Lemierre's syndrome caused by Fusobacterium necrophorum complicated with multiple brain abscesses-A case report, literature review, and suggested management.

We present an unusual case of Lemierre´s syndrome complicated by multiple brain abscesses, a literature review and suggested management. A young man with multiple brain abscesses deteriorated despite two weeks of directed antibiotics. A multidisciplinary approach was successful. Hyperbaric oxygen treatment (HBOT) should be considered in refractory or severe cases.

From cytogenetics to cytogenomics: whole-genome sequencing as a first-line test comprehensively captures the diverse spectrum of disease-causing genetic variation underlying intellectual disability.

BACKGROUND: Since different types of genetic variants, from single nucleotide variants (SNVs) to large chromosomal rearrangements, underlie intellectual disability, we evaluated the use of whole-genome sequencing (WGS) rather than chromosomal microarray analysis (CMA) as a first-line genetic diagnostic test. METHODS: We analyzed three cohorts with short-read WGS: (i) a retrospective cohort with validated copy number variants (CNVs) (cohort 1, n = 68), (ii) individuals referred for monogenic multi-gene panels (cohort 2, n = 156), and (iii) 100 prospective, consecutive cases referred to our center for CMA (cohort 3). Bioinformatic tools developed include FindSV, SVDB, Rhocall, Rhoviz, and vcf2cytosure. RESULTS: First, we validated our structural variant (SV)-calling pipeline on cohort 1, consisting of three trisomies and 79 deletions and duplications with a median size of 850 kb (min 500 bp, max 155 Mb). All variants were detected. Second, we utilized the same pipeline in cohort 2 and analyzed with monogenic WGS panels, increasing the diagnostic yield to 8%. Next, cohort 3 was analyzed by both CMA and WGS. The WGS data was processed for large (> 10 kb) SVs genome-wide and for exonic SVs and SNVs in a panel of 887 genes linked to intellectual disability as well as genes matched to patient-specific Human Phenotype Ontology (HPO) phenotypes. This yielded a total of 25 pathogenic variants (SNVs or SVs), of which 12 were detected by CMA as well. We also applied short tandem repeat (STR) expansion detection and discovered one pathologic expansion in ATXN7. Finally, a case of Prader-Willi syndrome with uniparental disomy (UPD) was validated in the WGS data. Important positional information was obtained in all cohorts. Remarkably, 7% of the analyzed cases harbored complex structural variants, as exemplified by a ring chromosome and two duplications found to be an insertional translocation and part of a cryptic unbalanced translocation, respectively. CONCLUSION: The overall diagnostic rate of 27% was more than doubled compared to clinical microarray (12%). Using WGS, we detected a wide range of SVs with high accuracy. Since the WGS data also allowed for analysis of SNVs, UPD, and STRs, it represents a powerful comprehensive genetic test in a clinical diagnostic laboratory setting.

Standardised guidelines and reference networks for treating neuroinflammatory conditions in children are lacking.

AIM: To investigate whether local or national guidelines are used in treating neuroinflammatory conditions in children and if there is a perceived need for more guidelines and forums of cooperation. METHODS: A web-based questionnaire sent to all university hospitals in the Nordic countries (n = 21) between March and July 2015. RESULTS: All 21 centres replied to the survey. Markers of neuronal or glial damage and markers of inflammation were used at varying rates. Neuronal antibodies were used at all sites except two. Only three hospitals collaborated with their laboratories in developing new assays for biomarkers. Although most centres used some form of guideline for neuroinflammatory conditions, no single disease had a guideline prevalence over 60%. For some diagnoses, access to guidelines was as low as 10%. Standardised follow-up programs were lacking in 50-95%. A clear majority of the centres perceived a need for more guidelines. Also, forums of cooperation were few. However, there was a great interest in developing paediatric neuroinflammatory guidelines and to create platforms for further consensus work and discussion. CONCLUSION: There is a need for developing treatment guidelines within the field of paediatric neuroinflammation to aid in clinical decision-making, and to establish forums of cooperation.

[Acute flaccid myelitis amongst Swedish children with a possible link to an outbreak of enterovirus D68]. / Misstänkt koppling mellan enterovirus D68 och akut slapp myelit hos svenska barn - Ansamling av fall under några veckor hösten 2016.

Acute flaccid myelitis amongst Swedish children with a possible link to an outbreak of enterovirus D68 In september 2016 we had several cases of acute flaccid myelitis in our clinic. This coincided with an outbreak of enterovirus D68 (EV-D68) in Sweden during the same period. We describe three cases, of which one tested positive for EV-D68. Acute flaccid paralysis of one or more limbs preceded by an upper respiratory tract infection is highly suspicious of myelitis, and a viral cause must be included in the clinical work-up. In order to detect infection with EV-D68 in suspected acute flaccid myelitis, nasopharyngeal aspirate should be performed as early as possible. EV-D68 is normally not found in stool or cerebrospinal fluid tests but should be included in the clinical work-up. Treatment of acute flaccid myelitis is supportive only. There is no effective antiviral treatment and immunomodulating therapies show little effect. Persisting neurological deficits are common but lethal cases are rare.