Voxel-based morphometric magnetic resonance imaging postprocessing in non-lesional pediatric epilepsy patients using pediatric normal databases.

BACKGROUND AND PURPOSE: Pre-surgical evaluation of pediatric patients with drug-resistant focal epilepsy and negative (non-lesional) magnetic resonance imaging (MRI) is particularly challenging. Focal cortical dysplasia (FCD), a frequent pathological substrate in such setting, may be subtle on MRI and evade detection. The aim of this study was to use voxel-based MRI postprocessing to improve the detection of subtle FCD in pediatric surgical candidates. METHODS: A consecutive cohort of pediatric patients undergoing pre-surgical evaluation with a negative MRI by visual analysis was included. MRI postprocessing was performed using a voxel-based morphometric analysis program (MAP) on T1-weighted volumetric MRI, with comparison to an age-specific normal pediatric database. The pertinence of MAP-positive areas was confirmed by surgical outcome and pathology. RESULTS: A total of 78 patients were included. Forty-four patients (56%) had positive MAP regions. Complete resection of the MAP-positive regions was positively associated with seizure-free outcome compared with the no/partial resection group (P < 0.001). Patients with no/partial resection of the MAP-positive regions had worse seizure outcomes than the MAP-negative group (P = 0.002). The MAP-positive rate was 100%, 77%, 63% and 40% in the 3-5, 5-10, 10-15 and 15-21 year age groups, respectively. MAP-positive rates were 45% in patients with temporal resection and 63% in patients with extratemporal resection. Complete resection of the MAP-positive regions was positively associated with seizure-free outcome in the extratemporal group (P = 0.001) but not in the temporal group (P = 0.070). CONCLUSION: Our data suggest the importance of using MRI postprocessing in the pre-surgical evaluation process of pediatric epilepsy patients with apparently normal MRI.

Home use of a compact, 12­lead ECG recording system for newborns.

BACKGROUND: An easy-to-operate ECG recorder should be useful for newborn screening for heart conditions, by health care workers - or parents. We developed a one-piece electrode strip and a compact, 12­lead ECG recorder for newborns. METHOD: We enrolled 2582 newborns in a trial to assess abilities of parents to record a 12­lead ECG on their infants (2-4 weeks-old). Newborns were randomized to recordings by parents (1290) or our staff (1292 controls). Educational backgrounds of parents varied, including 64% with no more than a high school diploma. RESULTS: For newborns randomized to parent recorded ECGs, 94% of parents completed a 10-minute recording. However, 42.6% asked for verbal help, and 12.7% needed physical help. ECG quality was the same for recordings by parents versus staff. CONCLUSIONS: By use of a one-piece electrode strip and a compact recorder, 87% of parents recorded diagnostic quality ECGs on their newborn infants, with minimal assistance.

Health economic burden of COVID-19 in Saudi Arabia.

Background: The coronavirus disease 2019 (COVID-19) pandemic has added a massive economic burden on health care systems worldwide. Saudi Arabia is one of the numerous countries that have been economically affected by this pandemic. The objective of this study was to provide real-world data on the health economic burden of COVID-19 on the Saudi health sector and assess the direct medical costs associated with the management of COVID-19. Methods: A retrospective cohort study was conducted based on data collected from patients hospitalized with COVID-19 across 10 institutions in eight different regions in Saudi Arabia. The study calculated the direct medical costs of all cases during the study period by using SAS statistical analysis software. These costs included costs directly related to medical services, such as the health care treatment, hospital stays, laboratory investigations, treatment, outcome, and other related care. Results: A total of 5,286 adult patients admitted with COVID-19 during the study period were included in the study. The average age of the patients was 54 years, and the majority were male (79%). Among the COVID-19 patients hospitalized in a general ward, the median hospital length of stay was 5.5 days (mean: 9.18 days), while the ICU stay was 4.2 days (mean: 7.94 days). The total medical costs for general ward and ICU patients were US$ 38,895 and US$ 24,207,296.9, respectively. The total laboratory investigations ranked as the highest-cost services US$ 588,975 followed by treatment US$ 3,886,509.8. Overall, the total cost of all medical services for patients hospitalized with COVID-19 was US$ 51,572,393.4. Conclusion: This national study found that COVID-19 was not only a serious concern for patients but also a serious economic burden on the health care system in Saudi Arabia.

