Misdiagnosis of functional neurological symptom disorders in paediatrics: Narrative review and relevant case report.

Functional neurological symptom disorders (FNSD) pose a common challenge in clinical practice, particularly in pediatric cases where the clinical phenotypes can be intricate and easily confused with structural disturbances. The frequent coexistence of FNSDs with other medical disorders often results in misdiagnosis. In this review, we highlight the distinctions between FNSD and various psychiatric and neurological conditions. Contrary to the misconception that FNSD is a diagnosis of exclusion, we underscore its nature as a diagnosis of inclusion, contingent upon recognizing specific clinical features. However, our focus is on a critical learning point illustrated by the case of a 14-year-old male initially diagnosed with FNSD, but subsequently found to have a rare primary monogenic movement disorder (paroxysmal kinesigenic dyskinesia, PKD). The crucial takeaway from this case is the importance of avoiding an FNSD diagnosis based solely on psychiatric comorbidity and suppressible symptoms. Instead, clinicians should diligently assess for specific features indicative of FNSD, which were absent in this case. This emphasizes the importance of making a diagnosis of inclusion. Extended follow-up and clinical-oriented genetic testing might help identify comorbidities, prevent misdiagnosis, and guide interventions in complex cases, which cannot be simply classified as "functional" solely because other conditions can be excluded.

Understanding and Avoiding Mistakes in Diagnosing Children with Functional Neurological Symptom Disorders: A Review and Case Report: This article discusses Functional Neurological Symptom Disorders (FNSDs), focusing on misdiagnosis, differential diagnosis, and other diagnostic challenges, particularly in pediatric cases. FNSDs involve motor or sensory symptoms that are inconsistent over time and unexplained by neurological disease, often associated with psychosocial factors. The article highlights the complexity of distinguishing FNSDs from other neurological and psychiatric conditions, emphasizing the importance of careful evaluation. The authors review various conditions that can mimic FNSDs, such as epileptic seizures, syncope, and different motor disorders. They emphasize the need to consider psychiatric conditions in the differential diagnosis, including factitious disorders, and malingering. The article presents a case study of a 14-year-old with involuntary movements, initially diagnosed as having a Functional Movement Disorder. After careful evaluation, the patient was diagnosed with a genetic dystonia (PRRT2 mutation). The case shows the importance of not rely solely on psychological problems, bizarre presentations or suppressible symptoms when diagnosing FNSDs.

Biallelic variants in GTPBP3: New patients, phenotypic spectrum, and outcome.

INTRODUCTION: COXPD23 is a rare mitochondrial disease caused by biallelic pathogenic variants in GTPBP3. We report on two siblings with a mild phenotype. CASE REPORTS: The young boy presented with global developmental delay, ataxic gait and upper limbs tremor, and the older sister with absence seizures and hypertrophic cardiomyopathy. Respiratory chain impairment was confirmed in muscle. DISCUSSION: Reviewed cases point toward clustering around two prevalent phenotypes: an early-onset presentation with severe fatal encephalopathy and a late milder presentation with global developmental delay/ID and cardiopathy, with the latter as, is the main feature. Our patients showed an intermediate phenotype with intrafamilial variability.

Perfectionistic Children and Their Parents: Is There Room for an Intergenerational Transmission? A Study of a Clinical Sample of Italian Children and Their Parents.

INTRODUCTION: The relationship between maladaptive perfectionism and Internalizing (ID) and Externalizing Disorders (ED) in children needs to be better understood, along with the intergenerational transmission of these traits from parents to children. The present work aimed to share light on both these issues. METHOD: 39 children with ID, 19 with ED, and their parents were recruited*. The Multidimensional Perfectionism Scale, the Big Five Inventory, the Child and Adolescent Perfectionism Scale, and the Hierarchical Personality Inventory for Children were used. The association between parent personality and perfectionism traits and children's perfectionism dimensions was evaluated through hierarchical regression analysis. RESULTS: ID and ED groups did not differ significantly concerning perfectionism. Fathers presented higher scores than mothers in Self-Oriented Perfectionism, Other-Oriented Perfectionism, and Socially-Prescribed Perfectionism. Parents of children with ID report higher levels of Obedience in their children, while parents of children with ED reported higher levels of Creativity and Perseverance. Significant associations were found between perfectionism in parents and their children, as well as between perfectionism and the personality of children. CONCLUSION: Results suggest a transdiagnostic nature of Perfectionism and support the transgenerational transmission of the personality traits investigated.

Validation of the Concise Assessment Scale for Children's Handwriting (BHK) in an Italian Population.

