Neurofilament Light Chain Is a Promising Biomarker in Alcohol Dependence

Background: Alcohol dependence, a global public health problem, leads to structural and functional damage in the brain. Alcohol dependence patients present complex and varied clinical manifestations and live with general complaints existing in contemporary society, making most people with alcohol dependence hard to identify. Therefore, it is important to find potential biomarkers for the diagnosis and evaluation of alcohol dependence. In the study, we explored potential biomarkers for the diagnosis and monitoring of diseases and evaluated brain structural changes in alcohol dependence patients.Methods: Enzyme-linked immunosorbent assay (ELSA) was employed to detect the expression of serum nucleotide-binding oligomerization domain containing 3 (NLRP3) and single-molecule array (Simoa) assay was used to detect the expression of serum neurofilament light (NfL) in 50 alcohol dependence patients and 50 controls with no drinking history. Alcohol consumption was measured by standard drinks. Neuropsychological assessments, including the Montreal cognitive assessment (MoCA), Pittsburgh sleep quality index (PSQI), generalized anxiety disorder (GAD-7), and patient health questionnaire-9 (PHQ-9), were conducted to evaluate cognitive function and psychological state. The degree of white matter lesions (WMLs) was rated using the Fazekas scale based on magnetic resonance imaging analysis. White matter structure was quantified using the voxel-based morphometry method. The correlations between NLRP3 levels, NfL levels, neuropsychological dysfunction, the degree of WMLs, and white matter volume (WMV) were analyzed in alcohol dependence patients.Results: Serum NLRP3 and NfL levels were higher in the alcohol dependence group. NLRP3 levels were irrelevant to monthly alcohol assumption as well as to the MoCA, PSQI, GAD-7, PHQ-9, and Fazekas scale scores and WMV. NfL levels were positively correlated with the PSQI and PHQ-9 scores as well as the degree of WMLs and negatively correlated with the MoCA scores and WMV. No associations were evident between NfL and monthly alcohol assumption and GAD-7 scores in the alcohol dependence group.Conclusion: This study supports the potential value of serum NfL as a non-invasive biomarker in alcohol dependence. The association with neuropsychological dysfunction and degree of WMLs has implications to use NfL as a promising biomarker to assess the severity of brain damage as well as the progression and prognosis of alcohol dependence.

Dutch multicentre, prospective follow-up, cohort study comparing the neurological and neuropsychological sequelae of hospitalised non-ICU- and ICU-treated COVID-19 survivors: a study protocol

IntroductionOwing to the novelty of COVID-19, there are still large knowledge gaps concerning its effect on the brain and the resulting impact on peoples’ lives. This large-scale prospective follow-up study investigates COVID-19-associated brain damage, neuropsychological dysfunction and long-term impact on the well-being of patients and their close ones. It is hypothesised that structural brain damage and cognitive dysfunction primarily occur in severely ill patients, as compared with moderately ill patients. Cognitive complaints, emotional distress and impact on well-being are hypothesised to be less dependent on illness severity.Methods and analysisFor this multicentre study, 200 patients with COVID-19 (100 intensive care unit (ICU) patients and 100 non-ICU patients) formerly hospitalised in one of the six recruiting hospitals during the first European infection wave (ie, March to June 2020) and their close ones will be recruited. At minimally 6 months posthospital discharge, patients will perform a set of neuropsychological tests and are subjected to a 3T MRI scan. Patients and close ones will fill out a set of questionnaires, also at minimally 6 months posthospital discharge and again another 6 months thereafter. Data related to COVID-19 hospitalisation will be extracted from the patients’ medical records. MRI abnormalities will ultimately be related to neuropsychological test performance and questionnaire outcomes.Ethics and disseminationEthics approval was granted by the medical research ethics committee of Maastricht University Medical Centre and Maastricht University (NL75102.068.20). The project is sponsored by The Brain Foundation Netherlands. Findings will be presented at national and international conferences, as well as published in peer-reviewed scientific journals.Trial registration numberNCT04745611.