Life goes on: the resilience of maternal primary care during the Ebola outbreak in rural Sierra Leone.

Setting: All 100 health facilities providing maternal services in Moyamba, Sierra Leone, a rural district that experienced a smaller Ebola outbreak than other areas. Objective: To compare trends in antenatal care (the first and fourth visit [ANC1 and ANC4]), delivery, and postnatal care (PNC1) service utilisation before, during and after the Ebola outbreak (2014-2016). Design: Cross-sectional study using secondary programme data. Results: A total of 211 Ebola cases occurred in Moyamba District. The mean number of monthly ANC visits remained stable over time, except for the subset of care provided via outreach visits where, compared with before the outbreak (n = 390), ANC1 visits declined during (n = 331, P = 0.002) and after the outbreak (n = 342, P = 0.03). Most (>97%) deliveries occurred in health facilities, assisted by maternal and child health aides (>80%). During the outbreak, the mean number of community-based deliveries per month declined from 31 to 21 (P = 0.03), and the mean number of deliveries performed by midwives increased from 49 to 78 (P < 0.001) compared with before the outbreak. Before, during and after Ebola, there was no significant change in the mean number of live births (respectively n = 1134, n = 1110, n = 1162), maternal PNC1 (respectively n = 1110, n = 1105, n = 1165) or neonatal PNC1 (respectively n = 1028, n = 1050, n = 1085). Conclusion: In a rural district less affected by Ebola transmission than other areas, utilisation of maternal primary care remained robust, despite the outbreak.

Contexte : Les 100 structures de santé offrant des services de santé maternelle à Moyamba, Sierra Leone, un district rural qui a connu une petite flambée épidémique d'Ebola.Objectif : Comparer les tendances en matière d'utilisation des services de consultation prénatale (ANC1 et ANC4, c'est-à-dire la première consultation and la quatrième consultation ANC), d'accouchement et de soins postnataux (PNC1) avant, pendant et après la flambée épidémique d'Ebola (2014­2016).Schéma : Etude transversale recourant aux données secondaires du programme.Résultats : Il y a eu 211 cas d'Ebola dans le district. Le nombre moyen mensuel des ANC est resté stable dans le temps, à l'exception du sous-ensemble de soins offert à travers des stratégies avancées où, comparé à la période précédant la flambée épidémique (n = 390), les ANC1 ont décliné pendant (n = 331 ; P = 0,002) et après Ebola (n = 342 ; P = 0,03). La majorité des activités (<97%) a eu lieu dans des structures de santé, assistées par des auxiliaires de santé maternelle et infantile (<80%). Pendant la flambée épidémique, le nombre moyen d'accouchements ayant eu lieu en communauté par mois a décliné de 31 à 21 (P = 0,03), et le nombre moyen d'accouchements réalisés par des sages-femmes est passé de 49 à 78 (P < 0,001) par comparaison à la période antérieure. Il n'y a pas eu de changement significatif avant, pendant et après Ebola, dans le nombre moyen de naissances vivantes (n = 1134, n = 1110, n = 1162), de ANC1 maternelles (n = 1110, n = 1105, n = 1165) ou de consultation néonatales (n = 1028, n = 1050, n = 1085).Conclusion : Dans un district rural moins affecté par la transmission d'Ebola, l'utilisation des soins de santé primaires maternels a résisté à la flambée épidémique.

