Eficacia de la zonisamida en un caso de enfermedad de Lafora y breve revisión en la epilepsia mioclónica progresiva / Efficacy of zonisamide in a case of Lafora disease and brief review in progressive myoclonic epilepsy

Introducción: La epilepsia mioclónica progresiva constituye un grupo complejo de enfermedades neurodegenerativas clínica y genéticamente heterogéneas que asocian mioclonías espontáneas o inducidas por la acción y el deterioro neurológico progresivo. Dentro de estas entidades se encuentra la enfermedad de Lafora, una patología autosómica recesiva causada por mutación en el gen responsable de la síntesis de una proteína llamada laforina (EPM2A) o el gen responsable de la síntesis de la proteína malina (EPM2B o NHLRC1). Son entidades cuyas crisis, en especial las mioclonías, son frecuentemente resistentes a los fármacos anticrisis epilépticas. Caso clínico: Presentamos el caso de una paciente con diagnóstico de enfermedad de Lafora que, tras varios regímenes terapéuticos ineficaces, presentó buena respuesta a la introducción de la zonisamida, con una respuesta favorable mantenida en el tiempo. Asimismo, hacemos una breve revisión de la eficacia de la zonisamida en cuadros de epilepsia mioclónica progresiva. Conclusión: La zonisamida puede ser una buena alternativa en el tratamiento de cuadros con epilepsia mioclónica progresiva.(AU)

INTRODUCTION: Mioclonic progressive epilepsy (MPE) includes a clinical and genetical heterogeneous group of neuro­degenerative disorders that associate spontaneous and action-induced myoclonus as well as progressive cognitive impairment. Lafora`s disease is a subtype of MPE with autosomical recessive inheritance due to a mutation in EPM2A or EPM2B genes. Seizures, especially myoclonus, are often refractary to antiepileptic drugs (AD). CASE REPORT: In this article we report a patient with Lafora´s disease diagnosis, previously resistant to several AD tested with good and sustained response to zonisamide. Indeed, we describe a brief review about the efficacy of zonisamida in MPE. CONCLUSION. Zonisamide may be considered as a good therapeutic alternative in MPE.(AU)

Variante interhemisférica media de holoprosencefalia: diagnóstico mediante resonancia magnética fetal / The diagnosis of the middle interhemispheric variant of holoprosencephaly with fetal MRI

Las anomalías congénitas del sistema nervioso central constituyen un amplio grupo de malformaciones asociadas a una gran variedad de síndromes genéticos y anomalías cromosómicas, y una de las principales causas de morbimortalidad infantil. Dentro de ellas, la holoprosencefalia conlleva un trastorno de la diferenciación del prosencéfalo, con una falta completa o parcial de división entre los hemisferios cerebrales. Para su diagnóstico prenatal es fundamental la realización de pruebas de imagen y el conocimiento de los posibles hallazgos, debido a que su pronóstico es variable, comenzando normalmente con la ecografía y confirmando lo visualizado con la resonancia magnética.(AU)

Congenital anomalies of the central nervous system comprise a wide spectrum of malformations associated with a wide variety of genetic syndromes and chromosomal anomalies, and they are among the principal causes of morbidity and mortality in infants. Among these anomalies, holoprosencephaly arises from the complete or partial failure of the brain to divide into the cerebral hemispheres. Imaging tests are fundamental for the prenatal diagnosis of holoprosencephaly; the diagnostic process usually starts with sonography and then the findings are refined with fetal MRI. Radiologists need to be familiar with the possible findings because the prognosis varies.(AU)

Fetal central nervous system anomalies according to RT-PCR and trimester of maternal infection with Zika virus: A prospective cohort study.

