, length, and whole-body bone mineral content, and in smaller babies, head circumference for the first year of life.

Orthostatic hypotension in Parkinson disease: Impact on health care utilization.

INTRODUCTION: Orthostatic hypotension (OH) represents a frequent yet overlooked source of disability in Parkinson disease (PD). In particular, its impact on health care utilization has been insufficiently examined. We sought to determine the differential health care utilization in PD patients with (PDOH+) and without OH (PDOH-). METHODS: We quantified the emergency room (ER) visits, hospitalizations, outpatient clinic evaluations, phone calls, and e-mails from PD patients on whom supine and orthostatic blood pressure (BP) measurements were obtained during routine clinical practice between June 2013 and July 2016. Comparative costs between PDOH+ and PDOH- were adjusted for age, disease duration, motor severity, levodopa equivalent daily dose, and Montreal Cognitive Assessment. RESULTS: From a total of 317 PD patients, 29.3% were classified as PDOH+ (n = 93) and 70.6% as PDOH- (n = 224) over 30.2 ± 11.0 months, in which there were 247 hospitalizations, 170 ER visits, 2386 outpatient evaluations, and 4747 telephone calls/e-mails. After-adjusting for relevant covariates, PDOH+ was associated with more hospitalization days (+285%; p = 0.041), ER visits (+152%; p = 0.045), and telephone calls/e-mails than PDOH- (+142%; p = 0.009). The overall health care-related cost in PDOH+ was 2.5-fold higher than for PDOH- ($25,205 ± $6546 vs. $9831 ± $4167/person/year; p = 0.037). CONCLUSION: OH increases health care utilization in PD independently from age, disease duration, motor severity, dopaminergic treatment, and cognitive function.

Tablet-Based Application for Objective Measurement of Motor Fluctuations in Parkinson Disease.

BACKGROUND: The motor subscale of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS-III) has limited applicability for the assessment of motor fluctuations in the home setting. METHODS: To assess whether a self-administered, tablet-based application can reliably quantify differences in motor performance using two-target finger tapping and forearm pronation-supination tasks in the ON (maximal dopaminergic medication efficacy) and OFF (reemergence of parkinsonian deficits) medication states, we recruited 11 Parkinson disease (PD) patients (age, 60.6 ± 9.0 years; disease duration, 12.8 ± 4.1 years) and 11 healthy age-matched controls (age, 62.5 ± 10.5 years). The total number of taps, tap interval, tap duration, and tap accuracy were algorithmically calculated by the application, using the more affected side in patients and the dominant hand in healthy controls. RESULTS: Compared to the OFF state, PD patients showed a higher number of taps (84.2 ± 20.3 vs. 54.9 ± 26.9 taps; p = 0.0036) and a shorter tap interval (375.3 ± 97.2 vs. 708.2 ± 412.8 ms; p = 0.0146) but poorer tap accuracy (2,008.4 ± 995.7 vs. 1,111.8 ± 901.3 pixels; p = 0.0055) for the two-target task in the ON state, unaffected by the magnitude of coexistent dyskinesia. Overall, test-retest reliability was high (r >0.75) and the discriminatory ability between OFF and ON states was good (0.60 ≤ AUC ≤ 0.82). The correlations between tapping data and MDS-UPDRS-III scores were only moderate (-0.55 to 0.55). CONCLUSIONS: A self-administered, tablet-based application can reliably distinguish between OFF and ON states in fluctuating PD patients and may be sensitive to additional motor phenomena, such as accuracy, not captured by the MDS-UPDRS-III.

Bone marrow aspirate microscopy v. bone marrow trephine biopsy microscopy for detection of Mycobacterium tuberculosis infection.