Marco de referencia: Los 100 establecimientos de atención de salud que cuentan con servicios de maternidad en Moyamba, un distrito rural de Sierra Leona donde el brote epidémico por enfermedad del Ébola fue menos intenso.Objetivo: Comparar las tendencias de la utilización de los servicios de atención prenatal (ANC1 et ANC4, es decir, la primera y la cuarta atención ANC), parto y atención posnatal (primera cita postnatal) antes del brote de enfermedad del Ébola, durante el mismo y después de él (del 2014 al 2016).Método: Fue este un estudio transversal con datos secundarios de los programas.Resultados: Se presentaron 211 casos de enfermedad por el virus del Ébola en el distrito. El promedio de consultas mensuales de atención prenatal permaneció estable con el transcurso del tiempo, con la excepción del subconjunto de cuidados prestados por conducto de citas extrainstitucionales, donde en comparación con el periodo anterior al brote (n = 390), las citas por ANC1 disminuyeron durante el brote (n = 331; P = 0,002) y después del mismo (n = 342; P = 0,03). La mayoría de los partos (>97%) tuvo lugar en los establecimientos sanitarios, atendido por auxiliares de salud maternoinfantil (>80%). Durante el brote epidémico, el promedio mensual de partos atendidos en la comunidad disminuyó de 31 a 21 (P = 0,03) y el promedio de partos atendidos por parteras aumentó de 49 a 78 (P < 0,001) en comparación con el período anterior al brote. No se observó ningún cambio significativo antes del brote, durante el mismo o después de él, con respecto al promedio de nacidos vivos (n = 1134, n = 1110 y n = 1162), ANC1 (n = 1110, n = 1105 y n = 1165) ni de primeras consultas posnatales del recién nacido (n = 1028, n = 1050 y n = 1085).Conclusión: En un distrito rural menos afectado por la transmisión de la enfermedad del Ébola, la utilización de los servicios primarios de atención materna resistió al brote epidémico.

Ganglion cell analysis in acute optic neuritis.

BACKGROUND: Optic neuritis has a diagnostic and prognostic significance in predicting the development of multiple sclerosis. Optical coherence tomography is being increasingly used to detect and monitor axonal damage in MS by measuring the retinal nerve fiber layer (RNFL). However, RNFL can be affected by edema and inflammation and obscure early axonal damage. OBJECTIVE: To study the pattern of change in the ganglion cell and inner plexiform layer compared to retinal nerve fibber layer in acute optic neuritis using spectral domain OCT. METHODS: Ten patients with acute optic neuritis were followed prospectively for 6 months with spectral domain optical coherence tomography. A group of 40 of eyes of 20 healthy controls was used for baseline comparison. RESULTS: The ganglion cell and inner plexiform layer (GCIPL) was significantly lower (thinner) at onset in patients' affected (p=0.009) eyes. Both RNFL and GCIPL were significantly lower in affected eyes at 6 months (p=0.012 and p=0.007) respectively compared to baseline. CONCLUSION: The GCIPL is probably more sensitive index of axonal loss than the RNFL in acute optic neuritis and could be a better index to detect neurodegeneration in multiple sclerosis. This can helpful in estimating early axonal loss and can potentially be used in therapeutic trials of neuroprotective drugs.

Automated MRI Volumetric Analysis in Patients with Rasmussen Syndrome.

BACKGROUND AND PURPOSE: Rasmussen syndrome, also known as Rasmussen encephalitis, is typically associated with volume loss of the affected hemisphere of the brain. Our aim was to apply automated quantitative volumetric MR imaging analyses to patients diagnosed with Rasmussen encephalitis, to determine the predictive value of lobar volumetric measures and to assess regional atrophy differences as well as monitor disease progression by using these measures. MATERIALS AND METHODS: Nineteen patients (42 scans) with diagnosed Rasmussen encephalitis were studied. We used 2 control groups: one with 42 age- and sex-matched healthy subjects and the other with 42 epileptic patients without Rasmussen encephalitis with the same disease duration as patients with Rasmussen encephalitis. Volumetric analysis was performed on T1-weighted images by using BrainSuite. Ratios of volumes from the affected hemisphere divided by those from the unaffected hemisphere were used as input to a logistic regression classifier, which was trained to discriminate patients from controls. Using the classifier, we compared the predictive accuracy of all the volumetric measures. These ratios were used to further assess regional atrophy differences and correlate with epilepsy duration. RESULTS: Interhemispheric and frontal lobe ratios had the best prediction accuracy for separating patients with Rasmussen encephalitis from healthy controls and patient controls without Rasmussen encephalitis. The insula showed significantly more atrophy compared with all the other cortical regions. Patients with longitudinal scans showed progressive volume loss in the affected hemisphere. Atrophy of the frontal lobe and insula correlated significantly with epilepsy duration. CONCLUSIONS: Automated quantitative volumetric analysis provides accurate separation of patients with Rasmussen encephalitis from healthy controls and epileptic patients without Rasmussen encephalitis, and thus may assist the diagnosis of Rasmussen encephalitis. Volumetric analysis could also be included as part of follow-up for patients with Rasmussen encephalitis to assess disease progression.