INTRODUCTION: In October 2015, an epidemic of Zika began in Colombia's geographic areas with a high population of mosquitoes of the genus Aedes. We aimed to describe the fetal brain ultrasound findings in pregnant women with active symptoms or a history of symptoms suggestive of Zika virus (ZIKV) infection. MATERIAL AND METHODS: Eligible pregnant women were tested with reverse transcriptase-polymerase chain reaction (RT-PCR) for ZIKV and followed prospectively using detailed anatomic ultrasound and transvaginal neurosonography to detect structural anomalies of the fetal central nervous system (CNS). RESULTS: A total of 115 symptomatic women with a positive ZIKV RT-PCR and 55 with a negative ZIKV RT-PCR were enrolled in the study; CNS compromise of the fetus occurred in 22% and 17%, respectively (p = 0.255). Callosal dysgenesis (14.5%) was the most frequent anomaly of the CNS, followed by microcephaly (13.6%) and neuronal migration disorders (8.3%). When symptomatic ZIKV RT-PCR-positive women were categorized by trimester of infection, CNS anomalies were present in 40% of first-trimester infections, compared with 21% and 7% in second- and third-trimester infections (p = 0.002). CNS anomalies were also more severe in first-trimester-infected fetuses than in second- and third-trimester-infected fetuses. The high prevalence of CNS anomalies in fetuses of symptomatic ZIKV RT-PCR negative women suggests a high rate of false-negative cases and an even higher prevalence of CNS anomalies than observed in this study. CONCLUSIONS: The prevalence of fetal CNS anomalies was higher than previously reported in the literature for both symptomatic RT-PCR-positive and -negative pregnant women. Corpus callosum anomalies, microcephaly, neuronal migration disorders, and brain parenchymal hyperechogenicities were the most frequent CNS anomalies detected. In addition, CNS anomalies were more frequent and severe in infected fetuses during the first trimester of pregnancy than during the second or third trimester.

CNS-3 status remains an independent adverse prognosis factor in children with acute lymphoblastic leukemia (ALL) treated without cranial irradiation: Results of EORTC Children Leukemia Group study 58951.

AIM: To evaluate the prognostic significance of initial central nervous system (CNS) involvement of children with acute lymphoblastic leukemia (ALL) enrolled in the EORTC 58951 trial. PATIENTS AND METHODS: From 1998 to 2008, 1930 ALL patients were included in the randomized EORTC 58951 trial. Overall treatment intensity was adjusted according to known prognostic factors including the level of minimal residual disease after induction treatment. CNS-directed therapy comprised four to 11 courses of i.v. methotrexate (5g/m2), and 10 to 19 intrathecal chemotherapy injections, depending on risk group and CNS status. Cranial irradiation was omitted for all patients. RESULTS: The overall 8-year event-free survival (EFS) and overall survival (OS) rates were 81.3% and 88.1%, respectively. In the CNS-1, TPL+, CNS-2, and CNS-3 groups, the 8-year EFS rates were 82.1%, 77.1%, 78.3%, and 57.4%, respectively. Multivariable analysis indicated that initial CNS-3 status, but not CNS-2 or TLP+, was an independent adverse predictor of outcome. The 8-year incidence of isolated CNS relapse was 1.7% and of isolated or combined CNS relapse it was 3.7%. NCI high-risk group, male sex, CNS-2 and CNS-3 status were independent predictors for a higher incidence of any CNS relapse. CONCLUSIONS: CNS-3 status remains associated with poor prognosis and requires intensification of both systemic and CNS-directed therapy. This trial was registered at https://clinicaltrials.gov/under/NCT00003728.

Ocular Phenotype Associated with DYRK1A Variants.

