Mild Clinical Presentation Research Articles

Outbreaks of Invasive Kingella kingae Infections in Closed Communities

To describe the results of the epidemiologic investigation of outbreaks of invasive Kingella kingae infections among attendees at daycare facilities located in 4 closed communities in Israel. The preschool-aged population of communities with clusters of Kingella cases had oropharyngeal cultures performed. K kingae isolates from infected patients and healthy contacts were genotyped by pulsed field gel electrophoresis to determine the spread of outbreak strains. The affected closed communities (3 military bases and 1 "kibbutz" commune) were characterized by tight social and family networks and intensive mingling. The outbreaks affected 9 of 51 attendees (attack rate: 17.6%) age 8-19 months (median: 12 months), within a 21-day period. Cases included skeletal system infections (n = 8) and bacteremia (n = 1); K kingae isolates were confirmed by the use of blood culture vials and selective media. Clinical presentation was mild and acute-phase reactants were usually normal or only moderately elevated. Thirty out of 55 (54.5%) asymptomatic children carried the outbreak strains. Analysis of the 3 clusters in which the entire preschool-aged population was cultured revealed that 31 of 71 (43.7%) children younger than 24 months of age were colonized with K kingae organisms compared with 8 of 105 (7.6%) older children (P < .001). Clusters of invasive K kingae infections characterized by sudden onset, high attack rate, and wide dissemination of the outbreak strain can occur in daycare facilities and closed communities. Because the mild clinical presentation of invasive K kingae infections and the fastidious nature of the organism, a high index of suspicion and use of sensitive detection methods are recommended.

MG-102 Coffin-siris syndrome caused by a missense mutation in arid1a

Coffin-Siris syndrome (CSS; OMIM # 135900) is caused by mutations in genes encoding components of the BRMassociated factor (BAF) complex, also known as the mammalian SWItch/sucrose nonfermentable (mSWI/SNF)-like complex. Clinical features are variable and may include hypoplasia of the distal phalanx of the fifth digit, developmental delay, dysmorphic or coarse facial features, growth restriction, and malformations of the brain, heart, and other organs. No widely accepted diagnostic criteria yet exist. Mutations in the ARID1A gene account for approximately 13% of CSS cases with eight patients reported to date. 1 Here we describe a 20-month-old boy with clinical features consistent with CSS, including feeding difficulties, hypotonia, speech delay, CNS anomalies, hypoplastic 5th digits, thick lower lip vermillion, and hypertrichosis. Our patient was found to have a de novo missense mutation (p. Leu1713Pro) in a highly conserved amino acid residue located in one of the leucine-rich motifs of ARID1A . All reported mutations of ARID1A associated with CSS thus far have been truncating, and are believed to be mosaic in lymphocytes. ARID1A heterozygous knock out mice are embryonic lethal, suggesting a vital role in embryonic development. Notably, while mutations in ARID1A noted in cancer are typically nonsense or frameshift, missense mutations in this same leucine-rich motif have been reported. These findings suggest several possibilities including: 1. This mutation resides in a critical position key to the function of ARID1A in human development; 2. This effect may be mild or specific enough to be tolerated and not cause lethality; or 3. This mutation causes moderate instability of the protein leading to a milder clinical presentation. Studies are underway to determine the functional consequences of this missense mutation on ARID1A mRNA and protein production. Reference Kosho T, Okamoto N, Coffin-Siris Syndrome InternationalCollaborators. Genotype-phenotype correlation of Coffin-Siris syndrome causedby mutations in SMARCB1, SMARCA4, SMARCE1, and ARID1A. Am J Med Genet C Semin Med Genet . 2014; 166C (3):262–75

Increased fascial thickness of the deltoid muscle in dermatomyositis and polymyositis: An ultrasound study

We investigated the use of ultrasound to detect fascial thickening of the deltoid, vastus lateralis (VL), and rectus femoris (RF) muscles in dermatomyositis (DM) and polymyositis (PM). Fascial thickness of 7 DM and 5 PM patients was compared with that of healthy controls (n = 54). The deltoid fascial thickness was 2-fold greater in the DM/PM group (1.15 mm vs. 0.54 mm; P < 0.001) compared with healthy controls. Eight patients had markedly thickened deltoid fascia (>5 SD). Only 1 patient with a mild clinical presentation had normal deltoid fascial thickness. Four patients also had fascial thickening of the VL and/or RF. Deltoid fascial thickness was increased significantly in DM and PM patients, whereas the quadriceps muscle only showed thickened fascia in severely affected patients. This study suggests that a concomitant fasciitis may be present more often than previously believed.

