William S. MacAllister, Ph.D.

Cognitive and behavioral functioning in Coffin-Siris syndrome and epilepsy: a case presentation
Bender, H Allison; Zaroff, Charles M; Karantzoulis, Stella; Nakhutina, Luba; MacAllister, William S; Luciano, Daniel
2011 Jan-Mar;172(1):56-66, Journal of genetic psychology
The authors characterized the cognitive, adaptive, and behavioral sequelae of Coffin-Siris (CS) syndrome and epilepsy in a 7.5-year-old child. Little is known about the early neurobehavioral presentation of CS. Clinical features consistent with this genetic anomaly include underdeveloped tips and nails of the fifth fingers, extended infranasal depression, and craniofacial abnormalities. MRI findings often reveal callosal agenesis. The authors conducted a neuropsychological evaluation and obtained parental ratings of behavioral and adaptive functioning. Attentional abilities were limited. As assessed by the Mullen Scales of Early Learning, receptive language abilities (age equivalent [AE]: 3-3) were relatively stronger than expressive skills (AE: 1-4). Adaptive functioning was low across all domains (Vineland Adaptive Behavior Composite AE: 1-9). On the Behavior Assessment for Children (BASC-2), social skills dysfunction, stereotyped and self-stimulatory behaviors, restricted interests, ritualistic play, and inappropriate object usage were noted. No significant mood disturbances were endorsed. Study findings indicate a diffuse pattern of neurobehavioral deficits in a child with CS and epilepsy. Further clinical assessment and research should include multidimensional assessment techniques, including evaluation of adaptive behavior, in an effort to capture the full range developmental sequelae in children with CS
— id: 134211, year: 2011, vol: 172, page: 56, stat: Journal Article,

Quality of life following epilepsy surgery for children with tuberous sclerosis complex
Roth, Jonathan; Olasunkanmi, Adeolu; Macallister, William S; Weil, Emily; Uy, Catherine C; Devinsky, Orrin; Weiner, Howard L
2011 Mar;20(3):561-565, Epilepsy & behavior
Parents of children with tuberous sclerosis complex who underwent multistage resections for treatment of refractory seizures were offered a telephone questionnaire regarding quality of life (QOL) of child and family since surgery. Of 53 families, 39 responded. Age at epilepsy onset was birth to 3months. Average duration of epilepsy before the first surgery was 5.1years, and average age at surgery was 5.8. The average follow-up was 3.9. Seventy-seven percent had a >90% reduction in disabling seizures. In all outcome categories, 46-85% had at least a moderate improvement in QOL. There was a significant correlation between QOL variables and Engel outcome class. Despite the potential burden posed by the aggressive surgical approach, including multiple surgeries and long hospitalization periods, 94% of parents would choose the same course once again. We conclude that aggressive surgical treatment of tuberous sclerosis complex-related refractory seizures is associated with significant control of epilepsy as well as improved QOL for the patient and family
— id: 128790, year: 2011, vol: 20, page: 561, stat: Journal Article,

The clinical utility of the Social Responsiveness Scale and Social Communication Questionnaire in tuberous sclerosis complex
Granader, Yael E; Bender, Heidi A; Zemon, Vance; Rathi, Sipra; Nass, Ruth; Macallister, William S
2010 Jul;18(3):262-266, Epilepsy & behavior
Tuberous sclerosis complex (TSC) is often associated with epilepsy, mental retardation, and autism spectrum disorders (ASDs). Thus, screening for ASDs is important when evaluating these individuals. We examined the utility of the Social Responsiveness Scale (SRS) and Social Communication Questionnaire (SCQ), two measures for screening for ASDs, in a TSC population. Twenty-one children were evaluated, with 52.4% classified as having ASDs on the SRS and 42.9% classified as such on the SCQ. Number of antiepileptic drugs significantly correlated with SRS Total score, as did level of intellectual functioning. Evidence for convergent validity was obtained between the SRS and SCQ Total scores (r=0.605). Moreover, all SRS subscales correlated with SCQ Total score (r>0.400). All SCQ subscales except for Communication correlated with SRS total. Overall, the results demonstrate that these questionnaires appear to be effective screens for ASDs in a TSC population and are measuring similar constructs
— id: 110875, year: 2010, vol: 18, page: 262, stat: Journal Article,

