NCOG-48. LONGITUDINAL ASSESSMENT OF SUBJECTIVE COGNITIVE FUNCTION IN A BRAIN TUMOR SAMPLE: IMPROVED CORRESPONDENCE WITH NEUROPSYCHOLOGICAL PERFORMANCE OVER TIME

INTRODUCTION Estimates of subjective cognitive function (SCF) generally show minimal correlation with objective measures of neurocognitive function (NCF). Our group recently validated a new metric of SCF in neuro-oncology patients, creating the Cognitive Index of the Functional Assessment of Cancer Therapy-Brain (FACT-Br-CI). This study examines whether brain tumor (BT) patients evaluated on more than one occasion show improved relationship between SCF and NCF. We hypothesized that change scores in SCF and NCF across evaluation would be more highly correlated than SCF and NCF at either timepoint. METHODS A retrospective study of BT patients who completed two neuropsychological evaluations (baseline, follow-up) was conducted. NCF was measured by the clinical trial battery composite (CTBC), a mean of 6 commonly used neuropsychological test scores. SCF was measured by the FACT-Br-CI. Mood/Anxiety were measured by the Beck scales (BAI/BDI-II). Change over time on each metric was evaluated with paired t-test. Correlational analyses evaluated relationships between NCF, SCF, and mood within and between time points. RESULTS Twenty-nine patients (16 female; mean age=54.6y; mean education=15.5y) completed all CTBC measures and FACT-Br-CI, 28 of whom completed and BDI and/or BAI. On group analyses, there were no significant differences between baseline and follow-up on CTBC (t=-.53;p=ns) or FACT-Br-CI (t=-.98;p=ns). Correlations between CTBC and FACT-Br-CI were nonsignificant at baseline (r=.24;p=ns), but significant at follow-up (r=.56;p=0.002). Change scores over time were unrelated (r=-.104;p=ns). Similar to previous studies, the FACT-BR-CI correlated with the BDI-II at baseline (r=-.38;p=0.04) and follow-up (r=-.59;p< 0.001) and with the BAI at follow-up (r=-.44;p=0.02). CONCLUSION In this small group of brain tumor patients seen for repeated neuropsychological evaluations, we found that agreement between SCF and NCF was much higher on their second than initial evaluation. These findings suggest that patients may develop enhanced awareness of their cognitive function from an initial evaluation that persists over time.

ALS Cognitive Behavioral Screen-Phone Version (ALS-CBS™-PhV): norms, psychometrics, and diagnostics in an Italian population sample

Background Up to 50% of motor neuron disease (MND) patients show neuropsychological deficits which negatively affect prognosis and care. However, disability-related logistical issues and uneven geographical coverage of healthcare services may prevent MND patients from accessing neuropsychological evaluations. This study thus aimed to standardize for the Italian population the ALS Cognitive Behavioral Screen-Phone Version (ALS-CBS™-PhV), an MND-specific, telephone-based screening for frontotemporal dysfunction. Methods The cognitive section of the ALS-CBS™-PhV, the Italian telephone-based Mini-Mental State Examination (Itel-MMSE), and the Telephone Interview for Cognitive Status (TICS) was administered to 359 healthy individuals (143 males, 216 females; age, 52.7 ± 15.8; education, 13.1 ± 4.4). Norms were derived through equivalent scores. Validity, factorial structure, reliability, diagnostic accuracy, and item difficulty and discrimination were examined. Statistical equivalence between the telephone-based and in-person versions was tested. Results ALS-CBS™-PhV measures were predicted by age and education. The ALS-CBS™-PhV reflected a mono-component structure, converged with Itel-MMSE and TICS scores (rs = .23–.51) and was equivalent to its in-person format (t = .37; p = .72). Good internal (Cronbach’s α = .61), test–retest (ICC = .69), and inter-rater (ICC = .96) reliability was detected. High accuracy was found when tested against both the Itel-MMSE and the TICS (AUC = .82–89). Backward digit span items were the most discriminative. Discussion The ALS-CBS™-PhV is a statistically solid screening test for frontotemporal disorders featuring MND. Its standardization allows for (1) improvements in tele-healthcare for MND patients, (2) epidemiological applications, and (3) effective assessments in decentralized clinical trials. The ALS-CBS™-PhV can be also suitable for assessing bedridden and visually impaired patients with motor disorders.

