'I was never broken-I just don't fit in this world.' A case report series of misdiagnosed women with higher functioning ASD.

BACKGROUND: Differentiating between autism spectrum disorders (ASD) and borderline personality disorder (BPD) is hampered by diagnostic difficulties as there seems to be a significant overlap in symptoms. METHODS: A case series of six women with ASD and a previous diagnosis of BPD is presented. RESULTS: In retrospect, the women did not present with significant symptoms until they had developed comorbidity, which clinicians in turn misinterpreted. The missed diagnosis or misdiagnosis had significant implications for their prognosis and current level of functioning. This suggests in line with previous research, that women with higher functioning ASD are more at risk of being overlooked. CONCLUSION: It is suggested in the literature and supported by this case series that ASD should be ruled out by obtaining a thorough developmental history by an experienced clinician before considering a BPD diagnosis.

Methylphenidate for children and adolescents with attention deficit hyperactivity disorder (ADHD).

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is one of the most commonly diagnosed and treated psychiatric disorders in childhood. Typically, children and adolescents with ADHD find it difficult to pay attention and they are hyperactive and impulsive. Methylphenidate is the psychostimulant most often prescribed, but the evidence on benefits and harms is uncertain. This is an update of our comprehensive systematic review on benefits and harms published in 2015. OBJECTIVES: To assess the beneficial and harmful effects of methylphenidate for children and adolescents with ADHD. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, three other databases and two trials registers up to March 2022. In addition, we checked reference lists and requested published and unpublished data from manufacturers of methylphenidate. SELECTION CRITERIA: We included all randomised clinical trials (RCTs) comparing methylphenidate versus placebo or no intervention in children and adolescents aged 18 years and younger with a diagnosis of ADHD. The search was not limited by publication year or language, but trial inclusion required that 75% or more of participants had a normal intellectual quotient (IQ > 70). We assessed two primary outcomes, ADHD symptoms and serious adverse events, and three secondary outcomes, adverse events considered non-serious, general behaviour, and quality of life. DATA COLLECTION AND ANALYSIS: Two review authors independently conducted data extraction and risk of bias assessment for each trial. Six review authors including two review authors from the original publication participated in the update in 2022. We used standard Cochrane methodological procedures. Data from parallel-group trials and first-period data from cross-over trials formed the basis of our primary analyses. We undertook separate analyses using end-of-last period data from cross-over trials. We used Trial Sequential Analyses (TSA) to control for type I (5%) and type II (20%) errors, and we assessed and downgraded evidence according to the GRADE approach. MAIN RESULTS: We included 212 trials (16,302 participants randomised); 55 parallel-group trials (8104 participants randomised), and 156 cross-over trials (8033 participants randomised) as well as one trial with a parallel phase (114 participants randomised) and a cross-over phase (165 participants randomised). The mean age of participants was 9.8 years ranging from 3 to 18 years (two trials from 3 to 21 years). The male-female ratio was 3:1. Most trials were carried out in high-income countries, and 86/212 included trials (41%) were funded or partly funded by the pharmaceutical industry. Methylphenidate treatment duration ranged from 1 to 425 days, with a mean duration of 28.8 days. Trials compared methylphenidate with placebo (200 trials) and with no intervention (12 trials). Only 165/212 trials included usable data on one or more outcomes from 14,271 participants. Of the 212 trials, we assessed 191 at high risk of bias and 21 at low risk of bias. If, however, deblinding of methylphenidate due to typical adverse events is considered, then all 212 trials were at high risk of bias. PRIMARY OUTCOMES: methylphenidate versus placebo or no intervention may improve teacher-rated ADHD symptoms (standardised mean difference (SMD) -0.74, 95% confidence interval (CI) -0.88 to -0.61; I² = 38%; 21 trials; 1728 participants; very low-certainty evidence). This corresponds to a mean difference (MD) of -10.58 (95% CI -12.58 to -8.72) on the ADHD Rating Scale (ADHD-RS; range 0 to 72 points). The minimal clinically relevant difference is considered to be a change of 6.6 points on the ADHD-RS. Methylphenidate may not affect serious adverse events (risk ratio (RR) 0.80, 95% CI 0.39 to 1.67; I² = 0%; 26 trials, 3673 participants; very low-certainty evidence). The TSA-adjusted intervention effect was RR 0.91 (CI 0.31 to 2.68). SECONDARY OUTCOMES: methylphenidate may cause more adverse events considered non-serious versus placebo or no intervention (RR 1.23, 95% CI 1.11 to 1.37; I² = 72%; 35 trials 5342 participants; very low-certainty evidence). The TSA-adjusted intervention effect was RR 1.22 (CI 1.08 to 1.43). Methylphenidate may improve teacher-rated general behaviour versus placebo (SMD -0.62, 95% CI -0.91 to -0.33; I² = 68%; 7 trials 792 participants; very low-certainty evidence), but may not affect quality of life (SMD 0.40, 95% CI -0.03 to 0.83; I² = 81%; 4 trials, 608 participants; very low-certainty evidence). AUTHORS' CONCLUSIONS: The majority of our conclusions from the 2015 version of this review still apply. Our updated meta-analyses suggest that methylphenidate versus placebo or no-intervention may improve teacher-rated ADHD symptoms and general behaviour in children and adolescents with ADHD. There may be no effects on serious adverse events and quality of life. Methylphenidate may be associated with an increased risk of adverse events considered non-serious, such as sleep problems and decreased appetite. However, the certainty of the evidence for all outcomes is very low and therefore the true magnitude of effects remain unclear. Due to the frequency of non-serious adverse events associated with methylphenidate, the blinding of participants and outcome assessors is particularly challenging. To accommodate this challenge, an active placebo should be sought and utilised. It may be difficult to find such a drug, but identifying a substance that could mimic the easily recognised adverse effects of methylphenidate would avert the unblinding that detrimentally affects current randomised trials. Future systematic reviews should investigate the subgroups of patients with ADHD that may benefit most and least from methylphenidate. This could be done with individual participant data to investigate predictors and modifiers like age, comorbidity, and ADHD subtypes.

