Showing papers in "Neurology in 2000"

The FAB A frontal assessment battery at bedside

Abstract: Objective: To devise a short bedside cognitive and behavioral battery to assess frontal lobe functions. Methods: The designed battery consists of six subtests exploring the following: conceptualization, mental flexibility, motor programming, sensitivity to interference, inhibitory control, and environmental autonomy. It takes approximately 10 minutes to administer. The authors studied 42 normal subjects and 121 patients with various degrees of frontal lobe dysfunction (PD, n = 24; multiple system atrophy, n = 6; corticobasal degeneration, n = 21; progressive supranuclear palsy, n = 47; frontotemporal dementia, n = 23). Results: The Frontal Assessment Battery scores correlated with the Mattis Dementia Rating Scale scores (rho = 0.82, p p p p Conclusion: The Frontal Assessment Battery is easy to administer at bedside and is sensitive to frontal lobe dysfunction.

Prevalence of dementia and major subtypes in Europe : A collaborative study of population-based cohorts

Abstract: Article abstract-The authors examined the association of incident dementia and subtypes with age, sex, and geographic area in Europe. Incidence data from eight population-based studies carried out in seven European countries were compared and pooled. The pooled data included 835 mild to severe dementia cases and 42,996 person-years of follow-up. In all studies a higher proportion of cases were diagnosed with AD (60 to 70% of all demented cases) than vascular dementia (VaD). The incidence of dementia and AD continued to increase with age up to age 85 years, after which rates increased in women but not men. There was a large variation in VaD incidence across studies. In the pooled analysis, the incidence rates increased with age without any substantial difference between men and women. Surprisingly, higher incidence rates of dementia and AD were found in the very old in northwest countries than in southern countries. This study confirms that AD is the most frequent dementing disorder in all ages, and that there is a higher incidence of dementia, specifically AD, in women than men among the very old. Finally, there may be regional differences in dementia incidence.

Practice parameter: Evidence-based guidelines for migraine headache (an evidence-based review) Report of the Quality Standards Subcommittee of the American Academy of Neurology

Abstract: Mission statement. The Quality Standards Subcommittee (QSS) of the American Academy of Neurology (AAN) is charged with developing practice parameters for physicians. This practice parameter summarizes the results from the four evidence-based reviews on the management of patients with migraine: specifically, acute, preventive, and nonpharmacologic treatments for migraine, and the role of neuroimaging in patients with headache. The full papers for these treatment guidelines are published elsewhere,1-6⇓⇓⇓⇓⇓ and only the specific treatment recommendations are summarized below. Migraine is a very common disorder. An estimated 18% of women and 6% of men experience migraine, but many go undiagnosed and undertreated.7 There have been a number of advances in the diagnosis and treatment of migraine as well as great strides in understanding its pathogenesis, making it one of the best understood of the neurologic disorders. Migraine is characterized by enhanced sensitivity of the nervous system. The attack is associated with activation of the trigeminal-vascular system. In June 1998, Duke University’s Center for Clinical Health Policy Research, in collaboration with the AAN, completed four Technical Reviews on migraine sponsored by the Agency for Health Care Policy and Research. These reviews covered self-administered drug treatments for acute migraine8; parenteral drug treatments for acute migraine9; drug treatments for the prevention of migraine10; and behavioral and physical treatments for migraine.11 The Education and Research Foundation of the AAN later funded additional reports on diagnostic testing for headache patients, an update on sumatriptan and other 5-HT1 agonists, and a report on butalbital-containing compounds for migraine and tension-type headache, using the same methodology that was used in the original Technical Reviews . A multidisciplinary panel of professional organizations (The US Headache Consortium) produced four treatment guidelines, each related to a distinct set of …

