Neuropsychiatric Issues Research Articles

Effects of levodopa/carbidopa intestinal gel infusion on autonomic symptoms in advanced Parkinson's disease: a systematic review.

Autonomic failure has a major impact on the quality of life of individuals with Parkinson's disease(PD), especially in advanced stages of the disease. Levodopa/carbidopa intestinal gel (LCIG) infusion is a well-established treatment for advanced PD with severe motor fluctuations and provides substantial benefit in managing some non-motor symptoms (NMS), such as sleep, fatigue, and neuropsychiatric issues. The effect of LCIG on autonomic symptoms is by contrastnot well known. Here we performed a systematic review on the influence of LCIG therapy on autonomic dysfunction in PD individuals. Following the PRISMA guidelines, we systematically searched for studies that included autonomic outcome measures in LCIG-treated PD individuals, limiting the search to articles written in English and published between January 2005 and June 2023. We evaluated improvement, stability, or worsening of gastrointestinal, urinary, and cardiovascular symptoms at six different timepoints according to clinimetric scale changes compared to baseline. Data on autonomic adverse events (AEs) possibly related to LCIG treatment were also collected. Of the 1476 studies identified in the initial search, 16 ultimately met the inclusion criteria and underwent quality assessment and data extraction, with data from 1361 PD patients (18.3months mean follow-up). Thirteen studies reported improvement or stability of gastrointestinal, urinary, and cardiovascular symptoms over the interventional period. One study found a worsening of cardiovascular symptoms and two of urological symptoms. Regarding safety, seven studies reported gastrointestinal (8.4%), urinary (0.5%), and cardiovascular (1.1%) autonomic LCIG-related AEs. LCIG infusion may help toreduce the burden ofautonomic symptoms in advanced PD. Prospective studies specifically addressing the effect of LCIG on autonomic function in advanced PD are warranted.

A Disease Hidden in Plain Sight: Pathways and Mechanisms of Neurological Complications of Post-acute Sequelae of COVID-19 (NC-PASC).

The global impact of coronavirus disease 2019 (COVID-19) marked by numerous pandemic peaks is attributed to its high variability and infectious nature, transforming it into a persistent global public health concern. With hundreds of millions of cases reported globally, the illness is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite its initial classification as an acute respiratory illness, recent evidence indicates that lingering effects on various bodily systems, such as cardiovascular, pulmonary, nervous, gastrointestinal (GI), and musculoskeletal, may endure well beyond the acute phase. These persistent manifestations following COVID-19, commonly known as long COVID, have the potential to affect individuals across the entire range of illness severity, with a tendency to be more prevalent in mild to moderate cases. At present, there are no established criteria for diagnosing long COVID. Nonetheless, it is conceptualized as a multi-organ disorder encompassing a diverse array of clinical manifestations. The most common, persistent, and debilitating symptoms of long COVID may be neurological, known as neurological complications of post-acute sequelae of COVID-19 (NC-PASC). More than one-third of individuals with a prior SARS-CoV-2 infection show involvement of both the central nervous system (CNS) and peripheral nervous system (PNS), as evidenced by an approximately threefold higher incidence of neurological symptoms in observational studies. The persistent neurological symptoms of long COVID encompass fatigue, headache, cognitive decline, "brain fog", dysautonomia, neuropsychiatric issues, loss of smell (anosmia), loss of taste (ageusia), and peripheral nerve problems (peripheral neuropathy). Reported pathogenic mechanisms encompass viral persistence and neuro-invasion by SARS-CoV-2, neuroinflammation, autoimmunity, coagulopathy, and endotheliopathy. Raising awareness of potential complications is crucial for preventing and alleviating the long-term effects of long COVID and enhancing the prognosis for affected patients. This review explores the hypothetical pathophysiological mechanisms and pathways of NC-PASC with a sole aim to increase awareness about this crippling disease.

Mental health, sleep, and respiratory health after initiating elexacaftor/tezacaftor/ivacaftor treatment in children with cystic fibrosis.