Psychiatric comorbidity in pediatric patients with demyelinating disorders
Weisbrot, Deborah M; Ettinger, Alan B; Gadow, Kenneth D; Belman, Anita L; MacAllister, William S; Milazzo, Maria; Reed, Michael L; Serrano, Daniel; Krupp, Lauren B
2010 Feb;25(2):192-202, Journal of child neurology
Little is known about psychiatric aspects of pediatric demyelinating conditions. A total of 23 youths (6-17 years) with demyelinating conditions underwent semistructured psychiatric interviews using the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version. Adolescents and parents completed the Child Symptom Inventory-4 and the Youth's Inventory-4. Fears and conceptions of their neurological problems were elicited. In all, 48% (n = 11) met criteria for current psychiatric diagnoses, including 27% (n = 3) with depressive disorders and 64% (n = 7) with anxiety disorders. Fears and conceptions of the illness were severe and diverse. Depressive and anxiety disorders are common in pediatric demyelinating disease. Clinicians should therefore screen for psychiatric comorbidity symptoms as part of the routine evaluation of such patients
— id: 107753, year: 2010, vol: 25, page: 192, stat: Journal Article,

The Clinical Utility of the RBANS Spanish Research Edition in a Neurological Sample
Bender, HA; Rodriguez, RM; Karantzoulis, S; Murphy, K; MacAllister, WS; Senior, E; Vazquez, BR; Barr, WB
2009 ;23(4):07-07, Clinical neuropsychologist
— id: 125470, year: 2009, vol: 23, page: 07, stat: Journal Article,

Negative affect predicts subsequent cognitive change in multiple sclerosis
Christodoulou, Christopher; Melville, Patricia; Scherl, William F; Macallister, William S; Abensur, Rebecca L; Troxell, Regina M; Krupp, Lauren B
2009 Jan;15(1):53-61, Journal of the International Neuropsychological Society
Baseline predictors of cognitive change were explored in a sample of persons with multiple sclerosis (MS). Potential predictors included demographic features, baseline clinical characteristics, and psychological state. Participants were 38 individuals diagnosed with either relapsing remitting or secondary progressive MS who did not meet criteria for a current major depressive episode. Subjects were tested at baseline and approximately 1 year in an ongoing longitudinal study of cognition in MS. Participants completed neuropsychological tests sensitive to impairment in MS. They also completed self-report measures of depression, anxiety, fatigue, apathy, and positive and negative affect. Baseline measures of negative affect (e.g., depressed mood, state anxiety, and negative affective state) consistently predicted cognitive change over the course of the study. Higher baseline levels of negative affect were associated with greater relative declines in cognitive performance. This longitudinal relation occurred in the absence of a cross-sectional relation between negative affect and overall cognition. High baseline negative affect particularly predicted a relative decline in episodic memory for newly learned verbal and visuospatial information. The negative affect measures were unique in their predictive value among all the baseline measures assessed. (JINS, 2009, 15, 53-61.)
— id: 95300, year: 2009, vol: 15, page: 53, stat: Journal Article,

Fatigue and quality of life in pediatric multiple sclerosis
MacAllister, William S; Christodoulou, Christopher; Troxell, Regina; Milazzo, Maria; Block, Pamela; Preston, Thomas E; Bender, Heidi A; Belman, Anita; Krupp, Lauren B
2009 Dec;15(12):1502-1508, Multiple sclerosis
Fatigue and quality of life are significant concerns in adult multiple sclerosis (MS) but little is known about these factors in pediatric MS. The present investigation evaluates fatigue and quality of life in 51 pediatric MS patients to determine the rate of fatigue and reduced quality of life and assesses the relations between these variables and clinical factors. Fatigue and quality of life were assessed by self- and parent-report via the PedsQL Multidimensional Fatigue Scale and the PedsQL Quality of Life Scale. One-sample t-tests determined if scores were below published data for healthy individuals. Moreover, scores falling one standard deviation from norms were considered mildly affected, with severe difficulties being defined as scores falling two or more standard deviations from norms. Associations between self- and parent-reported difficulties and clinical factors were examined via Pearson correlation analyses. In comparison with healthy samples, pediatric MS patients reported greater difficulties with respect to fatigue, sleep, cognition, physical limitations, and academics. In addition to significant difficulties on these factors, parents reported problems with respect to emotional functioning, and tended to report greater fatigue, sleep, and cognitive difficulties than were self-reported. Expanded Disability Status Scale score was the only neurologic variable significantly related to fatigue or quality of life scores. Fatigue was significantly correlated with reports of sleep difficulties, cognitive problems, and quality of life variables. These findings suggest that fatigue and poorer quality of life is a clear concern in pediatric MS, and is related to overall physical disability
— id: 107752, year: 2009, vol: 15, page: 1502, stat: Journal Article,