Cerebral aneurysms in atrial myxoma: a delayed, rare manifestation.

Atrial myxomas are the most common primary tumors of the heart. Neurologic involvement usually occurs as a stroke with ischemic episodes. Following excision of cardiac myxomas, delayed neurologic events owing to aneurysms are rare and have not been reported from India. We report an operated case of left atrial myxoma. The patient initially presented with a stroke and 6 months after the surgery, developed multiple intracerebral hemorrhages due to the rupture of fusiform cerebral aneurysms, without recurrence of the cardiac tumor.

Congenital insensitivity to pain with anhidrosis (CIPA): novel mutations of the TRKA (NTRK1) gene, a putative uniparental disomy, and a linkage of the mutant TRKA and PKLR genes in a family with CIPA and pyruvate kinase deficiency.

Congenital insensitivity to pain with anhidrosis is an autosomal recessive hereditary disorder characterized by recurrent episodic fever, anhidrosis (inability to sweat), absence of reaction to noxious stimuli, self-mutilating behavior, and mental retardation. The human TRKA gene (NTRK1), located on chromosome 1q21-q22 encodes the receptor tyrosine kinase for nerve growth factor. We reported that TRKA is the gene responsible for CIPA and we developed a comprehensive strategy to screen for TRKA mutations and polymorphisms, as based on the gene's structure and organization. Here we report eight novel mutations detected as either a homozygous or heterozygous state in nine CIPA families from five countries. Mendelian inheritance of the mutations was confirmed in seven families for which samples from either parent were available. However, non-mendelian inheritance seems likely for the family when only samples from the mother and siblings, (but not from the father) were available. A paternal uniparental disomy for chromosome 1 is likely to be the cause of reduction to homozygosity of the TRKA gene mutation in this family. Interestingly, a Hispanic patient from the USA has two autosomal genetic disorders, CIPA and pyruvate kinase deficiency, whose genetic loci are both mapped to a closely linked chromosomal region. A splice mutation and a missense mutation were detected in the TRKA and PKLR genes from the homozygous proband, respectively. Thus, concomitant occurrence of two disorders is ascribed to a combination of two separate mutant genes, not a contiguous gene syndrome. This finding suggests a mechanism responsible for two autosomal genetic disorders in one patient. All these data further support findings that TRKA defects can cause CIPA in various ethnic groups. This will aid in diagnosis and genetic counseling of this painless but severe genetic disorder.

Effect of phototherapy on nitrogen and electrolyte levels and water balance in jaundiced preterm infants.

Twenty-four-hour metabolic balance studies were performed in ten jaundiced preterm infants, five light-treated (phototherapy) and five controls. Each of the light-treated infants was studied twice, once during phototherapy (period I) and once 48 hours after phototherapy (period II). Control infants were similarly studied during the corresponding days. Compared to period II and control infants, during period I the light-treated infants had less weight gain. Intestinal transit time was decreased by 50%. Fecal excretion of nitrogen, sodium, and potassium was increased. Stool water loss was increased twofold to threefold with a decrease in water balance. Unmeasured water loss was increased. These studies underscore the need for careful attention to fluid and caloric supplementation during phototherapy.

Once daily ceftriaxone vs. chloramphenicol for treatment of typhoid fever in children.

In a prospective, randomized, open study ceftriaxone was compared with chloramphenicol for treatment of 59 children who had bacteriologically confirmed acute typhoid fever. Ceftriaxone was administered intramuscularly in a once a day dose of approximately 80 mg/kg body weight for 5 days. Chloramphenicol was given orally for 3 weeks in a daily dosage of 50 to 100 mg/kg body weight divided into 4 doses. In the ceftriaxone group 23 of 29 patients were cured, 2 improved, 1 failed and 2 relapsed. For those who received chloramphenicol 22 of the 30 patients were cured, 5 improved, 1 failed and 2 relapsed. In none of the patients in either group were adverse effects recorded. The overall results of this comparative study suggest that short term treatment of typhoid fever with ceftriaxone is as effective and safe as conventional treatment with chloramphenicol.