Cystic fibrosis transmembrane conductance regulator (CFTR) modulator elexacaftor/tezacaftor/ivacaftor (ETI) significantly improves lung function but its effect on mental health and sleep remains poorly understood. We report on mental health, sleep, and respiratory health outcomes of adolescents with CF commenced on ETI therapy, and monitored the prevalence of neuropsychiatric issues through thecoronavirus disease 2019 pandemic. We conducted a prospective longitudinal study of 31 adolescents (aged 10-18 years) from July 2021 to October 2022. Data collected include demographics, Patient Health Questionnaire-9 (PHQ-9), General Anxiety Disorder-7 (GAD-7), Pediatric Daytime Sleepiness Scale (PDSS), Sleep Disturbance Scale for Children (SDSC) scores, and FEV1 percent predicted. Twenty of 31 adolescents had data before and after ETI initiation. Mean differences (MD) in mental health, sleep, and respiratory health pre- and post-ETI therapy commencement were estimated using paired t-tests. The prevalence and trajectories of anxiety, depression, and sleep disturbance were described between the ETI epochs, and over the pandemic period. FEV1 improved following ETI therapy commencement (MD, 95% confidence interval [CI]: 7.1% (4.7%-9.6%) whereas PHQ-9, GAD-7, PDSS, and SDSC scores did not change significantly. Ten percent of participants developed new-onset anxiety/depression concerns and 10% developed new sleep concerns following ETI initiation. This is the first prospective longitudinal study of mental health and sleep changes after ETI commencement in adolescents with CF. Although respiratory outcomes improved, ETI did not improve anxiety, depression or sleep.

NR4A2 as a Novel Target Gene for Developmental and Epileptic Encephalopathy: A Systematic Review of Related Disorders and Therapeutic Strategies.

The NR4A2 gene encodes an orphan transcription factor of the steroid-thyroid hormone-retinoid receptor superfamily. This review focuses on the clinical findings associated with the pathogenic variants so far reported, including three unreported cases. Also, its role in neurodegenerative diseases, such as Parkinson's or Alzheimer's disease, is examined, as well as a brief exploration on recent proposals to develop novel therapies for these neurological diseases based on small molecules that could modulate NR4A2 transcriptional activity. The main characteristic shared by all patients is mild to severe developmental delay/intellectual disability. Moderate to severe disorder of the expressive and receptive language is present in at least 42%, while neuro-psychiatric issues were reported in 53% of patients. Movement disorders, including dystonia, chorea or ataxia, are described in 37% patients, although probably underestimated because of its frequent onset in late adolescence-young adulthood. Finally, epilepsy was surprisingly present in 42% of patients, being drug-resistant in three of them. The age at onset varied widely, from five months to twenty-six years, as did the classification of epilepsy, which ranged from focal epilepsy to infantile spasms or Lennox-Gastaut syndrome. Accordingly, we propose that NR4A2 should be considered as a first-tier target gene for the genetic diagnosis of developmental and epileptic encephalopathy.

Evaluate the in vitro effect of anthracycline and alkylating cytophosphane chemotherapeutics on dopaminergic neurons.

Iatrogenesis is an inevitable global threat to healthcare that drastically increases morbidity and mortality. Cancer is a fatal pathological condition that affects people of different ages, sexes, and races around the world. In addition to the detrimental cancer pathology, one of the most common contraindications and challenges observed in cancer patients is severe adverse drug effects and hypersensitivity reactions induced by chemotherapy. Chemotherapy-induced cognitive neurotoxicity is clinically referred to as Chemotherapy-induced cognitive impairment (CICI), chemobrain, or chemofog. In addition to CICI, chemotherapy also causes neuropsychiatric issues, mental disorders, hyperarousal states, and movement disorders. A synergistic chemotherapy regimen of Doxorubicin (Anthracycline-DOX) and Cyclophosphamide (Alkylating Cytophosphane-CPS) is indicated for the management of various cancers (breast cancer, lymphoma, and leukemia). Nevertheless, there are limited research studies on Doxorubicin and Cyclophosphamide's pharmacodynamic and toxicological effects on dopaminergic neuronal function. This study evaluated the dopaminergic neurotoxic effects of Doxorubicin and Cyclophosphamide. Doxorubicin and Cyclophosphamide were incubated with dopaminergic (N27) neurons. Neuronal viability was assessed using an MTT assay. The effect of Doxorubicin and Cyclophosphamide on various prooxidants, antioxidants, mitochondrial Complex-I & IV activities, and BAX expression were evaluated by Spectroscopic, Fluorometric, and RT-PCR methods, respectively. Prism-V software (La Jolla, CA, USA) was used for statistical analysis. Chemotherapeutics dose-dependently inhibited the proliferation of the dopaminergic neurons. The dopaminergic neurotoxic mechanism of Doxorubicin and Cyclophosphamide was attributed to a significant increase in prooxidants, a decrease in antioxidants, and augmented apoptosis without affecting mitochondrial function. This is one of the first reports that reveal Doxorubicin and Cyclophosphamide induce significant dopaminergic neurotoxicity. Thus, Chemotherapy-induced adverse drug reaction issues substantially persist during and after treatment and sometimes never be completely resolved clinically. Consequently, failure to adopt adequate patient care measures for cancer patients treated with certain chemotherapeutics might substantially raise the incidence of numerous movement disorders.