Immediate and Long-Term Outcome of Acute H2S Intoxication Induced Coma in Unanesthetized Rats: Effects of Methylene Blue

BackgroundAcute hydrogen sulfide (H2S) poisoning produces a coma, the outcome of which ranges from full recovery to severe neurological deficits. The aim of our study was to 1- describe the immediate and long-term neurological effects following H2S-induced coma in un-anesthetized rats, and 2- determine the potential benefit of methylene blue (MB), a compound we previously found to counteract acute sulfide cardiac toxicity.MethodsNaHS was administered IP in un-sedated rats to produce a coma (n = 34). One minute into coma, the rats received MB (4 mg/kg IV) or saline. The surviving rats were followed clinically and assigned to Morris water maze (MWM) and open field testing then sacrificed at day 7.ResultsSixty percent of the non-treated comatose rats died by pulseless electrical activity. Nine percent recovered with neurological deficits requiring euthanasia, their brain examination revealed major neuronal necrosis of the superficial and middle layers of the cerebral cortex and the posterior thalamus, with variable necrosis of the caudate putamen, but no lesions of the hippocampus or the cerebellum, in contrast to the typical distribution of post-ischemic lesions. The remaining animals displayed, on average, a significantly less effective search strategy than the control rats (n = 21) during MWM testing. Meanwhile, 75% of rats that received MB survived and could perform the MWM test (P<0.05 vs non-treated animals). The treated animals displayed a significantly higher occurrence of spatial search than the non-treated animals. However, a similar proportion of cortical necrosis was observed in both groups, with a milder clinical presentation following MB.ConclusionIn conclusion, in rats surviving H2S induced coma, spatial search patterns were used less frequently than in control animals. A small percentage of rats presented necrotic neuronal lesions, which distribution differed from post-ischemic lesions. MB dramatically improved the immediate survival and spatial search strategy in the surviving rats.

Spectrum of mutations in Glutaryl-CoA dehydrogenase gene in glutaric aciduria type I – Study from South India

BackgroundGlutaric aciduria type I is an autosomal recessive organic acid disorder. The primary defect is the deficiency of Glutaryl-CoA dehydrogenase (EC number 1.3.99.7) enzyme that is involved in the catabolic pathways of the amino acids l-lysine, l-hydroxylysine, and l-tryptophan. It is a treatable neuro-metabolic disorder. Early diagnosis and treatment helps in preventing brain damage. MethodsThe Glutaryl-CoA dehydrogenase gene (GCDH) gene was sequenced to identify disease causing mutations by direct sequencing of all the exons in twelve patients who were biochemically confirmed with GA I. ResultsWe identified eleven mutations of which nine are homozygous mutations, one heterozygous and two synonymous mutations. Among the eleven mutations, four mutations p.Q162R, p.P286S, p.W225X in two families and p.V410M are novel. A milder clinical presentation is observed in those families who are either heterozygous or with a benign synonymous SNP. Multiple sequence alignment (MSA) of GCDH with its homologues revealed that the observed novel mutations are not tolerated by protein structure and function. ConclusionsThe present study indicates genetic heterogeneity in GCDH gene mutations among South Indian population. Genetic analysis is useful in prenatal diagnosis and prevention. Mutation analysis is a useful tool in the absence of non-availability of enzyme assay in GA I.