Myasthenia gravis: Recommendations for clinical research standards

Abstract: The need for universally accepted classifications, grading systems, and methods of analysis for patients undergoing therapy for MG is widely recognized and is particularly needed for therapeutic research trials. The Medical Scientific Advisory Board (MSAB) of the Myasthenia Gravis Foundation of America (MGFA) formed a Task Force in May 1997 to address these issues. Initially, the Task Force planned to develop classifications and outcome measures pertaining only to standardizing thymectomy trials. However, it quickly became apparent that their efforts should apply to all therapeutic trials for MG, and thus the scope of the mission was expanded. During the development of these recommendations, the Task Force faced numerous dilemmas for which no universally satisfactory solution was available. Dilemmas were defined as “situations that require one to choose between two equally balanced alternatives or predicaments that seemingly defy satisfactory solutions.” The Task Force members agreed at the outset, however, that their primary goal was to develop a uniform set of classifications to be used in the comparative analysis of the various therapeutic interventions for MG. With this as the primary goal, a consensus was gradually developed. In developing a consensus, at least two meetings were held each year during a 3-year period. Between meetings there was exchange of all proposals by electronic and surface mail, consultation with national and international experts in the field, critical analysis of all proposals, and many revisions. All conflicts (both minor and major) were resolved by vote. Virtually all issues were eventually approved unanimously; a few received a plurality of six. This report presents the work of the Task Force and proposes classification systems and definitions of response to therapy designed to achieve more uniformity in recording and reporting clinical trials and outcomes research. Although designed primarily for research purposes, we think physicians may find some of …

Practice parameter: Screening and diagnosis of autism Report of the Quality Standards Subcommittee of the American Academy of Neurology and the Child Neurology Society

Abstract: Autism is a common disorder of childhood, affecting 1 in 500 children. Yet, it often remains unrecognized and undiagnosed until or after late preschool age because appropriate tools for routine developmental screening and screening specifically for autism have not been available. Early identification of children with autism and intensive, early intervention during the toddler and preschool years improves outcome for most young children with autism. This practice parameter reviews the available empirical evidence and gives specific recommendations for the identification of children with autism. This approach requires a dual process: 1) routine developmental surveillance and screening specifically for autism to be performed on all children to first identify those at risk for any type of atypical development, and to identify those specifically at risk for autism; and 2) to diagnose and evaluate autism, to differentiate autism from other developmental disorders.

A 5-month, randomized, placebo-controlled trial of galantamine in AD

Abstract: Objective: To investigate the efficacy and tolerability of galantamine, using a slow dose escalation schedule of up to 8 weeks, in 978 patients with mild to moderate AD. Methods: A 5-month multicenter, placebo-controlled, double-blind trial. Following a 4-week placebo run-in, patients were randomized to one of four treatment arms: placebo or galantamine escalated to final maintenance doses of 8, 16, or 24 mg/day. Outcome measures included the cognitive subscale of the AD Assessment Scale (ADAS-cog), the Clinician’s Interview-Based Impression of Change plus Caregiver Input (CIBIC-plus), the AD Cooperative Study Activities of Daily Living inventory, and the Neuropsychiatric Inventory. Standard safety evaluations and adverse event monitoring were carried out. Results: After 5 months, the galantamine–placebo differences on ADAS-cog were 3.3 points for the 16 mg/day group and 3.6 points for the 24 mg/day group ( p Conclusions: Galantamine 16 and 24 mg/day significantly benefits the cognitive, functional, and behavioral symptoms of AD as compared with placebo. Slow dose escalation appears to enhance the tolerability of galantamine, minimizing the incidence and severity of adverse events.

Interatrial septal abnormalities and stroke: a meta-analysis of case-control studies.

