Mike R. Schoenberg

Prospective randomized double-blind trial of bilateral thalamic deep brain stimulation in adults with Tourette syndrome

OBJECT The severity of Tourette syndrome (TS) typically peaks just before adolescence and diminishes afterward. In some patients, however, TS progresses into adulthood, and proves to be medically refractory. The authors conducted a prospective double-blind crossover trial of bilateral thalamic deep brain stimulation (DBS) in five adults with TS. METHODS Bilateral thalamic electrodes were implanted. An independent programmer established optimal stimulator settings in a single session. Subjective and objective results were assessed in a double-blind randomized manner for 4 weeks, with each week spent in one of four states of unilateral or bilateral stimulation. Results were similarly assessed 3 months after unblinded bilateral stimulator activation while repeated open programming sessions were permitted. RESULTS In the randomized phase of the trial, a statistically significant (p < 0.03, Friedman exact test) reduction in the modified Rush Video-Based Rating Scale score (primary outcome measure) was identified in the bilateral on state. Improvement was noted in motor and sonic tic counts as well as on the Yale Global Tic Severity Scale and TS Symptom List scores (secondary outcome measures). Benefit was persistent after 3 months of open stimulator programming. Quality of life indices were also improved. Three of five patients had marked improvement according to all primary and secondary outcome measures. CONCLUSIONS Bilateral thalamic DBS appears to reduce tic frequency and severity in some patients with TS who have exhausted other available means of treatment.

Cognitive and behavioral effects of lamotrigine and topiramate in healthy volunteers

Background: The relative cognitive and behavioral effects of lamotrigine (LTG) and topiramate (TPM) are unclear. Methods: The authors directly compared the cognitive and behavioral effects of LTG and TPM in 47 healthy adults using a double-blind, randomized crossover design with two 12-week treatment periods. During each treatment condition, subjects were titrated to receive either LTG or TPM at a target dose of 300 mg/day for each. Neuropsychological evaluation included 17 measures yielding 41 variables of cognitive function and subjective behavioral effects. Subjects were tested at the end of each antiepileptic drug (AED) treatment period and during two drug-free conditions (pretreatment baseline and 1 month following final AED withdrawal). Results: Direct comparison of the two AEDs revealed significantly better performance on 33 (80%) variables for LTG, but none for TPM. Even after adjustment for blood levels, performance was better on 19 (46%) variables for LTG, but none for TPM. Differences spanned both objective cognitive and subjective behavioral measures. Comparison of TPM to the non-drug average revealed significantly better performance for non-drug average on 36 (88%) variables, but none for TPM. Comparison of LTG to non-drug average revealed better performance on 7 (17%) variables for non-drug average and 4 (10%) variables for LTG. Conclusions: Lamotrigine produces significantly fewer untoward cognitive and behavioral effects compared to topiramate (TPM) at the dosages, titrations, and timeframes employed in this study. The dosages employed may not have been equivalent in efficacy. Future studies are needed to delineate the cognitive and behavioral effects of TPM at lower dosages.

Age- and Education-Corrected Independent Normative Data for the RBANS in a Community Dwelling Elderly Sample

The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS, Randolph, 1998) is likely to become a popular screening instrument for measuring cognitive functioning, particularly in elderly patients. As such, the present study attempted to extend the original normative data by reporting on RBANS performances in a group of 718 community dwelling older adults. Participants were recruited from an outpatient primary care setting, and were assessed for demographic, medical status, functional status, and quality of life information. Utilizing four empirically supported overlapping midpoint age ranges, individual subtest raw scores were converted to age-corrected scaled scores based on their position within a cumulative frequency distribution. These age-corrected scaled scores were also converted into education-corrected scaled scores using the same methodology across four education levels. Independent Index and Total scores were also calculated based on the data from this large elderly sample. These data may considerably advance the clinical utility of the RBANS by allowing clinicians to interpret individual subtests and make direct comparisons between subtests. Practitioners and researchers who elect to use the current normative data are encouraged to consider the similarities and differences between the present sample and their individual patients or research participants.