I can’t count, but I can beat you playing cards: a case report on autoimmune encephalitis

Background Autoimmune encephalitis (AE) is a rare inflammatory disorder characterized by important psychiatric and neurologic symptoms. The literature documents high rates of neuropsychological dysfunction in N-methyl D-aspartate-receptor (NMDAr) encephalitis but papers don’t consider specifically calculation disturbances between the long-term deficits, although deficits in executive control and episodic memory were less likely to resolve. Case report Here we present a severe case of NMDAr encephalitis in a young patient without a relevant past medical history. Upon first examination he presented psycho-motor slowdown, speech disorders, severe cognitive deficits in all areas: concentration, attention, memory, language, dual task functions, increased latency in responses, severe dyscalculia. Upon first evaluation, the young patient underwent a battery of neuropsychological tests and he showed a dysexecutive syndrome with performances significantly low for age and education. Our patient hence underwent 1 month of intensive cognitive rehabilitation. After the rehabilitation treatment, he presented an amelioration in all domains except calculations. Conclusions In our patient the calculation disorder has proved to be the most relevant problem and the most difficult to treat. Clinicians should consider a careful approach to determine the prognosis of this syndrome because of the wide range of deficits, the need of prolonged treatment and the rate of long-term sequelae.

A-55 Neuropsychological Findings Associated with Progressive Lesion Development in Cerebral Cavernous Malformation Secondary to PDCD10 Mutation

Objective A rare mutation in the PDCD10 gene causes cerebral cavernous malformations, which can result in multiple brain hemorrhages and hundreds of lesions. Up to 50% of individuals with the PDCD10 mutation remain symptom-free throughout their lives; however, others can suffer from seizures or focal neurologic deficits. Participant: A 67-year-old Caucasian male presented for a neuropsychological re-evaluation (2020) following a progressive decline in his memory and attention dating back 20 years. A baseline neuropsychological evaluation was obtained 7 years ago. Relevant medical history included a 5 mm left falcine meningioma, epilepsy, obstructive sleep apnea, hypertension, and type II diabetes. Neuroimaging revealed over 250 scattered lesions that had advanced over the past 7 years, particularly in the paramedian pontine reticular formation, left inferior cerebellum, and right middle frontal gyrus. Results His neurocognitive profile was marked by mild impairments in immediate verbal memory. The remainder of his cognitive profile was average. Compared to his 2013 evaluation, he showed only a minimal decline in verbal memory, but he showed slight improvements in the domains of executive functioning, visuospatial abilities, and language. Conclusion Despite the marked progression of lesions documented on current neuroimaging, aside from immediate verbal memory problems the patient’s neurocognitive functioning was relatively well-preserved. He even exhibited minor improvements within several domains. Given the patient’s current neurocognitive status, this case illustrates the importance of comprehensive neuropsychological testing in cases that would appear more severe based on neuroimaging data alone. Relatedly, progression of neuropathological disease burden on neuroimaging is not necessarily accompanied by consistent progression of neuropsychological dysfunction.

Brain responsivity to emotional faces differs in men and women with and without a history of alcohol use disorder

Inclusion of women in research on Alcohol Use Disorder (AUD) has shown that gender differences contribute to unique profiles of cognitive, emotional, and neuropsychological dysfunction. We employed functional magnetic resonance imaging (fMRI) of abstinent individuals with a history of AUD (21 women [AUDw], 21 men [AUDm]) and demographically similar non-AUD control (NC) participants without AUD (21 women [NCw], 21 men [NCm]) to explore how gender and AUD interact to influence brain responses during emotional processing and memory. Participants completed a delayed match-to-sample emotional face memory fMRI task, and brain activation contrasts between a fixation stimulus and pictures of emotional face elicited a similar overall pattern of activation for all four groups. Significant Group by Gender interactions revealed two activation clusters. A cluster in an anterior portion of the middle and superior temporal gyrus, elicited lower activation to the fixation stimulus than to faces for the AUDw as compared to the NCw; that abnormality was more pronounced than the one observed for men. Another cluster in the medial portion of the superior frontal cortex elicited higher activation to the faces by AUDm than NCm, a difference that was more evident than the one observed for women. Together, these findings have added new evidence of AUD-related gender differences in neural responses to facial expressions of emotion.