Assessing Effort During Neuropsychological Evaluation with the TOMM in Children and Adolescents with Epilepsy
Macallister, William S; Nakhutina, Luba; Bender, Heidi A; Karantzoulis, Stella; Carlson, Chad
2009 Nov;15(6):521-531, Child neuropsychology : a journal on normal & abnormal development in childhood & adolescence
Effort assessment is of particular importance in pediatric epilepsy where neuropsychological findings may influence treatment decisions, especially if surgical interventions are being considered. The present investigation examines the Test of Memory Malingering (TOMM) in 60 children and adolescents with epilepsy. The overall pass rate for the sample was 90%. TOMM scores were unrelated to age, though there was a significant correlation between TOMM Trial 2 scores and intelligence estimates. Overall, the TOMM appears to be a valid measure of effort in young epilepsy patients, though caution should be used when interpreting scores for those with very low IQ, especially if behavioral problems are also evident. Caution should also be exercised in interpreting scores in children with ongoing interictal epileptiform activity that may disrupt attention
— id: 138384, year: 2009, vol: 15, page: 521, stat: Journal Article,

Comparing the convergent validity and clinical utility of the Behavior Assessment System for Children-Parent Rating Scales and Child Behavior Checklist in children with epilepsy
Allison Bender, H; Auciello, Dominick; Morrison, Chris E; MacAllister, William S; Zaroff, Charles M
2008 Jul;13(1):237-242, Epilepsy & behavior
The convergent validity and clinical utility of two parent-report child behavior rating scales, the Behavior Assessment System for Children-Parent Rating Scales (BASC-PRS) and Child Behavior Checklist/Ages 6-18 (CBCL), in children with epilepsy were examined. Analogous broadband and narrowband behavior rating scales were evaluated in 60 subjects aged 6-17 years (mean=11.0, SD=3.4) with Full Scale IQ >70. Correlations for each similarly labeled scale were statistically significant (P<0.002) and greater with broadband (r=0.71-0.79) than with narrowband (r=0.41-0.78) scales. The BASC captured significantly less composite internalizing symptoms (P<0.002), but more unusual thought processes (P<0.0002) and attention problems versus a CBCL DSM-oriented attention-deficit/hyperactivity disorder scale (P<0.002). Variation in the correlations between measures may stem from underlying differences between rationally-and empirically-derived approaches to test construction. Both the CBCL and BASC have diagnostic and clinical utility in assessing behavior problems in pediatric epilepsy
— id: 79398, year: 2008, vol: 13, page: 237, stat: Journal Article,

Treatment of cognitive impairment in multiple sclerosis: is the use of acetylcholinesterase inhibitors a viable option?
Christodoulou, Christopher; MacAllister, William S; McLinskey, Nancy A; Krupp, Lauren B
2008 ;22(2):87-97, CNS drugs
Approximately half of all patients with multiple sclerosis (MS) experience cognitive impairment, most commonly with regard to new learning and memory. Cognitive dysfunction is a leading cause of disability in MS and it can have profound social and economic consequences for patients and their families.Research on treatment for cognitive impairment in MS is still in the early stages, as it is for most neurological conditions. The available disease-modifying therapies in MS may provide some modest benefit to cognition, but patients with MS clearly need better treatment for cognitive dysfunction. A number of studies have assessed symptomatic treatments of cognition in MS, and the results of these small, underpowered studies have been mixed. Regardless, acetylcholinesterase inhibitors (AChEIs) have been the most promising class of medications tested in MS to date. Seven of eight studies on AChEIs have shown positive results, although it is difficult to assess their adequacy since only three of the studies have been published in peer reviewed journals, with the rest appearing only as abstracts. The earliest AChEI studies in MS examined physostigmine, but the short half-life and prominent adverse effects of this medication may have limited its use compared with other AChEIs. All of the more recent AChEI studies have used donepezil, which, from the limited data available to date, appears to have been relatively well tolerated among MS patients. The largest randomized controlled trial of donepezil included 69 subjects and found that donepezil improved verbal learning and memory compared with placebo during neuropsychological testing. That study also found that patients receiving donepezil were more likely to report memory improvement than those receiving placebo, and the study clinician also noted a cognitive benefit among those on donepezil as opposed to placebo.There are still many unanswered questions regarding the use of AChEIs in MS, including the effects of their long-term use in a chronic disease such as MS. On the whole, to date the research on AChEIs in MS must be considered preliminary, and it is premature to recommend the clinical use of this class of medications at the present time
— id: 95301, year: 2008, vol: 22, page: 87, stat: Journal Article,