Estimation of WAIS-III Intelligence from Combined Performance and Demographic Variables: Development of the OPIE-3

Data from the WAIS-III standardization sample (The Psychological Corporation, 1997) was used to generate several FSIQ estimation formulas that used demographic variables and current WAIS-III subtest performance. The standardization sample (N =2,450) was randomly divided into two groups, the first was used to develop the formulas and the second group was used to validate the prediction equations. Age, education, ethnicity, gender, region of the country as well as Vocabulary, Information, Matrix Reasoning, and Picture Completion subtests raw scores were used as predictor variables. Regression formulas were generated using four subtest, two subtest, single verbal, two performance subtest, and single performance algorithms. The four-subtest model combined Information, Vocabulary, Matrix Reasoning, and Picture Completion raw scores with demographic variables. The two-subtest algorithm used Vocabulary and Matrix Reasoning raw scores with demographic variables. Formulas to estimate FSIQ using only verbal or performance subtests were developed for use with lateralized populations. The formulas for estimating premorbid FSIQ were highly significant and accurate in predicting FSIQ scores of participants in the WAISIII normative sample.

Pre-MCI and MCI: neuropsychological, clinical, and imaging features and progression rates.

OBJECTIVE To compare clinical, imaging, and neuropsychological characteristics and longitudinal course of subjects with pre-mild cognitive impairment (pre-MCI), who exhibit features of MCI on clinical examination but lack impairment on neuropsychological examination, to subjects with no cognitive impairment (NCI), nonamnestic MCI (naMCI), amnestic MCI (aMCI), and mild dementia. METHODS For 369 subjects, clinical dementia rating sum of boxes (CDR-SB), ApoE genotyping, cardiovascular risk factors, parkinsonism (UPDRS) scores, structural brain MRIs, and neuropsychological testing were obtained at baseline, whereas 275 of these subjects received an annual follow-up for 2-3 years. RESULTS At baseline, pre-MCI subjects showed impairment on tests of executive function and language, higher apathy scores, and lower left hippocampal volumes (HPCV) in comparison to NCI subjects. Pre-MCI subjects showed less impairment on at least one memory measure, CDR-SB and UPDRS scores, in comparison to naMCI, aMCI and mild dementia subjects. Follow-up over 2-3 years showed 28.6% of pre-MCI subjects, but less than 5% of NCI subjects progressed to MCI or dementia. Progression rates to dementia were equivalent between naMCI (22.2%) and aMCI (34.5%) groups, but greater than for the pre-MCI group (2.4%). Progression to dementia was best predicted by the CDR-SB, a list learning and executive function test. CONCLUSION This study demonstrates that clinically defined pre-MCI has cognitive, functional, motor, behavioral and imaging features that are intermediate between NCI and MCI states at baseline. Pre-MCI subjects showed accelerated rates of progression to MCI as compared to NCI subjects, but slower rates of progression to dementia than MCI subjects.

Test-Retest Stability and Practice Effects of the RBANS in a Community Dwelling Elderly Sample

Repeated neuropsychological assessments are common with older adults, and the determination of true neurocognitive change is important for diagnostic assessment. Several statistical formulas are available to assist in this determination, but they rely on access to test-retest stability coefficients and practice effect values. The current study presents data on these psychometric properties of the RBANS in a large community dwelling elderly sample. Across a one-year retest interval, stability coefficients ranged from .58 to .83 for the Index scores, and from .51 to .83 for the subtest scores. Practice effects were largely absent, with most performances slightly decreasing at retest. These psychometric properties are contrasted with those reported in the RBANS manual, and possible reasons for these differences are discussed. A case example is provided that demonstrates the use of the current findings in conjunction with existing change formulas.

Defining Mild Cognitive Impairment: Impact of Varying Decision Criteria on Neuropsychological Diagnostic Frequencies and Correlates

OBJECTIVE To examine the impact of varying decision criteria on neuropsychological diagnostic frequencies and on their correlates. DESIGN Descriptive and correlational study. SETTING Florida Alzheimers Disease Research Center. PARTICIPANTS A sample of 373 individuals with comprehensive baseline analyses participating in a longitudinal study of cognitive decline and early Alzheimer disease. MEASUREMENTS Mild cognitive impairment (MCI) diagnoses were made on the basis of four sets of decision criteria created by crossing two approaches: varying the number of impaired test results required for a diagnosis within any domain (1 test versus 2) and varying the performance level required to determine impairment (1.5 or 2 standard deviations [SDs] below the normative mean) for any test. RESULTS Under each criteria set, single-domain amnestic MCI was the most frequent MCI diagnosis. MCI global and subtype diagnosis frequencies were inversely related to the stringency of the criteria. The single test-1.5 SD criterion identified the largest number of cases as qualifying for an MCI diagnosis, and the two test-2.0 SD cutoff identified the fewest. Across all sets of criteria, the authors found significant positive associations between neuropsychological diagnoses and Clinical Dementia Rating score categories. Significant relationships between diagnoses and both apolipoprotein E (APOE) genotype and magnetic resonance imaging ratings of medial temporal atrophy (MTA) application were found only for the two test-1.5 SD and two test-2.0 SD cutoffs. CONCLUSION MCI diagnosis frequencies are substantively affected by the stringency of the criteria, but the relative rankings of MCI subtype diagnoses are fairly consistent regardless of the stringency of the criteria. Significant associations of neuropsychological diagnoses with independent markers such as APOE genotype and MTA are only found with more stringent criteria, suggesting that a coherent network of associations reflecting cognitive decline occurs with more restrictive definitions for impairment.