Abstract: Objective: To examine the association between patent foramen ovale (PFO) and atrial septal aneurysm (ASA) and stroke. Method:— Data from case-control studies that examined the relative frequency of PFO, ASA, or both, in all patients with ischemic stroke, cryptogenic stroke, and known stroke cause as well as control subjects were included. Trials were categorized by age, clinical comparison, and abnormality. Combined OR were calculated using fixed effect (FE) and random effect (RE) methods. Results: Comparing patients with ischemic stroke with control subjects using RE, OR for all ages was 1.83 (95% CI, 1.25 to 2.66) for PFO (15 studies), 2.35 (95% CI, 1.46 to 3.77) for ASA (nine studies), and 4.96 (95% CI, 2.37 to 10.39) for PFO plus ASA (four studies). Homogeneous results were found within the group younger than age 55: using FE, OR was 3.10 (95% CI, 2.29 to 4.21) for PFO, 6.14 (95% CI, 2.47 to 15.22) for ASA, and 15.59 (95% CI, 2.83 to 85.87) for PFO plus ASA. For patients older than age 55, using FE, OR was 1.27 (95% CI, 0.80 to 2.01) for PFO, 3.43 (95% CI, 1.89 to 6.22) for ASA, and 5.09 (95% CI, 1.25 to 20.74) for PFO plus ASA. Comparing cryptogenic stroke with known stroke cause, heterogeneous results were derived from total group examination using RE: OR was 3.16 (95% CI, 2.30 to 4.35) for PFO (22 studies), 3.65 (95% CI, 1.34 to 9.97) for ASA (five studies), and 23.26 (95% CI, 5.24 to 103.20) for PFO plus ASA (two studies). In patients younger than age 55, using FE the OR was 6.00 (95% CI, 3.72 to 9.68) for PFO; only one study examined ASA or PFO plus ASA. In patients aged 55 years or older, three studies produced heterogeneous results for PFO: using RE, OR was 2.26 (95% CI, 0.96 to 5.31); no data were available on ASA prevalence. Conclusions: PFO and ASA are significantly associated with ischemic stroke in patients younger than 55 years. Further studies are needed to establish whether an association exists between PFO and ischemic stroke in those older than 55.

Rates of hippocampal atrophy correlate with change in clinical status in aging and AD

Abstract: Background: The cognitive continuum in the elderly population can be conceptually divided into those who are functioning normally (control subjects), those with a mild cognitive impairment (MCI), and those with probable AD. Objectives: To test the hypothesis that the annualized rates of hippocampal atrophy differ as a function of both baseline and change in clinical group membership (control, MCI, or AD). Methods: The authors identified 129 subjects from the Mayo Clinic AD Research Center/AD Patient Registry who met established criteria for normal control subjects, MCI, or probable AD, both at entry and at the time of a subsequent clinical follow-up evaluation 3 ± 1 years later. Each subject underwent an MRI examination of the head at the time of the initial assessment and at follow-up clinical assessment; the annualized percentage change in hippocampal volume was computed. Subjects who were classified as controls or patients with MCI at baseline could either remain cognitively stable or could decline to a lower functioning group over the period of observation. Results: The annualized rates of hippocampal volume loss for each of the three initial clinical groups decreased progressively in the following order: AD > MC > control. Within the control and MCI groups, those who declined had a significantly greater rate of volume loss than those who remained clinically stable. The mean annualized rates of hippocampal atrophy by follow-up clinical group were: control-stable 1.73%, control-decliner 2.81%, MCI-stable 2.55%, MCI-decliner 3.69%, AD 3.5%. Conclusion: Rates of hippocampal atrophy match both baseline cognitive status and the change in cognitive status over time in elderly persons who lie along the cognitive continuum from normal to MCI to AD.

A brief cognitive test battery to differentiate Alzheimer's disease and frontotemporal dementia