The presence and burden of cognitive issues: discordance between the perception of neurologists and people living with multiple sclerosis.

Cognitive impairment is a common symptom of multiple sclerosis (MS) and occurs in more than 40% of people living with MS (plwMS). No real-world study has assessed the perception of neurologists and plwMS on cognitive issues. Using data from the 2011-2019 Adelphi MS Disease Specific Programme database, this real-world, retrospective, cross-sectional multi-cohort study included people aged ≥18 years with relapsing-remitting MS and secondary progressive MS from the United States, UK and the EU. Neurologists provided data on the patient record form for plwMS, with the same plwMS invited to voluntarily complete a patient self-completion form: a questionnaire about their experiences with MS. Of 25,374 plwMS, 4817 who provided information on cognitive and mood symptoms were included in the analysis. Of the plwMS, 68% and 59% reported feeling 'mentally fatigued' and having 'difficulty concentrating', respectively. Neurologists reported only 27% of plwMS as having 'difficulty concentrating' and 15% of plwMS as having 'short-/long-term memory problems'. Neurologists reported cognitive or mood symptoms as 'not experienced' by a higher percentage of participants with relapsing-remitting MS than secondary progressive MS. Of the plwMS who experienced 'difficulty concentrating', most had a concomitant feeling of being 'mentally fatigued' (52%), followed by 'feeling anxious or tense' (49%) and 'feeling depressed' (44%). In plwMS, caregivers reported 'difficulty concentrating' (16%) as the most common cognitive issue. A clear discordance was observed between neurologists and plwMS regarding the perception of the cognitive and neuropsychiatric issues. These results underline the under-perception of cognitive and emotional affective symptoms in plwMS during neurological consultations.

Paroxysmal Dystonic Posturing Mimicking Nocturnal Leg Cramps as a Presenting Sign in an Infant with DCC Mutation, Callosal Agenesis and Mirror Movements.

Background/Objectives: Pathogenic variants in the deleted in colorectal cancer gene (DCC), encoding the Netrin-1 receptor, may lead to mirror movements (MMs) associated with agenesis/dysgenesis of the corpus callosum (ACC) and cognitive and/or neuropsychiatric issues. The clinical phenotype is related to the biological function of DCC in the corpus callosum and corticospinal tract development as Netrin-1 is implicated in the guidance of developing axons toward the midline. We report on a child with a novel inherited, monoallelic, pathogenic variant in the DCC gene. Methods: Standardized measures and clinical scales were used to assess psychomotor development, communication and social skills, emotional and behavioural difficulties. MMs were measured via the Woods and Teuber classification. Exome sequencing was performed on affected and healthy family members. Results: The patient's clinical presentation during infancy consisted of paroxysmal dystonic posturing when asleep, mimicking nocturnal leg cramps. A brain magnetic resonance imaging (MRI) showed complete ACC. He developed typical upper limb MMs during childhood and a progressively evolving neuro-phenotype with global development delay and behavioural problems. We found an intrafamilial clinical variability associated with DCC mutations: the proband's father and uncle shared the same DCC variant, with a milder clinical phenotype. The atypical early clinical presentation of the present patient expands the clinical spectrum associated with DCC variants, especially those in the paediatric age. Conclusions: This study underlines the importance of in-depth genetic investigations in young children with ACC and highlights the need for further detailed analyses of early motor symptoms in infants with DCC mutations.

Maternal Substance Use and Early-Life Adversity: Inducing Drug Dependence in Offspring, Interactions, Mechanisms, and Treatments.