Genetic and functional study of StAR (steroidogenic acute regulatory protein) deficiency

Congenital lipoid adrenal hyperplasia (lipoid CAH) is the most severe form of CAH, impairing adrenal and gonadal steroidogenesis. Most cases of lipoid CAH are caused by recessive mutations in the gene encoding steroidogenic acute regulatory protein (StAR), a protein that plays an essential role in cholesterol transfer from the outer to inner mitochondrial membrane, thus providing the substrate for steroid hormone biosynthesis. Affected children typically present with life-threatening adrenal insufficiency in early infancy due to a failure of glucocorticoid (cortisol) and mineralocorticoid (aldosterone) biosynthesis, and 46,XY genetic males have complete lack of androgenization and appear phenotypically female due to impaired testicular androgen secretion in utero. Previously, the Q258X mutation of StAR was shown to account for about 70% of affected alleles in most patients of Japanese and Korean ancestry. However, it is more prevalent (92.3%) in the Korean population. These results suggest that the genetic defect in the StAR gene in Korean patients with lipoid CAH is highly homogeneous, probably reflecting a founder effect. Recently, some patients have been reported that they showed late and mild clinical presentation. These cases and studies establish a new entity of ‘non-classic lipoid CAH’ showing that the phenotypic spectrum of StAR mutations is substantially broader than previously appreciated.

Prospective evaluation of rhinovirus infection in healthy young children

BackgroundAlthough the incidence of human rhinovirus (HRV) infection is highest in young, no study has yet been published concerning the types of HRV circulating in this population, the incidence of symptomatic infections due to the different types, or duration of shedding ObjectivesThis prospective study evaluated the circulation of HRV species and types, and established the incidence of asymptomatic and symptomatic infections in young children. Study designThe study enrolled 93 healthy children aged <2 years, 88 of whom completed the follow-up of weekly household visits from November 2013 to February 2014. At each visit, a record was made of any signs and symptoms of acute infection, and a nasopharyngeal (NP) swab was taken in order to identify the HRVs by means of RT-polymerase chain reaction and to construct the phylogenetic tree of the HRV-positive cases. ResultsA total of 1408 NP samples were obtained and 326HRV infections were diagnosed (23.1%), leading to a mean number of 3.7±2.3 infections per child: HRV-A in 72 cases (22.1%), HRV-B in 29 (8.9%), HRV-C in 122 (37.4%), and non-typeable HRV in 103 (31.6%). Shedding was significantly longer for HRV-A (14 days) and HRV-B (14 days) than HRV-C (7 days; p=0.002 and p=0.012). Most of the HRV infections (209/326, 64.1%) remained asymptomatic and, when symptomatic, were of marginal clinical relevance. ConclusionsIn healthy young children, HRV infection is extremely frequent, generally asymptomatic or with a mild clinical presentation, and viral shedding is limited in time.

Massive catheter‐related thrombosis of vena cava superior protruding into the right atrium in a hemodialysis patient

A 36-year-old man with chronic renal insufficiency secondary to type 1 diabetes mellitus was on hemodialysis via central venous catheter (CVC), newly placed into the right subclavian vein after his arteriovenous fistula became dysfunctional. Seven days after CVC insertion, the patient developed fever and on day 11 echocardiography showed a large nearly occluding thrombus in the superior vena cava (SVC) extending into the right atrium (RA). Emergency surgical thrombectomy was successfully performed and an 11 cm long thrombus extending from the RA cranially into the SVC occupying majority of the vein's lumen was removed. Cultures from the thrombus and CVC were negative, but polymerase chain reaction was positive for Staphylococcus aureus. This particular case was interesting for a marked discrepancy between large SVC occluding thrombosis and a relatively mild clinical presentation with fever, and it highlights the importance of correct timing of echocardiography exam which might prevent potentially fatal consequences such as pulmonary embolism.

Rare case of primary orbital osteoma

We report a case of primary orbital osteoma originated from the sphenoid and notable for a mismatch between its giant size and mild clinical presentation. A lot of attention has been paid to the choice of surgical technique.