BACKGROUND: Tuberculosis (TB) remains a global health problem. According to the 2013 Global Report on Tuberculosis, 8.6 million people developed TB in 2012 and 1.3 million died from the disease. An estimated 13% of people who developed TB in 2012 were HIV-positive, and 75% of these lived in Africa. While pulmonary TB is the commonest form of Mycobacterium tuberculosis infection, extrapulmonary TB is increasingly being detected in HIV-positive patients. Definitive diagnosis of disseminated TB is a challenge owing to atypical presentations and diagnostic difficulties (negative chest radiograph and sputum microscopy and culture). A rapid diagnosis of disseminated TB is desirable, as early initiation of treatment can reduce mortality. Although TB culture is the gold standard for diagnosis of TB, it has a long turnaround time (up to 6 weeks). OBJECTIVES: To identify a potentially faster and more effective diagnostic strategy for disseminated TB. METHODS: A retrospective 18-month review, conducted at a tertiary hospital, comparing histological findings of an auramine O-stained bone marrow aspiration (BMA) smear and a bone marrow trephine (BMT) biopsy specimen with the gold standard of TB culture. RESULTS: Microscopic examination of BMA smears and BMT biopsy specimens offers a rapid diagnostic strategy, with results available on the same day for the former and within 4 days for the latter. BMT histological examination had a significantly higher detection rate than BMA auramine O staining compared with TB culture. CONCLUSION: We recommend that BMT biopsies remain an essential part of the diagnostic work-up for disseminated TB.

Influence of paper color and a monetary incentive on response rate.

This study examined whether survey response rate differed based on the color of the paper the survey was printed on (blue vs green) and presence of a monetary incentive. A 4-page survey on eating disorders was mailed to Division 1A and 1AA college head athletic trainers (N=223) with half of the surveys on blue paper and half on green paper. Half of the athletic trainers (n = 111) received a $1.00 monetary incentive, and half (n = 112) received no monetary incentive. A total of 166 (71%) athletic trainers returned completed surveys. Response rates did not differ based on survey color but did differ based on presence of a monetary incentive. Athletic trainers who received a monetary incentive were significantly more likely than those who did not to return completed surveys (86% vs 63%, respectively).

Gone exercising: mental contrasting promotes physical activity among overweight, middle-aged, low-SES fishermen.

OBJECTIVE: Fantasy realization theory (Oettingen, 2012) proposes that fantasizing about a desired future or dwelling upon negative reality rarely changes behavior whereas mentally contrasting fantasy with reality can be an effective behavior change technique. This is because mental contrasting energizes people to overcome obstacles that stand in the way of their desired future. The present study tested whether mental contrasting promotes rates of physical activity among overweight, middle-aged, and low-SES men. METHOD: A randomized controlled trial was conducted with members of an angling club in the north of England (N = 467). At baseline, participants completed a postal questionnaire that measured cognitions about physical activity. The intervention was embedded in the questionnaire for relevant participants. Behavior was followed up via telephone at 1 month and 7 months postbaseline. The key outcome measure was a validated, self-report measure of physical activity (Godin, Jobin & Bouillon, 1986) taken at all three time-points. RESULTS: Longitudinal, explanatory, and intention-to-treat analyses each indicated that mental contrasting was effective in enhancing rates of physical activity. Mental contrasting also aided the translation of beliefs about the value and worth of physical activity (instrumental attitudes) into action. CONCLUSION: Mental contrasting appears to be an effective self-regulatory intervention for promoting physical activity and warrants further tests in health psychology.

Growth outcomes and complications after radiologic gastrostomy in 120 children.