The likelihood of substance dependency in offspring is increased in cases when there is a family history of drug or alcohol use. Mothering is limited by maternal addiction because of the separation. Maternal separation (MS) leads to the development of behavioural and neuropsychiatric issues in the future. Despite the importance of this issue, empirical investigations of the influences of maternal substance use and separation on substance use problems in offspring are limited, and studies that consider both effects are rare. This study aims to review a few studies on the mechanisms, treatments, genetics, epigenetics, molecular and psychological alterations, and neuroanatomical regions involved in the dependence of offspring who underwent maternal addiction and separation. The PubMed database was used. A total of 95 articles were found, including the most related ones in the review. The brain's lateral paragigantocellularis (LPGi), nucleus accumbens (NAc), caudate-putamen (CPu), prefrontal cortex (PFC), and hippocampus, can be affected by MS. Dopamine receptor subtype genes, alcohol biomarker minor allele, and preproenkephalin mRNA may be affected by alcohol or substance use disorders. After early-life adversity, histone acetylation in the hippocampus may be linked to brain-derived neurotrophic factor (BDNF) gene epigenetics and glucocorticoid receptors (GRs). The adverse early-life experiences differ in offspring›s genders and rewire the brain›s dopamine and endocannabinoid circuits, making offspring more susceptible to dependence. Related psychological factors rooted in early-life stress (ELS) and parental substance use disorder (SUD). Treatments include antidepressants, histone deacetylase inhibitors, lamotrigine, ketamine, choline, modafinil, methadone, dopamine, cannabinoid 1 receptor agonists/antagonists, vitamins, oxytocin, tetrahydrocannabinol, SR141716A, and dronabinol. Finally, the study emphasizes the need for multifaceted strategies to prevent these outcomes.

Late onset Darier’s Disease with Palmoplantar Keratoderma: A Case Report

Darier’s disease is an infrequently encountered autosomal dominant condition characterised by complete penetrance but variable expression. It is characterised by abnormal keratinisation and epidermal adhesion deficiency, clinically presenting as greasy keratotic or warty papules and plaques, primarily affecting seborrheic regions and flexures. Additional manifestations include palmar pits, nail abnormalities, cobble-stoning of the oral mucosa, and even neuro-psychiatric issues. In extremely rare cases, mucosal involvement can occur in the oral, laryngeal, Oesophageal, or rectal areas. Familial Darier’s disease typically emerges during puberty. Here, the authors present a unique case of 55 years old male patient of Darier’s disease with delayed onset, despite a significant family history of the condition. The clinico-pathological aspects, highlighting the presence of palmo-plantar keratoderma are also discussed. Treatment included the application of topical hydrocortisone 1% cream twice daily for two weeks, then once daily for two weeks along with dexpanthenol once daily for eight weeks.

Assessing the impact of falls on neuropsychiatric symptoms in patients with neurodegenerative disease

AbstractBackgroundFalls are the most common injury faced by older adults and those with neurodegenerative diseases. Falls can result in concussion/mild traumatic brain injury(mTBI). Concussions in older adults or those with neurodegenerative disease can have a significant impact on behavior as post‐concussion symptoms include neuropsychiatric issues. We hypothesized that there is a relationship between past fall and neuropsychiatric symptoms and neuropsychiatric symptom severity.MethodsWe used data on falls and Neuropsychiatric Inventory (NPI) from the Ontario Neurodegenerative Disease Research Initiative dataset for 480 individuals with neurodegenerative diseases (Alzheimer’s Disease, Parkinson’s Disease, Amyotrophic lateral sclerosis, frontotemporal dementia and vascular cognitive impairment). We used the Chi‐squared and Mann‐Whitney tests to compare frequency of NPI symptoms (anxiety, depression, irritability, disinhibition, apathy, delusions, hallucinations, agitation, euphoria, motor‐disturbance, night‐time behaviour, appetite), and total NPI severity and distress, respectively, between patients with and without falls in the past 12 months.ResultsComparing patients with falls (n = 169; mean‐age = 68.3±9; 36% F) to patients without falls (n = 311; mean‐age = 68.7±7; 32% F), there was a significantly higher frequency of anxiety (Chi‐squared test, X2 (df = 1, N = 480) = 12.859, P‐value = 0.0003); higher median anxiety severity (Mann‐Whitney/Wilcoxon‐test p‐value = 0.0002); and higher median partner anxiety distress (Wilcox test p‐value = 0.0006) in those who had had a previous fall compared to those who had not, even with multiple comparison correction. Depression, apathy, disinhibition, night‐time behaviours, and eating/appetite changes and total NPI severity were significantly worse in those with previous falls but did not survive multiple comparison correction.ConclusionWe found that anxiety frequency, severity and distress were much higher in patients with neurodegenerative disease who had a fall in the preceding 12 months compared to those without falls. Our study suggests that neuropsychiatric symptoms, especially anxiety are frequent and should be assessed in those with previous falls as they can be a consequence of mild brain injury and may contribute to worsening cognition or behaviors.