Handwriting difficulties represent a common complaint among children and may cause a significant delay in motor skills achievement. The Concise Assessment Scale for Children's Handwriting (BHK) assesses handwriting skill in clinical and experimental settings, providing a quick evaluation of handwriting quality and speed through a copying text. The aim of the present study was to validate the Italian adaptation of the BHK in a representative primary school population. Overall, 562 children aged 7-11 from 16 public primary schools of Rome were included and asked to copy a text in 5 min using cursive handwriting. Handwriting quality and copying speed were measured. The included population followed a normal distribution for the BHK quality scores. Sex influenced the total quality scores, whereas school level influenced the copying speed. The BHK quality score was higher in girls (p < 0.05) and resulted as a stable parameter along the school years, without significant variations with regard to the years spent in handwriting exercise (p = 0.76). The handwriting speed was influenced by school level, and significant differences were found for each of the grades from the second to the fifth (p < 0.05), but not for gender (p = 0.47). Both BHK measures represent a helpful tool for the characterization and assessment of children with handwriting difficulties. The present study confirms that sex influences total BHK quality score, while school level influences handwriting speed.

Validation of the Italian version of the clinician affective reactivity index (CL-ARI).

INTRODUCTION: Irritability represents a transdiagnostic symptom in youths, which can become a predictor of long-term psychosocial adversity. Yet, few tools investigate this symptom in childhood. The aim of this study was to evaluate the psychometric properties of the CL-ARI in an Italian population, analyzing the correlations between irritability and other pathological constructs. MATERIALS AND METHODS: A cross-sectional study was carried out in a Child Neuropsychiatry Unit in Rome. A transdiagnostic sample of 67 youths aged 7-17 years, which underwent to a psychodiagnostic evaluation, was administered by a clinician with the translated version of the CL-ARI, along with tools exploring irritability and other constructs (depressive symptoms, anxiety, global impairment in functioning). RESULTS: The most frequent diagnosis obtained by the psychodiagnostic evaluation was anxiety disorder, followed by disruptive mood dysregulation disorder (DMDD) and no diagnosis. Cronbach's alpha values revealed good internal consistency for the total score (0.86), as well as for the score of each subscale of the tool (0.81 for temper outbursts, 0.89 for irritable mood, 0.71 for impairment). Test-retest reliability showed excellent values (ICC 0.89 to 0.98), and criterion validity exhibited good correlation among the sub-scales and between each sub-scale and the total score. Finally, positive correlations were found between total scores of the parent and the child interview, and between the CL-ARI, the measure of DMDD severity (CGI) and of depressive symptoms (CDI 2). CONCLUSIONS: These data confirmed that the CL-ARI is a promising tool designed to intercept irritability, with good psychometric properties. Further research on the assessment of irritability is critical and thus encouraged.

A Narrative Review about Prosocial and Antisocial Behavior in Childhood: The Relationship with Shame and Moral Development.

We conducted a literature review aimed at identifying the origins of shame as well as its effects on moral development, especially in terms of behavioral outcomes, and we reflected on the practical implications of our findings. We explored the role of shame in moral development through cultural differences and parental influences, collecting evidence of psychopathological consequences of primary moral emotion dysregulation. These studies showed a dichotomous feature of shame, as a prosocial behavior enhancer in morally relevant situations and, simultaneously, a risk factor for aggressive and antisocial behaviors on other occasions. Dysregulated shame leads to maladaptive interpersonal behaviors, which could evolve towards psychopathological paths. Therefore, an integrated intervention is recommended in children with emotional/behavioral problems.

Safety and Efficacy of Monoclonal Antibodies for Alzheimer's Disease: A Systematic Review and Meta-Analysis of Published and Unpublished Clinical Trials.

BACKGROUND: Monoclonal antibodies (mAbs) are currently among the most investigated targets for potential disease-modifying therapies in Alzheimer's disease (AD). OBJECTIVE: Our objectives were to identify all registered trials investigating mAbs in MCI due to AD or AD at any stage, retrieve available published and unpublished data from all registered trials, and analyze data on safety and efficacy outcomes. METHODS: A systematic search of all registered trials on ClinicalTrials.gov and EUCT was performed. Available results were searched on both platforms and on PubMed, ISI Web of Knowledge, and The Cochrane Library. RESULTS: Overall, 101 studies were identified on 27 mAbs. Results were available for 50 trials investigating 12 mAbs. For 18 trials, data were available from both published and unpublished sources, for 21 trials only from published sources, and for 11 trials only from unpublished sources. Meta-analyses of amyloid-related imaging abnormalities (ARIA) events showed overall risk ratios of 10.65 for ARIA-E and of 1.75 for ARIA-H. The meta-analysis of PET-SUVR showed an overall significant effect of mAbs in reducing amyloid (SMD -0.88), but when considering clinical efficacy, data on CDR-SB showed that treated patients had a statistically significant but clinically non-relevant lower worsening (MD -0.15). CONCLUSION: Our results suggest that the risk-benefit profile of mAbs remains unclear. Research should focus on clarifying the effect of amyloid on cognitive decline, providing data on treatment response rate, and accounting for minimal clinically important difference. Research on mAbs should also investigate the possible long-term impact of ARIA events, including potential factors predicting their onset.