Tinnitus and Neuropsychological Dysfunction in the Elderly: A Systematic Review on Possible Links

Introduction: Tinnitus is a common and disabling symptom often associated with hearing loss. While clinical practice frequently shows that a certain degree of psychological discomfort often characterizes tinnitus suffers, it has been recently suggested in adults as a determining factor for cognitive decline affecting attention and memory domains. The aim of our systematic review was to provide evidence for a link between tinnitus, psychological distress, and cognitive dysfunction in older patients and to focus on putative mechanisms of this relationship. Methods: We performed a systematic review, finally including 192 articles that were screened. This resulted in 12 manuscripts of which the full texts were included in a qualitative analysis. Results: The association between tinnitus and psychological distress, mainly depression, has been demonstrated in older patients, although only few studies addressed the aged population. Limited studies on cognitive dysfunction in aged patients affected by chronic tinnitus are hardly comparable, as they use different methods to validate cognitive impairment. Actual evidence does not allow us with certainty to establish if tinnitus matters as an independent risk factor for cognitive impairment or evolution to dementia. Conclusion: Tinnitus, which is usually associated with age-related hearing loss, might negatively affect emotional wellbeing and cognitive capacities in older people, but further studies are required to improve the evidence.

In Vivo Characterization of Cortical and White Matter Microstructural Pathology in Growth Hormone-Secreting Pituitary Adenoma

BackgroundThe growth hormone (GH) and insulin-like-growth factor 1 (IGF-1) axis has long been recognized for its critical role in brain growth, development. This study was designed to investigate microstructural pathology in the cortex and white matter in growth hormone-secreting pituitary adenoma, which characterized by excessive secretion of GH and IGF-1.Methods29 patients with growth hormone-secreting pituitary adenoma (acromegaly) and 31 patients with non-functional pituitary adenoma as controls were recruited and assessed using neuropsychological test, surface-based morphometry, T1/T2-weighted myelin-sensitive magnetic resonance imaging, neurite orientation dispersion and density imaging, and diffusion tensor imaging.ResultsCompared to controls, we found 1) acromegaly had significantly increased cortical thickness throughout the bilateral cortex (pFDR < 0.05). 2) T1/T2-weighted ratio in the cortex were decreased in the bilateral occipital cortex and pre/postcentral central gyri but increased in the bilateral fusiform, insular, and superior temporal gyri in acromegaly (pFDR < 0.05). 3) T1/T2-weighted ratio were decreased in most bundles, and only a few areas showed increases in acromegaly (pFDR < 0.05). 4) Neurite density index (NDI) was significantly lower throughout the cortex and bundles in acromegaly (pTFCE < 0.05). 5) lower fractional anisotropy (FA) and higher mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) in extensive bundles in acromegaly (pTFCE < 0.05). 6) microstructural pathology in the cortex and white matter were associated with neuropsychological dysfunction in acromegaly.ConclusionsOur findings suggested that long-term persistent and excess serum GH/IGF-1 levels alter the microstructure in the cortex and white matter in acromegaly, which may be responsible for neuropsychological dysfunction.

Priftis et al_Alexia without agraphia_COVID_2021

SARS-CoV-2 resulting in COVID-19 can affect the brain and cause neuropsychological disorders (e.g., executive dysfunction and memory difficulties). Recently the presence of more focal and isolated neuropsychological signs has been also reported, in the domain of language disorders (e.g., alexia without agraphia, conduction aphasia). We reported on patient LM affected by a left occipito-temporal ischemic stroke after SARS-CoV-2. LM had a largely preserved overall cognitive profile, but he presented with severe alexia without agraphia. We suggest that focal and isolated neuropsychological dysfunction can be observed in patients with stroke after SARS-CoV-2. Neuropsychological assessment and rehabilitation should be promptly provided to these patients.

