Cognitive Status & Dementia Severity in CVLT-II-SF Forced Choice Recognition: Implications for Effort Assessment

Effort testing is critical to neuropsychological practice, including dementia assessment. Questions exist around whether cognitive status or impairment severity impacts effort test performance in this population. Presently, we examined whether scores on an embedded effort test - the California Verbal Learning Test II Short Form (CVLT-II-SF) Forced Choice Recognition (FCR) - differed across diagnostic cognitive status groups and how severity of impairment modulated test performance. In a sample of memory clinic patients, three cognitive status groups were identified: subjective cognitive impairment (SCI; n = 92), amnestic mild cognitive impairment (a-MCI; n = 18), and dementia due to Alzheimer’s Disease (AD; n = 70). Significant group differences in FCR performance were observed using one-way ANOVA (p < .001), with post-hoc analysis indicating the AD group performed significantly worse scores than the other groups. Using multiple regression, FCR performance was modelled as a function of cognitive status, impairment severity indexed MMSE, and their interaction, with a parallel analysis for the Clinical Dementia Rating Sum of Boxes (CDR-SOB) scores as an alternate severity measure. Results yielded significant main effects for MMSE (p = 0.019) and cognitive status (p = 0.026), as well as a significant interaction (p = 0.021). Thus, increases in impairment severity disproportionately impaired FCR performance for persons with AD, calling into question research-based cut scores for effort determination in dementia contexts. Corresponding CDR-SOB analyses were non-significant. Future research should examine whether CVLT-II-SF-FCR is an appropriately specific inclusion in a best-practice testing battery for evaluating effort in dementia populations.

Cerebral Visual Impairment in CDKL5 Deficiency Disorder Correlates With Developmental Achievement

Cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder is a rare neurodevelopmental disorder characterized by infantile-onset refractory epilepsy, profound developmental delays, and cerebral visual impairment. Although there is evidence that the presence of cerebral visual impairment in CDKL5 deficiency disorder is common, the potential impact of cerebral visual impairment severity on developmental attainment has not been explored directly. Focusing on a cohort of 46 children with CDKL5 deficiency disorder, examination features indicative of cerebral visual impairment were quantified and compared to developmental achievement. The derived cerebral visual impairment severity score was inversely correlated with developmental attainment, bolstering the supposition that cerebral visual impairment severity may provide a useful early biomarker of disease severity and prognosis. This study demonstrates the utility of a cerebral visual impairment score to better capture the range of cerebral visual impairment severity in the CDKL5 deficiency disorder population and further elucidates the interaction between cerebral visual impairment and developmental outcomes.

Is Palmar Cutaneous Branch of the Median Nerve More Swollen in Carpal Tunnel Syndrome?

Objective To investigate the characteristics of the palmar cutaneous branch of the median nerve (PCBMN) in patient with carpal tunnel syndrome (CTS) using high-resolution ultrasound.Methods Fourteen healthy volunteers (17 wrists) and 31 patients with CTS (41 wrists) were evaluated by high-resolution ultrasound. All patients were classified into three groups based on the electrophysiologic CTS impairment severity: mild, moderate, and severe. Using high-resolution ultrasound, the cross-sectional areas (CSAs) of the PCBMN were measured at the proximal wrist crease, bistyloid line, and distal wrist crease, and the largest CSA was defined as the maximal CSA.Results The maximal CSA of the PCBMN of the control, mild, moderate, and severe CTS groups were 0.27±0.08, 0.30±0.07, 0.35±0.10, and 0.47±0.13 mm2, respectively. The maximal CSA of the PCBMN was significantly larger in the severe CTS group than in the other groups.Conclusion The PCBMN could be concomitantly affected in patients with severe CTS.