Dual-specificity tyrosine phosphorylation-regulated kinase 1A or DYRK1A, contributes to central nervous system development in a dose-sensitive manner. Triallelic DYRK1A is implicated in the neuropathology of Down syndrome, whereas haploinsufficiency causes the rare DYRK1A-related intellectual disability syndrome (also known as mental retardation 7). It is characterised by intellectual disability, autism spectrum disorder and microcephaly with a typical facial gestalt. Preclinical studies elucidate a role for DYRK1A in eye development and case studies have reported associated ocular pathology. In this study families of the DYRK1A Syndrome International Association were asked to self-report any co-existing ocular abnormalities. Twenty-six patients responded but only 14 had molecular confirmation of a DYRK1A pathogenic variant. A further nineteen patients from the UK Genomics England 100,000 Genomes Project were identified and combined with 112 patients reported in the literature for further analysis. Ninety out of 145 patients (62.1%) with heterozygous DYRK1A variants revealed ocular features, these ranged from optic nerve hypoplasia (13%, 12/90), refractive error (35.6%, 32/90) and strabismus (21.1%, 19/90). Patients with DYRK1A variants should be referred to ophthalmology as part of their management care pathway to prevent amblyopia in children and reduce visual comorbidity, which may further impact on learning, behaviour, and quality of life.

The Genetics of Sudden Infant Death Syndrome-Towards a Gene Reference Resource.

Sudden infant death syndrome (SIDS) is the unexpected death of an infant under one year of age that remains unexplained after a thorough investigation. Despite SIDS remaining a diagnosis of exclusion with an unexplained etiology, it is widely accepted that SIDS can be caused by environmental and/or biological factors, with multiple underlying candidate genes. However, the lack of biomarkers raises questions as to why genetic studies on SIDS to date are unable to provide a clearer understanding of the disease etiology. We sought to improve the identification of SIDS-associated genes by reviewing the SIDS genetic literature and objectively categorizing and scoring the reported genes based on the strength of evidence (from C1 (high) to C5 (low)). This was followed by analyses of function, associations between genes, the enrichment of gene ontology (GO) terms, and pathways and gender difference in tissue gene expression. We constructed a curated database for SIDS gene candidates consisting of 109 genes, 14 of which received a category 4 (C4) and 95 genes received the lowest category of C5. That none of the genes was classified into the higher categories indicates the low level of supporting evidence. We found that genes of both scoring categories show distinct networks and are highly diverse in function and involved in many GO terms and pathways, in agreement with the perception of SIDS as a heterogeneous syndrome. Genes of both scoring categories are part of the cardiac system, muscle, and ion channels, whereas immune-related functions showed enrichment for C4 genes. A limited association was found with neural development. Overall, inconsistent reports and missing metadata contribute to the ambiguity of genetic studies. Considering those parameters could help improve the identification of at-risk SIDS genes. However, the field is still far from offering a full-pledged genetic test to identify at-risk infants and is still hampered with methodological challenges and misunderstandings of the vulnerabilities of vital biological mechanisms.

Chromosomal microarray analysis in fetuses with central nervous system anomalies: An 8-year long observational study from a tertiary care university hospital.

OBJECTIVES: To evaluate the prevalence of DNA copy number variants (CNVs) detected with array comparative genomic hybridization (CGH) in fetuses with central nervous system (CNS) anomalies. Secondary objectives were to describe the prevalence of CNV in specific CNS abnormalities, in isolated defects or associated with other malformations or fetal growth restriction (FGR). METHODS: Observational cohort study in 238 fetuses with CNS anomalies in which an array-CGH had been performed between January 2009 and December 2017. Pathogenic CNV and variants of unknown significance (VUS) were reported. RESULTS: Pathogenic CNVs were found in 16/238 cases (6.7%), VUS in 18/238 (7.6%), and normal result in 204/238 (85.7%) cases. Pathogenic CNVs were more frequent in posterior fossa anomalies (cerebellar hypoplasia 33%, megacisterna magna 20%), moderate ventriculomegaly (11%) and spina bifida (3.7%). Pathogenic CNVs and VUS were found in 7/182 (3.8%) and 14/182 (7.7%) cases of isolated anomalies, in 9/49 (18.4%) and 4/49 (8.2%) presenting another malformation, and in 0/7 and 0/7 cases with associated FGR (P = .001, P = .741, respectively). CONCLUSION: These results provide strong evidence toward performing array in fetuses with CNS anomalies, particular in cases of posterior fossa anomalies. The prevalence of pathogenic CNVs is higher in association with other malformations.