Extreme pathological avoidance behaviour in children with autism.

Requests for pathological demand avoidance (PDA) diagnoses have increased over recent years. However, PDA remains controversial. It was first coined by Elisabeth Newson who hypothesised that PDA differed from autism in specific areas. This case report presents two boys from different families whose parents have suggested PDA as the core problem. But both boys were diagnosed with autism and when reviewing their history, it became clear that they had been subjected to great stress for years as they had not been supported sufficiently at school. PDA may be the resulting behaviour of this.

Extreme pathological avoidance behaviour in children with autism.

Requests for pathological demand avoidance (PDA) diagnoses have increased over recent years. However, PDA remains controversial. It was first coined by Elisabeth Newson who hypothesised that PDA differed from autism in specific areas. This case report presents two boys from different families whose parents have suggested PDA as the core problem. But both boys were diagnosed with autism and when reviewing their history, it became clear that they had been subjected to great stress for years as they had not been supported sufficiently at school. PDA may be the resulting behaviour of this.

[ADHD in adults is still overlooked].

It is well known that ADHD extends into adulthood, but if left untreated, has consequences in a range of areas. In this case report, a young man is described who, since childhood, has tried to draw attention to his problems with attention management. He smoked 60 cigarettes a day to deal with inner turmoil and restlessness. His medical history, interview with DIVA 2.0 and testing with CPT-3 point to significant problems in executive functions. Initiating medical treatment improves his level of function markedly. The clinician must uncover potential use of coping strategies when screening for ADHD.

Long-Term Comparison of 7 SARS-CoV-2 Antibody Assays in the North Zealand Covid-19 Cohort.