Frequency and predictors of autism in children with tuberous sclerosis complex
Zelleke, TZ; Rubin, MR; Cohen, BC; Lai, GL; LaJoie, JL; Miles, DM; Devinsky, OD; Zaroff, CZ; MacAllister, WM; Weiner, HW; Nass, RN
2008 SEP ;64(3):S115-S115, Annals of neurology
— id: 104238, year: 2008, vol: 64, page: S115, stat: Journal Article,

The psychosocial consequences of pediatric multiple sclerosis
MacAllister, W S; Boyd, J R; Holland, N J; Milazzo, M C; Krupp, L B
2007 Apr 17;68(16 Suppl 2):S66-S69, Neurology
Although psychological distress and cognitive dysfunction are well documented in adults with multiple sclerosis (MS), they are poorly understood in children with the disease. Psychosocial difficulty experienced by children and adolescents with MS involves factors common to all chronic illnesses in children, as well as MS-specific factors. The psychosocial manifestations of the disease may affect the patient's self-image, role functioning, mood, and cognition to adversely affect schooling, interpersonal relationships, and treatment compliance. Furthermore, the impact of having a family member with MS may affect overall family functioning. Assessment and interventions for psychosocial and cognitive problems in pediatric MS should be multidisciplinary in nature and address the child's functioning at home, school, and among peers, as well as the effect on the family
— id: 73844, year: 2007, vol: 68, page: S66, stat: Journal Article,

Longitudinal neuropsychological assessment in pediatric multiple sclerosis
MacAllister, William S; Christodoulou, Christopher; Milazzo, Maria; Krupp, Lauren B
2007 ;32(2):625-644, Developmental neuropsychology
Although Multiple Sclerosis (MS) occurring in childhood and adolescence has received increasing attention in recent years, the impact of the disease on cognitive function in this subgroup remains poorly understood. It has been posited that children and adolescents with MS may be particularly susceptible to cognitive dysfunction because the pathological processes, including inflammation, blood brain barrier breakdown, and demyelination, occur concurrently with ongoing myelination. Early work has documented that a number of these children present with cognitive deficits. However, there is no available information on the progression of these deficits, or on what clinical factors may predict further decline. The current article reviews what is currently known about pediatric MS and follows a cohort of pediatric MS patients and assesses cognitive function longitudinally. Participants were evaluated with a brief neuropsychological test battery on two separate occasions and correlational analyses assessed the relations between changes in cognition and several clinical variables including level of neurologic impairment, number of relapses prior to baseline assessment, number of interim relapses, age of disease onset, and disease length. The results indicate that a number of these patients experience further cognitive decline over time, or decline from previously normal functioning. Baseline level of neurologic disability was significantly correlated with changes in cognition. The number of interim relapses (i.e., relapses occurring between baseline assessment and re-evaluation) showed a modest relationship to changes in cognitive function, but this did not reach statistical significance
— id: 95302, year: 2007, vol: 32, page: 625, stat: Journal Article,