Fetal akinesia deformation sequence with pontocerebellar hypoplasia, and migration and gyration defects

Fetal akinesia deformation sequence (FADS), or Pena-Shokeir phenotype is a constellation of deformational changes resulting from decreased or absent fetal movement, and include arthrogryposis, and craniofacial and central nervous system anomalies. We report an autopsy case of a 36-6/7week female neonate with a normal female karyotype and chromosome microarray demonstrating findings consistent with FADS. We provide a detailed examination of the severe and complex central nervous system abnormalities, including marked pontocerebellar hypoplasia and cortical and cerebellar migration and gyration defects. This case represents a rare detailed examination of the central nervous system of a patient with FADS.

Cirugía ablativa del núcleo subtalámico en la Enfermedad de Parkinson. Consideraciones necesarias / Ablative subthalamic nucleus surgery in Parkinson's disease. Necessary considerations

RESUMEN La enfermedad de Parkinson según la Organización Mundial de Salud, en el año 2016, afectó una persona por cada 100 mayores de 60 años, siendo en cifras absolutas 6,3 millones de personas, y para el año 2030 serán aproximadamente 12 millones de personas en todo el mundo con dicha patología. Este desorden neurodegenerativo, caracterizado por la degradación nigro-estriatal y potenciación de la vía indirecta del circuito motor de los Ganglios Basales sumado al acúmulo de Cuerpos de Lewy en diversas estructuras del Sistema Nervioso Central, afecta progresiva e inevitablemente la calidad de vida de los pacientes, los procederes ablativos del núcleo subtalámico constituyen una alternativa que propicia efecto y seguridad probada en el control de los síntomas de esta enfermedad. Por lo cual se decide describir la ablación del Núcleo subtalámico como tratamiento de la Enfermedad de Parkinson avanzada (AU).

Summary According to the World Health Organization, in 2016 Parkinson's disease affected one person per every 100 people elder 60 years, meaning 6.3 millions of people, and by 2030 it will be around 12 million persons across the world. This neurodegenerative disorder, characterized by the nigro-striatal degradation and potentiation of the indirect route of the basal ganglia motor circuit, added to the accumulation of Lewy bodies in several structures of the Central Nervous System, progressively and inevitably affects the life quality of patients. The ablative procedures of the subthalamic nucleus are an alternative that propitiates proven effect and safety in the control of this disease symptoms. Therefore, the authors decided to describe the subthalamic nucleus ablation as a treatment for advanced Parkinson's disease (AU).

A sart1 Zebrafish Mutant Results in Developmental Defects in the Central Nervous System.

The spliceosome consists of accessory proteins and small nuclear ribonucleoproteins (snRNPs) that remove introns from RNA. As splicing defects are associated with degenerative conditions, a better understanding of spliceosome formation and function is essential. We provide insight into the role of a spliceosome protein U4/U6.U5 tri-snRNP-associated protein 1, or Squamous cell carcinoma antigen recognized by T-cells (Sart1). Sart1 recruits the U4.U6/U5 tri-snRNP complex to nuclear RNA. The complex then associates with U1 and U2 snRNPs to form the spliceosome. A forward genetic screen identifying defects in choroid plexus development and whole-exome sequencing (WES) identified a point mutation in exon 12 of sart1 in Danio rerio (zebrafish). This mutation caused an up-regulation of sart1. Using RNA-Seq analysis, we identified additional upregulated genes, including those involved in apoptosis. We also observed increased activated caspase 3 in the brain and eye and down-regulation of vision-related genes. Although splicing occurs in numerous cells types, sart1 expression in zebrafish was restricted to the brain. By identifying sart1 expression in the brain and cell death within the central nervous system (CNS), we provide additional insights into the role of sart1 in specific tissues. We also characterized sart1's involvement in cell death and vision-related pathways.