BACKGROUND: Throughout the coronavirus disease 2019 (Covid-19) pandemic numerous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody assays have been approved through Emergency Use Authorization and require further evaluation of sensitivity and specificity in clinical laboratory settings prior to implementation. METHODS: We included 1733 samples from 375 PCR-confirmed SARS-CoV-2-positive individuals of the North Zealand Covid-19 Cohort in an 8-month period. We investigated diagnostic sensitivity and specificity against consensus and PCR and interassay agreement over time for 5 SARS-CoV-2 immunoassays [Roche-nucleocapsid (NC)-total, Roche-receptor binding domain (RBD)-total, Siemens-RBD-IgG, Siemens-RBD-total, Thermo Fisher Scientific (TFS)-RBD-IgG] commercially available on automated platforms and 2 ELISA assays (TFS-RBD-total, Wantai-RBD-total). RESULTS: Early interassay discrepancy in up to 49% of samples decreased steadily during the first 18 days. By day 18, all assays had reached a plateau between 82.3% and 90.5% seropositivity compared to PCR. Assays ranked by closest agreement with the consensus model beyond day 18 (sensitivity/specificity against consensus) were as follows: Roche-RBD-total, 99.8%/100.0%; Wantai-RBD-total, 99.8%/99.7%; Roche-NC-total, 97.8%/100.0%; Siemens-RBD-total, 98.0%/98.7%; TFS-RBD-total, 96.9%/99.7%; TFS-RBD-IgG, 91.5%/100.0%; and Siemens-RBD-IgG, 94.6%/89.9%. We found that 7.8% of PCR-positive patients remained seronegative in all assays throughout the study. CONCLUSIONS: All included assays had sensitivities against consensus >90% past day 18. For the current recommended use of antibody assays to detect former, undocumented Covid-19, our data suggest the use of total antibody assays rather than IgG-specific assays due to higher long-term sensitivity. Finally, a nonresponding subpopulation of 7.8% in our cohort with persistent seronegative results raises concern of a possible substantial number of people with continued low protection following natural SARS-CoV-2 infection.

Remarkable high frequency of insecure attachment in children with ADHD persists in a three-year follow-up.

BACKGROUND: Studies have pointed to a complicated and mutual relationship between attention deficit hyperactivity disorder (ADHD) and attachment. In an observational follow-up study conducted in 2015 60 children from 7 years to 12 years recently diagnosed with ADHD were included and assessed according to attachment representation showing 85% of the children to be insecurely attached. AIM: The aim of this study was to investigate the stability of this remarkably high frequency of insecure attachment in the same cohort of children. METHODS: Children previously assessed using the child attachment interview (CAI) when diagnosed with ADHD were contacted three years later for a follow-up CAI assessment. RESULTS: At follow-up, 31 children participated in the CAI-interviews. Since their diagnosis with ADHD, the children had received treatment as usual. The CAI-interviews showed a continued high rate of insecure attachment with 90% of the children classifying as insecurely attached compared to expected 38% in the normal population. Of these, the majority of children (77%) were classified as dismissing. CONCLUSION: Our findings suggest that targeting ADHD-symptoms with our current treatment strategies does not in itself improve attachment security. Attachment security may in turn be a factor of importance when evaluating general functioning and prognosis.

Can attachment predict core and comorbid symptoms of attention-deficit/hyperactivity disorder beyond executive functions and emotion regulation?

OBJECTIVE: Previous findings propose an association between attachment and symptoms of attention-deficit/hyperactivity disorder (ADHD). However, the predictive ability of attachment beyond deficits in executive functioning (EF) and emotion regulation is understudied. METHOD: Using a dimensional perspective, we examined the longitudinal role of attachment on ADHD and comorbid symptoms, accounting for EF and emotion regulation. The sample consisted of 84 children (aged 8-13 years), oversampled for ADHD symptoms (42% had a diagnosis of ADHD). We assessed attachment with the Child Attachment Interview, EF with laboratory tests, and emotion regulation with parental ratings. Parents and teachers rated symptoms at baseline (T1) and at follow-up 2 years later (T2). RESULTS: Attachment insecurity was positively correlated with ADHD symptoms at T2 but with no unique contribution to symptoms beyond EF and emotion regulation. In contrast, poor EF and emotion regulation contributed to more ADHD and ODD/CD symptoms at T2. Poor emotion regulation contributed to more anxiety at T2. CONCLUSIONS: The results have important implications for understanding the mechanisms underpinning symptom expression in middle childhood/early adolescence and may guide the search for tailored interventions to reduce and prevent symptoms. PRACTITIONER POINTS: Executive functions and emotion regulation should be explored as targets for intervention in personalized treatment. The current results do not support attachment as a target for intervention at a group level, although this does not rule out that individuals/families with attachment difficulties may benefit from training programmes promoting secure attachment bonds.

