Thiamine Deficiency and Neurological Symptoms in Patients with Hematological Cancer Receiving Chemotherapy: A Retrospective Analysis

Objectives Patients with hematological cancer receiving chemotherapy have a high risk of thiamine deficiency due to accelerated thiamine usage by tumor cells. Mild or severe thiamine deficiency can lead to varying degrees of neurological symptoms. We evaluated the relationship between thiamine deficiency and neurological symptoms, including mild or nonspecific symptoms, and the influence of chemotherapy on thiamine serum levels in patients with hematological cancer receiving chemotherapy. Materials and Methods We retrospectively identified 42 patients diagnosed with hematological cancer at our hospital, using electronic medical records collected from March 2019 to March 2020. We evaluated the risk factors associated with neurological symptoms (mild-to-severe cognitive impairment, attention impairment, and mood or emotional disorder), the relationship between the presence of neurological symptoms and thiamine serum levels, and changes in thiamine serum levels after chemotherapy. Results Thiamine deficiency was significantly associated with neurological symptoms. The thiamine serum levels in the group with neurological symptoms were significantly lower than those in the group without neurological symptoms. The Wilcoxon rank-sum test showed that thiamine serum levels after chemotherapy were significantly lower than those before administration of chemotherapy. Conclusion Thiamine serum levels in patients with hematological cancer may be used as a reference to maintain neurological status during chemotherapy.

Impact of SARS-CoV-2 Infection on Cognitive Function: A Systematic Review

The prevalence and etiology of COVID-19's impact on brain health and cognitive function is poorly characterized. With mounting reports of delirium, systemic inflammation, and evidence of neurotropism, a statement on cognitive impairment among COVID-19 cases is needed. A substantial literature has demonstrated that inflammation can severely disrupt brain function, suggesting an immune response, a cytokine storm, as a possible cause of neurocognitive impairments. In this light, the aim of the present study was to summarize the available knowledge of the impact of COVID-19 on cognition (i.e., herein, we broadly define cognition reflecting the reporting on this topic in the literature) during the acute and recovery phases of the disease, in hospitalized patients and outpatients with confirmed COVID-19 status. A systematic review of the literature identified six studies which document the prevalence of cognitive impairment, and one which quantifies deficits after recovery. Pooling the samples of the included studies (total sample n = 644) at three standards of quality produced conservative estimates of cognitive impairment ranging from 43.0 to 66.8% prevalence in hospitalized COVID-19 patients only, as no studies which report on outpatients met criteria for inclusion in the main synthesis. The most common impairment reported was delirium and frequent reports of elevated inflammatory markers suggest etiology. Other studies have demonstrated that the disease involves marked increases in IL-6, TNFα, and IL-1β; cytokines known to have a profound impact on working memory and attention. Impairment of these cognitive functions is a characteristic aspect of delirium, which suggests these cytokines as key mediators in the etiology of COVID-19 induced cognitive impairments. Researchers are encouraged to assay inflammatory markers to determine the potential role of inflammation in mediating the disturbance of cognitive function in individuals affected by COVID-19.

A Randomised Computer-assisted Rehabilitation Trial of Attention in Pediatric Multiple Sclerosis: A Post-hoc Analysis.