Detection of submicroscopic chromosomal aberrations by chromosomal microarray analysis for the prenatal diagnosis of central nervous system abnormalities.

BACKGROUND: Central nervous system (CNS) abnormalities are a group of serious birth defects associated with high rates of stillbirths, infant death, or abnormal development, and various disease-causing copy number variations play a much more important role in the etiology of CNS abnormalities. This study intends to present a retrospective study of the prenatal diagnosis and the pregnancy outcome of fetuses diagnosed with CNS abnormalities, and evaluate the clinical value of chromosomal microarray analysis (CMA) in prenatal diagnosis of CNS abnormalities. METHODS: A total of 356 fetuses with CNS abnormalities with or without other ultrasound abnormalities subjected to invasive prenatal diagnosis at the first affiliated hospital of Air Force Medical University from January 2015 to August 2018. All cases have performed both karyotyping and CMA concurrently, but 20 fetuses with chromosome aneuploidy were excluded in the current study. RESULTS: The CMA identified pathogenic copy number variants (pCNVs) in 27/336 (8.03%) fetuses, likely pCNVs in 8/336 (2.38%) fetuses, and variants of unknown significance (VOUS) in 11/336 (3.27%) fetuses. A total of 222 cases had single CNS abnormalities and the pCNVs detection rate was 5.86% (13/222), the remaining 114 cases including CNS abnormalities plus other structural abnormalities, ultrasonographic soft markers and two or more CNS abnormalities, the pCNVs detection rate was 12.3% (14/114). CONCLUSIONS: Fetuses with CNS abnormalities have a higher risk of chromosomal abnormalities, our study showed that CNVs play an important role in the etiology of CNS abnormalities. The application of CMA could increase the detection rate of pCNVs causing CNS abnormalities.

Primary anaplastic large cell lymphoma of the central nervous system in a child: A case report.

INTRODUCTION: To report the clinical characteristics of primary central nervous system T-cell lymphoma with anaplastic lymphoma kinase-1 (ALK-1) positive in an 8-year-old male. PATIENT CONCERNS: The patient presented cognitive impairment, dizziness, vomiting, fever, and convulsions during the disease, followed by progressive and persistent severe headache, progressive increase of intracranial pressure, indifference, disorder of consciousness, mild increase in white blood cells in cerebrospinal fluid, progressive decrease of sugar, progressive increase of protein, abnormal signal of left parietal-occipital, local meningeal enhancement, and cerebrospinal fluid cytology. DIAGNOSIS: He was diagnosed with ALK-1-positive central nervous system T-cell lymphoma. INTERVENTIONS: Meropenem and vancomycin were administered to counter the infection, while dexamethasone alleviated the inflammation. OUTCOMES: The patient died of cerebral hernia due to intracranial hypertension in the eighth week of the disease. CONCLUSIONS: PCNS ALK-1-positive anaplastic large cell lymphoma is extremely rare. Also, it is difficult to distinguish from central meningeal lymphoma and central nervous system infection, which might lead to delayed diagnosis. However, early diagnosis depends on the pathological diagnosis of brain tissue biopsy.

Associated anomalies in cases with congenital clubfoot.