Mothers of Children Diagnosed with ADHD: A Descriptive Study of Maternal Experience during the First Three Years of Treatment.

Background: Attention deficit hyperactivity disorder is the most common childhood psychiatric disorder. Current treatment strategies do not provide a convincing improvement on overall functioning, and further, reciprocity between ADHD and attachment has been suggested. This suggests that we do not fully comprehend the mechanisms of the disorder. This study was part of a larger project investigating factors of potential importance when a child is diagnosed with ADHD. Aim: In this current study we aimed to gain a clearer understanding about whether the mothers experienced the diagnostic process and treatment as helpful. Method: Sixty children newly diagnosed with ADHD and their mothers were included three years prior to this study. Fifty-two (87%) completed a survey about their experience with the diagnostic process and the years after in the psychiatric system and the secondary healthcare sector. Forty-three had also participated in an attachment interview in the original study and answered questions about this. Discussion: The follow-up questionnaire was based on conversations with the mothers was not meant to be used as a quantitative measure. However, one point to take is that the mothers did often not feel the help offered to be sufficient. In our opinion, this underlines that we are still far from understanding what ADHD is and what causes the differences in developmental trajectories as well as how differences in etiological factors may call for more customized approaches in treatment strategies.

Attachment and Epigenetics: A Scoping Review of Recent Research and Current Knowledge.

BACKGROUND: Epigenetic research has pointed to that the interaction between genetics and environmental factors may play a role in making some individuals more vulnerable than others. AIM: The aim of this article was to present a broad perspective on the current state of knowledge in a relatively new and complex field of "attachment and epigenetic processes." METHOD: We conducted a scoping review based on a systematic literature search in PsycINFO, PubMed, and Embase databases for relevant abstracts using the terms attachment and epigenet*. RESULTS: In total, 11 studies were included. Research predating 2009 and animal studies were excluded in order to review the current state of research in humans. CONCLUSION: Overall, there seems to be a consistency in the literature, pointing to a link between early childhood adversity, attachment processes, and epigenetic changes. However, research in human subjects is still limited.

Campylobacter jejuni Virulence Factors Identified by Modulating Their Synthesis on Ribosomes With Altered rRNA Methylation.

Campylobacter jejuni is a major cause of food poisoning worldwide, and remains the main infective agent in gastroenteritis and related intestinal disorders in Europe and the USA. As with all bacterial infections, the stages of adhesion to host tissue, survival in the host and eliciting disease all require the synthesis of proteinaceous virulence factors on the ribosomes of the pathogen. Here, we describe how C. jejuni virulence is attenuated by altering the methylation of its ribosomes to disrupt the composition of its proteome, and how this in turn provides a means of identifying factors that are essential for infection and pathogenesis. Specifically, inactivation of the C. jejuni Cj0588/TlyA methyltransferase prevents methylation of nucleotide C1920 in the 23S rRNA of its ribosomes and reduces the pathogen's ability to form biofilms, to attach, invade and survive in host cells, and to provoke the innate immune response. Mass spectrometric analyses of C. jejuni TlyA-minus strains revealed an array of subtle changes in the proteome composition. These included reduced amounts of the cytolethal distending toxin (CdtC) and the MlaEFD proteins connected with outer membrane vesicle (OMV) production. Inactivation of the cdtC and mlaEFD genes confirmed the importance of their encoded proteins in establishing infection. Collectively, the data identify a subset of genes required for the onset of human campylobacteriosis, and serve as a proof of principle for use of this approach in detecting proteins involved in bacterial pathogenesis.