Abstract: Objectives: To validate a simple bedside test battery designed to detect mild dementia and differentiate AD from frontotemporal dementia (FTD). Methods: Addenbrooke9s Cognitive Examination (ACE) is a 100-point test battery that assesses six cognitive domains. Of 210 new patients attending a memory clinic, 139 fulfilled inclusion criteria and comprised dementia (n = 115) and nondementia (n = 24) groups. The composite and the component scores on the ACE for the two groups were compared with those of 127 age- and education-matched controls. Norms and the probability of diagnosing dementia at different prevalence rates were calculated. To evaluate the ACE9s ability to differentiate early AD from FTD, scores of the cases diagnosed with dementia with a Clinical Dementia Rating Results: Two cut-off values for the ACE composite score (88 and 83) were of optimal utility depending on the target population. The ACE had high reliability, construct validity, and sensitivity (93%, using 88 as cut-off). Using the lower cut-off of 83, the ACE had a higher sensitivity (82%) and predictive value than the Mini-Mental State Examination for a wide range of dementia prevalence. The ACE differentiated AD from FTD, and the VLOM ratio (derived using component scores: [verbal fluency + language]/[orientation + memory]) of 3.2 for AD was highly discriminating. Conclusion: The ACE is a brief and reliable bedside instrument for early detection of dementia, and offers a simple objective index to differentiate AD and FTD in mildly demented patients.

Documented head injury in early adulthood and risk of Alzheimer’s disease and other dementias

Abstract: Background: The association between antecedent head injury and AD is inconsistent. Objective: To examine the association between early adult head injury, as documented by military hospital records, and dementia in late life; and to evaluate the interaction between head injury and APOE e4 as risk factors for dementia. Methods: The study had a population-based prospective historical cohort design. It included men who were World War II Navy and Marine veterans, and were hospitalized during their military service with a diagnosis of either a nonpenetrating head injury or another unrelated condition. In 1996 to 1997, military medical records were abstracted to document the occurrence and details of closed head injury. The entire sample was then evaluated for dementia and AD using a multistage procedure. There were 548 veterans with head injury and 1228 without head injury who completed all assigned stages of the study. The authors estimated risk of dementia, specifically AD, using proportional hazards models. Results: Both moderate head injury (hazard ratio [HR] = 2.32; CI = 1.04 to 5.17) and severe head injury (HR = 4.51; CI = 1.77 to 11.47) were associated with increased risk of AD. Results were similar for dementia in general. The results for mild head injury were inconclusive. When the authors stratified by the number of APOE e4 alleles, they observed a nonsignificant trend toward a stronger association between AD and head injury in men with more e4 alleles. Conclusions: Moderate and severe head injuries in young men may be associated with increased risk of AD and other dementias in late life. However, the authors cannot exclude the possibility that other unmeasured factors may be influencing this association.

Early stroke treatment associated with better outcome The NINDS rt-PA Stroke Study

Abstract: Background: The National Institute of Neurological Disorders and Stroke (NINDS) rt-PA Stroke Study showed a similar percentage of intracranial hemorrhage and good outcome in patients 3 months after stroke treatment given 0 to 90 minutes and 91 to 180 minutes after stroke onset. At 24 hours after stroke onset more patients treated 0 to 90 compared to 91 to 180 minutes after stroke onset had improved by four or more points on the NIH Stroke Scale (NIHSS). The authors performed further analyses to characterize the relationship of onset-to-treatment time (OTT) to outcome at 3 months, early improvement at 24 hours, and intracranial hemorrhage within 36 hours. Methods: Univariate analyses identified potentially confounding variables associated with OTT that could mask an OTT–treatment interaction. Tests for OTT–treatment interactions adjusting for potential masking confounders were performed. An OTT–treatment interaction was considered significant if p ≤ 0.10, implying that treatment effectiveness was related to OTT. Results: For 24-hour improvement, there were no masking confounders identified and there was an OTT–treatment interaction ( p = 0.08). For 3-month favorable outcome, the NIHSS met criteria for a masking confounder. After adjusting for NIHSS as a covariate, an OTT–treatment interaction was detected ( p = 0.09): the adjusted OR (95% CI) for a favorable 3-month outcome associated with recombinant tissue-type plasminogen activator (rt-PA) was 2.11 (1.33 to 3.35) in the 0 to 90 minute stratum and 1.69 (1.09 to 2.62) in the 91 to 180 minute stratum. In the group treated with rt-PA, after adjusting for baseline NIHSS, an effect of OTT on the occurrence of intracranial hemorrhage was not detected. Conclusions: If the NINDS rt-PA Stroke Trial treatment protocol is followed, this analysis suggests that patients treated 0 to 90 minutes from stroke onset with rt-PA have an increased odds of improvement at 24 hours and favorable 3-month outcome compared to patients treated later than 90 minutes. No effect of OTT on intracranial hemorrhage was detected within the group treated with rt-PA, possibly due to low power.