The issue of dementia in migrants and ethnic minorities: the perspective of National Dementia Plans.

BACKGROUND: The occurrence of dementia among individuals with a migration background and composing ethnic minorities is being recognized as a global public health issue. AIMS: In the present study, we sought to explore if and how this phenomenon is mentioned and addressed by the existing National Dementia Plans (NDPs). METHODS: The 32 NDPs listed on the Alzheimer's Disease International (ADI)'s website were considered for the present analysis. First, the plans mentioning the issue of dementia among migrants and/or ethnic minorities were identified. Subsequently, the sections addressing this topic and the pertaining proposed actions were analyzed and their contents were unbundled in descriptive categories. RESULTS: Overall, nine NDPs (28.1% of the total), namely those promulgated by Australia, Austria, England, Israel, Norway, Switzerland, Taiwan, United States, and Wales, mentioned the issue of dementia among migrants and/or ethnic minorities and only eight proposed targeted actions to tackle this issue. With few exceptions, the proposed strategies were only marginally dashed within NDPs and crucial information on their objectives, timeline, conduction, and monitoring was missing. DISCUSSION AND CONCLUSIONS: To our knowledge, this is the first attempt to describe and discuss how the issue of dementia among migrants and ethnic minority groups is addressed within NDPs. The issue of dementia in migrants and ethnic minorities is assuming a growing relevance under a of global health perspective. The timely identification and implementation of dedicated policies at the national and international level are fundamental to limit its future clinical and socioeconomic burden.

A systematic review on the epidemiology of normal pressure hydrocephalus.

BACKGROUND: The aim of this systematic review is to gather all available studies reporting prevalence and incidence rates of iNPH and to assess their methodological quality and consistency. METHODS: All available studies published up to June 2019 were retrieved searching the databases PubMed, ISI Web of Science, and the Cochrane Database of Systematic Reviews. All included studies were qualitatively assessed by two independent reviewers using the MORE Checklist for Observational Studies of Incidence and Prevalence. KEY RESULTS: Bibliographic searches and other sources yielded 659 records. A total of 28 studies were selected and applied the predefined inclusion and exclusion criteria. Fourteen studies were further excluded, and 14 studies (10 on prevalence and 6 on incidence) were included in the qualitative analysis. Results from the prevalence studies reported crude overall rates ranging from 10/100 000 to 22/100 000 for probable iNPH and 29/100 000 for possible iNPH, and age-specific rates ranging from 3.3/100 000 in people aged 50-59 to 5.9% in people aged ≥ 80 years. Results from incidence studies reported overall crude rates ranging from 1.8/100 000 to 7.3/100 000 per year, and age-specific rates ranging from 0.07/100 000/year in people aged < 60 years to 1.2/1000/year in people aged ≥ 70 years. CONCLUSIONS & INFERENCES: The high methodological and clinical heterogeneity of included studies does not allow drawing adequate conclusions on the epidemiology of iNPH. Further, high-quality, population-based studies should be carried out to allow for a better understanding of the epidemiology of this condition. Moreover, the implementation in current clinical practice of guidelines on the diagnosis and management of iNPH should also be endorsed.

Integrated care pathways on dementia in Italy: a survey testing the compliance with a national guidance.

Dementias are chronic, degenerative neurological disorders with a complex management that require the cooperation of different healthcare professionals. The Italian Ministry of Health produced the document "Guidance on Integrated Care pathway for People with Dementia" (GICPD) with the specific objective of providing a standardized framework for the definition, development, and implementation of integrated care pathways (ICP) dedicated to people with dementia. We searched all available Italian territorial ICPs. Two raters assessed the retrieved ICPs with a 2-point scale on a 43-item checklist based on the GICPD. Only 5 out of 21 regions and 5 out of 101 local health authorities had an ICP, with most ICPs having a moderate compliance to the GICPD, in particular for the items referring to the development and implementation of the care pathways. A low to moderate inter-rater agreement was observed, mainly due to a lack of standardized models to describe ICPs for dementias. Results suggest that policy- and decision-makers should pay more attention to the GICPD when producing ICPs. The direct communication with clinicians, and the implementation of more precise and appropriate clinical outcomes, could increase the involvement of clinicians, whose participation is crucial to guarantee that ICPs meet needs of patients and their carers.

Mild Cognitive Impairment in the Migrant Population Living in Europe: An Epidemiological Estimation of the Phenomenon.