Neuropsychological deficits in childhood epilepsy syndromes
MacAllister, William S; Schaffer, Sarah G
2007 Dec;17(4):427-444, Neuropsychology review
Seizure disorders are relatively common in childhood, and the International League Against Epilepsy (ILAE) provides a hierarchical classification system to define seizure types. At the final level of classification, specific epilepsy syndromes are defined that represent a complex of signs and symptoms unique to an epilepsy condition. The present review discusses the issues related to several of these epilepsy syndromes in childhood, including those classified as generalized idiopathic epilepsies (e.g., childhood absence epilepsy, juvenile absence epilepsy, juvenile myoclonic epilepsy), focal epilepsies (benign rolandic epilepsy, occipital epilepsy, temporal lobe epilepsy, frontal lobe epilepsy) and the 'epileptic encephalopathies,' including Dravet's Syndrome, West Syndrome, Lennox-Gastaut Syndrome, Myoclonic Astatic Epilepsy, and Landau-Kleffner Syndrome. For each syndrome, the epidemiology, clinical manifestations, treatments, and neuropsychological findings are discussed
— id: 76083, year: 2007, vol: 17, page: 427, stat: Journal Article,

Effects of donepezil on memory and cognition in multiple sclerosis
Christodoulou, Christopher; Melville, Patricia; Scherl, William F; Macallister, William S; Elkins, Leigh E; Krupp, Lauren B
2006 Jun 15;245(1-2):127-136, Journal of the neurological sciences
Acetylcholinesterase inhibitors are used to treat dementia associated with Alzheimer's disease, but their cognitive benefits may extend to additional disorders such as multiple sclerosis (MS). A single-center double-blind placebo-controlled randomized clinical trial evaluated the effectiveness of donepezil in a sample of 69 MS persons selected for initial memory difficulties. Subjects received neuropsychological assessment at baseline and after 24 weeks of treatment. The primary outcome was change in total recall on the Selective Reminding Test, a measure of verbal learning and memory. Secondary outcomes included other neuropsychological tests from the Brief Repeatable Battery, patient-reported change in memory, and physician-reported impression of cognitive change. Donepezil improved memory performance on the SRT compared to placebo. This benefit remained significant after controlling for various covariates including Expanded Disability Status Scale (EDSS), MS subtype, interferon beta use, treatment group beliefs, gender, baseline selected reminding test (SRT) score, and reading ability. Subjects on donepezil were more likely to report memory improvement (65.7%) than those on placebo (32.4%). The clinician also reported cognitive improvement in more donepezil (54.3%) than placebo (29.4%) subjects. No serious adverse events related to study medication occurred. However, more donepezil (34.3%) than placebo (8.8%) subjects reported unusual/abnormal dreams. Donepezil improved learning and memory in MS patients with initial cognitive difficulties in a single-center clinical trial. Replication of results in a larger multi-center investigation is warranted in order to more definitively assess the efficacy of this intervention
— id: 69678, year: 2006, vol: 245, page: 127, stat: Journal Article,

Perceived cognitive dysfunction and observed neuropsychological performance: longitudinal relation in persons with multiple sclerosis
Christodoulou, Christopher; Melville, Patricia; Scherl, William F; Morgan, Tina; MacAllister, William S; Canfora, Dawn M; Berry, Stephen A; Krupp, Lauren B
2005 Sep;11(5):614-619, Journal of the International Neuropsychological Society
The relation between self-reported cognitive dysfunction and neuropsychological performance over 24 weeks was assessed in a sample of 53 multiple sclerosis patients. Subjects were assessed at Weeks Zero and 24 as part of a clinical trial to enhance cognition. At baseline, subjects had at least mild cognitive impairment on the Rey Auditory Verbal Learning Test and an absence of depression. Neuropsychological performance was assessed with a modification of the well standardized Brief Repeatable Battery. The 5-item Perceived Deficits Questionnaire and a 2-item memory and attention/concentration questionnaire assessed self-perceived cognitive impairment. Self-assessed cognition did not correlate with neuropsychological performance at either baseline or 24 weeks. However, changes in the self-assessment measures did correlate with changes in neuropsychological performance. Patients accurately perceived some changes in their level of cognitive dysfunction, though they were insensitive to the degree of their current dysfunction. Possible explanations of this pattern of results are discussed
— id: 69679, year: 2005, vol: 11, page: 614, stat: Journal Article,