Congenital clubfoot CTEV is a common congenital anomaly, its etiology is unclear and its pathogenesis is controversial. Cases with CTEV often have other non-CTEV associated congenital anomalies. The purpose of this study was to assess the prevalence and the types of these associated anomalies in a defined population. The associated anomalies in cases with CTEV were collected in all livebirths, stillbirths, and terminations of pregnancy during 29 years in 387,067 consecutive births in the area covered by our population-based registry of congenital malformations. Of the 504 cases with CTEV, representing a prevalence of 13.02 per 10,000, 107 (21.2%) had associated anomalies. There were 31 (6.1%) cases with chromosomal abnormalities, and 21 (4.2%) non-chromosomal recognized dysmorphic conditions including syndromes: 6 arthrogryposis multiplex congenita, 2 22q11.2 microdeletion, and one fetal alcohol syndrome. Fifty-five (10.9%) of the cases had nonsyndromic multiple congenital anomalies (MCA). Anomalies in the cardiovascular, the central nervous, the urinary, the orofacial, and the musculoskeletal systems were the most common other anomalies in the cases with MCA. The anomalies associated with CTEV could be classified into a recognizable malformation syndrome in 52 of the 107 cases (48.6%) with associated anomalies. This study included special strengths: it is population-based, each affected child was examined by a geneticist, all elective terminations were ascertained, and the surveillance for anomalies was continued until 2 years of age. In conclusion the overall prevalence of associated anomalies, one of five cases, emphasizes the need for a screening for other anomalies in cases with CTEV.

Etiology of Microcephaly and Central Nervous System Defects during the Zika Epidemic in Colombia.

OBJECTIVE: To estimate the prevalence of microcephaly and central nervous system (CNS) defects during the Zika virus (ZIKV) epidemic in Colombia and proportion attributable to congenital ZIKV infection. STUDY DESIGN: Clinical and laboratory data for cases of microcephaly and/or CNS defects reported to national surveillance between 2015 and 2017 were reviewed and classified by a panel of clinical subject matter experts. Maternal and fetal/infant biologic specimens were tested for congenital infection and chromosomal abnormalities. Infants/fetuses with microcephaly and/or CNS defects (cases) were classified into broad etiologic categories (teratogenic, genetic, multifactorial, and unknown). Cases classified as potentially attributable to congenital ZIKV infection were stratified by strength of evidence for ZIKV etiology (strong, moderate, or limited) using a novel strategy considering birth defects unique or specific to ZIKV or other infections and laboratory evidence. RESULTS: Among 858 reported cases with sufficient information supporting a diagnosis of microcephaly or CNS defects, 503 were classified as potentially attributable to congenital ZIKV infection. Of these, the strength of evidence was considered strong in 124 (24.7%) cases; moderate in 232 (46.1%) cases; and limited in 147 (29.2%). Of the remaining, 355 (41.4%) were attributed to etiologies other than ZIKV infection (syphilis, toxoplasmosis, rubella, cytomegalovirus, herpes 1 and herpes 2 viruses only, n = 32 [3.7%]; genetic, n = 16 [1.9%]; multifactorial, n = 42 [4.9%]; unknown, n = 265 [30.9%]). CONCLUSIONS: Fifty-eight percent of cases of microcephaly and/or CNS defects were potentially attributable to congenital ZIKV infection; however, the strength of evidence varied considerably. This surveillance protocol might serve as a model approach for investigation and etiologic classification of complex congenital conditions.

Inflammatory Bowel Disease and Risk of Birth Defects in Offspring.

BACKGROUND AND AIMS: The relationship between inflammatory bowel disease in pregnancy and birth defects is not understood. We evaluated whether Crohn's disease and ulcerative colitis in pregnant women were associated with the risk of birth defects in the offspring. METHODS: We undertook a retrospective cohort study of 2 184 888 pregnancies in Quebec, Canada, between 1989 and 2016. We calculated risk ratios [RR] and 95% confidence intervals [CI] for the association between inflammatory bowel disease and the risk of birth defects, using generalised estimating equations adjusted for maternal characteristics. We assessed associations in the period before 2000, when immunosuppressive biologic therapy and folic acid food fortification were not yet available, compared with the period after 2000 when these interventions were more widespread. RESULTS: This study included 13 099 women with Crohn's disease and 7798 with ulcerative colitis. Crohn's disease was associated with 1.90 times [95% CI 1.10-3.28] the risk of abdominal wall defects [gastroschisis, omphalocoele, and diaphragmatic hernia] and ulcerative colitis was associated with 1.53 times [95% CI 1.02-2.30] the risk of central nervous system defects. The association of Crohn's disease with abdominal wall defects was stronger before 2000 [RR 3.62, 95% CI 1.71-7.67] than after 2000 [RR 1.23, 95% CI 0.55-2.75]. Ulcerative colitis was associated with central nervous system defects regardless of time period. CONCLUSIONS: These findings suggest that inflammatory bowel disease is associated with the risk of abdominal wall and central nervous system defects, and that introduction of immunobiologic medications is unlikely to be associated with added risk. PODCAST: This article has an associated podcast which can be accessed at https://academic.oup.com/ecco-jcc/pages/podcast.