Diazepam induced sleep spindle increase correlates with cognitive recovery in a child with epileptic encephalopathy

Background Continuous spike and wave of sleep with encephalopathy (CSWS) is a rare and severe developmental electroclinical epileptic encephalopathy characterized by seizures, abundant sleep activated interictal epileptiform discharges, and cognitive regression or deceleration of expected cognitive growth. The cause of the cognitive symptoms is unknown, and efforts to link epileptiform activity to cognitive function have been unrevealing. Converging lines of evidence implicate thalamocortical circuits in these disorders. Sleep spindles are generated and propagated by the same thalamocortical circuits that can generate spikes and, in healthy sleep, support memory consolidation. As such, sleep spindle deficits may provide a physiologically relevant mechanistic biomarker for cognitive dysfunction in epileptic encephalopathies. Case presentation We describe the longitudinal course of a child with CSWS with initial cognitive regression followed by dramatic cognitive improvement after treatment. Using validated automated detection algorithms, we analyzed electroencephalograms for epileptiform discharges and sleep spindles alongside contemporaneous neuropsychological evaluations over the course of the patient’s disease. We found that sleep spindles increased dramatically with high-dose diazepam treatment, corresponding with marked improvements in cognitive performance. We also found that the sleep spindle rate was anticorrelated to spike rate, consistent with a competitively shared underlying thalamocortical circuitry. Conclusions Epileptic encephalopathies are challenging electroclinical syndromes characterized by combined seizures and a deceleration or regression in cognitive skills over childhood. This report identifies thalamocortical circuit dysfunction in a case of epileptic encephalopathy and motivates future investigations of sleep spindles as a biomarker of cognitive function and a potential therapeutic target in this challenging disease.

A-78 Interdisciplinary Consultation in a Case of Herpes Simplex Encephalitis with Unique Neuropsychiatric Symptoms

Objective Herpes simplex encephalitis (HSE) is a rare neurological condition (~2–4 per million) marked by brain inflammation caused by herpes simplex virus (HSV). HSE is associated with both cognitive and neuropsychiatric symptoms, particularly memory and executive dysfunction. We present the case of a 63-year-old, right-handed, St. Lucian female who completed serial neuropsychological evaluations (NPE). Method The patient presented with a six-day history (per collateral) of fever, confusion, and nausea. The patient denied cognitive changes. Magnetic Resonance Imaging (MRI) revealed leptomeningeal enhancement in the right sylvian fissure, multiple right temporal sulci, and inferior right frontal lobe (Figure 1). There was no indication of seizures. Cerebrospinal fluid analysis was positive for HSV-1. A two-week course of intravenous acyclovir was initiated on hospital day three. Results (Table 1). Initial NPE results (day five) revealed global cognitive impairment with sparing of auditory attention; exam was limited secondary to significant fatigue. Following completion of antivirals, subsequent NPE (day 17) revealed similar findings, despite improved alertness; left neglect (Figure 2) and significant anosagnosia (i.e., lack of disease awareness) and anosodiaphoria (i.e., indifference reaction to neurological deficits) were noted. Two-month outpatient follow-up NPE revealed marginal improvement in aspects of language and learning, but continued memory impairment, dense anosagnosia, and anosodiaphoria. Conclusion In this case, the patient presented with salient neuropsychiatric sequelae of HSE that have not been commonly associated with this condition in the extant literature. Her denial of cognitive symptoms may have initially confounded the differential diagnosis, emphasizing the importance of multi-specialty collaboration. Limitations of available normative data also complicated examination.