BACKGROUND: Enteral feeding is ideal for children with low caloric intake. It can be provided through different methods, including nasogastric, nasojejunal, gastrostomy, or gastrojejunostomy tubes. OBJECTIVE: To assess growth outcomes of pediatric patients following retrograde percutaneous gastrostomy (RPG) and compare complications with those following other gastrostomy methods. MATERIALS AND METHODS: We retrospectively reviewed 120 random RPG patients from 2002 to 2003 (mean follow-up, 2.7 years). Patient weights and growth percentiles were recorded at insertion, and at 0-5 months, 6-12 months, and 18-24 months after insertion, and then compared using a Student's t-test. Complications and tube maintenance issues (TMIs) were recorded. RESULTS: Gastrostomy tube insertion was successful in all 120 patients (59 boys, 61 girls; mean age 4.3 years). The most common underlying diagnosis was neurologic disease (29%, 35/120) and the main indication was inadequate caloric intake (24%, 29/120). Significant increases in growth percentile for the entire population were demonstrated between insertion and 0-5 months (18.7-25.3; P<0.001) and between insertion and 18-24 months (18.7-25.8; P<0.001). In boys and girls significant growth increases occurred between insertion and 0-5 months (boys P=0.004; girls P=0.01). There were 11 major postprocedural complications, 100 minor complications and 169 TMIs. CONCLUSION: RPG provides long-term enteral nutrition in the pediatric population and increases growth significantly 6 and 24 months after insertion. Minor complications and TMIs are frequent.

Growth and nutrient intakes of human milk-fed preterm infants provided with extra energy and nutrients after hospital discharge.

OBJECTIVES: The purpose of this pilot study was to determine whether mixing a multinutrient fortifier to approximately one half of the human milk fed each day for a finite period after discharge improves the nutrient intake and growth of predominantly human milk-fed low birth weight infants. We also assessed the impact of this intervention on the exclusivity of human milk feeding. METHODS: Human milk-fed (> or = 80% feeding per day) low birth weight (750-1800 g) infants (n = 39) were randomly assigned at hospital discharge to either a control or an intervention group. Infants in the control group were discharged from the hospital on unfortified human milk. Nutrient enrichment of human milk in the intervention group was achieved by mixing approximately one half of the human milk provided each day with a powdered multinutrient human milk fortifier for 12 weeks after discharge. Milk with added nutrients was estimated to contain approximately 80 kcal (336 kJ) and 2.2 g protein/100 mL plus other nutrients. Intensive lactation support was provided to both groups. RESULTS: Infants in the intervention group were longer during the study period, and those born < or = 1250 g had larger head circumferences than infants in the control group. There was a trend toward infants in the intervention group to be heavier at the end of the intervention compared with those in the control group. Mean protein, zinc, calcium, phosphorus, and vitamins A and D intakes were higher in the intervention group. CONCLUSIONS: Results from this study suggest that adding a multinutrient fortifier to approximately one half of the milk provided to predominantly human milk-fed infants for 12 weeks after hospital discharge may be an effective strategy in addressing early discharge nutrient deficits and poor growth without unduly influencing human milk feeding when intensive lactation support is provided.

Collegiate Athletic Trainers' Confidence in Helping Female Athletes With Eating Disorders.

OBJECTIVE: To examine college athletic trainers' confidence in helping female athletes who have eating disorders. DESIGN AND SETTING: We mailed a 4-page, 53-item survey to head certified athletic trainers at all National Collegiate Athletic Association Division IA and IAA institutions (N = 236). A 2- wave mailing design was used to increase response rate. SUBJECTS: A total of 171 athletic trainers returned completed surveys for a response rate of 77%. Eleven institutions either did not identify their head athletic trainer or did not have an identifiable mailing address. Two surveys were undeliverable because of incorrect mailing addresses. MEASUREMENTS: The survey consisted of 4 subscales: (1) efficacy expectation, (2) outcome expectation, (3) outcome value, and (4) experience in dealing with eating disorders. Content validity was established by review from a national panel of experts. Reliability ranged from.66 to.73 for the subscales. RESULTS: Although virtually all athletic trainers (91%) had dealt with a female athlete with an eating disorder, only 1 in 4 (27%) felt confident identifying a female athlete with an eating disorder, and only 1 in 3 (38%) felt confident asking an athlete if she had an eating disorder. One in 4 athletic trainers (25%) worked at an institution that did not have a policy on handling eating disorders. Almost all athletic trainers (93%) felt that increased attention needs to be paid to preventing eating disorders among collegiate female athletes. CONCLUSIONS: Collegiate athletic programs are encouraged to develop and implement eating-disorder policies. Continuing education on the prevention of eating disorders among athletes is also strongly recommended.