Performance of Cognitively Normal African Americans on the RBANS in Community Dwelling Older Adults

Recent research suggests that cognitively normal African Americans are more likely to be misdiagnosed as impaired compared to Caucasians due to lower neuropsychological test scores (e.g., Manly et al., 1998). Given this, the present study sought to determine whether such racial discrepancies exist on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Performances of 50 cognitively normal older African Americans on the RBANS were compared to those of 50 Caucasians matched on age, education, and gender. The African Americans scored significantly lower on 10 of 12 subtests, 3 of 5 Index scores, and the Total Scale score. Results underscored the utility of demographically appropriate norms when serving minority clients. Given that there remains a paucity of normative data for minority groups, RBANS normative data for older African Americans are provided. Although preliminary, it is hoped that data presented will offer the practitioner assistance with clinical diagnosis and decision-making in a manner that will help minimize diagnostic errors.

Laser ablation therapy: An alternative treatment for medically resistant mesial temporal lobe epilepsy after age 50

Selective anterior mesial temporal lobe (AMTL) resection is considered a safe and effective treatment for medically refractory mesial temporal lobe epilepsy (MTLE). However, as with any open surgical procedure, older patients (aged 50+) face greater risks. Magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) has shown recent potential as an alternative treatment for MTLE. As a less invasive procedure, MRgLITT could be particularly beneficial to older patients. To our knowledge, no study has evaluated the safety and efficacy of MRgLITT in this population. Seven consecutive patients (aged 50+) undergoing MRgLITT for MTLE were followed prospectively to assess surgical time, complications, postoperative pain control, length of stay (LOS), operating room (OR) charges, total hospitalization charges, and seizure outcome. Five of these patients were assessed at the 1-year follow-up for seizure outcome. These data were compared with data taken from 7 consecutive patients (aged 50+) undergoing AMTL resection. Both groups were of comparable age (mean: 60.7 (MRgLITT) vs. 53 (AMTL)). One AMTL resection patient had a complication of aseptic meningitis. One MRgLITT patient experienced an early postoperative seizure, and two MRgLITT patients had a partial visual field deficit. Seizure-freedom rates were comparable (80% (MRgLITT) and 100% (AMTL) (p>0.05)) beyond 1year postsurgery (mean follow-up: 1.0years (MRgLITT) vs. 1.8years (AMTL)). Mean LOS was shorter in the MRgLITT group (1.3days vs. 2.6days (p<0.05)). Neuropsychological outcomes were comparable. Short-term follow-up suggests that MRgLITT is safe and provides outcomes comparable to AMTL resection in this population. It also decreases pain medication requirement and reduces LOS. Further studies are necessary to assess the long-term efficacy of the procedure.

An evaluation of the clinical utility of the OPIE-3 as an estimate of premorbid WAIS-III FSIQ.

The clinical utility of the Oklahoma Premorbid Intelligence Estimate – 3 (OPIE-3; Schoenberg, Scott, Duff, & Adams, 2002) in estimating premorbid FSIQ was investigated with the WAIS-III standardization sample. The OPIE-3 algorithms combine Vocabulary, Information, Matrix Reasoning, and Picture Completion subtest raw scores with demographic variables to predict FSIQ. Estimated WAIS-III FSIQ scores are presented for patients’ diagnosed with dementia, traumatic brain injury, Huntington’s disease, Korsakoff’s disease, chronic alcohol use, temporal lobectomy, and schizophrenia. A group of patients with depression was employed as a clinical control group. The OPIE-3Vand OPIE-3MR algorithms performed well, with the average predicted FSIQ of the combined clinical sample approximating the mean FSIQ of healthy adults. The OPIE-3(Best), which is a procedure that employs either the OPIE-3V, OPIE-3MR, or OPIE-3(2ST) algorithms in a best performance method, is presented. Recommendations in the application of the OPIE-3 are made and future research is proposed.