Essential tremor: predictors of disease progression in a clinical cohort.

OBJECTIVES: To examine the utility of baseline factors to predict disease progression among a clinical cohort of patients diagnosed with essential tremor. MEASURES: Tremor Rating Scale (TRS). METHODS: A clinical series of 128 consecutive patients diagnosed with essential tremor was included for study. 45 (35%) patients had at least one follow-up exam (mean = 3.6 years). Baseline predictive factors examined included age, age at onset of symptoms, disease duration, sex, handedness, total tremor rating score, asymmetric tremor ratings, location of initial tremor onset, use of drugs for movement disorders, ETOH responsiveness of tremor, association of head or neck tremor, history of depression, familial history of essential tremor, Parkinson's disease, Alzheimer's disease and other movement disorders. RESULTS: On average, the TRS total score increased by <1 point per year before the first visit to the clinic and by about 2 points per year during the observed study period. The increase of 2 points per year during the observed study period represented an approximate 12% annual change from the mean TRS total score at the first clinic visit. Significant (p<0.05) predictive factors associated with increased tremor severity at the initial clinic visit included older age, longer disease duration, use of movement disorder drugs and the presence of voice tremor (r = 0.24, 0.27, 0.25, 0.19). The major factors associated with an increase in tremor severity from the initial clinic visit to the last follow up included asymmetrical tremor ratings, unilateral initial tremor onset and longer follow-up duration (r = 0.32, 0.31, 0.30). Multivariate regression analysis accounted for about 17-30% of the variance in tremor ratings (p<0.05). CONCLUSION: Essential tremor is a slow, progressive disease. The rate of disease progression and the factors associated with disease progression may vary throughout the disease course.

Parkinson disease: handedness predicts asymmetry.

OBJECTIVE: To determine the proportion of individuals in a clinic-based setting that present with asymmetric Parkinson disease (PD) and identify predictive factors associated with asymmetric symptoms. METHODS: The authors examined right vs left difference scores on the Unified Parkinson Disease Rating Scale motor subscale in a consecutive clinical series of 1,277 individuals diagnosed with PD. Predictors of asymmetry included sex, symptomatic disease duration, age at onset, initial motor symptom laterality, handedness, and medical history variables (e.g., family history of PD). RESULTS: Nearly half the sample (46%) met criteria for asymmetric disease based on a right vs left difference score of > or =5 points, and 12% of the sample had a difference score of > or =10 (difference score: mean = 4, SD = 3.4). All three cardinal features of PD showed characteristics of asymmetric disease presentation. Multiple regression analyses showed that an increased discrepancy between right- and left-sided symptoms was significantly associated with a shorter disease duration, younger age at symptomatic onset, asymmetric initial symptom onset, hand dominance, and a positive self-reported family history of "other" neurodegenerative disorder. Hand dominance was related to the side of asymmetric disease such that left-handed individuals tended to have more severe disease on the left side of the body. CONCLUSION: Asymmetric presentation of Parkinson disease features was a common occurrence in the clinical cohort. Asymmetry was reliably predicted by several clinical characteristics, although the moderate level of explained variance (i.e., between 16 and 23%) highlighted the need for additional research examining predictive models of asymmetric disease. Recommendations for the classification and measurement of asymmetric disease are discussed.

Bilateral thalamic deep brain stimulation: midline tremor control.

OBJECTIVES: To determine the efficacy of bilateral deep brain stimulation (DBS) for management of midline tremor (head, voice, tongue, trunk) in patients with essential tremor. DESIGN: Prospective assessment of tremor at baseline (presurgical), and postoperatively at 1, 3, and 12 months, and annually thereafter. METHODS: A clinical series of 22 individuals undergoing staged, bilateral DBS for treatment of essential tremor. The tremor rating scale was the primary outcome measure. RESULTS: Midline tremor showed significant improvement with stimulation "on" at nearly every postoperative interval when compared with stimulation "off" and with baseline tremor. Bilateral stimulation was associated with a significant incremental improvement in midline tremor control compared with unilateral stimulation: average "stimulation on" percentage change in midline tremor from the unilateral to bilateral period was 81%. Head and voice tremor showed the most consistent improvement. Among those requiring a change in stimulation parameters because of side effects, dysarthria, disequilibrium, motor disturbances, and paraesthesiae were the most common. Dysarthria was more common with bilateral (n = 6; 27%) than with unilateral (n = 0) stimulation. Stimulation parameters remained largely unchanged after the first three months. Nine of 44 leads placed (20%) required subsequent repositioning or replacement. CONCLUSIONS: Unilateral thalamic stimulation significantly improves midline tremor, and subsequent bilateral thalamic stimulation offers an additional incremental improvement in midline tremor control.

