Post-Stroke Depression in Older Adults: An Overview.

Detailed data on post-stroke depression (PSD) in older adults are limited in spite of the high vulnerability of this population to stroke. In fact, PSD prevalence in older adults ranges from 16.0 to 43.9%; however, timing and instruments of evaluation often differ significantly across all available studies. The etiology, genetic and inflammatory factors, as well as structural brain alterations, are claimed as part of a multifaceted mechanism of action in PSD onset. Thus, the aim of this narrative review was to further elaborate on the prevalence, etiology, diagnosis, consequences and treatment of PSD in older adults. The consequences of PSD in older adults may be devastating, including a poor functional outcome after rehabilitation and lower medication adherence. In addition, lower quality of life and reduced social participation, higher risk of new stroke, rehospitalization, and mortality have been reported. In this scenario, treating PSD represents a crucial step to prevent these complications. Both pharmacological and non-pharmacological therapies are currently available. The pharmacological treatment utilizes antidepressant drugs, such as selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants (TAs) and new multimodal antidepressants (NMAs). Non-pharmacological therapies include psychological interventions and non-invasive brain stimulation techniques, while excluding drug administration. In the general population experiencing PSD, SSRIs (sertraline in particular) are the most prescribed, whereas the combination of antidepressants and psychotherapy is underused. Furthermore, about one-third of patients do not receive treatment for PSD. In regard to older adults with PSD, the possibility of more adverse effects or contraindications to antidepressant prescription due to comorbidities may limit the therapeutic window. Although drugs such as citalopram, escitalopram, sertraline, venlafaxine, and vortioxetine are usually well tolerated by older patients with PSD, the few randomized controlled trials (RCTs) specifically considering older adults with PSD have been conducted with fluoxetine, fluvoxamine, reboxetine, citalopram and nortriptyline, often with very small patient samples. Furthermore, data regarding the results of non-pharmacological therapies are scarce. High-quality RCTs recruiting large samples of older adults are needed in order to better manage PSD in this population. In addition, adequate screening and diagnosis instruments, with reliable timing of evaluation, should be applied.

Evaluation of mild-to-moderate COVID-19 through dual-task paradigm: a longitudinal case-controlled study.

INTRODUCTION: Coronavirus disease (COVID-19) was associated with cognitive alterations affecting everyday life activities. These need input integration of both motor and cognitive systems. The study aim is to evaluate cognitive-motor interference phenomenon in previously independent patients with mild-to-moderate COVID-19 (PwMCOVID-19) compared with healthy controls (HC), through dual-task (DT) paradigm. METHODS: PwMCOVID-19 were included if being independent at home, had no previous referred cognitive impairment, mechanical ventilation or oxygen need. They were assessed at admission and after 6 months with a motor-cognitive DT test (counting backward by twos while walking 2 min). HC were enrolled as control group. Differences between single-task (ST) and DT performance, DT effect (DTE) and task prioritization amongst groups and during time points were analyzed. RESULTS: One-hundred PwMCOVID-19 [mean age=67.32(12.08) years; 53 M/47 F] and 39 HC [mean age=63.11(9.90) years; 20 M/19 F] were recruited. Upon T0, PwMCOVID-19 showed lower cognitive and motor DT performances than ST and HC. Mutual interference pattern was predominant in PwMCOVID-19. At T1, 41 PwMCOVID-19 were examined [mean age=64.85(10.75); 22 M/19 F]. They had a worse DT performance compared to ST, although DT improved at T1. A stronger cognitive ST-DT difference was present at T0, compared to ST-DT difference at T1, while motor ST-DT difference was unchanged over time in PwCOVID-19. CONCLUSION: In PwMCOVID-19, there is an impairment of DT counting while walking at baseline and after 6 months from hospitalization, with a more pronounced DT mutual interference pattern at T0. After 6 months, the motor and cognitive ST and DT performances ameliorated, not reaching the HC level.

Previously independent patients with mild-symptomatic COVID-19 are at high risk of developing cognitive impairment but not depression or anxiety.