BACKGROUND: The construct of mild cognitive impairment (MCI) is triggering growing clinical and research interest. The detection of MCI may be affected by diverse ethno-cultural determinants possibly influencing the personal and social perception of the individual cognitive functioning as well as the reliability of objective cognitive assessment. These challenges may acquire special relevance in subjects with a migration background and composing ethnic minority groups. OBJECTIVE: The present study is aimed at providing an estimate of the number of MCI cases occurring in the migrant population living in the extended European Union (EU) in 2018. METHODS: The number of MCI cases in older migrants living in Europe and in each of the 32 considered countries was estimated by multiplying the number of migrants, provided by Eurostat, with the age-specific prevalence rates, derived by the harmonized data produced by the COSMIC collaboration and based on different operational definitions of MCI. RESULTS: Nearly 686,000 cases of MCI were estimated in the extended EU by applying age-specific prevalence rates based on the International Working Group criteria. Higher figures were obtained when the Clinical Dementia Rating- and the Mini Mental State Examination-based criteria were applied. The proportion of MCI cases in migrant subjects ranged from 1.1% (Romania) to 54.1% (Liechtenstein) (median: 8.4%; IQR: 4.7%-14.2%). CONCLUSIONS: MCI represents and will increasingly constitute a relevant issue in the migrant population living in Europe. The present data reinforce the need of developing approaches and models of care that may be diversity-sensitive and inclusive for a culturally variegated population.

Race reporting and disparities in clinical trials on Alzheimer's disease: A systematic review.

INTRODUCTION: Race is an important health determinant and should adequately be considered in research and drug development protocols targeting Alzheimer's disease (AD). METHODS: A systematic review of available randomized controlled trials (RCTs) on the currently marketed treatments for AD was conducted with the aim of 1) documenting the reporting of race, and 2) exploring the impact of race on the efficacy and safety/tolerability of the considered medications. RESULTS: Overall, 59.2% of the 49 retained RCTs reported information concerning the race of participants. Only a striking minority of enrolled patients was constituted of blacks and Hispanics. None on the retained studies reported results on the efficacy and safety/tolerability of the tested treatment separately for racial groups nor performed sensitivity analyses accounting for the race of participants. DISCUSSION: Race has insufficiently been reported in previous interventional studies on AD. Its potential association with the effectiveness and safety/tolerability of the tested medications has completely been neglected.

Migrants seeking help for cognitive disturbances: exploratory data from an Italian memory clinic.

INTRODUCTION: The phenomenon of dementia occurring in migrants and minority groups constitutes an emerging issue for Western countries. Nevertheless, it has been poorly explored from the perspective of "real-world" clinical services. We aimed to quantify the number of migrants from LMIC attending an Italian university memory clinic and to document its modifications over time. METHODS: All the subjects undergoing a first neurological and cognitive assessment between 2001 and 2017 were considered for the present analyses. RESULTS: The proportion of subjects from LMIC performing a first cognitive evaluation was found to remain substantially stable between 2001 and 2017. No statistically significant difference was found between "HIC" and "LMIC" individuals with regard to sociodemographic and clinical characteristics. CONCLUSION: These findings seem to indicate that cognitive disorders in LMIC migrants still constitute a marginal public health issues for Italian dementia services. Nevertheless, the identification of eventual sociocultural and healthcare barriers may help to understand the real magnitude and relevance of this phenomenon.

Estimating dementia cases in the immigrant population living in Italy.

INTRODUCTION: The phenomenon of dementia among immigrants and ethnic minorities represents an emerging challenge for Western countries. The aim of the present study was to estimate the number of dementia cases among immigrant subjects residing in Italy and in each Italian region to provide pivotal information on the magnitude of such public health issue. METHOD: The number of immigrant individuals, aged 65 years or older, living in Italy and in the 20 Italian regions was derived by the 2017 data of the National Institute for Statistics. The dementia prevalence rates were taken from the European data provided by the Neurologic Diseases in the Elderly Research Group. The estimated dementia cases were calculated by multiplying the number of immigrants with the age- and sex-specific prevalence rates. RESULTS:  Overall, 186,373 older immigrant subjects lived in Italy in January 2017. Nearly 7700 dementia cases were estimated in this population (5022 among women, 2725 among men). When considering each specific Italian region, the number of estimated cases ranged from 19 (Basilicata) to 1500 (Lombardia) with a marked inter-regional variability. DISCUSSION: Our findings indicate that the occurrence of dementia among immigrants and ethnic minorities constitutes a novel but already relevant issue for our healthcare systems. A non-negligible number of immigrant individuals is probably already seeking or might seek help for cognitive disturbances, thus potentially referring to general practitioners and/or to the Italian dementia services. The forecasted increasing magnitude of this phenomenon reinforces the need for tailored and locally oriented initiatives and policies.