Thalamic deep brain stimulation for essential tremor: recommendations for long-term outcome analysis.

OBJECTIVES: Determine the efficacy of thalamic deep brain stimulation (DBS) for tremor control among individuals with essential tremor (ET). METHODS: A clinical series of 52 consecutive individuals undergoing placement of a DBS system for treatment of ET completed an unblinded battery of subjective and objective measures at postoperative intervals of one, three, and 12 months, and annually thereafter up to three years. The assessment battery included measures of tremor and activities of daily living. RESULTS: Both subjective and objective measures showed that stimulation was associated with significant improvement at nearly every postoperative interval as compared to pre-operative and stimulation 'off' ratings of activities of daily living functioning, midline tremor, contralateral upper extremity tremor, and contralateral lower extremity tremor. Ipsilateral tremor showed some improvement with stimulation, but only within the first three months. Trend analysis showed stable tremor control. Stimulation settings remained largely unchanged after the first three months. Dysarthria was more common among those with bilateral stimulation. A range of missing data estimation methods were performed, and subsequent analyses corroborated the main findings of the study. CONCLUSION: Thalamic DBS is generally a well-tolerated and effective treatment for ET. Methodological and analytical recommendations are provided for the evaluation of long-term outcome.

Nitric oxide is not involved in the control of vasopressin release during acute forced swimming in rats.

Neurons of the hypothalamo-neurohypophyseal system (HNS) are known to contain high amounts of neuronal nitric oxide (NO) synthase (nNOS). NO produced by those neurons is commonly supposed to be involved as modulator in the release of the two nonapeptides vasopressin (AVP) and oxytocin into the blood stream. Previous studies showed that forced swimming fails to increase the release of AVP into the blood stream while its secretion into the hypothalamus is triggered. We investigated here whether hypothalamically acting NO contributes to the control of the AVP release into blood under forced swimming conditions. Intracerebral microdialysis and in situ hybridization were employed to analyze the activity of the nitrergic system within the supraoptic nucleus (SON), the hypothalamic origin of the HNS. A 10-min forced swimming session failed to significantly alter the local NO release as indicated both by nitrite and, the main by-product of NO synthesis, citrulline levels in microdialysis samples collected from the SON. Microdialysis administration of NO directly into the SON increased the concentration of AVP in plasma samples collected during simultaneous forced swimming. In an additional experiment the effect of the defined stressor exposure on the concentration of mRNA coding for nNOS within the SON was investigated by in situ hybridization. Forced swimming increased the expression of nNOS mRNA at two and four hours after onset of the stressor compared to untreated controls. Taken together, our results imply that NO within the SON does not contribute to the regulation of the secretory activity of HNS neurons during acute forced swimming. Increased nNOS mRNA in the SON after forced swimming and the increase in AVP release in the presence of exogenous NO under forced swimming points to a possible role of NO in the regulation of the HNS under repeated stressor exposure.

Thalamic deep brain stimulation for tremor-predominant Parkinson's disease.

OBJECTIVES: Determine the long-term efficacy of thalamic deep brain stimulation (DBS) for treatment of tremor among individuals with tremor-predominant Parkinson's disease (PD).Design. Longitudinal, unblinded assessment of tremor and activities of daily living (ADL) at baseline (pre-surgical), and post-operative intervals of 1, 3, and 12 months, and annually thereafter up to 3 years. METHODS: A clinical series of 19 individuals undergoing placement of a DBS system for treatment of PD-related tremor. A battery of subjective and objective measures of tremor was completed at planned pre- and post-operative intervals. RESULTS: Stimulation was associated with significant improvement on subjective and objective measures of ADL performance, midline tremor, and contralateral upper and lower extremity tremor, including parkinsonian resting and action tremors, over the follow-up period. Ipsilateral tremor showed little or no effect of stimulation after the first 3 months. Antiparkinsonian medication use and stimulation parameters showed little or no change over the course of follow-up. About half (53%) of all individuals reported at least one side effect, generally mild, during the follow-up period, with paresthesias and dysarthria being the most common. A total of two leads required replacement due to (1) infection, and (2) adverse side effects (i.e. burning and tingling with stimulation). CONCLUSION: DBS is associated with stable tremor control in PD. Side-effects are typically easily managed with stimulation adjustments, although in some cases lead replacement may be required.