Increased concentration of interferon lambda-3, interferon beta and interleukin-10 in the cerebrospinal fluid of patients with tick-borne encephalitis

Tick-borne encephalitis (TBE) has a wide clinical spectrum, from asymptomatic to severe encephalitis, and host-dependent factors determining the outcome remain elusive. We have measured concentrations of pro-inflammatory/Th1 interferon-γ (IFNγ), immunomodulatory/Th2 interleukin-10 (IL-10), anti-viral type I (IFNβ) and type III (IFNλ3) interferons in cerebrospinal fluid (csf) and serum of 18 TBE patients, simultaneously genotyped for polymorphisms associated with the expression of genes IFNL3 (coding IFNλ3), IL10, CD209 and CCR5. IL-10, IFNβ and IFNλ3 were up-regulated in csf, with IFNλ3 level higher in patients with the milder clinical presentation (meningitis) than in meningoencephalitis. There was an increased serum IFNβ and a tendency for increased serum IL-10 in meningitis patients. Genotype in rs12979860 locus upstream of IFNL3 was associated with IFNλ3 expression and in rs287886 (CD209) – IL-10 expression. IL-10, IFNβ and IFNλ3 are expressed and play a protective role in TBE and their expression in TBE patients is associated with genetic polymorphisms.

Idiopathic aquaporin-4 antibody negative longitudinally extensive transverse myelitis

Background: Longitudinally extensive transverse myelitis (LETM) is a characteristic manifestation of neuromyelitis optica (NMO). However, not all patients with LETM are positive for aquaporin-4 (AQP4) antibodies. We evaluated the characteristics of idiopathic isolated LETM negative for AQP4 antibodies. Methods: From the National Cancer Center registry of inflammatory diseases of the central nervous system, patients with LETM as an initial manifestation and follow-up for at least two years were enrolled. Their medical records and MRIs were reviewed retrospectively. AQP4 antibody was confirmed by three different validated methods at least three times. Cerebrospinal fluid (CSF) glial fibrillary acidic protein (GFAP) levels were measured to investigate astrocyte damage. Results: Among 108 patients with first-ever LETM, 55 were positive for AQP4 antibodies (P-LETM) and 53 were consistently negative. Of them, seven were later diagnosed with seronegative NMO, and four were positive for MOG antibodies. The remaining 42 patients (N-LETM) showed several features distinct from P-LETM: male predominance, older age of onset, milder clinical presentation, spinal cord confinement and absence of combined autoimmunity. CSF GFAP levels were not increased in N-LETM but were markedly elevated in P-LETM. Conclusions: Idiopathic isolated N-LETM is not that rare among first-ever LETM, and has many features distinct from P-LETM where astrocytic damage is evident.

PO-0214 Complicated Kingella Kingae Osteoarthritis

Introduction Kingella kingae is increasingly being recognised as a common aetiology of osteoarticular infections, especially in younger children. Infections are usually mild with a favourable outcome. However, unusually complicated cases have been rarely reported. Case Report Three children with complicated K. kingae osteoarticular infection were identified. The age varied between 2 to 3 years-old and the diagnostic delay was 12 ± 6 days. All had lower limb claudication, low grade fever and normal-to-mild elevated acute-phase reactants. Radiologic exams showed unifocal bone lytic lesions compatible with abscess (astragalus, calcaneus and external malleolus). Cultures of bone exudate or joint fluid identified Kingella kingae . Osseous lytic lesions were drained in all cases and joint fluid was aspirated in one. Antibiotherapy with cephalosporins or amoxicillin-clavulanate was done: intravenous for 8 ± 2 days, followed by oral treatment for 26 ± 5 days (total duration 34 ± 6 days). There was complete clinical recovery at 3 month, with disappearance of the osteolytic lesions in two patients. Conclusions In these cases several characteristics of Kingella kingae infections are identified, as young age, mild clinical presentation, normal-to-mild elevated inflammatory markers, single focus and favourable response to antibiotics. Although K. kingae bone lytic lesions are rarely identified they could led to important sequels and should be vigorously treated.

Can intensive exercise harm the heart? You can get too much of a good thing.

