Hearing impairment in Estonia: An algorithm to investigate genetic causes in pediatric patients

PurposeThe present study was initiated to establish the etiological causes of early onset hearing loss (HL) among Estonian children between 2000–2009.MethodsThe study group consisted of 233 probands who were first tested with an arrayed primer extension assay, which covers 199 mutations in 7 genes (GJB2, GJB6, GJB3, SLC26A4, SLC26A5 genes, and two mitochondrial genes – 12S rRNA, tRNA^Ser(UCN)). From probands whose etiology of HL remained unknown, DNA analysis of congenital cytomegalovirus (CMV) infection and G-banded karyotype and/or chromosomal microarray analysis (CMA) were performed.ResultsIn 110 (47%) cases, the etiology of HL was genetic and in 5 (2%) congenital CMV infection was diagnosed. We found mutations with clinical significance in GJB2 (100 children, 43%) and in 2 mitochondrial genes (2 patients, 1%). A single mutation in SLC26A4 gene was detected in 5 probands (2.2%) and was considered diagnostic. In 4 probands a heterozygous IVS2-2A>G change in the SLC26A5 gene was found. We did not find any instances of homozygosity for this splice variant in the probands. CMA identified in 4 probands chromosomal regions with the loss of one allele. In 2 of them we were able to conclude that the found abnormalities are definitely pathogenic (12q13.3-q14.2 and 17q22-23.2 microdeletion), but the pathogenity of 2 other findings (3p26.2 and 1p33 microdeletion) remained unknown.ConclusionThis practical diagnostic algorithm confirmed the etiology of early onset HL for 115 Estonian patients (49%). This algorithm may be generalized to other populations for clinical application.     

Rheumatoid forefoot deformity: pathophysiology, evaluation and operative treatment options

Despite recent advances in pharmacological management of rheumatoid arthritis, forefoot deformity, with its symptoms, remains a common problem, often requiring operative treatment. Typical deformities in these patients comprise hallux valgus and deformity of the lesser metatarsophalangeal (MTP) joints and toes. With regard to the lesser rays the standard operative procedure, advocated for the disabling forefoot pain in these patients, remains metatarsal head resection. It should be considered that with increasing success of pharmacological treatment the degree of forefoot deformity in these patients is becoming less and that resection of the lesser MTP joints is becoming more and more superfluous. This supports a trend towards metatarsal head-preserving surgery. The optimal treatment of the hallux deformity remains unclear. Fusion of the first MTP joint is, generally, recommended. This article will discuss the current surgical options in rheumatoid forefoot pathology.     

Early conversion to below-elbow cast for non-reduced diaphyseal both-bone forearm fractures in children is safe: preliminary results of a multicentre randomised controlled trial

Introduction

This multicentre randomised controlled trial was designed to explore whether 6 weeks above-elbow cast (AEC) or 3 weeks AEC followed by 3 weeks below-elbow cast (BEC) cause similar limitation of pronation and supination in non-reduced diaphyseal both-bone forearm fractures in children.

Materials and methods

Children were randomly allocated to 6 weeks AEC or to 3 weeks AEC followed by 3 weeks BEC. The primary outcome was limitation of pronation and supination after 6 months. The secondary outcomes were re-displacement of the fracture, complication rate, limitation of flexion and extension of wrist and elbow, cast comfort, cosmetics, complaints in daily life and assessment of radiographs.

Results

A group of 23 children was treated with 6 weeks AEC and 24 children with 3 weeks AEC and 3 weeks BEC. The follow-up rate was 98 % with a mean follow-up of 7.0 months. The mean limitation of pronation and supination was 23.3 ± 22.0 for children treated with AEC and 18.0 ± 16.9 for children treated with AEC and BEC. The other study outcomes were similar in both groups.

Conclusions

Early conversion to BEC is safe in the treatment of non-reduced diaphyseal both-bone forearm fractures in children.

Level of evidence

Multicentre randomised controlled trial, Level II.     

Characteristics of differentiated CD8+ and CD4+ T cells present in the human brain

