Faculty Bibliography

OBJECTIVE:To identify cognitive phenotypes in temporal lobe epilepsy (TLE) and test their reproducibility in a large, multi-site cohort of patients using both data-driven and clinically driven approaches. METHOD/METHODS:Four-hundred seven patients with TLE who underwent a comprehensive neuropsychological evaluation at one of four epilepsy centers were included. Scores on tests of verbal memory, naming, fluency, executive function, and psychomotor speed were converted into z-scores based on 151 healthy controls (HCs). For the data-driven method, cluster analysis (k-means) was used to determine the optimal number of clusters. For the clinically driven method, impairment was defined as >1.5 standard deviations below the mean of the HC, and patients were classified into groups based on the pattern of impairment. RESULTS:Cluster analysis revealed a three-cluster solution characterized by (a) generalized impairment (29%), (b) language and memory impairment (28%), and (c) no impairment (43%). Based on the clinical criteria, the same broad categories were identified, but with a different distribution: (a) generalized impairment (37%), (b) language and memory impairment (30%), and (c) no impairment (33%). There was a 82.6% concordance rate with good agreement (κ = .716) between the methods. Forty-eight patients classified as having a normal profile based on cluster analysis were classified as having generalized impairment (n = 16) or an isolated language/memory impairment (n = 32) based on the clinical criteria. Patients with generalized impairment had a longer disease duration and patients with no impairment had more years of education. However, patients demonstrating the classic TLE profile (ie, language and memory impairment) were not more likely to have an earlier age at onset or mesial temporal sclerosis. SIGNIFICANCE/CONCLUSIONS:We validate previous findings from single-site studies that have identified three unique cognitive phenotypes in TLE and offer a means of translating the patterns into a clinical diagnostic criteria, representing a novel taxonomy of neuropsychological status in TLE.

BACKGROUND AND PURPOSE/OBJECTIVE:Efficacy of restorative cognitive rehabilitation can be predicted from baseline patient factors. In addition, patient profiles of functional connectivity are associated with cognitive reserve and moderate the structure-cognition relationship in people with multiple sclerosis (PwMS). Such interactions may help predict which PwMS will benefit most from cognitive rehabilitation. Our objective was to determine whether patient response to restorative cognitive rehabilitation is predictable from baseline structural network disruption and whether this relationship is moderated by functional connectivity. METHODS:For this single-arm repeated measures study, we recruited 25 PwMS for a 12-week program. Following magnetic resonance imaging, participants were tested using the Symbol Digit Modalities Test (SDMT) pre- and postrehabilitation. Baseline patterns of structural and functional connectivity were characterized relative to healthy controls. RESULTS:= .385, P = .017, Interaction β = -.415). CONCLUSION/CONCLUSIONS:Patient response to restorative cognitive rehabilitation is predictable from the interaction between structural network disruption and functional connectivity in the default-mode network. This effect may be related to cognitive reserve.

Pediatric neuropsychologists are increasingly recognizing the importance of performance validity testing during evaluations. The use of such measures to detect insufficient effort is of particular importance in pediatric epilepsy evaluations, where test results are often used to guide surgical decisions and failure to detect poor task engagement can result in postsurgical cognitive decline. The present investigation assesses the utility of the Medical Symptom Validity Test (MSVT) in 104 clinically referred children and adolescents with epilepsy. Though the overall failure rate was 15.4% of the total group, children with 2nd grade or higher reading skills (a requirement of the task) passed at a very high rate (96.6%). Of the three failures, two were unequivocally deemed true positives, while the third failed due to extreme somnolence during testing. Notably, for those with ≥2nd grade reading levels, MSVT validity indices were unrelated to patient age, intellectual functioning, or age of epilepsy onset, while modest relations were seen with specific memory measures, number of epilepsy medications, and seizure frequency. Despite these associations, however, this did not result in more failures in this population of children and adolescents with substantial neurologic involvement, as pass rates exceeded 92% for those with intellectual disability, high seizure frequency, high medication burden, and even prior surgical resection of critical memory structures.

BACKGROUND:Transcranial direct current stimulation (tDCS) is a method of noninvasive neuromodulation and potential therapeutic tool to improve functioning and relieve symptoms across a range of central and peripheral nervous system conditions. Evidence suggests that the effects of tDCS are cumulative with consecutive daily applications needed to achieve clinically meaningful effects. Therefore, there is growing interest in delivering tDCS away from the clinic or research facility, usually at home. OBJECTIVE:To provide a comprehensive guide to operationalize safe and responsible use of tDCS in home settings for both investigative and clinical use. METHODS:Providing treatment at home can improve access and compliance by decreasing the burden of time and travel for patients and their caregivers, as well as to reach those in remote locations and/or living with more advanced disabilities. RESULTS:To date, methodological approaches for at-home tDCS delivery have varied. After implementing the first basic guidelines for at-home tDCS in clinical trials, this work describes a comprehensive guide for facilitating safe and responsible use of tDCS in home settings enabling access for repeated administration over time. CONCLUSION/CONCLUSIONS:These guidelines provide a reference and standard for practice when employing the use of tDCS outside of the clinic setting.