Incidence of dementia and major subtypes in Europe: A collaborative study of population-based cohorts. Neurologic Diseases in the Elderly Research Group.

Abstract: The authors examined the association of incident dementia and subtypes with age, sex, and geographic area in Europe. Incidence data from eight population-based studies carried out in seven European countries were compared and pooled. The pooled data included 835 mild to severe dementia cases and 42,996 person-years of follow-up. In all studies a higher proportion of cases were diagnosed with AD (60 to 70% of all demented cases) than vascular dementia (VaD). The incidence of dementia and AD continued to increase with age up to age 85 years, after which rates increased in women but not men. There was a large variation in VaD incidence across studies. In the pooled analysis, the incidence rates increased with age without any substantial difference between men and women. Surprisingly, higher incidence rates of dementia and AD were found in the very old in northwest countries than in southern countries. This study confirms that AD is the most frequent dementing disorder in all ages, and that there is a higher incidence of dementia, specifically AD, in women than men among the very old. Finally, there may be regional differences in dementia incidence.

Galantamine in AD A 6-month randomized, placebo-controlled trial with a 6-month extension

Abstract: Background: Galantamine is a reversible, competitive cholinesterase inhibitor that also allosterically modulates nicotinic acetylcholine receptors. These mechanisms of action provided the rationale for a therapeutic trial of galantamine in AD. Methods: A 6-month, multicenter, double-blind trial was undertaken in 636 patients with mild to moderate AD. Patients were randomly assigned to placebo or galantamine and escalated to maintenance doses of 24 or 32 mg/d. Eligible patients then entered a 6-month, open-label study of the 24 mg/d dose. Primary efficacy measures were the 11-item AD Assessment Scale cognitive subscale (ADAS-cog/11) and the Clinician’s Interview-Based Impression of Change plus Caregiver Input (CIBIC-plus). The Disability Assessment for Dementia (DAD) scale was a secondary efficacy variable. Results: Galantamine significantly improved cognitive function relative to placebo; the treatment effects were 3.9 points (lower dose) and 3.8 points (higher dose) on the ADAS-cog/11 scale at month 6 ( p p APOE genotype. At 12 months, mean ADAS-cog/11 and DAD scores had not significantly changed from baseline for patients who received galantamine 24 mg/d throughout the 12 months. The most common adverse events, which were predominantly gastrointestinal, decreased in frequency during long-term treatment. There was no evidence of hepatotoxicity. Conclusions: Galantamine is effective and safe in AD. At 6 months, galantamine significantly improved cognition and global function. Moreover, cognitive and daily function were maintained for 12 months with the 24 mg/d dose.

Practice parameter: Anticonvulsant prophylaxis in patients with newly diagnosed brain tumors Report of the Quality Standards Subcommittee of the American Academy of Neurology