Test-retest reliability of the Donovan spinal cord injury pain classification scheme.

STUDY DESIGN: Videotape rating by independent viewers. OBJECTIVE: To determine the test-retest reliability of the Donovan spinal cord injury (SCI) pain classification scheme. SETTING: Rehabilitation Centre, Alabama, USA. METHODS: A total of 28 individuals with SCI reported 60 pain sites. A structured interview and physical exam were used to illicit information to classify each pain site according to the Donovan criteria. All structured interviews and exams were videotaped. Three independent raters viewed the videotapes on two occasions, separated by a 3-month interval, and classified each pain site using the Donovan pain classification scheme. RESULTS: Considering all three raters together, 78% of the pain sites were consistently classified from one period to the next. Within each rater, consistent classification ranged from 67 to 83%. However, inter-rater agreement for the classification of each pain site into the various types of pain was low for both periods (about 50-60%). CONCLUSIONS: Pain classification within each rater generally showed adequate test-retest reliability when using the Donovan SCI pain classification scheme. However, reliability estimates of agreement across raters highlight the ongoing need to exam and improve the psychometric characteristics of the various pain classification schemes.

Pain classification following spinal cord injury: the utility of verbal descriptors.

OBJECTIVES: To determine the predictive utility of verbal descriptors to distinguish between pain types following spinal cord injury (SCI). DESIGN: Cross-sectional. SETTING: USA. METHODS: Participants (n=29) completed the Short Form - McGill Pain Questionnaire (SF-MPQ) for each pain site reported. A total of 64 pain sites were reported with 80% of the sample reporting multiple pain sites. Each pain site was categorized using three different SCI pain classification schemes. The predictive utility of verbal descriptors to distinguish between pain types was examined statistically using (1) each word separately, (2) a combination of words (ie, the SF-MPQ total subscales, the number of words chosen on each scale), and (3) discriminant function analysis. RESULTS: There was a substantial overlap in the use of verbal descriptors across pain types. Few differences across pain types were found for endorsement of individual words, and differences across pain types were not found for any of the word combination scores. The majority of the verbal descriptors did not enter the step-wise discriminant functions for each SCI pain classification scheme, however, 'tingling' and 'aching' showed modest predictive utility for neuropathic and musculoskeletal pain, respectively. Correct classification was in the low range (ie, 39% to 82%, average=60%, with a 33% chance level). All three pain classification schemes showed the same general pattern of results. CONCLUSION: In general, verbal descriptors alone offered marginal utility with regard to identifying specific pain types following SCI. Future directions alone and implications are discussed.

Impact of demographic and medical factors on satisfaction with life after spinal cord injury: a normative study.

OBJECTIVE: The aim of this study was (1) to examine demographic and medical predictors of the Satisfaction With Life Scale (SWLS) among individuals with spinal cord injury (SCI) and (2) to provide a normative table for the SWLS that includes appropriate adjustments for the most important predictors of life satisfaction. STUDY DESIGN: We examined predictors of the SWLS including age, education, sex, race, injury duration, number of rehospitalizations, marital status, employment status, SCI etiology, and level of neurological impairment. PARTICIPANTS: Individuals in the National Spinal Cord Injury Statistical Center database [from 18 SCI model systems (1995-1999)] undergoing follow-up assessment were included for study. OUTCOME MEASURE: Satisfaction With Life Scale. RESULTS: Univariate analyses indicated that marital and employment status, race, sex, education, and injury duration were significant factors associated with scores on the SWLS. In general, individuals who were female, white, married, and currently employed and had a higher education and longer injury duration reported significantly higher scores on the SWLS (P < .01). Effect-size estimates for these factors ranged from 0.16 to 0.41. Regression analyses showed that education, employment status, and injury duration were the strongest unique predictors of satisfaction with life but accounted for only 10% of the variance. CONCLUSION: The SWLS is a global measure of life satisfaction and is relatively unrelated to demographic and medical characteristics. Normative tables are provided for epidemiologic comparison.