Treatment of Pediatric Multiple Sclerosis
Krupp LB; Macallister WS
2005 May;7(3):191-199, Current treatment options in neurology
An increasing number of children and adolescents with multiple sclerosis (MS) are being identified and treated with disease-modifying therapies. Yet, there currently is little experience to guide clinicians. As more rapid diagnosis is made possible with magnetic resonance imaging, the number of pediatric MS patients requiring treatment will increase with time. This review draws on information from adult and pediatric neurology sources and summarizes current available data. Additional research is clearly needed. Nonetheless, there are several treatment principles: 1) establishing the diagnosis by differentiating MS from acute disseminated encephalomyelitis or recurrent acute disseminated encephalomyelitis; 2) emphasizing that there are parallels between adult and pediatric MS regarding the clinical presentation, disease course, and ability to tolerate therapy (the more extensive experience in adult MS can be applied to most pediatric cases); 3) explaining the importance of starting treatment early in the disease course and that these therapies seem well-tolerated in children; 4) providing reassurance that the family is not alone; as approximately 5% of the MS population has symptom onset before age 18 years (experience with pediatric MS is growing and centers with pediatric MS programs exist in other countries and are developing within the United States); and 5) reviewing symptom management and addressing issues such as academic performance that are unique to the pediatric MS subpopulation
— id: 69682, year: 2005, vol: 7, page: 191, stat: Journal Article,

Cognitive functioning in children and adolescents with multiple sclerosis
MacAllister, W S; Belman, A L; Milazzo, M; Weisbrot, D M; Christodoulou, C; Scherl, W F; Preston, T E; Cianciulli, C; Krupp, L B
2005 Apr 26;64(8):1422-1425, Neurology
OBJECTIVE: To examine cognitive functioning in children with multiple sclerosis (MS). METHODS: The authors examined the neuropsychological profile of 37 children with a diagnosis of clinically definite MS and assessed the associations between cognitive function and clinical features. RESULTS: Of 37 children and adolescents evaluated, 35% demonstrated significant cognitive impairment. Cognitive functioning was strongly related to several clinical variables, including current Expanded Disability Status Scale, total number of relapses, and total disease length. The consequences of MS adversely affected academic functioning in over a third of the children. CONCLUSIONS: Cognitive deficits occur in children with multiple sclerosis. Comprehensive treatment planning should involve recognition that they may require academic accommodations for their education
— id: 69681, year: 2005, vol: 64, page: 1422, stat: Journal Article,

Multiple sclerosis-related fatigue
MacAllister, William S; Krupp, Lauren B
2005 May;16(2):483-502, Physical medicine & rehabilitation clinics of North America
Fatigue is a significant factor in the lives of many MS patients and the most commonly reported symptom in many studies. Fatigue is an important symptom to consider because it affects patients' social lives, occupations, and activities of daily living. Efforts to predict fatigue have been mixed, but it appears to be related to overall quality of life and mood. From a pathophysiologic perspective, fatigue in MS is multifactorial and complex,involving dysregulation of the immune system, changes in the nervous system related to the disease process, neuroendocrine and neurotransmitter changes, and other factors such as physical deconditioning, sleep disturbance, pain, and medication side effects. Various attempts to assess fatigue have been made, and many measures are now available for use in clinical practice and research. In clinical practice, these measures help guide treatment considerations. Recent research has provided valuable strategies to ameliorate fatigue in MS, and although many patients continue to experience fatigue despite interventions, many receive substantial relief.Nonpharmacologic approaches-considered the first step in treatment-include exercise programs, cooling, dietary considerations, and energy conservation strategies. For patients who continue to experience significant fatigue, several medications (although not specifically approved for use in the reduction of MS-related fatigue) have proved effective in this regard.The first-line agents include amantadine for mild fatigue and modafinil for more severe cases. Second-line agents include pemoline and antidepressant medications. Other pharmacologic agents have also shown some promise
— id: 69680, year: 2005, vol: 16, page: 483, stat: Journal Article,