Update on Neonatal Isolated Hyperthyrotropinemia: A Systematic Review

The purpose of this paper was to systematically summarize the published literature on neonatal isolated hyperthyrotropinemia (HTT), with a focus on prevalence, L-T4 management, re-evaluation of thyroid function during infancy or childhood, etiology including genetic variation, thyroid imaging tests, and developmental outcome. Electronic and manual searches were conducted for relevant publications, and a total of 46 articles were included in this systematic review. The overall prevalence of neonatal HTT was estimated at 0.06%. The occurrence of abnormal imaging tests was found to be higher in the persistent than in the transient condition. A continuous spectrum of thyroid impairment severity can occur because of genetic factors, environmental factors, or a combination of the two. Excessive or insufficient iodine levels were found in 46% and 16% of infants, respectively. Thirty-five different genetic variants have been found in three genes in 37 patients with neonatal HTT of different ethnic backgrounds extracted from studies with variable design. In general, genetic variants reported in the TSHR gene, the most auspicious candidate gene for HTT, may explain the phenotype of the patients. Many practitioners elect to treat infants with HTT to prevent any possible adverse developmental effects. Most patients with thyroid abnormalities and/or carrying monoallelic or biallelic genetic variants have received L-T4 treatment. For all those neonates on treatment with L-T4, it is essential to ensure follow-up until 2 or 3 years of age and to conduct medically supervised trial-off therapy when warranted. TSH levels were found to be elevated following cessation of therapy in 44% of children. Withdrawal of treatment was judged as unsuccessful, and medication was restarted, in 78% of cases. Finally, data extracted from nine studies showed that none of the 94 included patients proved to have a poor developmental outcome (0/94). Among subjects presenting with normal cognitive performance, 82% of cases have received L-T4 therapy. Until now, the precise neurodevelopmental risks posed by mild disease remain uncertain.

Number of Synergies Impacts Sensitivity of Gait to Weakness and Contracture

Muscle activity during gait can be described by a small set of synergies, weighted groups of muscles, that are often theorized to reflect underlying neural control. For people with neurologic injuries, like in cerebral palsy or stroke, even fewer (e.g., < 5) synergies are required to explain muscle activity during gait. This reduction in synergies is thought to reflect simplified control strategies and is associated with impairment severity and treatment outcomes. Individuals with neurologic injuries also develop secondary musculoskeletal impairments, like weakness or contracture, that can also impact gait. The combined impacts of simplified control and musculoskeletal impairments on gait remains unclear. In this study, we use a musculoskeletal model constrained to synergies to simulate unimpaired gait. We vary the number of synergies (3-5), while simulating muscle weakness and contracture to examine how altered control impacts sensitivity to muscle weakness and contracture. Our results highlight that reducing the number of synergies increases sensitivity to weakness and contracture. For example, simulations using five-synergy control tolerated 40% and 51% more knee extensor weakness than those using four- and three-synergy control, respectively. Furthermore, the model became increasingly sensitive to contracture and proximal muscle weakness, such as hamstring and hip flexor weakness, when constrained to four- and three-synergy control. However, the models sensitivity to weakness of the plantarflexors and smaller bi-articular muscles was not affected by the number of synergies. These findings provide insight into the interactions between altered control and musculoskeletal impairments, emphasizing the importance of incorporating both in future simulation studies.

Relationship of Homocysteine Plasma Levels with Mild Cognitive Impairment, Alzheimer’s Disease, Vascular Dementia, Psychobehavioral, and Functional Complications