Predictors of pain 1 year post-spinal cord injury.

OBJECTIVE: To determine the predictive validity of demographic and medical characteristics to the subsequent development of pain 1 year post-spinal cord injury (SCI). DESIGN: Prospective longitudinal design using data from 18 Model Spinal Cord Injury Systems of Care. PARTICIPANTS: Adults 18 years or older with traumatic-onset SCI (n = 540) evaluated at 1 year postinjury. OUTCOME MEASURES: A single item from the Short Form-12 that assessed pain interference in day-to-day activities using a 5-point Likert scale. PREDICTOR VARIABLES: Demographic and medical characteristics, individual and total medical complications during rehabilitation, and insurance provider. RESULTS: Univariate analyses showed age, education, marital status, primary occupation at the time of injury, American Spinal Injury Association motor score, and sponsor of care to be related to pain interference 1 year post-SCI. Polychotomous logistic regression indicated that age and occupational status at the time of injury were the only significant unique predictors of pain interference. The youngest (aged 18-29 years) and oldest (aged 60 years and older) age groups reported the least amount of pain interference, whereas individuals unemployed at the time of injury were significantly more likely to report pain interference. None of the other predictor variables was significant. CONCLUSION: Age and occupational status appear to be important predictors of pain interference 1 year post-SCI. Future directions of study and limitations are discussed.

Quality of life after spinal cord injury caused by gunshot.

OBJECTIVE: To determine what effect gunshot-caused spinal cord injury (SCI) has on self-reported quality of life (QOL) and on the frequency of pain sufficient to interfere with day-to-day activities. DESIGN: Follow-up, case-control design. SETTING: Analysis of data obtained from the (US) National Spinal Cord Injury Statistical Center from 18 funded Spinal Cord Injury Model Systems. PARTICIPANTS: Individuals with traumatic onset SCI (n = 1901). From these, 111 persons with gunshot-caused SCI were matched to persons with nongunshot SCI. MAIN OUTCOME MEASURES: Satisfaction with Life Scale (SWLS), the Craig Handicap Assessment and Reporting Technique (CHART), Medical Outcomes Study Short-Form Health Survey (SF-12), and an individual pain item from the SF-12. RESULTS: No between-group differences were found on any of the QOL outcome measures. In contrast, those with SCI caused by gunshot reported that pain more frequently interfered with day-to-day activities than the matched comparison group. CONCLUSIONS: SCI caused by gunshot appears largely unrelated to QOL, after controlling for demographic and medical characteristics associated with this group. Gunshot as a mechanism of SCI may place individuals at an increased risk of subsequent development of pain that interferes with activities of daily living.

Nursing home residence: quality of life among individuals with spinal cord injury.

OBJECTIVE: To examine the quality of life among individuals with spinal cord injury currently living in a nursing home vs. community residence. DESIGN: A case-control design matched nursing home and community residents on numerous demographic and medical characteristics. Two groups of 37 individuals (nursing home vs. community residents) were matched case-for-case on age (i.e., within 10 yr), education, gender, race, marital status, and impairment level. Etiology of spinal cord injury, American Spinal Injury Association Impairment Index at the time of rehabilitation discharge, and injury duration, although not specifically matched, were not significantly different between groups (P > 0.05). Outcome measures included the Satisfaction With Life Scale, and the Craig Handicap Assessment and Reporting Technique (CHART). RESULTS: Results indicated that overall self-reported quality of life was significantly lower among nursing home residents compared with matched community-dwelling residents (mean = 18 and 14, respectively). Similarly, self-reported handicap was significantly higher among the nursing home residents compared with community residents (mean = 337 and 181, respectively), particularly in the areas of physical independence, mobility, occupational functioning, and economic self-sufficiency (P < 0.05). In contrast, the score on the CHART social integration subscale was similar across groups (P > 0.05). CONCLUSION: Despite matching numerous variables, the nursing home residents demonstrated significantly lower quality of life across multiple domains as compared with their community-dwelling counterparts. Additional research is needed to examine the specific mechanisms associated with these differences.