Acute kidney injury in children with chronic kidney disease is associated with faster decline in kidney function.

BACKGROUND: This study aimed to investigate the association of acute kidney injury (AKI) with change in estimated glomerular filtration rate (eGFR) in children with advanced chronic kidney disease (CKD). METHODS: Single centre, retrospective longitudinal study including all prevalent children aged 1-18 years with nondialysis CKD stages 3-5. Variables associated with CKD were analysed for their potential effect on annualised eGFR change (ΔGFR/year) following multiple regression analysis. Composite end-point including 25% reduction in eGFR or progression to kidney replacement therapy was evaluated. RESULTS: Of 147 children, 116 had at least 1-year follow-up in a dedicated CKD clinic with mean age 7.3 ± 4.9 years with 91 (78.4%) and 77 (66.4%) with 2- and 3-year follow-up respectively. Mean eGFR at baseline was 29.8 ± 11.9 ml/min/1.73 m2 with 79 (68%) boys and 82 (71%) with congenital abnormalities of kidneys and urinary tract (CAKUT). Thirty-nine (33.6%) had at least one episode of AKI. Mean ΔGFR/year for all patients was - 1.08 ± 5.64 ml/min/1.73 m2 but reduced significantly from 2.03 ± 5.82 to - 3.99 ± 5.78 ml/min/1.73 m2 from youngest to oldest age tertiles (P < 0.001). There was a significant difference in primary kidney disease (PKD) (77% versus 59%, with CAKUT, P = 0.048) but no difference in AKI incidence (37% versus 31%, P = 0.85) between age tertiles. Multiple regression analysis identified age (ß = - 0.53, P < 0.001) and AKI (ß = - 3.2, P = 0.001) as independent predictors of ΔGFR/year. 48.7% versus 22.1% with and without AKI reached composite end-point (P = 0.01). CONCLUSIONS: We report AKI in established CKD as a predictor of accelerated kidney disease progression and highlight this as an additional modifiable risk factor to reduce progression of kidney dysfunction. Graphical abstract.

Mapping factors facilitating resilience in mothers - potential clinical relevance for children with ADHD.

Background: Attention Deficit Hyperactivity Disorder (ADHD) is one of the most common neurobiological disorders in childhood. Maternal resilience has been linked to treatment outcome in child ADHD. However, not much is known about factors that may facilitate maternal resilience.Aim: The aim of this study was to explore factors potentially facilitating resilience in mothers to children with ADHD.Method: The current study was part of a naturalistic observational study. 64 mothers to children diagnosed with ADHD completed a set of questionnaires and a short protocol including demographic and psychosocial items. Correlation matrix were estimated for each of the scores to establish the relationship between them.Results: We found significant negative correlations between maternal self-reported attachment style and self-reported resilience and between self-reported ADHD-symptoms and resilience-score.Conclusion: The findings indicate that selected factors in maternal functioning may contribute to development of resilience, which may in turn be a factor of importance in parenting.

Proteomic Changes of Klebsiella pneumoniae in Response to Colistin Treatment and crrB Mutation-Mediated Colistin Resistance.