OBJECTIVES: The aim of the study was to explore the cognitive functions of a large sample of hospitalised subjects with mild symptomatic Coronavirus Disease (COVID-19) who were previously independent at home and without neurological diseases. METHODS: Patients admitted in a COVID-19 Unit for Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection between November 2020 and March 2021 were recruited. Inclusion criteria were: being independent at home before the infection, radiologically confirmed COVID-19 pneumonia, positive reverse transcriptase-polymerase chain reaction nasopharyngeal swab and no oxygen supplementation at the time of evaluation. EXCLUSION CRITERIA: cognitive impairment or neurological diseases previous to the infection, delirium episodes, and history of any mechanical ventilation use. They were evaluated with Montreal Cognitive Assessment (MoCA), Hamilton Depression Rating Scale (HAM-D) and Hamilton Anxiety Rating Scale (HAM-A). RESULTS: Out of 522 subjects admitted in the COVID-19 Unit, 90 were enrolled [mean age = 68.32(11.99); 46M/44F]. An impaired MoCA (cut-off < 23) was found in 60 subjects (66.66 %). Pathological scores were obtained by 36.7 % of the subjects with <65 years and 78.3 % of those older than 65 years. A high prevalence of executive function and memory impairment was detected. CONCLUSIONS: The results underline a high rate of cognitive impairment in previously independent mild COVID-19 patients. This might represent a potential threat for the everyday independence of these patients due to the consequences on everyday life activities and work following discharge from hospital. These subjects should, therefore, be monitored in order to allow a better understanding of the progression and consequences of the so-called "Long COVID".

Guillain-Barré Syndrome Related and Unrelated to COVID-19: Clinical Follow-Up in the COVID-19 Era.

OBJECTIVE: COVID-19 has been associated with neurological complications such as Guillain-Barre syndrome (GBS). Several cases have been reported but without functional outcome data after intensive rehabilitation and medium-term follow-up. METHODS: In this observational study, patients were admitted in 2019 and 2020 to inpatient rehabilitation for GBS and were examined using the Barthel index, GBS-Disability Scale, and Medical Research Scale-sum score at admission, discharge, and at least 6 months after onset of symptoms. All the participants received personalized, goal-oriented inpatient rehabilitative treatment for the recovery of self-sufficiency in everyday life. RESULTS: Eleven people with GBS-3 cases related to COVID-19-were admitted in 2019 and 2020 to inpatient rehabilitation. Eight patients with GBS not related to COVID-19 experienced a high complication rate during inpatient rehabilitation, with 2 deaths due to sepsis. In this cohort, a higher prevalence than expected of acute motor axonal neuropathy was also detected. The COVID-19-related GBS group did not have any complications. After a mean of 10.11 months (SD = 4.46 months), 55.55% of patients regained autonomous walking. CONCLUSION: COVID-19-related GBS appeared to have a better clinical outcome than GBS that was not COVID-19 related. A higher than usual prevalence of acute motor axonal neuropathy form was encountered. More follow-up studies are needed to understand whether the recovery of GBS related to COVID-19 might be different from that of GBS unrelated to COVID-19. IMPACT: No data are currently available on the follow-up of GBS in the COVID-19 era and on the functional outcome of those patients. This study provides important information indicating that GBS related to COVID-19 might have a better clinical outcome than GBS unrelated to COVID-19.

Imaging and depression in multiple sclerosis: a historical perspective.

PURPOSE: Patients affected with multiple sclerosis suffer from depression more frequently than the general population. Beyond psychosocial, genetic and immune-inflammatory factors, also the brain damage which is peculiar of multiple sclerosis has been claimed to have a role in the aetiology of depression in those patients. The study of this interesting relation has been implemented with both conventional and advanced magnetic resonance imaging techniques. The aim of this review is to provide a historical perspective on the link between multiple sclerosis-related depression and structural and functional brain damage. METHODS: In this review, the results of the MRI studies regarding multiple sclerosis-related brain damage and the presence of depression are presented. RESULTS: The findings of the reports reveal a link between brain pathology and depressive symptoms or the diagnosis of depression in multiple sclerosis. CONCLUSIONS: Although a multifactorial aetiology has been theorized for depression and depressive symptoms in patients with multiple sclerosis, this review supports the hypothesis that the structural and functional brain impairment might substantially be amongst those factors. Thus, depression itself might be a symptom with a neuro-biological basis and not only the consequence of the disability derived from the neurological impairment.