INTRODUCTION/BACKGROUND:To demonstrate the broad utility of the remotely supervised transcranial direct current stimulation (RS-tDCS) protocol developed to deliver at-home rehabilitation for individuals with multiple sclerosis (MS). METHODS:Stimulation delivered with the RS-tDCS protocol and paired with adaptive cognitive training was delivered to three different study groups of MS patients to determine the feasibility and tolerability of the protocol. The three studies each used consecutively increasing amounts of stimulation amperage (1.5, 2.0, and 2.5 mA, respectively) and session numbers (10, 20, and 40 sessions, respectively). RESULTS:High feasibility and tolerability of the stimulation were observed for n = 99 participants across three tDCS pilot studies. CONCLUSIONS:RS-tDCS is feasible and tolerable for MS participants. The RS-tDCS protocol can be used to reach those in locations without clinic access and be paired with training or rehabilitation in locations away from the clinic. This protocol could be used to deliver tDCS paired with training or rehabilitation activities remotely to service members and veterans.

There has been considerable public interest in the topic of traumatic brain injury (TBI) as a risk factor for development of late-life dementia. A review was performed on empirical studies examining the relationship between these two conditions. Although results from a number of studies clearly demonstrate that TBI is a positive risk factor for developing dementia, there are an equivalent number of studies that obtain inconclusive or negative findings. Inconsistencies across studies are often the result of methodological findings including the nature of the investigational design, choice of comparison groups, and criteria used to define cases. In many studies, the diagnosis of TBI is obtained retrospectively in a manner that is subject to bias. Accurate identification of dementia cases is often compromised by the use of inappropriately brief follow-up periods and variations in diagnostic methods. There remains no universally accepted neurobiological mechanism to explain the transition from acute TBI to the chronic effects of dementia. Studies of specialty populations, including athletes and military personnel are beset by secular and cohort effects, raising questions about the applicability of findings to the general population. No existing studies have been able to exclude the possible effects of confounding medical or lifestyle factors in facilitating the onset of dementia following TBI. Although the research findings suggest a general association between TBI and dementia, the specifics of the relationship remain poorly defined.

Pediatric multiple sclerosis (MS) is an increasingly recognized rare subgroup of patients presenting with a unique set of diagnostic challenges. Understanding the early development of MS may offer a window into the pathogenesis of disease; however further research is needed, particularly within the field of genetics and to understand the complex environmental and biological interactions at work. Acute disseminated encephalomyelitis (ADEM) remains a hallmark presentation of early pediatric disease and can be a monophasic illness or end up being reclassified as a relapsing disorder. The clinical expression is shaped in part by the prepubertal or postpubertal state of the patient. Other syndromes can also present with ADEM, and a specific differential diagnosis exists for children presenting with any initial demyelinating event (IDE). New definitions and criteria have allowed early detection of MS. However applying adult criteria to very young children should be approached with caution. There is now a major effort in studying disease-modifying therapy (DMT) in children due to requirements from regulatory authorities. Pediatric patients respond well to therapy and often do best with an interdisciplinary approach focusing on social aspects, cognition, and fatigue which enhances the achievement of successful outcomes.
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This paper describes ten core features of a neuropsychological assessment with the aim of helping neurologists understand the unique contribution the evaluation can make within the wider context of diagnostic methods in epilepsy. The possibilities, limitations and cautions associated with the investigation are discussed under the headings below: 1. A neuropsychological assessment is a collaborative investigation. 2. Assessment prior to treatment allows for the accurate assessment of treatment effects. 3. The nature of an underlying lesion and its neurodevelopmental context play an important role in shaping the associated neuropsychological deficit. 4. Cognitive and behavioural impairments result from the essential comorbidities of epilepsy which can be considered as much a disorder of cognition and behaviour as of seizures. 5. Patient's subjective complaints can help us understand objective cognitive impairments and their underlying neuroanatomy, resulting in improved patient care. At other times, patient complaints reflect other factors and require careful interpretation. 6. The results from a neuropsychological assessment can be used to maximise the educational and occupational potentials of people with epilepsy. 7. Not all patients are able to engage with a neuropsychological assessment. 8. There are limitations in assessments conducted in a second language with tests that have been standardized on different populations to that of the patient. 9. Adequate intervals between assessments maximise sensitivity to meaningful change. 10. Patients should be fully informed about the purpose of the assessment and have realistic expectations of the outcome prior to referral.