Developmental memory performance: inter-task consistency and base-rate variability on the WRAML.

Two studies examined developmental memory test consistency and base-rate variability on the Wide Range Assessment of Memory and Learning (WRAML) using three age cohorts from the standardization sample. Study 1 examined inter-subtest correlation coefficients across the nine subtests of the WRAML and compared across three age cohorts (5, 11, 16 to 17 year olds). An age-related increase in inter-task consistency was found (mean r = .26 and .42 for the youngest and oldest age groups, respectively). However, correlation coefficients were generally in the low to moderate range (rs = .2 to .5) for all three cohorts suggesting considerable performance variability across memory subtests. Study 2 examined base-rate variability in the WRAML standardization sample using several different methods. More specifically, base-rate information is provided for the maximum discrepancy between subtests, profile strengths and weakness (i.e., discrepancies from the mean scaled score), and the prevalence of individuals within the "deficient" performance range (i.e., < = 2 SD below normative means). In addition, performance variability across the four WRAML index scores was examined by determining the prevalence rates for the maximum discrepancy (1) between index scores, and (2) from the General Memory Index compared to the other three index scores. Performance discrepancies tended to be higher among the youngest group. Again, however, considerable performance variability was observed across all three age cohorts. Implications for clinical practice are discussed.

Gunshot versus nongunshot spinal cord injury: acute care and rehabilitation outcomes.

OBJECTIVE: To examine the impact of gunshot-caused spinal cord injury on acute and rehabilitative care outcome using a case control design. DESIGN: Two groups (i.e., gunshot- vs. nongunshot-caused spinal cord injury) of 212 individuals were matched case-for-case on age (i.e., within 10 yr), education, gender, race, marital status, primary occupation, impairment level, and Model System region. Outcome measures included length of hospital stay, functional status (FIM), treatment charges, and home discharge rates. RESULTS: The two groups did not differ in the length of stay during acute and rehabilitative care, charges during rehabilitative care, or postrehabilitation discharge placement. Several significant between-group differences in treatment procedures were noted (e.g., prevalence of spinal surgery), which may, in part, account for the higher acute-care charges among those persons with nongunshot-caused spinal cord injury. CONCLUSION: Once an individual is stabilized and admitted for rehabilitative care, gunshot etiology of spinal cord injury seems largely unrelated to the initial rehabilitation outcome.

The anti-craving compound acamprosate acts as a weak NMDA-receptor antagonist, but modulates NMDA-receptor subunit expression similar to memantine and MK-801.

NMDA-receptor-mediated mechanisms may be crucial in addictive states, e.g. alcoholism, and provide a target for the novel anti-craving compound acamprosate. Here, the pharmacological effects of acamprosate on NMDA-receptors were studied using electrophysiological techniques in different cell lines in vitro. Additionally, a possible modulation of brain NMDA-receptor subunit expression was examined in vivo in rats, and compared to two effective non-competitive NMDA-receptor antagonists, memantine and MK-801. Electrophysiology in cultured hippocampal neurons (IC(50) approx. 5.5mM) and Xenopus oocytes (NR1-1a/NR2A assemblies: IC(50) approx. 350 microM, NR1-1a/NR2B: IC(50) approx. 250 microM) consistently revealed only a weak antagonism of acamprosate on native or recombinant NMDA-receptors. In HEK-293 cells, acamprosate showed almost no effect on NR1-1a/NR2A or NR1-1a/NR2B recombinants (IC(50)s not calculated). Protein blotting demonstrated an up-regulation of NMDA-receptor subunits after acamprosate as well as after memantine or MK-801, in comparison to controls. After acamprosate, protein levels were increased in the cortex (NR1-3/1-4: 190+/-11% of controls) and hippocampus (NR1-1/1-2: 163+/-11%). The up-regulations observed after memantine (cortex, NR2B: 172+/-17%; hippocampus, NR1-1/1-2: 156+/-8%) or MK-801 (cortex, NR2B: 174+/-22%; hippocampus, NR1-1/1-2: 140+/-3%) were almost identical. No changes were detected in the brainstem. The present data indicate an extremely weak antagonism of NMDA-receptors by acamprosate. However, its ability to modulate the expression of NMDA-receptor subunits in specific brain regions - shared with the well established NMDA-antagonists memantine and MK-801 - may be of relevance for its therapeutic profile, especially considering the growing importance of NMDA-receptor plasticity in the research of ethanol addiction.