Feasibility and Safety of the First-in-Human Chemotherapy-Light Combination of Rituximab, Polatuzumab Vedotin and Glofitamab in Previously Untreated Aggressive B-Cell Lymphoma Patients Above 60 Years of Age Ineligible for a Fully Dosed R-CHOP - R-Pola-Glo/Ikf-t062, a Study of the Austrian Group for Medical Tumor Therapy (AGMT-NHL-16) and the German Lymphoma Alliance (GLA2022-10)

Background. Diffuse large B-cell lymphoma is the most common aggressive B-cell lymphoma mainly affecting elderly patients. The treatment goal is usually cure, however, older and frail patients typically exhibit a growing number of comorbidities that significantly increase treatment-related morbidity and mortality thus limiting the treatment goal due to switching to less effective treatments. Particular in the frail population there is an urgent medical need to establish highly effective therapies suitable for patients with limited functional organ reserve. To this end, we developed the chemotherapy-light combination therapy R-Pola-Glo, which is composed of the anti-CD20 antibody rituximab in combination with the antibody-drug conjugate polatuzumab vedotin (anti-CD79b) and the bispecific antibody glofitamab (CD20×CD3). Here, we report the safety data report of the run-in phase following treatment of the first 10 patients with this first-in-human chemotherapy-light combination. Methods. R-Pola-Glo (EudraCT No.: 2022-003398-51) is a prospective, bi-national (Germany/Austrian), multicenter, one arm, phase II trial designed to estimate the 1-year progression free survival of the chemotherapy-light combination rituximab, polatuzumab vedotin and glofitamab as the primary endpoint. Previously untreated DLBCL patients above 60 years of age, who are not eligible for a fully dosed R-CHOP-like therapy were eligible for enrollment, including patients with a lymphoma-related ECOG 3 and reduced kidney function. The study treatment plan includes a mandatory prephase with prednisolone or dexamethasone followed by 12 treatment cycles of 3 weeks each (Fig. 1). The step-up cycle (cycle 1) is comprised of intravenous (i.v.) application of obinutuzumab 1000 mg on D1, followed by i.v. application of polatuzumab vedotin 1.8 mg/kg on D2 and i.v. application of glofitamab in escalating doses of 2.5 mg on D8 and 10 mg on D15. This is followed by the target dose phase (cycles 2-6). Each of the 5 target dose cycles included rituximab 375 mg/m 2 and polatuzumab 1.8 mg/kg, both administered i.v. on D1 and i.v. glofitamab 30 mg on D2. The consolidation phase (cycles 7-12) comprises 6 cycles of glofitamab 30 mg administered intravenously on D1. As this is the first in human combination of these antibodies, the initial 10 patients were analyzed in a planned safety run-in phase and are reported here. Results. The median age of the first 10 patients was 79 years (range 69-81), with 70% of patients presenting with stage III/IV disease and elevated LDH; ECOG of all patients was <3 (ECOG 0: 4 patients; ECOG 1: 4 patients; ECOG 2: 2 patients). Extranodal involvement was present in 40%. Overall, 70% patients had a high-intermediate/high-risk IPI representing a high-risk population. The median follow-up time presented here from registration to time of data cut July 20, 2023 is 62 days (range 38-122) and longer follow-up will be presented at the time of the meeting. We observed 34 adverse events (AEs) including infections (6/10 patients; grade 1: 2; grade 2: 2; grade 3:2; no grade 4/5), neuropsychiatric issues (prednisone induced psychosis, fatigue, dysgeusia (4/10; all grade 1), CRS (3/10; all grade 1), cardiovascular side effects (3/10; all grade 2), infusion related reactions (2/10; grade 2), anemia (1/10; grade 2), bleeding (1/10; grade 3), and renal toxicity (1/10; grade 3). Notably, so far neither polyneuropathy nor ICANs were reported. Ten of the AEs occurring in 5 patients over all courses administered so far required hospitalization and were therefore classified as serious AEs and included infections (4 in two patients, peribronchitis and urosepsis) CRS (2), renal toxicity (1), deep vein thrombosis (1) and bleeding (1). Neither of the events were life threatening and no death occurred. Conclusion. R-Pola-Glo is a chemotherapy-light treatment regimen that exhibits an excellent safety profile in a vulnerable patient population. Specifically, no life-threating adverse events, ICANS, high grade polyneuropathy or deaths of any cause occurred, and CRS events were limited to grade 1. Acknowledgements. Study sponsor of R-Pola-Glo (EudraCT No.: 2022-003398-51) is the Institut für Klinische Krebsforschung (IKF) Frankfurt, Germany; financial support is provided by F. Hoffmann-La Roche Ltd. TM and RWK contributed equally as first authors; RG and BC contributed equally as senior authors.