A-176 Undercover Performance Validity Testing: Proposed Embedded Validity Indicators for Pediatric Neuropsychological Assessment

Objective Literature supports the use of the Delis-Kaplan Executive Function System Trail Making Test Conditions 4/2 ratio (TMT 4/2) and Stroop Color Word Test Word Reading (WR) as embedded validity indicators (EVIs) with adults (Erdodi et al., 2018; Guise et al., 2012) and the Wechsler Abbreviated Scale of Intelligence, 2nd Edition Matrix Reasoning (MR) as an EVI with children (Sussman et al., 2017). This study assessed the utility of these measures as EVIs in healthy children, compared to the Test of Memory Malingering Trial 1 (TOMM1 < 45; Perna & Loughan, 2013) and Reliable Digit Span (RDS). Method Participants (n = 99, 68.7% male, Mage = 11.9) completed baseline neuropsychological evaluations for sport participation, including the aforementioned measures. Receiver operator characteristic curve analysis was used to determine whether TMT 4/2, MR, and WR accurately categorized valid performance. Results TMT 4/2 yielded adequate sensitivity (0.83–1.00) but poor specificity (0.07–0.09) when predicting TOMM1 and RDS pass/fail performances. MR yielded adequate sensitivity (1.00) and specificity (0.92) when predicting RDS pass/fail performance and adequate specificity (0.92) and poor sensitivity (0.18) when predicting TOMM1 pass/fail performance. The only EVI that produced better than chance accuracy was MR when predicting RDS pass/fail performance (area under the curve [AUC] = 0.98). All participants failed the WR cutoff, suggesting poor specificity. Conclusion Results suggest that MR was the only EVI that achieved minimally acceptable specificity (≥0.90) in children. MR performed adequately when detecting valid performances but variably when detecting invalid performances; therefore, MR may be used alongside well-established performance validity tests with children but not independently.

A-24 An Evaluation of Anxiety, Depression, and Neuropsychological Performance before and during the COVID-19 Pandemic

Objective High levels of depression and anxiety have been consistently linked to performance on neuropsychological evaluations. In this regard, recent evidence of increased emotional distress due to COVID-19 may exacerbate impairment typically demonstrated on evaluations. The current study examined differences in the severity of depression and anxiety ratings reported before and during COVID-19, and the relationship between mood and cognitive functioning before and during COVID-19. Method 75 adults seeking neuropsychological assessment services from a private outpatient clinic in January 2020 and 2021 were included in the study. Depression, anxiety, and cognitive functioning were measured using the BDI-II, BAI, RDS, FAS, and Trailmaking test. T-tests were conducted to examine mood and cognitive differences between groups. Correlations were used to assess the relationship between mood and cognitive functioning. Results T-tests revealed no significant differences between groups for anxiety, depression, performance validity, verbal fluency, and Trailmaking tests. No significant relationship was observed between reported mood level and cognitive functioning before and during COVID-19. A significant correlation was observed between age and anxiety, which showed that older adults reported less anxiety. All statistical findings will be reported fully in the poster. Conclusions No significant change in emotional distress was found between pre- and during COVID-19 groups. The absence of measurable change may also suggest measures commonly employed should be reviewed and possibly modified to better capture the distress experienced by patients during the pandemic.

A-70 Differences in Cognition and Disease Characteristics in Adult Vs. Late Onset Multiple Sclerosis

Objective Cognitive impairment is a common sequelae of multiple sclerosis(MS), however, relatively little is known about cognitive impairment in late-onset MS (LOMS; symptom onset >50 years old). The present study investigated differences in disease characteristics and cognition in LOMS and adult-onset MS (AOMS). Methods Archival medical records and neuropsychological evaluations from an MS specialty center were reviewed. Differences in disease characteristics between 57 LOMS and 124 AOMS patients were compared using chi-square or ANOVA. To investigate differences in cognitive functioning, age-adjusted standardized scores were compared via ANCOVA, using cardiac risk factors and disease duration as covariates. Results Compared to AOMS (age range: 21–88; mean age: 49.66 +/−12.83), LOMS patients (age range 42–82; mean age: 61.88 +/− 8.57) had significantly more cardiac comorbidities (mean: 1.12+/−1.1 vs. 0.6+/−0.9; p < 0.01), shorter disease duration (mean years: 13.14+/−7.9 vs. 21.0+/−12.6; p < 0.001), and shorter time to diagnosis (mean years: 3.0+/−4.2 vs 6.5+/−8.5; p < 0.01). LOMS patients had similar Expanded Disability Status Scale scores and number of prescribed disease-modifying therapy as AOMS. LOMS patients demonstrated greater impairment on Brief Visuospatial Memory Test-Revised learning (F(1,169) = 8.03, p < 0.05; d = 0.36) and delayed recall (F(1,169) = 4.44, p < 0.05; d = 0.27), and on Wechsler Adult Intelligence Scale-4th edition Digit Span Backward (F(1,176) = 5.68, p < 0.05; d = 0.41) and Sequencing (F(1, 176) = 11.90, p < 0.001; d = 0.55) subtests. Conclusion Despite a shorter disease duration and quicker diagnosis, LOMS patients demonstrate similar levels of physical impairment. Moreover, even after accounting for differences in disease duration and cardiac risk, LOMS showed a greater burden of cognitive impairment than AOMS, which taken together, suggests an elevated rate of disease progression in LOMS.