A prospective study of ERCP and endoscopic sphincterotomy in the diagnosis and treatment of gallstone acute pancreatitis. A rational and safe approach to management.

From a consecutive series of 112 patients with acute pancreatitis, 70 patients with suspected gallstones were randomized to urgent endoscopic retrograde cholangiopancreatography (ERCP) (less than 72 hours) and endoscopic sphincterotomy (ES) if choledochal stones were present (n = 35), or to conventional treatment (n = 35). Endoscopic retrograde cholangiopancreatography, successful in 89% of cases, indicated choledochal stones in 11 patients, all of whom underwent successful stone retrieval by ES. Later during hospital admission, ERCP was performed in 13 more patients and choledochal calculi were extracted from two patients by ES. No complications were attributable to ERCP or ES. Two patients died of biliary pancreatitis; both had been conventionally treated and may have benefited from urgent ERCP/ES. Our experience, which extends to another 24 patients with ERCP and ten with ES during acute pancreatitis, indicates that these are safe techniques and deserve wider consideration in the management of acute pancreatitis.

Correlation of single fibre EMG and muscle histochrmistry using an open biopsy recording technique.

Single fibre electromyographic (SFEMG) recordings were carried out during open muscle biopsy. Nine patients were studied, including 5 with Duchenne muscular dystrophy, 2 with spinal muscular atrophy and 1 each with limb-girdle dystrophy and myotonic dystrophy. Correlations were possible between the SFEMG fibre density determinations and histochemical evidence of grouping in some biopsies, particularly involving Type I fibres. This combined technique permits an improved assessment of the functional state of abnormal muscle.

Evaluation of immunoregulatory cells in Duchenne muscular dystrophy and spinal muscular atrophy among African and Indian patients.

Suppressor cells were assayed by numerical and functional tests in Duchenne muscular dystrophy (DMD) and spinal muscular atrophy (SMA) among African and Indian children in order to contribute to an understanding of the pathogenesis of these neurological disorders. Peripheral blood mononuclears (PBM) were classified as total T cells and T cell subsets by the OKT series of monoclonal antibodies and as B cells by the presence of surface immunoglobulin. The suppressive effects of PBM pretreated with concanavalin A (Con A) on normal homologous phytohaemagglutinin (PHA) transformation of mononuclear cells was determined. PBM stimulation by PHA was also assessed. Patients with DMD had a significant increase (P = 0.0353) in the number of T suppressor/cytotoxic cells (1218 +/- 142 cells/mm3, mean +/- SE) as compared to controls (815 +/- 95 cells/mm3) and a significant reduction (P = 0.0282) in OKT4+ cells expressed as a percentage of OKT3+, 50% +/- 3 compared to 61% +/- 3. No differences were detected in any of the numerical assays employed in SMA as compared to controls, or within SMA patients according to severity of disease. Suppressor function and PHA transformation were normal in both groups of patients. No significant correlations were detected between numerical and functional assays of suppression. The implication of the results obtained for the role of immunoregulatory cells in the pathogenesis of DMD in these children is discussed.

Mitomycin C and cisplatin increase survival in a human pancreatic cancer metastatic model.

Pancreatic cancer is one of the most intractable of all human cancers. We have previously developed a patient-like model of human pancreatic cancer by surgical orthotopic implantation (SOI). After SOI of the human tumor xenograft PAN-12-JCK into the tail of the nude mouse pancreas, mitomycin C (MMC) and cisplatin (DDP) were administered intraperitoneally at a dose of 4 and 6 mg/kg, respectively, on day-7. The mice were observed for 95 days. There was a statistically significant increase in disease-free and overall survival rates in the MMC- and MMC + DDP-treated groups. Local tumor growth was eliminated only in the group treated with MMC + DDP. Hepatic metastasis and peritoneal disseminations were completely inhibited by MMC but not DDP. This study demonstrates the usefulness of the SOI model of pancreatic cancer to study the differential efficacy of agents affecting primary tumor growth metastasis and survival, thus presenting an opportunity for the discovery of new agents for this highly resistant cancer.