Polymyxins are increasingly used as the critical last-resort therapeutic options for multidrug-resistant Gram-negative bacteria. Unfortunately, polymyxin resistance has increased gradually over the past few years. Although studies on polymyxin mechanisms are expanding, systemwide analyses of the underlying mechanism for polymyxin resistance and stress response are still lacking. To understand how Klebsiella pneumoniae adapts to colistin (polymyxin E) pressure, we carried out proteomic analysis of a K. pneumoniae strain cultured with different concentrations of colistin. Our results showed that the proteomic responses to colistin treatment in K. pneumoniae involve several pathways, including (i) gluconeogenesis and the tricarboxylic acid (TCA) cycle, (ii) arginine biosynthesis, (iii) porphyrin and chlorophyll metabolism, and (iv) enterobactin biosynthesis. Interestingly, decreased abundances of class A ß-lactamases, including TEM, SHV-11, and SHV-4, were observed in cells treated with colistin. Moreover, we present comprehensive proteome atlases of paired polymyxin-susceptible and -resistant K. pneumoniae strains. The polymyxin-resistant strain Ci, a mutant of K. pneumoniae ATCC BAA 2146, showed a missense mutation in crrB This crrB mutant, which displayed lipid A modification with 4-amino-4-deoxy-l-arabinose (l-Ara4N) and palmitoylation, showed striking increases in the expression of CrrAB, PmrAB, PhoPQ, ArnBCADT, and PagP. We hypothesize that crrB mutations induce elevated expression of the arnBCADTEF operon and pagP via PmrAB and PhoPQ. Moreover, the multidrug efflux pump KexD, which was induced by crrB mutation, also contributed to colistin resistance. Overall, our results demonstrated proteomic responses to colistin treatment and the mechanism of CrrB-mediated colistin resistance, which may offer valuable information on the management of polymyxin resistance.

Vitamin and trace element concentrations in infants and children with chronic kidney disease.

BACKGROUND: There are limited data regarding vitamin and trace element blood concentrations and supplementation needs in children with non-dialysis stages 3-5 of chronic kidney disease (CKD). METHODS: Retrospective cross-sectional review for nutritional blood concentrations measured over a recent 2-year period. In our CKD clinics, nutritional bloods including copper, zinc, selenium and vitamin A, vitamin E, active vitamin B12 and folate are monitored annually. Vitamin D status is monitored every 6-12 months. RESULTS: We reviewed 112 children (70 boys) with median (IQ1, IQ3) age 8.97 (4.24, 13.80) years. Estimated median (IQ1, IQ3) GFR (mL/min/1.73 m2) was 28 (21, 37). Vitamin A, active vitamin B12 and vitamin E concentrations were within normal range in 19%, 23% and 67% respectively, with all others being above normal range. Vitamin D blood concentrations were within desired range for 85% (15% had low levels) and folate blood concentrations were within normal range in 92%, with the remainder above or below target. For trace elements, 60%, 85% and 87% achieved normal ranges for zinc, selenium and copper respectively. Deficiencies were seen for zinc (35%), copper (7%), folate (3%) and selenium (1%), whilst 5%, 6% and 14% had zinc, copper and selenium levels above normal ranges. CONCLUSIONS: Several vitamin and trace element blood concentrations were outside normal reference ranges. Monitoring vitamin D and zinc blood concentrations is indicated due to the percentages with low levels in this group. Targeted vitamin and trace element supplementation should be considered where indicated rather than commencing multivitamin and/or mineral supplementation. Graphical abstract Vitamin and trace element concentrations in infants and children with non-dialysis chronic kidney disease.

Complement mediated Klebsiella pneumoniae capsule changes.

The Gram-negative bacterium Klebsiella pneumoniae is an opportunistic pathogen, which can cause life-threatening infections such as sepsis. Worldwide, emerging multidrug resistant K. pneumoniae infections are challenging to treat, hence leading to increased mortality. Therefore, understanding the interactions between K. pneumoniae and the immune system is important to develop new treatment options. We characterized ten clinical K. pneumoniae isolates obtained from blood of bacteremia patients. The interaction of the isolates with human serum was investigated to elucidate how K. pneumoniae escapes the host immune system, and how complement activation by K. pneumoniae changed the capsule structure. All K. pneumoniae isolates activated the alternative complement pathway despite serum resistance of seven isolates. One serum sensitive isolate activated two or all three pathways, and this isolate was lysed and had numerous membrane attack complexes in the outer membrane. However, we also found deposition of complement components in the capsule of serum resistant isolates resulting in morphological capsule changes and capsule shedding. These bacteria did not lyse, and no membrane attack complex was observed despite deposition of C5b-9 within the capsule, indicating that the capsule of serum resistant K. pneumoniae isolates is a defense mechanism against complement-mediated lysis.