47 Social Cognition and Moral Decision Making in Korsakoff's Syndrome

Objective:Korsakoff's syndrome (KS) is a neuropsychiatric disorder, caused by vitamin B1 insufficiency. KS is characterized by severe declarative amnesia. Often, also executive disorders are present. Emotion recognition and theory of mind are gold-standard measures of social cognition. Moral decision making is often assessed by means of moral dilemmas. Surprisingly social cognition and moral decision making has received hardly any attention in research on KS, although the severity of behavioural problems in KS suggest possible problems in both domains. The aim of this study was therefore to broadly assess social cognition and moral decision-making capacities in patients with KS.Participants and Methods:20 KS patients and 20 age-, education-, and gender-matched healthy controls were assessed on standardized tests for social cognition, namely the mini-Social Cognition and Emotional Assessment battery (mini-SEA), and a specialized version of the Sally-Anne Test. Moral decision making was assessed by means of the Moral Behaviour Inventory (MBI) for everyday moral dilemmas, and ten cartoons of abstract moral dilemmas. For moral decision making, “yes” and “no” responses were scored, together with a scoring for moral reasoning according to the Kohlberg stages of moral maturity.Results:KS patients have large impairments in both cognitive and affective aspects of social cognition. Their ability to recognize emotions, take the perspective of others, and understand socially awkward situations is vastly compromised. While KS patients were able to replicate the Sally Anne storyline, their task performance was on chance level. Regarding moral decision making, there was a tendency to more frequently carry out the moral dilemma. Moral maturity, as indexed by means of their reasoning behind the decision was of a lower level. Of interest, moral immaturity could find its origin already before the onset of the KS diagnosis, as suggested by elevated premorbid levels of delinquent behavior.Conclusions:Both social cognition and moral decision making are compromised in KS patients. Specifically social cognitive disorders are the direct result of KS, and are likely to strongly relate to social and neuropsychiatric issues in KS. Moral decision making was more likely to be already of a lower level of maturity, based on a strong relationship between premorbid delinquency and moral immaturity in KS patients. This study highlights the importance to properly index social cognition in neuropsychological assessments for individuals with a possible KS diagnosis

The Role of the Patient Partnership in Designing Research on Neuropsychiatric Issues in Hypoparathyroidism.

Hypoparathyroidism is a rare endocrine disease that is associated with hypocalcemia and insufficient parathyroid hormone (PTH) levels. Neuropsychiatric complaints are common in hypoparathyroidism. Yet there is a large knowledge gap in our understanding of cognitive dysfunction in hypoparathyroidism and partnering with patients is essential for filling this hole. Input from hypoparathyroid patients is needed to define objective, performance-based cognitive impairments. Creating patient advisory boards that provide input for planning clinical trials would enable patient perspectives to be shared. This would ensure that meaningful, standardized neuropsychological instruments that prioritize patients' cognitive concerns are selected. Patient partnership is also needed to understand the wide inter-individual variability of cognitive symptoms in hypoparathyroidism, as well as mechanisms aside from calcium shifts that might explain cognitive symptoms, such as low PTH itself, alterations in brain structure, or other hypoparathyroidism-associated comorbidities. With new PTH replacement therapies on the horizon, patient input about studying how these therapies impact, and maybe even reverse, cognitive impairment will also be critical. Ultimately, the inclusion of patient partners in hypoparathyroidism research will advance the design of neuropsychiatric studies and generate key input for understanding how to reduce the burden of this disease.

Reversible Neuroimaging findings associated with Kratom use. (P12-5.021)

<h3>Objective:</h3> To report a case of reversible ischemic changes on MRI associated with chronic kratom use in a patient presenting with encephalopathy and seizures <h3>Background:</h3> Mitragyna speciosa, or kratom, is a psychoactive substance that targets multiple opioid receptors and has been an unregulated and under-reported substance of abuse. Its use has been reported to cause liver toxicity, respiratory depression, neuropsychiatric issues and even death. Its neurological side effects at this time are not well established. <h3>Design/Methods:</h3> We report a case of a 23-year-old male with a medical history significant for polysubstance abuse who presented for acute encephalopathy and seizure-like episode, requiring ICU admission and intubation for airway protection. <h3>Results:</h3> Patient initially presented with hypotension, leukocytosis, and lactic acidosis concerning sepsis. He was started on broad spectrum antibiotics for meningitis coverage and Keppra to prevent further seizures. Urine toxicology screen was negative. Once examined off sedation, the patient was noted to have right upper extremity weakness with babinski reflex on right concerning stroke therefore an MRI was obtained. It revealed small areas of confluent juxtacortical white matter abnormality high in the posterior frontal lobes bilaterally with some true diffusion restriction on the left suggestive of acute infarct. However, the appearance was unusual for a stroke. Further history from the family revealed that the patient uses Kratom on a daily basis for a number of years to help with anxiety. He had no further seizures and his mental status improved during the remainder of his hospitalization. Repeat MRI Brain 2 months after initial presentation showed resolution of the abnormalities. <h3>Conclusions:</h3> Kratom has been reported in the past to cause neurological issues like seizures or PRES. This case shows reversible ischemic neuroimaging findings of Kratom use in a patient with a stroke-like presentation. <b>Disclosure:</b> Dr. Pisati has nothing to disclose. Dr. Shah has nothing to disclose. Dr. Thaliath has nothing to disclose. Dr. Maryala has nothing to disclose. Dr. Allam has nothing to disclose.

