Diagnostic and interventional implications of telemedicine in Alzheimer's disease and mild cognitive impairment: A literature review.

INTRODUCTION: Worldwide, life expectancy, and aging-related disorders as mild cognitive impairment (MCI) and Alzheimer disease (AD) are increasing, having a rising impact on patients' quality of life and caregivers' distress. Telemedicine offers many possibilities, such as remote diagnosing and monitoring of patients. OBJECTIVE: The purpose of this study is to provide a narrative synthesis of the literature about the implementation of telemedicine for diagnosis, treatment, and follow-up of patients with AD and MCI and their caregivers. METHODS: A systematic literature review was conducted on MEDLINE, EMBASE, and the Cochrane Library databases up to September 2018. MCI or AD diagnoses were the conditions of interest. We excluded other dementias. RESULTS: Fifty-six articles met inclusion criteria. We identified two main categories: diagnosis group (DG) and follow-up/interventional group (FIG). Fifteen articles suggested how to make a remote or earlier diagnosis: four were case-control accuracy studies, nine were paired comparative accuracy studies, and two were prospective single-arm accuracy studies. Among these, four focused on MCI, six on AD, and five on both. Forty one focused on supporting patients during the stages of the disease (28 articles), patient's caregivers (nine articles), or both (four articles). CONCLUSIONS: The rising use of telemedicine could actively improve AD and MCI patients' lives, reduce caregivers' burden, and facilitate an early diagnosis if patients live in remote places. However, as some studies report, it is relevant to take into account the emotional impact of telemedicine on patients and not only on the effectiveness.

Role of COMT V158M Polymorphism in the Development of Dystonia after Administration of Antipsychotic Drugs.

Antipsychotics (APDs) represent the main pharmacological strategy in the treatment of schizophrenia; however, their administration often may result in severe adverse effects, such as extrapyramidal symptoms. Typically, dystonic movements are considered the result of impaired function and/or abnormalities of dopaminergic neurotransmission/signaling in the basal ganglia. The catechol O-methyltransferase (COMT) gene is located within the 22q11.2 region, and its product is an enzyme involved in transferring a methyl group from S-adenosylmethionine to catecholamines, including dopamine. Studies showed that COMT Val158Met polymorphism modifies enzymatic activity and, consequently, synaptic dopamine concentration in specific brain areas. We identified a patient with 22q11.2 deletion syndrome presenting with cervical and trunk dystonia after paliperidone administration, which persisted even after drug discontinuation. Given the patient's genetic condition, we hypothesized that the dopaminergic dysfunction had been aggravated by COMT involvement, thus causing dystonia. In line with this hypothesis, we carried out a study on psychiatric patients in chronic treatment with APD to evaluate the distribution of the COMT Val158Met polymorphism and its role in the onset of adverse extrapyramidal symptoms. The study included four patients with dystonia after administration of APDs compared to 17 patients who never presented adverse drug reactions. Our data suggest that the Val/Val and Met/Met polymorphisms of the COMT gene are associated with a protective effect for the development of collateral extrapyramidal symptoms in patients treated with APDs, while the Val/Met genotype could be considered a risk factor for the development of dystonia after APDs administration.

Novel compound heterozygous mutation in NPC1 gene cause Niemann-Pick disease type C with juvenile onset.

Niemann-Pick disease type C (NPC) is a progressive lysosomal storage disorder caused by mutations in the NPC1 (in 95% of cases) or NPC2 (in ~5% of cases) genes, inherited in an autosomal recessive manner. We report the case of a 38-year-old woman with learning disorder from her first year of schooling, and could notice slow progressed cognitive impairment, social withdrawal, apathy, handwriting alterations, deterioration of language skills and dysphagia. Brain magnetic resonance imaging showed severe cerebellar atrophy, hypoplasia of the corpus callosum, asymmetric lateral ventricular enlargement, and severe enlargement of frontal and parietal subarachnoid spaces. Next generation sequencing for NPC genes (NPC1 and NPC2) detected compound heterozygous mutations in NPC1 gene, including c.1553G[A (p.Arg518Gln), paternally inherited, and c.1270C[T (p.Pro424Ser) maternally inherited. The first mutation has been already described in literature and correlated to NPC, while the second mutation is still unknown. Moreover, filipin test and quantification of plasma oxysterols confirmed NPC diagnosis. We can suggest the missense mutation c.1270C[T (p.Pro424Ser) as a new causative mutation of NPC.

Gene-environment interaction between an endocannabinoid system genetic polymorphism and cannabis use in first episode of psychosis.

Alterations of the endocannabinoid system (ECS) may play an important role in the development of schizophrenia and other psychotic disorders. Cannabis use is one of the environmental factors more repeatedly related to an increase the risk of developing a psychotic episode, while its use modifies the ECS normal function. In the present study we purposed to examine the gene by environment (GxE) interaction between 15 selected single nucleotide polymorphisms (SNPs) related to the ECS and cannabis use in a cohort of 321 patients with a first episode of psychosis (FEP) and 241 matched healthy controls. We found the fatty-acid amide hydrolase (FAAH) rs2295633 SNP genetic polymorphism was associated with a greater risk of presenting a FEP in subjects with relevant cannabis use, but not in subjects without a history of cannabis use. The probability of presenting a FEP was tenfold higher (OR: 10.69) in cannabis users who were homozygote carriers of the T allele of the FAAH rs2295633 SNP, compared to users of cannabis without this genotype. We also found that a higher a proportion of TT carriers of the FAAH rs2295633 SNP with a positive history of cannabis use was treated with high potency antipsychotic. This study has identified a GxE-environment interaction between a genetic polymorphism from the ECS and cannabis use involved in the risk of presenting a FEP. Although this preliminary data should be replicated with independent samples, our results highlight the importance of the pro-psychotic effects of exogenous cannabis use over the ECS in certain subjects.