Cleft lip repair: are outcomes between unilateral and bilateral clefts comparable?

This study sought to compare patient demographics, operative course, and peri-operative outcomes between unilateral and bilateral cleft patients. Primary cleft lip repairs were isolated from the National Surgical Quality Improvement Program Pediatric Database (NSQIP-P). Unilateral and bilateral cases of primary cleft lip were identified by ICD codes. Demographics, comorbidities, and post-operative outcomes were compared between cohorts. Patients were propensity matched to control for differences before repeating the analysis. About 4550 cleft lip repairs were evaluated over the 5-year period. Of the cases where the cleft type was identifiable, 75.5% were unilateral clefts and 24.5% were bilateral clefts. The bilateral cleft population had significantly more comorbidities including higher rates of ventilator dependence (1.0% versus 0.4%, p = 0.02), asthma (1.6% versus 0.7%, p = 0.011), tracheostomy (1.6% versus 0.5%, p < 0.001), gastrointestinal disease (16.9% versus 12.7%, p < 0.001), previous cardiac surgery (3.6% versus 2.2%, p = 0.015), developmental delay (9.9% versus 4.6%, p < 0.001), structural central nervous system abnormalities (5.0% versus 2.5%, p < 0.001), and nutritional support (8.0% versus 3.2%, p < 0.001). Following propensity matching, there were no significant differences in complications, readmissions, or reoperations between the cohorts. Patients with bilateral cleft lip have significantly more comorbidities than unilateral cleft lip patients. However, peri-operative outcomes are comparable between the groups.

Treatment of military cases of cerebrospinal fever during WWI: the concerted efforts of the RAMC, MRC and Lister Institute to make serum therapy work.

Cerebrospinal fever was rare in the British Army prior to World War I. An outbreak of the disease on Salisbury Plain in late 1914 posed new challenges. The War Office established the Central Cerebrospinal Fever Laboratory at the Royal Army Medical (RAM) College early in 1915 to conduct research, develop diagnostic tests and coordinate the military response. The Royal Army Medical Corps (RAMC) set up dedicated cerebrospinal wards for the hospitalisation and treatment of patients. The new Medical Research Committee (MRC) supported bacteriological studies of epidemic strains of the meningococcus responsible for the outbreak. The Lister Institute of Preventive Medicine, an independent research institution, acted as a key supplier of antimeningococcus serum. The mortality of military patients during 1915 was poor because the testing infrastructure was still developing, the RAMC had limited experience of treating cases, and the therapeutic serums available at the time seemed ineffective. The survival rate of home troops improved during the war-through the concerted efforts of the RAMC, MRC and Lister Institute-due to timely diagnosis, and early, intensive and prolonged treatment with improved serums. The Official History of the War highlights subsequent trials undertaken with strain-specific MRC serums in late 1918 and 1919 but fails to acknowledge that in late 1917/early 1918 the Lister Institute supplied the RAM College with large quantities of an efficacious multivalent serum and corresponding monovalent serums that were not included in a formal trial.

Congenital disorders and community genetic services in Nigeria: A systematic review.