Background: Cognitive decline is one of the most remarkable features of Multiple Sclerosis (MS) and particularly in pediatric onset MS (POMS). The Simbol Digit Modalities Test (SDMT), a simple, brief measure of information processing speed (IPS) has been proposed and it is increasingly used to explore cognitive functions in MS clinical trials. Recently a 4-point worsening on the SDMT score has been demonstrated to significantly correlate with a clinically meaningful cognitive decline.Methods: The primary objective of this post-hoc analysis of a randomised computer-assisted rehabilitation trial for attention impairment in POMS was to test the clinical meaningfulness of the changes of SDMT scores by applying a 4-point SDMT cut-off. POMS exposed to specific computer training (ST) and nonspecific training (nST) were compared. All analyses were post hoc and not pre-specified. To evaluate the clinical meaningfulness of longitudinal changes over time of the SDMT in the ST and nST groups we applied a categorization of the delta SDMT scores (delta SDMT: SDMT score at T1 – SDMT score at T0) as follow: between -3 and 3 = not clinically significant; ≤ - 4 = clinically significant worsening; ≥ 4 = clinically significant improvement. The proportion of patients reporting a clinically significant SMDT improvement were compared between the 2 groups by using the chi-square test.Results: Twenty-five % of POMS reported no clinically significant changes, 12.5% a clinically significant worsening and 62.5% patients a clinically significant improvement in the SDMT score at the end of the training program. The proportion of patients reporting a clinically significant improvement of the SDMT was significantly (p=0.008) higher (100%) in patients exposed to the ST in comparison to that (25%) in nST group. Conclusions: In our RCT the use of the 4-point SDMT cut-off allows us to demonstrate the clinical meaningfulness of the results obtained by a home-based computerized program for retraining attention dysfunction in POMS patients with attention impairment. Further studies are needed to confirm the clinical validity of this cut-off and its applicability in the routine clinical practice setting

Early Attention Impairment in a Patient with COVID-19

A 47-year-old physician suddenly noticed a persistent difficulty maintaining attention. He was awake, alert, and oriented. After two hours he developed fever, ageusia, and anosmia. He denied any previous history of psychiatric illness and was hydrated at the time of the subjective attention impairment. On admission, the patient remained oriented. He reported the persistence of attention problems, anosmia, and mild fatigue. The oxygen saturation 99% while he was breathing ambient air. Laboratory tests were unremarkable. A high-resolution computed tomography of the chest was normal. Nasopharyngeal and throat swabs specimens on reverse transcription-polymerase chain reaction analysis tested positive for SARS-CoV2. On illness day 3, the examination was unchanged, but he continued to complain of difficulties to stay focused. Then, he performed an objective attention test. The test demonstrated a moderate attentional impairment. On day 6, the patient reported a subjective worse in his concentration and performed a second test. Although his physical examination remained normal, the attention performance was worse as compared to day 3. Eight hours after worsening of attention impairment, the patient’s oxygen saturation dropped to 94%. From illness days 9 to 14, the patient evolved with clinical improvement. On day 10, a third objective attention test indicated a mild deficit. On day 16, he did not report any other symptom and the attention test was completely normal. Then, the patient returned to work. Neurological symptoms had been previously described in COVID- 19 patients. However, no previous research had investigated early cognitive deficits preceding the traditional symptoms.

T89. THE RELIABILITY OF THE CORE NEGATIVE SYMPTOMS SCALE OF SCHIZOPHRENIA USING THE STANDARD FOR CLINICIANS’ INTERVIEW IN PSYCHIATRY (SCIP)