Can intensive exercise harm the heart? You can get too much of a good thing.

G.P.77: The Lymphoid Follicle Variant of juvenile dermatomyositis

Juvenile dermatomyositis (jDM) is an inflammatory disease that affects small vessels of the muscle, the skin, and other organs, which may lead to severe systemic disease. Muscle biopsy can help to secure a firm diagnosis and thus serve as an important adjunct to atypical clinical presentation. As previously suggested, ectopic lymphoid follicle-like structures (LFLS) in inflamed muscle could indicate a severe course of disease. Histological evaluation of frozen muscle samples was employed to visualize the cellular organisation of ectopic lymphoid structures in muscle biopsies obtained from 2 patients diagnosed with juvenile dermatomyositis (jDM). Clinical presentation, morphological features, as well as treatment and follow-up were assessed and documented. Electron microscopy was used to confirm the light microscopic diagnosis of jDM. Clonality analysis of B-cell populations using polymerase chain reaction (PCR) was performed. Muscle biopsy of both patients fulfilled the morphological ENMC criteria of DM. Analyses of muscle biopsy samples revealed LFLS that showed a remarkable similarity to secondary lymphoid organs (SLOs) with distinct T- and B-cell compartmentalization. In contrast to previous reports our two patients exhibited a mild clinical presentation and responded favourably to therapy. Together, our data suggest that the clinical spectrum of jDM appears to be more diverse than so far documented, and that the presence of SLOs is not inevitably linked to unfavourable prognosis.

Adult-onset vanishing white matter disease as differential diagnosis of primary progressive multiple sclerosis: A case report

We report the case of a 42-year-old woman with a slowly progressive cerebellar syndrome. In contrast to a relatively mild clinical presentation, the magnetic resonance imaging (MRI) showed extensive leukencephalopathy with cystic degeneration. Initially primary progressive multiple sclerosis (PPMS) was suspected. Additional diffusion-weighted imaging revealed restricted diffusion in the white matter lesions with a reduced apparent diffusion coefficient. Genetic testing showed vanishing white matter disease (VWM) with c.260C>T EIF2B3 mutation. In conclusion, in cases with relatively mild symptoms and extensive white matter lesions, adult-onset VWM should be considered as differential diagnosis of PPMS and diffusion-weighted imaging may be helpful to identify suspected cases.

The lymphoid follicle variant of dermatomyositis.

Objective:To investigate the clinical and morphologic spectrum of early adult–onset dermatomyositis (DM), an inflammatory disease that affects small vessels of the muscle and the skin.Methods:Histologic evaluation of frozen muscle samples was employed to visualize the cellular organization of ectopic lymphoid structures in muscle biopsies obtained from 2 patients diagnosed with DM. Clinical presentation and morphologic features, as well as treatment and follow-up, were assessed and documented. Electron microscopy was used to confirm the light microscopic diagnosis of DM. Clonality analysis of B-cell populations using PCR was performed.Results:Muscle biopsy of both patients fulfilled the morphologic European Neuromuscular Centre criteria of DM. Analyses of muscle biopsy samples revealed ectopic lymphoid follicle-like structures that showed a remarkable similarity to secondary lymphoid organs (SLOs) with distinct T- and B-cell compartmentalization. Our 2 patients exhibited an atypical and mild clinical presentation and responded favorably to therapy.Conclusions:The clinical and histopathologic features of DM can be atypical, and the presence of SLOs is not inevitably linked to an unfavorable prognosis.