Nigeria has a large number of congenital disorders (CD). For instance, two out of every hundred children born in Nigeria have sickle cell disorders (SCD). Making Nigeria the country with the highest incidence of SCD. This article reviews the prevalence of CD in Nigeria; with emphasis on those having a heavy statistical burden on the country, the availability of community genetics services in Nigeria and the efforts being made to tackle the challenges of CD. A systematic review of birth prevalence of congenital malformations (CM) in Nigeria was done through a literature search, with no time restriction for publication dates. Only studies that included the birth prevalence of CM were included. Eligible studies with incorrect or missing data were excluded. This revealed a dearth of data on CD in Nigeria, as in most Low- and Middle-Income Countries. A predominance of CM of the musculoskeletal and gastrointestinal systems was found in Nigeria. However, the pattern of CM in the South-South region was more of the central nervous system. There is scarcity of resources to address the challenges of CD in Nigeria with feeble government assistance. Meanwhile, 70% of CD can be prevented and adequately managed by well implemented community genetics services.

Serum metallome in pregnant women and the relationship with congenital malformations of the central nervous system: a case-control study.

BACKGROUND: Congenital malformations of the central nervous system (CNS) consist of a wide range of birth defects of multifactorial origin. METHODS: Concentrations of 44 metals were determined by Inductively Coupled Plasma Mass Spectrometry in serum of 111 mothers in the second trimester of pregnancy who carried a malformed fetus and compared them with serum concentrations of the same metals in 90 mothers with a normally developed fetus at the same week of pregnancy. Data are reported as means ± standard deviations. RESULTS: We found a direct relationship between congenital defects of the CNS and maternal serum concentration of aluminum: it was statistically higher in women carrying a fetus with this class of malformation, compared both to mothers carrying a fetus with another class of malformation (6.45 ± 15.15 µg/L Vs 1.44 ± 4.21 µg/L, p < 0.0006) and to Controls (i.e. mothers carrying a normally-developed fetus) (6.45 ± 15.15 µg/L Vs 0.11 ± 0.51 µg/L, p < 0.0006). Moreover, Aluminum abundances were below the limit of detection in the majority of control samples. CONCLUSION: CAluminum may play a role in the onset of central nervous system malformations, although the exact Aluminum species and related specific type of malformation needs further elucidation.

Incidence, spectrum and outcome of congenital anomalies seen in a neonatal intensive care unit in Southern Nigeria.

BACKGROUND: Congenital anomalies (CAs) refer to defects that are present in a newborn but occurred during intrauterine life. They can be due to genetic, modifiable environmental or multifactorial causes. There was no prior report of their burden in our state. AIMS: This study aims to describe the incidence, spectrum, predisposing factors and outcome of CAs in our setting. METHODS: It was a total population study of all neonates with major birth defects admitted into the unit during the study period. Their clinical-demographic features, diagnoses and outcome were entered into an excel sheet. Clinical detection of birth defects was based on standard diagnostic criteria. The data were analysed using IBM SPSS Statistics for Windows, Version 20.0. Armonk, NY: IBM Corp. Patterns and outcome of birth defects were presented as proportions. Selected characteristics were tested for possible association with birth defect using Fisher's exact test. The level of significance was set at P < 0.05. RESULTS: The incidence of major CAs was 4.3/1000 live births. Female neonates were more affected (59.0%). Participants' mean gestational age was 37.7 ± 3.3 weeks. Central nervous system anomalies were the most common (38.5%) birth defects. These were followed by musculoskeletal, body wall and digestive system anomalies: 28.2%, 23.1% and 10.3%, respectively. One-third (33.3%) of the infants had multiple anomalies. Nearly three quarters of them (74.0%) were referred, 18.0% died while 5.0% were discharged alive. CONCLUSION: A wide range of CAs occur in our setting with dire consequences. Provision of relevant specialised multidisciplinary care is desirable. Furthermore, pubic enlightenment on its modifiable possible causes can reduce the burden.