A rare case of acute motor axonal neuropathy and myelitis related to SARS-CoV-2 infection.

We describe a rare case of post-infective Acute Motor Axonal Neuropathy (AMAN) variant of Guillain-Barrè Syndrome (GBS) associated with myelitis and anti-GD1b positivity after SARS-CoV-2 infection. The patient referred to the hospital reporting a history of ten days lasting moderate fever, myalgia and anosmia, with the onset of progressive quadriparesis and ascending paraesthesias in the four limbs since five days from defervescence. A chest computed tomography demonstrated interstitial pneumonia with "ground glass opacities", suggesting Coronavirus disease (COVID-19). The patient exhibited three negative reverse-transcription polymerase chain reaction (RT-PCR) nasopharyngeal swabs, while SARS-CoV-2 IgG was found in plasma. The electrophysiological examination demonstrated an AMAN and the spinal cord Magnetic Resonance Imaging (MRI) showed a T2-weighted hyperintense lesion in the posterior part of the spinal cord at the C7-D1 levels. Furthermore, anti-GD1b IgM was detected. GBS and myelitis could exceptionally develop simultaneously. Our findings reasonably support a causality link between COVID-19 and the neurological symptoms, suggesting a post-infective autoimmune reaction.

Benign SARS-CoV-2 infection in MOG-antibodies associated disorder during tocilizumab treatment.

Myelin Oligodendrocyte Glycoprotein Antibody Disease (MOGAD) represents a demyelinating disorder for which tocilizumab, an anti-IL6 receptor, has been tested to prevent disabling relapses. In a subgroup of patients affected with novel Coronavirus disease (COVID-19), tocilizumab has also increased the survival rate. We present the case of a 31-years-old Caucasian patient who experienced an almost asymptomatic Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) infection during treatment with tocilizumab, which was continued due to the very high risk of relapses of the patient. According to this case, tocilizumab might be not discontinued during COVID-19.

Depression in Multiple Sclerosis: Epidemiology, Aetiology, Diagnosis and Treatment.

Depressive disorders are common in patients with multiple sclerosis, influencing their quality of life and adherence to treatments, as well as becoming more frequent with the progression of the disease and in the secondary progressive form of multiple sclerosis. Patients with multiple sclerosis often experience a typical cluster of symptoms in association with depression, such as fatigue, pain and cognitive impairment. However, the pathogenesis of multiple sclerosis-related depression remains partially unclear, even though genetic, immune-inflammatory and psychosocial factors might be seen to play a role, in addition to the brain structural alterations documented by magnetic resonance imaging studies. The high incidence and burden of depression in people affected with multiple sclerosis are matters of crucial importance. Despite such importance, the efficacy of pharmacologic treatments has been poorly studied and, for the most part, the access to non-pharmacological treatments is partially dependent on the local health system availability. It has been determined that interferon-beta and glatiramer acetate do not cause depressive symptoms; however, no definitive data in this regard are avaible for the newer disease-modifyng medications. In this review, we discuss the diagnosis, prevalence, pathogenesis, clinical aspects, magnetic resonance imaging findings and treatments available in patients experiencing multiple sclerosis-related depression.

GNRH analog therapy in girls with early puberty is associated with the achievement of predicted final height but also with increased risk of polycystic ovary syndrome.

OBJECTIVE: GNRH analog (GNRHa) therapy has not been supported by beneficial effects on adult stature in girls with early puberty. Furthermore, an increased prevalence of polycystic ovary syndrome (PCOS) has been described in girls treated for central precocious puberty. Women with PCOS are at increased risk of cardiometabolic dysfunctions and infertility. Our aim was to assess GNRHa effectiveness on reaching adult stature and the risk of PCOS in girls with early puberty. DESIGN: Longitudinal study of GNRHa-treated and GNRHa-untreated girls at baseline and at final height. METHODS: Twenty-five GNRHa-treated girls and 55 controls were compared. Insulin resistance (IR; homeostasis model assessment of IR (HOMA-IR) and glucose-to-insulin ratio (G/I)), the effect of GNRHa on final height, and the prevalence of PCOS were assessed. RESULTS: In GNRHa-treated girls, no significant difference was found between predicted final height and final height, whereas a significant difference was detected in untreated girls (P=0.0001). At final height, GNRHa-treated girls showed higher HOMA-IR and lower G/I (P=0.03 for both) as well as higher DHEAS and androstenedione levels (P=0.02 and P=0.01 respectively) than untreated girls. The prevalence of PCOS and hyperandrogenemia was significantly higher in GNRHa-treated adolescents than in untreated adolescents (36 and 14.5% respectively, P=0.04; 56 and 23.6% respectively, P=0.01). Finally, gonadotropin-suppressive therapy was significantly related to PCOS during adolescence (P=0.03). CONCLUSIONS: In girls with early puberty, GNRHa therapy is associated with the achievement of predicted final height; nevertheless, this treatment seems to act as an independent risk factor for the development of PCOS already during adolescence.