Identification of Two Novel BCKDHB Mutations in Korean Siblings with Maple Syrup Urine Disease Showing Mild Clinical Presentation

defect in branched-chain α -keto acid dehydrogenase complex. Mutations have been identified in the BCKDHA, BCKDHB, or DBT genes, which encode different subunits of the BCKDH complex. Although encephalopathy and progressive neurodegeneration are its major manifestations, the severity of the disease may range from the severe classic type to milder intermediate variants. We report two Korean siblings with the milder intermediate MSUD who were diagnosed with MSUD by a combination of newborn screening tests using tandem mass spectrometry and family genetic screening for MSUD. At diagnosis, the patients’ plasma levels were elevated for leucine, isoleucine, valine, and alloisoleucine, and branched-chain α -keto acids and branched-chain α -hydroxy acids were detected in their urine. BCKDHA, BCKDHB, and DBT analysis was performed, and two novel mutations were identified in BCKDHB. Our patients were thought to have the milder intermediate variant of MSUD, rather than the classic form. Although MSUD is a typical metabolic disease with poor prognosis, better outcomes can be expected if early diagnosis and prompt management are provided, particularly for milder forms of the disease.

Clinical presentation of dengue by serotype and year of epidemic in Martinique.

During the last decade Martinique experienced four dengue epidemics, each characterized by the predominance of 1 or 2 serotypes. In this retrospective database analysis, we investigated the relationship between dengue serotype and disease severity. Data on dengue were collected from 715 patients (male/female ratio 0.87), 14 to 91 years of age (median 35 years) examined in the adult emergency department between 2005 and 2010. In this series, DENV-4 infections more frequently had a milder clinical presentation. The DENV-2 infections were most often secondary infections admitted at the critical phase of dengue illness with signs of plasma leakage. The DENV-1 infections were disabling, particularly in females, and most often led to disease of intermediate severity, without overt plasma leakage. These data were consistent with there being differences in virulence between serotypes, regardless of the host's immune status. However, secondary DENV-2 infections showed an increased risk of plasma leakage.

39. Electrophysiological diagnosis of early cns involvement in HIV-1 infection – Pilot study

Introduction The aim of our study was to verify the possibility of early identification of HIV-related neural injury using visual evoked potentials (VEPs) in neurologically asymptomatic HIV seropositives. In the CART (combination antiretroviral therapy) era, the prevalence of neurocognitive impairment remains high, up to 50%, and HIV-associated neurocognitive disorder (HAND) has shifted towards a milder clinical presentation. Such a mild clinical presentation can escape detection [1]. Methods The examination consisted of the Montreal Cognitive Assessment (MoCA) [2], and VEPs to pattern-reversal, motion-onset stimulation (radial movement), and of visual ERPs recorded during an odd-ball test (http://www.lfhk.cuni.cz/elf). Subjects: 9 homosexual men and 3 heterosexually infected women were examined in this study. All patients had ⩾350×106 CD4 cells/l blood at inclusion. The duration of the HIV infection was 0.5 – 7years, and mean age of the patients was 35 (24–50) years. Results P100 potential was recorded with no alteration in the VEP amplitude or latency. However, in 5 patients with CD4 counts 350–750×106cells/l, there was prolonged latency of the N160 peak compared to the reference values obtained in our laboratory, which suggests a dysfunction of the motion-processing (magnocellular system or the dorsal cortical stream) [3]. P300 latencies and MoCA results were within the normal range in all HIV patients. Conclusions Our data suggest that motion-onset VEPs may be a sensitive measure of subclinical visual pathway dysfunction in early HIV-1 infection, however, we did not reveal any cognitive decline in this pilot group. Subsequently, the patients will be investigated using VEPs and visual ERPs at six-month intervals to evaluate the long-term development of the visual pathway involvement in HIV patients.

Ischemic enterocolitis and its differential diagnosis.

Ischemia is a common type of gastrointestinal injury that can be clinically misdiagnosed due to its often mild and transient clinical presentation as well as a tendency to masquerade as other disorders. A wide range of etiologies can contribute to the development of ischemia. These include hypovolemic states, systemic diseases such as vasculitis and hypercoagulable states, mechanical obstruction, therapeutic drug effects, infection, and a host of other diseases. An accurate diagnosis of ischemia relies on a strong clinical suspicion in combination with endoscopic and pathologic findings. Most cases show histologic features that are diagnostic of ischemia, but do not point to a specific differential diagnosis, whereas the cause of ischemia can be recognized or suspected based on careful review of vascular changes in others. This review is focused on providing an overview of ischemic enterocolitis and its differential diagnosis.