Self-report measures among transplant candidates: the impact of evaluative situations.

Experiment 1 was a between-subjects design comparing transplant candidates completing self-report measures under an evaluative versus an anonymous research condition. A cardiac disease group and a healthy community group served as controls. Transplant candidates in the anonymous research condition reported significantly more depression, anxiety, and negative affectivity as compared with transplant candidates in the evaluative condition and community controls. In contrast, the evaluative transplant group (a) did not differ from the community controls on any of the self-report measures, and (b) reported significantly less depression than cardiac disease controls. Experiment 2 was a within-subjects design with transplant candidates completing self-report measures under both an evaluative and an anonymous research condition. Significantly greater anxiety was reported under the anonymous research condition. Social desirability was significantly related to change in self-reported anxiety and depression across conditions, but was unrelated to change in endorsement of personality characteristics.

Differential role of the nitric oxide pathway on delta(9)-THC-induced central nervous system effects in the mouse.

This study investigated whether the nitric oxide pathway was involved in the central effects of Delta(9)-tetrahydrocannabinol (Delta(9)-THC), the major psychoactive constituent of cannabis sativa. Body temperature, nociception and locomotion were measured in neuronal nitric oxide synthase (nNOS) knock-out (KO) mice and wild-type (WT) controls after intraperitoneal application of Delta(9)-THC. These Delta(9)-THC-induced effects are known to be mediated through the brain-type cannabinoid receptor 1 (CB1). Therefore, in situ hybridization (ISH) experiments were performed in the adult murine brain to determine possible changes in CB1 mRNA levels in nNOS-KO, compared with WT mice, and to reveal brain areas where CB1 and nNOS were coexpressed in the same neurons. We found that an intraperitoneal injection of 10 mg/kg Delta(9)-THC led to the same increase in the hot plate latencies in both genotypes, suggesting that Delta(9)-THC-mediated antinociception does not involve nNOS. In contrast, a significant Delta(9)-THC-induced decrease of body temperature and locomotor activity was only observed in WT, but not in nNOS-KO mice. ISH revealed significantly lower levels of CB1 mRNA in the ventromedial hypothalamus (VMH) and the caudate putamen (Cpu) of the nNOS-KO animals, compared with WT mice. Both areas are known to be among the regions involved in cannabinoid-induced thermoregulation and decrease of locomotion. A numerical evaluation of nNOS/CB1 coexpression showed that approximately half of the nNOS-positive cells in the dorsolateral Cpu also express low levels of CB1. ISH of adjacent serial sections with CB1 and nNOS, revealed expression of both transcripts in VMH, suggesting that numerous nNOS-positive cells of VMH coexpress CB1. Our findings indicate that the nitric oxide pathway is involved in some, but not all of the central effects of Delta(9)-THC.

Bladder management and quality of life after spinal cord injury.

OBJECTIVE: This study examines the quality of life among individuals with spinal cord injury requiring assistance for bowel and bladder management vs. those with independent control of bowel and bladder. DESIGN: Two groups of 53 individuals each were matched case for case on age, education, sex, race, and lesion level. Outcome measures included the Satisfaction With Life Scale, the Craig Handicap Assessment and Reporting Technique (CHART), and the SF-12. RESULTS: Satisfaction with life was significantly lower among dependent individuals with impaired bowel and bladder functioning as compared with individuals with independent bowel and bladder control. Similarly, dependent individuals reported greater self-reported handicap (CHART) than independent individuals in the areas of physical independence, mobility, and occupational functioning. However, dependent and independent individuals did not differ in the areas of social integration and economic self-sufficiency. Item analysis on the CHART item assessing number of social contacts initiated in the previous month suggested that dependent individuals may have difficulty initiating new social contacts. Independent individuals reported better overall physical health (SF-12) than dependent individuals. Mental health (SF-12), however, did not differ across groups. CONCLUSIONS: Individuals with impaired bowel and bladder control reported lower quality of life on several domains compared with those with independent control of bowel and bladder. Though the two groups did not differ in self-reported social integration, dependent individuals may have greater difficulty creating new social relationships.