Biographical disruption or cohesion?: How parents deal with their child's autism diagnosis.

Currently, we are witnessing a precipitous rise in autism diagnoses among children, and several bodies of sociological research are attempting to explain this development. However, the experiences within parental contexts have been inadequately examined; that is, how parents feel about and act upon the awareness of their child's autism diagnosis. Drawing upon a qualitative study among Danish parents of 20 children recently diagnosed with autism, this paper contributes with situated insights into parents' experiences. We identify a spectrum of feelings towards the autism diagnosis, including both relief and grief. In the absence of theoretical notions drawing attention to how a child's diagnosis influences parents' self-conceptions and understandings of their child, we develop the concept of 'parent-biographical disruption': the parents' rethinking of themselves and their child that might be caused by a chronic condition such as autism. Based on the variety of findings, we discuss what we call 'parent-biographical cohesion' as a counterpart to 'disruption'. By 'cohesion' we refer to the diagnostic awareness potentially creating clarification for parents about the past, present and future parenting of their child instead of disrupting their self-understandings as parents. In this way, through the notion of a parental-biographical spectrum of disruption and cohesion, we emphasize the diversity in how parents deal with a child's autism diagnosis and the variety of needs for rethinking parental biographies in the wake of a diagnosis.

[Alice in Wonderland-syndrome may be confused with anxiety].

This case report describes a seven-year-old girl with autism and nightly "anxiety" attacks. A diagnosis of Alice in Wonderland syndrome (AIWS) presumably associated to migraine was made, and the girl was successfully treated with lamotrigine. Effective treatment of the AIWS depends on correct diagnosis. Symptoms are bizarre and affect the senses of vision, sensation, touch and hearing, as well as one's own body image. AIWS is associated with epilepsy, migraine, certain infectious diseases and rarely cerebral tumours.

Inhibiting phosphatase SHIP-1 enhances suboptimal IgE-mediated activation of human blood basophils but inhibits IgE-mediated activation of cultured human mast cells.

IgE-mediated activation of basophil granulocytes and mast cells follows a bell-shaped dose-response curve. The decreased activation at supraoptimal allergen stimulation is thought to be associated with SH2-containing inositol-5'-phosphatase 1 (SHIP-1). SHIP-1 phosphorylation is inversely related to IgE-mediated releasability of basophils. This study sought to clarify the regulatory role of SHIP-1 in degranulation of basophil granulocytes and mast cells by selective inhibition of the phosphatase function of SHIP-1with 3-α-aminocholestane (3-α-AC). Six grass pollen allergic patients, six non-responder patients and six cultured human primary mast cell lines were included. The effect of 3-α-AC (1-60 µM, 30 min, 37 °C) was analyzed at individual suboptimal, optimal and supra-optimal allergen concentrations. The activity, upregulation of CD63, measured at different conditions was compared to evaluate the maximal effect of selective SHIP-1 inhibition. Basophils of five non-responder patients were treated with 3-α-AC (10 µM, 30 min, 37 °C). At high concentrations (>60 µM) of 3-α-AC, cells appeared to enter apoptosis. The median reactivity increased from 27.1% to 44.9% CD63+ basophils at 10 µM of 3-α-AC and suboptimal allergen stimulation (p = 0.0153). There was no effect on blood basophils of 3-α-AC at optimal or supra-optimal allergen concentrations. In contrast, treatment with more than 6 µM 3-α-AC significantly inhibited mast cell reactivity. 10 µM 3-α-AC reduced median reactivity from 32.85% to 16.5% CD63+ mast cells (p = 0.0465). Treatment with 3-α-AC did not increase response of basophils of non-responder patients. Modulating blood basophils with 3-α-AC enhanced reactivity only at suboptimal allergen concentration, and basophils from non-responders did not regain responsiveness to IgE stimulation. 3-α-AC inhibited the IgE response of mast cells in a dose dependent manner.