INCOG 2.0 Guidelines for Cognitive Rehabilitation Following Traumatic Brain Injury: What's Changed From 2014 to Now?

INCOG 2.0 Guidelines for Cognitive Rehabilitation Following Traumatic Brain Injury: What's Changed From 2014 to Now?

A Molecular Basis Approach of Eczema and Its Link to Depression and Related Neuropsychiatric Outcomes: A Review.

"What about my eczema do I love the most? The hurt? A scratch? The humiliation of the public? Oh, there are so many options available!" Studies have shown an association between atopic eczema (AE), a common inflammatory skin condition, and an increased risk of mental health problems. Despite this, experts are still examining the causes of the links between common mental diseases (such as depression and anxiety) and skin conditions. We collected studies that were published in the past 10 years. We searched the following databases: PubMed, PubMed Central, Science Direct, and Google Scholar. Further relevant research was assessed by examining the bibliographies of eligible studies and related ones.Two reviewers looked at the titles and abstracts of the studies to see if they were eligible, and then they read the full texts. We went through eczema and depression relationships, their etiopathogenesis, molecular basis, immune response, the role of genetic factors, and possible interactions between neurons and the immune system. Another possible contributing factor could be a change in cutaneous microbiota in eczema patients. Part of the initial connection could be explained by psychological stress, which further leads to depression in eczema patients. Healthcare professionals treating eczema patients must be aware of the comorbidity of mental problems and the potential that people with poor mental health may need social or emotional support. Patients with eczema, especially youngsters, can benefit from routine health checks since they can help identify neuropsychiatric issues like depression early and lessen the burden of both physical sickness and poor mental health. Given that AE is a condition that appears to be related to depression and anxiety, more research with larger samples is needed to determine a potential role for targeted mental health screening in people with AE, as well as the possibility of mental health modification through improved AE control (e.g., using new biologic agents).

Levetiracetam "Narrative Review of Neuropsychiatric Issues"

Introduction&#x0D; Levetiracetam, an anti-epileptic drug, is usually used as an adjunctive treatment of partial-onset seizures with or without secondary generalization. In this article, various neuropsychiatric effects of Levetiracetam are investigated.&#x0D; Methods&#x0D; The following databases were searched: PUBMED, Google Scholar, MEDLINE, Embase, ProQuest, and Science Direct. The articles searched in the mentioned databases were from 2003 to 2021. Ninety-nine articles were selected, fifteen articles such as case reports and letters to the editor were removed due to low scientific credibility, and eighty-four articles were selected. Due to the small number of articles, articles in the form of case reports and letters to the editor were also used to write about mania.&#x0D; Results&#x0D; Case reports showed that some cases of behavioral disorders, aggression, and depression had been observed following the use of Levetiracetam. In this study, various evidence were collected to determine the performance of Levetiracetam and to what extent it can have important and vital side effects. This drug can strengthen suicidal thoughts and aggression in consuming patients, especially the patients with other underlying diseases.&#x0D; Conclusion&#x0D; According to the side effects mentioned for Levetiracetam, it is suggested that psychiatrists and neurologists pay more attention to these side effects when prescribing.