Donepezil improved memory in multiple sclerosis in a randomized clinical trial
Krupp, L B; Christodoulou, C; Melville, P; Scherl, W F; MacAllister, W S; Elkins, L E
2004 Nov 9;63(9):1579-1585, Neurology
OBJECTIVE: To determine the effect of donepezil in treating memory and cognitive dysfunction in multiple sclerosis (MS). METHODS: This single-center double-blind placebo-controlled clinical trial evaluated 69 MS patients with cognitive impairment who were randomly assigned to receive a 24-week treatment course of either donepezil (10 mg daily) or placebo. Patients underwent neuropsychological assessment at baseline and after 24 weeks of treatment. The primary outcome was change in verbal learning and memory on the Selective Reminding Test (SRT). Secondary outcomes included other tests of cognitive function, patient-reported change in memory, and clinician-reported impression of cognitive change. RESULTS: Donepezil-treated patients showed significant improvement in memory performance on the SRT compared to placebo (p = 0.043). The benefit of donepezil remained significant after controlling for various covariates including age, Expanded Disability Status Scale, baseline SRT score, reading ability, MS subtype, and sex. Donepezil-treated patients did not show significant improvements on other cognitive tests, but were more than twice as likely to report memory improvement than those in the placebo group (p = 0.006). The clinician also reported cognitive improvement in almost twice as many donepezil vs placebo patients (p = 0.036). No serious adverse events related to study medication occurred, although more donepezil (34.3%) than placebo (8.8%) subjects reported unusual/abnormal dreams (p = 0.010). CONCLUSIONS: Donepezil improved memory in MS patients with initial cognitive impairment in a single center clinical trial. A larger multicenter investigation of donepezil in MS is warranted in order to more definitively assess the efficacy of this intervention
— id: 69684, year: 2004, vol: 63, page: 1579, stat: Journal Article,

Normative data for the selective reminding test: a random digit dialing sample
Scherl, William F; Krupp, Lauren B; Christodoulou, Christopher; Morgan, Tina M; Hyman, Leslie; Chandler, Barbara; Coyle, Patricia K; MacAllister, William S
2004 Oct;95(2):593-603, Psychological reports
Healthy control participants (46 women, M age=44.3 yr., SD=7.6; 29 men) were recruited to undergo a comprehensive neuropsychological battery and serve as a comparison group in a study of cognitive functioning in patients with Lyme isease. Participants were selected using Mitofsky-Waksberg random digit dialing. The Buschke 12-word, six-trial Selective Reminding Test was administered as part of the neuropsychological battery and normative data are presented stratified by age and sex. Performance on alternate forms of this measure were examined. Mean education, intelligence quotient, and Wide Range Achievement Test-3 Reading scores are reported
— id: 69683, year: 2004, vol: 95, page: 593, stat: Journal Article,

Cognitive performance and MR markers of cerebral injury in cognitively impaired MS patients
Christodoulou, C; Krupp, L B; Liang, Z; Huang, W; Melville, P; Roque, C; Scherl, W F; Morgan, T; MacAllister, W S; Li, L; Tudorica, L A; Li, X; Roche, P; Peyster, R
2003 Jun 10;60(11):1793-1798, Neurology
OBJECTIVE: To relate neuropsychological performance to measures of cerebral injury in persons with MS selected for cognitive impairment. METHODS: Participants were 37 individuals with relapsing-remitting (59.5%) and secondary progressive (40.5%) MS. They were tested at baseline as part of a clinical trial to enhance cognition with an acetylcholinesterase inhibitor. Eligibility criteria included at least mild cognitive impairment on a verbal learning and memory task. A modified Brief Repeatable Battery of Neuropsychological Tests formed the core of the behavioral protocol. Neuroimaging measures were central (ventricular) cerebral atrophy, lesion volume, and ratios of N-acetyl aspartate (NAA) to both creatine and choline. RESULTS: A clear, consistent relation was found between cognitive and MR measures. Among neuroimaging measures, central atrophy displayed the highest correlations with cognition, accounting for approximately half the variance in overall cognitive performance. NAA ratios in right hemisphere sites displayed larger correlations than those on the left. Multiple regression models combining the MR measures accounted for well over half the variance in overall cognitive performance. The Symbol Digit Modalities Test was the neuropsychological task most strongly associated with the neuroimaging variables. CONCLUSIONS: If a strong and stable association can be firmly established between cognitive and MR variables in appropriate subsets of MS patients, it might aid in the investigation of interventions to enhance cognition and modify the course of the disease
— id: 69685, year: 2003, vol: 60, page: 1793, stat: Journal Article,