Novel compound heterozygous mutation in NPC1 gene cause Niemann–Pick disease type C with juvenile onset

Niemann–Pick disease type C (NPC) is a progressive lysosomal storage disorder caused by mutations in the NPC1 (in 95% of cases) or NPC2 (in *5% of cases) genes, inherited in an autosomal recessive manner. We report the case of a 38-year-old woman with learning disorder from her first year of schooling, and could notice slow progressed cognitive impairment, social withdrawal, apathy, handwriting alterations, deterioration of language skills and dysphagia. Brain magnetic resonance imaging showed severe cerebellar atrophy, hypoplasia of the corpus callosum, asymmetric lateral ventricular enlargement, and severe enlargement of frontal and parietal subarachnoid spaces. Next generation sequencing for NPC genes (NPC1 and NPC2) detected compound heterozygous mutations in NPC1 gene, including c.1553G [A (p.Arg518Gln), paternally inherited, and c.1270C [ T (p.Pro424Ser) maternally inherited. The first mutation has been already described in literature and correlated to NPC, while the second mutation is still unknown. Moreover, filipin test and quantification of plasma oxysterols confirmed NPC diagnosis. We can suggest the missense mutation c.1270C [ T (p.Pro424Ser) as a new causative mutation of NPC

What kind of diagnosis in a case of mobbing: post-traumatic stress disorder or adjustment disorder?

Over the last decade a consistent increase in stress-related psychological consequences at the workplace, usually called 'mobbing', has been seen. It claimed physical, psychical and social distress as its victims, leading to an increased incidence of many illnesses, such as psychosomatic disorders (ache, high blood pressure, chronic fatigue and insomnia) and psychiatric disturbances (high level of anxiety, depression and suicidal attempts). It was recently demonstrated that mobbing is significantly widespread among healthcare workers, especially among female nurses. In this report, we illustrate the case of a nurse who, after a brilliant career, underwent mobbing at the workplace, showing depression, anxiety and sleep disorders that required hospitalisation and a substantial intervention.

Una revisión de los trastornos del sueño en la esquizofrenia / Sleep disorders in schizophrenia: a review

La esquizofrenia se acompaña hasta en un 80% de los pacientes de trastornos del sueño, que son normalmente infradiagnosticados e infratratados debido a su falta de consideración en el manejo de esta enfermedad. Los principales trastornos son el insomnio, el síndrome de piernas inquietas, el síndrome de apnea obstructiva del sueño, la hipersomnia, las parasomnias y los trastornos del ritmo circadiano. Destaca en su importancia el insomnio, ya que puede ser un signo prodrómico de la enfermedad, así como un signo de alarma temprano de una descompensación psicótica incipiente. En pacientes con esquizofrenia se han encontrado alteraciones polisomnográficas en la arquitectura del sueño que se correlacionan tanto con la clínica subjetiva de insomnio como con las manifestaciones clínicas predominantes de la esquizofrenia. Los antipsicóticos pueden alterar la estructura del sueño, pero también tienen un papel importante en el tratamiento de las alteraciones del sueño en la esquizofrenia. Han demostrado una mejoría clínica del insomnio y la corrección polisomnográfica de las alteraciones de la arquitectura del sueño, mejorando la calidad de vida y la capacidad funcional de los pacientes. Sin embargo, pueden también exacerbar otros trastornos comórbidos del sueño, como el síndrome de piernas inquietas o el síndrome de apnea obstructiva del sueño, o provocar hipersomnia u obesidad. Existe evidencia de que los trastornos del sueño en esquizofrenia afectan de forma relevante la calidad de vida y de que influyen en la sintomatología de los pacientes con esquizofrenia, por lo que es muy importante reconocerlos y tratarlos de forma adecuada (AU)

Up to 80% of patients with schizophrenia suffer from sleep disorders, and are usually under-diagnosed and under-treated due to a lack of being taken into account in the management of this illness. The main disorders are insomnia, restless legs syndrome, obstructive sleep apnoea syndrome, hypersomnia, the parasomnias, and circadian rhythm disorders. The importance of insomnia is highlighted, as it can be a prodromic sign of the illness, as well as an early alarm sign of an incipient psychotic decompensation. Polysomnographic changes that correlate with subjective clinical insomnia and with the predominant clinical manifestations of schizophrenia. Antipsychotic drugs can alter the structure of sleep, but they also have an important role in the treatment of sleep alterations in schizophrenia. They have demonstrated a clinical improvement of the insomnia and the polysomnographic correction of the changes in sleep architecture, with an improvement in the quality of life and functional capacity of the patients. However, they can also exacerbate other comorbid sleep disorders such as restless legs syndrome and obstructive sleep apnoea syndrome, or trigger hypersomnia or obesity. There is evidence that sleep disorders in schizophrenia has a significant effect on the quality of life and has an influence on the symptoms of patients with schizophrenia, thus it is very important to recognise them and treat them accordingly (AU)