Weight gain and insulin resistance in children treated with valproate: the influence of time.

This study was undertaken in 2 parts to investigate the relationship between body size and insulin resistance during treatment with valproic acid in children. The cross-sectional part revealed differences in terms of body size and homeostasis model assessment of insulin resistance, which were higher in the group on medication. The longitudinal part showed a major increase in body size and insulin resistance during the first year of therapy. There was a subsequent decrease in insulin resistance in association with the rise of body size, however with a trend to level off. These results might be helpful to enhance the knowledge of valproic acid action on both insulin resistance and weight gain, allowing to plan appropriate approach for the prevention of the consequences of the treatment with valproic acid.

Insulin sensitivity in prepubertal Caucasian normal weight children.

BACKGROUND: Determining whether or not a child is insulin resistant is becoming a matter of fundamental interest even in childhood, as the incidence of metabolic complications of insulin resistance is rising. Thus reference values are needed. AIM: To set percentiles for HOMA-IR and WBISI in Caucasian normal weight prepubertal children. POPULATION: 238 normal weight prepubertal Caucasian children (126 males/112 females). METHODS: After physical examination including anthropometric measurements all children underwent an oral glucose tolerance test from which HOMA-IR and WBISI were calculated. RESULTS: HOMA-IR values above the 95th percentile (2.03) and WBISI values below the 5th percentile (5.67) represent the cut-off values for the determination of insulin resistance. CONCLUSION: These reference values are useful to easily detect insulin resistance within the prepubertal Caucasian population representing a helpful tool for clinicians to target such children in order to improve insulin sensitivity.

Liver steatosis in obese prepubertal children: a possible role of insulin resistance.

OBJECTIVE: To determine whether in obese prepubertal children insulin resistance (IR) is associated with the development of liver steatosis. METHODS AND PROCEDURES: Cross-sectional study evaluating the prevalence of liver steatosis in 100 severely obese prepubertal children and comparing IR indexes between children with (group 1) and without steatosis (group 2). Furthermore, IR indexes were compared to values of 50 normal weight children. Fasting blood samples were collected for the evaluation of liver function tests, lipid profile, plasma glucose, and insulin levels. All children underwent an oral glucose tolerance test and anthropometric measurements. Hepatic ultrasound was performed according to international criteria and by one single operator. Analysis was performed by Mann-Whitney U-test, Pearson correlation, and logistic regression. RESULTS: Liver steatosis was found in 52% obese children and was equally distributed between the two sexes. Obese children were more insulin resistant when compared to controls (homeostasis model assessment of IR (HOMA-IR): P = 0.0001; whole body insulin sensitivity index (WBISI): P = 0.0005; fasting glucose/fasting insulin ratio (G/I): P = 0.0001), and group 1 presented an even higher degree of IR when compared to group 2 (HOMA-IR P = 0.0001; WBISI P = 0.0004; G/I P = 0.0001). The area under the curve (AUC) for insulin was significantly higher in group 1 when compared to group 2, while no difference was found in the AUC for glucose. There was no association between IR and adiposity indexes (P >0.05). The role of IR as a predictor for the development of steatosis was analyzed by multiple logistic regression, which documented that IR indexes were significantly related to steatosis independently of BMI-SDS. DISCUSSION: Liver steatosis is an emerging problem in prepubertal severely obese children, and it appears to be an association between liver steatosis and IR in these subjects.