A-7 Improving Brain-Behavior Health in Pediatric Survivors of ECMO

Objective Extracorporeal Membrane Oxygenation (ECMO) is a lifesaving measure associated with developmental delays and disabilities among survivors. While guidelines recommend follow-up care for ECMO survivors, children miss care due to the lack of standardized follow-up programs and formalized medical homes. We identified deficiencies in follow-up and developed a novel, structured program at a tertiary care children’s hospital called Standardizing Therapies after ECMO program (STEp) for ECMO survivors. Methods An IRB approved program, STEp was implemented in 2017. If consented, a STEp physician formally evaluated the patient’s post ECMO needs, ordered necessary consults, provided parental education and a letter to pediatrician describing patient’s likely long term medical needs and entered patient in a structured post-discharge follow-up program. We conducted a retrospective chart review to collect data prior to and after implementation of the program in 2017. Results There were 33 survivors in the pre-STEp period (2011–16) and 46 survivors in the STEp period (2017–2020). Consent was provided for STEp in 40 patients (87%). The referral rate improved in all necessary specialties (audiology, PT/OT, Neurology). Neuropsychology evaluation referrals improved from 42% to 58% and the timely evaluation improved from 50% to 100%. 35% of the patients evaluated by neuropsychology in the STEp period were diagnosed with a neurodevelopmental/neurocognitive disorder and thus received appropriate therapies. Conclusions Implementation of a standardized follow-up program for ECMO is feasible and can be implemented successfully. STEp demonstrates that with a structured post-ECMO follow-up program, ECMO survivors can receive appropriate neuropsychological evaluations consistently, thereby identifying potential problems and treatment options.

A-163 Utility of the 7/24 Spatial Recall Test in Temporal Lobe Epilepsy

Objective To examine the utility of the 7/24 Spatial Recall Test (7/24) in the assessment of temporal lobe epilepsy (TLE) patients who have not undergone surgical resection. We hypothesized that patients with right TLE (RTLE) would perform significantly worse on the 7/24 than patients with left TLE (LTLE), but better on measures of verbal memory and naming. Participants and Methods Twenty-one patients with RTLE and 17 patients with LTLE were identified from a larger dataset of 152 epilepsy patients who underwent comprehensive neuropsychological evaluations at Brigham and Women’s Hospital. Exclusion criteria included: 1) Extratemporal, bitemporal, or unclear seizure onset, 2) Post-surgical evaluations, and 3) Co-morbid neurodegenerative or neurological conditions. The Rey Auditory Verbal Learning Test (RVLT) and Boston Naming Test (BNT) and were selected as outcome measures of verbal memory and naming, respectively. Results Independent samples t-tests revealed that patients with RTLE performed significantly worse on the 7/24 delayed recall than LTLE patients (p = 0.026), but there were no significant differences between groups in their 7/24 immediate recall across trials (p = 0.118). As predicted, patients with LTLE performed significantly worse than RTLE patients on the BNT (p = 0.005), however no significant differences were found between groups on the RVLT total learning, short delay, or long delay. Conclusions These findings support the use of the 7/24 for assessing nonverbal memory in patients with TLE, and more specifically, suggest that the 7/24 may be a sensitive measure for detecting lateralized dysfunction of the right temporal lobe in TLE patients.