Background Recent research on the negative symptoms of schizophrenia has produced reliable and validated scales such as the Scale for the Assessment of Negative Symptoms (SANS), the Schedule for the Deficit Syndrome, the Negative Symptoms Scale of Lewine, and others (1–3). More than 30 negative symptoms have been described, among these, avolition which is considered a core negative symptom (4). The DSM-5 recognizes five main negative symptoms: blunted affect, avolition, alogia, anhedonia and asociality (5). Other researchers consider attention impairment, poor self- care, and psychomotor retardation as negative symptoms (1, 6). There is a need to derive a short list of the core negative symptoms (CNS) of schizophrenia that are reliable and useful in clinical settings and clinical research. Methods The Standard for Clinicians’ Interview in Psychiatry (SCIP) is a new valid and reliable diagnostic interview that was tested in an international multisite study in three countries (USA, Canada and Egypt) between 2000 and 2012 (7–10). A total of 700 patients were interviewed at William R. Sharpe Jr. Hospital in Weston, West Virginia (670 patients) and Chestnut Ridge Center in Morgantown, West Virginia (30 patients). Mean patient age was 34, 59% male, 95% White and 34% had less than 12 years of education. The SCIP includes 8 items covering the main negative symptoms of schizophrenia: avolition, blunted affect, alogia, psychomotor retardation, poor self-care, anhedonia, attention impairment, and asociality. Results Inter-rater reliability Kappa (k) and standard error (SE) were calculated for each of the main negative symptoms: avolition (k=0.74, SE=0.04), blunted affect (k=0.68, SE=0.05), alogia (k=0.62, SE=0.05), psychomotor retardation (k=0.72, SE=0.04), poor self-care (k=0.79, SE=0.06), anhedonia (k=0.87, SE=0.04), attention impairment (k=0.92, SE=0.12), asociality (k=0.74, SE=0.04). Cronbach’s alpha for internal consistency and the mean interitem correlation (MIC) of several models were calculated. Cronbach’s alpha and the MIC of the five-factor negative dimension (blunted affect, avolition, alogia, psychomotor retardation and poor self-care) were: alpha = 0.83, MIC=0.49. The item-rest correlations (IRCs) of each of the 5 negative symptoms were: blunted affect = 0.68, avolition = 0.57, alogia = 0.67, psychomotor retardation = 0.61 and poor self-care = 0.57. The high item-rest correlations of all five negative symptoms may indicate that they represent the Core Negative Symptoms (CNS) of schizophrenia. Adding anhedonia to the five-factor model to create a six-factor model resulted in a low item-rest correlation (IRC) of anhedonia (IRC=0.06) and a lower alpha (0.76). Similarly, adding attention impairment to the five-factor model to create a six-factor model resulted in a low item-rest correlation (IRC) of attention impairment (IRC=0.02) and a lower alpha (0.75). Similarly, adding asociality to the five-factor model to create a six-factor model resulted in a low item-rest correlation (IRC) of asociality (IRC=0.05) and a lower alpha (0.75). Finally, adding anhedonia, attention impairment and asociality to the five-factor model to create an eight-factor model resulted in low IRCs for anhedonia, attention impairment and asociality (IRCs are 0.12, 0.06, 0.10 respectively) and a lower alpha (0.67). Discussion The Core Negative Symptoms (CNS) Scale includes five negative items. Three items (avolition, psychomotor retardation and poor self-care) have good agreement (kappa >0.7) and two items (alogia and blunted affect) have fair agreement (kappa ranges from 0.5 to 0.7). Cronbach’s alpha was also high (0.83). The CNS scale can therefore be considered reliable at the dimensional level.

Deep phenotyping of attention impairments and the ‘Inattention Biotype’ in Major Depressive Disorder

BackgroundAttention impairment is an under-investigated feature and diagnostic criterion of Major Depressive Disorder (MDD) that is associated with poorer outcomes. Despite increasing knowledge regarding mechanisms of attention in healthy adults, we lack a detailed characterization of attention impairments and their neural signatures in MDD.MethodsHere, we focus on selective attention and advance a deep multi-modal characterization of these impairments in MDD, using data acquired from n = 1008 patients and n = 336 age- and sex-matched healthy controls. Selective attention impairments were operationalized and anchored in a behavioral performance measure, assessed within a battery of cognitive tests. We sought to establish the accompanying neural signature using independent measures of functional magnetic resonance imaging (15% of the sample) and electroencephalographic recordings of oscillatory neural activity.ResultsGreater impairment on the behavioral measure of selective attention was associated with intrinsic hypo-connectivity of the fronto-parietal attention network. Not only was this relationship specific to the fronto-parietal network unlike other large-scale networks; this hypo-connectivity was also specific to selective attention performance unlike other measures of cognition. Selective attention impairment was also associated with lower posterior alpha (8–13 Hz) power at rest and was related to more severe negative bias (frequent misidentifications of neutral faces as sad and lingering attention on sad faces), relevant to clinical features of negative attributions and brooding. Selective attention impairments were independent of overall depression severity and of worrying or sleep problems.ConclusionsThese results provide a foundation for the clinical translational development of objective markers and targeted therapeutics for attention impairment in MDD.