MRI brain findings of cerebral malaria in children with acute encephalitis syndrome: a prospective study in 60 patients

Background: Acute encephalitis syndrome (AES) is defined as a person of any age group, at any time of the year with the acute onset of fever and change in mental sensorium (including confusion, disorientation, coma or inability to talk) and/or new onset of convulsions (excluding febrile seizures). Encephalitis is a inflammation of brain tissue which presents as a diffuse and/or a focal neuropsychological dysfunction and inflammation of adjacent meningitis. Objectives were to determine clinicoepidemiological profile in AES with special to reference cerebral malaria and to study various MRI findings in patients of AES especially in cerebral malaria.Methods: A prospective study of all cases of fever with unconsciousness or altered sensorium with or without convulsions admitted in PICU of MYH and CNBC Indore. Inclusion criteria was all those children who were previously neurologically normal, of age 1-14 years, patients with fever (<15days) with altered sensorium, with or without seizures and who stay in hospital long enough to complete essential diagnostic work up which includes (CBC with peripheral smear, RFT, LFT, MP, S. electrolytes, CSF, MRI brain).Results: The final study group comprised of 60 patients with age group 1-14 yrs and male to female ratio was 1.07:1. Patients with diagnosis of cerebral malaria were 17. High grade fever, headache, altered sensorium, generalized seizures In general examination pallor was present in 52.9%, icterus in 35.29% cases of cerebral malaria. Splenomegaly (70.5%) was more common finding than hepatomegaly (58.8%) in cerebral malaria. GCS was>6 in most cases, fundus abnormality and meningeal irritation was absent in all cases of cerebral malaria. MRI of brain in cerebral malaria was mostly normal, in (47.05%), second most common we get hyperintensity in periventricular and corpus callosum areas (23.52%), hyperintensity in basal ganglia and thalamus was found in17.64% cases and white matter changes in 2 cases. The final outcome of all cerebral cases was good, all were discharged, and there was no mortality.Conclusions: Our result demonstrate that cerebral malaria is a common cause of acute febrile encephalopathy in children. Presence of plasmodium falciparum is essential for diagnosis of cerebral malaria. No specific lesions have been identified in MRI brain.

Relationship between neuropsychology, clinical traits, psychopathology and attitudes towards change in eating disorders

Background:The interest of research on the neuropsychological characteristics of eating disorders (EDs) has primarily focused on inhibitory control, set-shifting and central coherence, as well as attention bias and decision making. These neuropsychological aspects may also influence attitudes towards therapeutic change and be related to a more severe clinical status. The objective of this paper was to analyse the relationship of psychopathological and clinical variables with neuropsychological characteristics of patients with EDs and to determine possible influence of these variables on patients’ attitude towards change. Methods: An observational analytical cross-sectional study was performed. The participants were 74 consecutive outpatients who received treatment at an ED unit during a 6-month period. They were assessed using clinical (Psychiatric Status Rating Scale, modified) and neuropsychological tests (Letter Number Sequencing test; Stroop test; Symbol Digit Modalities Test; Rey-Osterrieth Complex Figure Test). They were asked to complete several self-report psychopathological questionnaires (Body Shape Questionnaire; Eating Disorders Inventory; Beck Depression Inventory; State-Trait Anxiety Inventory; Dissociative Experiences Scale; Attitudes Towards Change in Eating Disorders Scale), but 23 participants (31.08%) did not return them. Descriptive statistics and multivariate analysis were performed to study the relationships between clinical and psychopathological neuropsychological variables.Results: Nineteen patients (25.68%) were diagnosed with restricting anorexia nervosa (AN), 19 (25.68%) with purging AN, 14 with bulimia nervosa (18.92%), 9 with binge eating disorder (12.16%) and 13 with ED not otherwise specified (17.57%). There were no significant differences among the groups in the scores on neuropsychological tests. BMI was related to the majority of the neuropsychological scores. “Precontemplation” was related to copy time (B=3.56; 95% CI (0.82-6.29), p<0.01) and memory time (B=-2.31; 95% CI (-4.58-(-0.05)); p<0.05). “Contemplation” was related to copy time (B=1.43; 95% CI (0.42-2.45); p<0.01) and style (B= -14.01; 95% CI (-24.98-(3.04)); p<0.01). “Decision” was related to working memory (SpanLN), the quantitative copy score, order and style.Conclusions: In EDs, neuropsychological dysfunction could be associated with decreased motivation to change. Hence, a comprehensive therapeutic framework should be established with the aim of providing neurocognitive training in addition to conventional therapy. This approach could enhance acknowledgment of the problem and improve the decisional balance.