Background: Alzheimer’s disease (AD) may be a vascular disorder with neurodegenerative consequences opening possibility of preventing AD by targeting vascular risk factors including homocysteine. Objective: The study aims were to assess homocysteine distribution in different forms and severity of cognitive impairment (CogI) [mild cognitive impairment (MCI), probable AD (Prob-AD), possible AD (Poss-AD), and vascular dementia (VaD)] and in NoCogI, and to estimate possible association between hyperhomocysteinemia levels with functional deficit severity and psychobehavioral complications. Methods: In total, 929 (M = 366, F = 563; mean age of 72.55±6.24 years) patients were evaluated with cognitive, neuropsychiatric, affective, and functional assessment scales. Homocysteine serum was set on two levels: between 0 and 10μmol/L and > 10μmol/L. For each patient, blood concentration of folate, vitamin B12, hemoglobin, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), cholesterol, triglycerides, and glycemia were measured. Results: CogI patients demonstrated significantly a higher frequency of homocysteine > 10 (p = 0.003), than NoCogI patients. Patients with moderate and severe dementia had a higher frequency of homocysteine > 10 (p < 0.0001), than MCI and mild dementia. Poss-AD and VaD had a higher frequency of homocysteine > 10 (p = 0.003), than Prob-AD patients. Homocysteine > 10 frequency is directly proportional to increased neuropsychiatric symptom severity (p < 0.0001), and functional impairment severity respectively for ADL (p < 0.0001) and IADL (p < 0.0001). Conclusion: Higher homocysteine level seems to be significantly related to cognitive impairment frequency and severity, possible AD and VaD, neuropsychiatric symptom severity, and functional impairment severity.

Validity, reliability, and sensitivity to motor impairment severity of a multi-touch app designed to assess hand mobility, coordination, and function after stroke

Background The assessment of upper-limb motor impairments after stroke is usually performed using clinical scales and tests, which may lack accuracy and specificity and be biased. Although some instruments exist that are capable of evaluating hand functions and grasping during functional tasks, hand mobility and dexterity are generally either not specifically considered during clinical assessments or these examinations lack accuracy. This study aimed to determine the convergent validity, reliability, and sensitivity to impairment severity after a stroke of a dedicated, multi-touch app, named the Hand Assessment Test. Methods The hand mobility, coordination, and function of 88 individuals with stroke were assessed using the app, and their upper-limb functions were assessed using the Fugl-Meyer Assessment for Upper Extremity, the Jebsen-Taylor Hand Function Test, the Box and Block Test, and the Nine Hole Peg Test. Twenty-three participants were further considered to investigate inter- and intra-rater reliability, standard error of measurement, and the minimal detectable change threshold of the app. Finally, participants were categorized according to motor impairment severity and the sensitivity of the app relative to these classifications was investigated. Results Significant correlations, of variable strengths, were found between the measurements performed by the app and the clinical scales and tests. Variable reliability, ranging from moderate to excellent, was found for all app measurements. Exercises that involved tapping and maximum finger-pincer grasp were sensitive to motor impairment severity. Conclusions The convergent validity, reliability, and sensitivity to motor impairment severity of the app, especially of those exercises that involved tapping and the maximum extension of the fingers, together with the widespread availability of the app, could support the use of this and similar apps to complement conventional clinical assessments of hand function after stroke.

Postural Control in Childhood: Investigating the Neurodevelopmental Gradient Hypothesis

Neurodevelopmental disorders (NDDs) have been suggested to lie on a gradient continuum, all resulting from common brain disturbances, but with different degrees of impairment severity. This case-control study aimed to assess postural stability against such hypothesis in 104 children/adolescents aged 5–17, of whom 81 had NDDs and 23 were healthy controls. Compared to healthy controls, Autism Spectrum Disorder (ASD) resulted in the most severely impaired neurodevelopmental condition, followed by Attention Deficit Hyperactive Disorder (ADHD) and Tourette Syndrome (TS). In particular, while ASD children/adolescents performed worse than healthy controls in a number of sensory conditions across all parameters, ADHD children/adolescents performed worse than healthy controls only in the sway area for the most complex sensory conditions, when their vision and somatosensory functions were both compromised, and performance in Tourette Syndrome (TS) was roughly indistinguishable from that of healthy controls. Finally, differences were also observed between clinical groups, with ASD children/adolescents, and to a much lesser extent ADHD children/adolescents, performing worse than TS children/adolescents, especially when sensory systems were not operationally accurate. Evidence from this study indicates that poor postural control may be a useful biomarker for risk assessment during neurodevelopment, in line with predictions from the gradient hypothesis.