Gene deletions in Arab patients with spinal muscular atrophy.

Spinal muscular atrophy is an autosomal recessive disorder characterized by degeneration of lower motor neurons. We have investigated the presence of survival motor neuron gene and neuronal apoptosis inhibitory protein gene deletions in 17 Arab and 1 Indian families with spinal muscular atrophy (15 type I and 3 type II). Homologous deletions were detected in exons 7 and 8 of the survival motor neuron gene and exon 5 of the neuronal apoptosis inhibitory protein gene in all patients with type I spinal muscular atrophy. Exon 13 of the neuronal apoptosis inhibitory protein gene was deleted in only one patient with type I spinal muscular atrophy. In two patients with type II spinal muscular atrophy, only exons 7 and 8 of the survival motor neuron gene were deleted whereas exons 5 and 13 of the neuronal apoptosis inhibitory protein gene were present. In another patient with spinal muscular atrophy type II, exons 7 and 8 of the survival motor neuron gene and exon 5 of the neuronal apoptosis inhibitory protein gene were deleted. This latter patient also had the Pierre Robin syndrome. No deletion was detected in healthy siblings or the parents. The deletions found in our patients are similar to those reported in other population groups.

Auditory brainstem responses (ABR) in children with neurological disorders.

Auditory brainstem responses (ABR) were studied in 35 children with neurological disorders and 24 controls. Abnormal results were obtained in 16 patients. All 5 of the patients with metachromatic leukodystrophy had evidence of peripheral and/or central delay in transmission in keeping with evidence of demyelination of both peripheral (i.e. auditory nerve) and central (i.e. brainstem) pathways as occurs in this disorder. Two children with lead poisoning had delayed conduction in the peripheral pathways only and in these there was good correlation between the degree of delay and the ulnar nerve conduction velocity; both improved after chelation therapy. One infant with lead poisoning had central delay only. One infant with osteopetrosis manifested progressive damage to the auditory nerves. Delayed conduction was also found in one patient each with hydrocephalus, spinal muscular atrophy, and in 2 infants with cerebral palsy. No responses were obtained in one infant with congenital rubella, one deaf-mute and one child with an undiagnosed degenerative neurological disease. Auditory brainstem responses are of value in detecting disturbances of the auditory nerve or brainstem in children with various neurological disorders.

Blindness, ophthalmoplegia and extensive radiculopathy: an unusual clinical syndrome in intracranial sino-venous thrombosis.

Isolated intracranial hypertension is a common manifestation of intracranial sino-venous thrombosis (ISVT). Markedly elevated intracranial tension presents with unusual features including cranial neuropathies and radiculopathy. We report two cases with ISVT, which presented with headache, papilledema, progressive visual loss, complete ophthalmoplegia and flaccid areflexic quadriparesis along with a normal sensorium. Magnetic resonance imaging (MRI) of the brain and cervical spinal cord showed no lesions that could account for the neurological deficits. Markedly elevated lumbar CSF pressure was noted in both cases. Nerve conduction study favored radiculopathy in one case and was normal in the other. Raised intracranial pressure was found to be the sole cause for the clinical manifestations. Visual impairment persisted in one patient despite lumbo-peritoneal shunting while the other died of septicemia. To our knowledge there are no previous reports of a syndrome comprising blindness, ophthalmoplegia and flaccid quadriplegia due to intracranial hypertension in ISVT.

Splenomegaly in Arab children with idiopathic thrombocytopenic purpura.

Splenomegaly was found in 31 (55%) of 56 Arab children with idiopathic thrombocytopenic purpura. Of those with splenomegaly, 84% had evidence of iron deficiency anemia compared to 48% in those without splenomegaly (P<0.001). There was no significant difference in the prevalence of ss-thalassemia trait or history of preceding viral infection between those with or without splenomegaly. This study demonstrates a much higher prevalence of splenomegaly in Arab children with idiopathic thrombocytopenic purpura, most probably related to associated iron deficiency.