A-153 Characteristics of Patients Seeking Treatment for “Brain Fog” Secondary to Post-Acute Sequelae of COVID-19 (PASC) in the Deep South

Objective: Describe those with persistent neuropsychiatric symptoms seeking treatment for Post-Acute Sequelae of COVID-19 (PASC).Method: Patients were referred for neuropsychological evaluation from the University of Alabama at Birmingham (UAB) Post-COVID Treatment Program. Ninety-seven patients completed a comprehensive set of self-report questionnaires.Results: Patients were 49 years old (range: 18 to 74), had 15.49 years (SD = 2.43) of education, and identified as female (77%), married (51%), and White/Caucasian (73%) or Black/AA (25%). Reported annual income ranged from ≤ $20,000 (11%) to ≥ $100,000 (32%), with 75% currently employed. Confirmed positive test result for COVID-19 was reported in 88%, with 87% having the original virus and 13% the Delta variant, based on estimated dates of infection. Symptoms during the acute illness included: headache (76%), fever (51%), cough (57%), shortness of breath (56%), and loss of smell or taste (54%). Most of the participants were not hospitalized (76%) nor required oxygen therapy (78%). Persistent symptoms included: headache (55%), shortness of breath (53%), muscle and joint pain (53%), cough (17%), congestion (40%) and loss of smell or taste (25%). Of these participants, 87% reported they had not returned to their baseline health because of COVID-19 and most indicated impaired job performance following COVID-19 infection.Conclusion: Those who sought treatment for persistent neuropsychiatric symptoms following a symptomatic course of COVID-19 were commonly middle aged, White, women, with at least a high school education. “Brain fog” secondary to PASC can result in reported persistent health and neuropsychiatric issues that can impact ability to work.

Characterizing and TRAPing a Social Stress-Activated Neuronal Ensemble in the Ventral Tegmental Area.

Social stress is a major contributor to neuropsychiatric issues such as depression, substance abuse and eating disorders. The ventral tegmental area (VTA) is involved in the effects of stress on cognitive and emotional processes perturbed in these disorders. However, the VTA is a cellularly heterogeneous brain area and it remains unclear which of its neuronal populations make up the social stress-sensitive ensemble. The current study characterizes the molecular, topographical and functional properties of VTA social stress-activated cells. First, we used immunohistochemical analysis of Fos protein, a marker of recent increased neuronal activity, to show that acute social stress activates a mainly neuronal ensemble in the VTA (VTASocial stress neurons). Topographical analysis showed that this ensemble, which comprises ∼11% of all VTA neurons, occurs across VTA subregions. Further analysis showed that approximately half of the VTASocial stress neurons express the dopamine synthesis rate-limiting enzyme tyrosine hydroxylase (TH). In a minority of cases this occurred with coexpression of vesicular glutamate transporter 2 (Vglut2). Also part of the ensemble were VTA cells expressing just Vglut2 without TH, and cells expressing the vesicular GABA transporter (VGAT) without TH. Next, using targeted recombination in active populations (TRAP2), we showed that VTASocial stress neurons can be permanently tagged and made tractable for future functional investigations. Using a combination of TRAP2 and patch-clamp electrophysiology we demonstrate that VTASocial stress neurons exhibit higher excitability than their non-TRAPed neighbor cells. Overall, this study shows that acute social stress activates an ensemble of neurons throughout the VTA, comprising distinct molecular identities, and with specific electrophysiological features. It also identifies TRAP2 as a tool to make this ensemble tractable for future functional studies.

The brain in oral clefting: preliminary results of a systematic review with meta-analyses

Introduction Previous neuroimaging studies of individuals with nonsyndromic oral clefts have revealed subtle brain structural differences compared to matched controls. Additional studies strongly suggest that the higher incidence of neuropsychiatric issues observed in these individuals may be explained by these neuroanatomical differences. Currently there are no studies that have assessed the overall empirical evidence of the effect of oral clefts on the brain.Objectives Our aim was to summarize available evidence on potential brain structure differences in individuals with nonsyndromic oral clefts and their matched controls. In the current presentation, we discuss the results of regional brain structural differences.Methods Five databases were systematically searched in September 2020 for case-control studies that reported neuroimaging in healthy individuals and individuals with nonsyndromic oral clefts. Duplicate study selection, data extraction, random effects meta-analyses of mean differences (MDs) and their 95% confidence intervals were performed in order to compare regional brain MRI volumes.Results We have identified 245 records following the database searches, from which 12 records met the inclusion criteria. Quantitative data on brain structure were available in three studies.The cerebellum, occipital and temporal lobes were significantly smaller in the cleft group compared to controls (MD: -12.46, 95% CI: -18.26, -6.67, n=3 studies; MD:-7.39, 95% CI: -12.80, -1.99, n=2 studies; MD: -10.53, 95% CI: -18.23, -2.82, n=2 studies, respectively).ConclusionsThere may be structural brain differences between individuals with nonsyndromic oral clefts and their controls based on the available evidence.DisclosureNo significant relationships.