Immune surveillance of the central nervous system (CNS) by T cells is important to keep CNS-trophic viruses in a latent state, yet our knowledge of the characteristics of CNS-populating T cells is incomplete. We performed a comprehensive, multi-color flow-cytometric analysis of isolated T cells from paired corpus callosum (CC) and peripheral blood (PB) samples of 20 brain donors. Compared to PB, CC T cells, which were mostly located in the perivascular space and sporadically in the parenchyma, were enriched for cells expressing CD8. Both CD4⁺ and CD8⁺ T cells in the CC had a late-differentiated phenotype, as indicated by lack of expression of CD27 and CD28. The CC contained high numbers of T cells expressing chemokine receptor CX3CR1 and CXCR3 that allow for homing to inflamed endothelium and tissue, but hardly cells expressing the lymph node-homing receptor CCR7. Despite the late-differentiated phenotype, CC T cells had high expression of the IL-7 receptor α-chain CD127 and did not contain the neurotoxic cytolytic enzymes perforin, granzyme A, and granzyme B. We postulate that CNS T cells make up a population of tissue-adapted differentiated cells, which use CX3CR1 and CXCR3 to home into the perivascular space, use IL-7 for maintenance, and lack immediate cytolytic activity, thereby preventing immunopathology in response to low or non-specific stimuli. The presence of these cells in this tightly regulated environment likely enables a fast response to local threats. Our results will enable future detailed exploration of T-cell subsets in the brain involved in neurological diseases.     

4D-CT angiography differentiating arteriovenous fistula subtypes

Objective and methods

In the diagnostic work-up of patients suspected of a dural arteriovenous fistula (dAVF), imaging has a key role in order to diagnose the dAVF, assess its bleeding risk and choose optimal treatment strategy. Digital subtraction angiography (DSA) is the gold standard for the most detailed image of a dAVF. Nowadays four-dimensional CT angiography (4D-CTA) could possibly be an additional first-line tool in the work-up of a patient suspected of a dAVF. We describe three cases clinically suspected of a dAVF which had a diagnostic work-up with 4D-CTA as well as DSA. We evaluated the angioarchitecture of the dAVF both on 4D-CTA and DSA, with emphasis on the patterns of venous drainage as this is important in assessing the bleeding risk of a dAVF.

Results and conclusion

4D-CTA identified the dAVF, revealed its angioarchitecture and correctly differentiated different patterns of venous drainage (Borden type I, II and III) as confirmed on DSA. Although DSA has the advantage of higher spatial and temporal resolution, 4D-CTA seems to be a new useful non-invasive tool in the diagnostic work-up of a patient suspected of a dAVF.     

Measuring disabilities in stroke patients with apraxia: A validation study of an observational method

The objective of the present study was to determine the clinical and construct validity of the assessment of disabilities in stroke patients with apraxia. Disabilities were assessed by means of observation of activities of daily living (ADL), such as washing the face and upper body and putting on a blouse or shirt. The study was carried out at occupational therapy departments in general hospitals, rehabilitation centres, and nursing homes. Patients diagnosed to have had a stroke in the left hemisphere and to have apraxia participated in the study (n = 45, 21 males, 24 females age 39–91). Guidelines were offered for the ADL observations and the assessment of disabilities in these activities. Clinical validity was investigated by comparing the scores of the patients with those of a group of stroke patients without apraxia (n = 36, 14 males, 22 females age 35–88). Construct validity was examined by investigating relationships between several measures of interest: an apraxia test, a motor functioning test, a set of ADL observations, and the Barthel index as a general measure of disability. Comparison of the results of the patients with apraxia with the control group of stroke patients without apraxia showed that the clinical validity of the ADL observations is good: On the basis of the ADL observations, differences between patients with apraxia and patients without apraxia are measured. Correlation analyses of the group of patients with apraxia showed that the ADL observations were highly associated with apraxia, but only to a lesser degree with motor impairments; while motor impairments correlated strongly with the Barthel index (a general measure of physical disability), but only marginally with ADL observations. A LISREL analysis supported these findings. The results indicate that ADL observations have clinical validity and that the construct validity of the observational method is good. ADL observations appear to measure disability ties caused by apraxia in stroke patients.     

Pericardial Effusions in Adolescent Girls With Anorexia Nervosa: Clinical Course and Risk Factors

The aim of this study was to evaluate cardiac, biochemical and endocrine differences between female adolescents with anorexia nervosa (AN) with and without pericardial effusions. We studied 128 female adolescents (9.8–17.7 years) with anorexia nervosa (AN) diagnosed according to DSM-IV (American Psychiatric Association, 1994 American Psychiatric Association. 1994. Diagnostic and statistical manual of mental disorders, 4th, Washington, DC: Author.  [Google Scholar]) criteria. They all underwent an echocardiographic evaluation. In 29 patients (22.2 %) a pericardial effusion (ranging between ≥ 0.35–2.5 cm) was noted. None of the patients were clinically symptomatic. After 3 months of refeeding, the effusions disappeared in 18/29 patients while in 7/29 patients a pericardial effusion > 0.3 cm persisted. Risk factors for development of effusions were a BMI ≤ 13,5 kg/m², weight loss ≥ 25% and IGF-1-level ≤100 ng/ml. Pericardial effusions are common in adolescent AN patients. They are mostly asymptomatic not requiring any intervention and spontaneously regress with refeeding. They are more common in the patients with the most significant weight loss.