Abstract: The Quality Standards Subcommittee seeks to develop scientifically sound, clinically relevant practice parameters for the practice of neurology. Practice parameters are strategies for patient management that assist physicians in clinical decision making. A practice parameter is one or more specific recommendations based on analysis of evidence on a specific clinical problem. These might include diagnosis, symptoms, treatment, or procedure evaluation. American Academy of Neurology (AAN) members have requested the publication of a practice parameter on the use of prophylactic anticonvulsants in patients with primary and metastatic brain tumors. Physicians often administer anticonvulsant medication prophylactically to patients with brain tumors, despite the lack of definitive evidence that prophylactic anticonvulsant therapy is effective in preventing first seizures.1-4 If anticonvulsant medications were free of side effects, their prophylactic use might be attractive even without such evidence. However, discomfort, expense, and inconvenience result from drug treatment and periodic monitoring of serum drug concentrations. Typical anticonvulsant-induced side effects, including cognitive impairment, myelosuppression, liver dysfunction, and dermatologic reactions (ranging from minor rashes to life-threatening Stevens–Johnson syndrome), appear to occur more frequently in patients with brain tumors than in other patient groups,3,5-16 although direct comparison studies have not been published. A spectrum of side effects unique to patients with brain tumors must also be considered. Phenytoin, carbamazepine, and phenobarbital reduce the efficacy of corticosteroids,17-21 which are administered almost universally to brain tumor patients. In addition, the ability of these anticonvulsants to stimulate the cytochrome P450 enzyme system results in markedly accelerated metabolism of a wide spectrum of chemotherapeutic agents including nitrosoureas, paclitaxel, cyclophosphamide, topotecan, irinotecan, thiotepa, 9-aminocampothecin, adriamycin, and methotrexate.22-34 As a result, inadequate chemotherapeutic dosing of brain tumor patients has been identified recently as a widespread and critically important problem.35 Conversely, …

Prognosis with Parkinson's disease in europe: A collaborative study of population-based cohorts. Neurologic Diseases in the Elderly Research Group.

Abstract: Data are lacking on the prognosis (institutionalization and death) of PD cases identified in population-based studies. Data from five population-based European studies were compared and pooled. Each study used comparable two-step screening methods to identify cases and performed one or more follow-up examinations of their respective participants after defined periods of time. PD was classified on the basis of questionnaire and clinical data. The studies include 16,143 participants (252 with PD). The relative risk (RR) (95% CI) of death associated with PD was 2.3 (1.8 to 3.0). The risk for death in men with PD (RR 3.1 [2.1 to 4.4]) was higher than in women with PD (RR 1. 8 [1.2 to 5.1]). The rate of institutionalization varied across studies, increased with age, and was considerably higher in PD cases compared to noncases. Women with PD had a fivefold higher risk to live in a care facility than did men with PD. These data on mortality and rate of institutionalization reflect the high burden of PD in the population.

Prevalence of dementia and major subtypes in Europe: A collaborative study of population-based cohorts. Neurologic Diseases in the Elderly Research Group.

Abstract: The last comparison of prevalence figures of dementia across European studies was 10 years ago. Using studies conducted in the 1990s, the authors compare the age- and sex-specific prevalence of dementia, AD, and vascular dementia (VaD) across European population-based studies of persons 65 years and older. Data from these studies were also pooled to obtain stable estimates of age- and sex-specific prevalence. A total of 2346 cases of mild to severe dementia were identified in 11 cohorts. Age-standardized prevalence was 6.4% for dementia (all causes), 4.4% for AD, and 1.6% for VaD. The prevalence of dementia increased continuously with age and was 0.8% in the group age 65 to 69 years and 28.5% at age 90 years and older. The corresponding figures for AD (53.7% of cases) were 0.6% and 22.2%, and for VaD (15.8% of cases), 0.3% and 5.2%. Variation of AD prevalence across studies was greatest for men. In the VaD subtype, a large variation across studies was observed, as well as a difference in prevalence between men and women that was age dependent. Dementia is more prevalent in women, and AD is the main contributor to the steep increase of prevalence with age.

Prevalence of nonconvulsive status epilepticus in comatose patients.

Abstract: To the Editor: We read with interest the article by Towne et al.1 and applaud their efforts in this extremely important and challenging issue in clinical neurology. The key finding was that 8% of comatose patients with no overt seizure activity were found by EEG to be in nonconvulsive status epilepticus (NCSE). This impressively high percentage largely depends on the definition of EEG status epilepticus, and we raise questions about the criteria used. The authors define NCSE as “continuous or nearly continuous electrographic seizure activity lasting at least 30 minutes.” However, there is no agreement on exactly what constitutes electrographic seizure activity. Some EEG patterns are relatively specific for NCSE—for example, repetitive and discrete partial electrographic seizures such as the one shown in the authors’ figure 4, or the continuous 3-Hz spike-wave complexes pattern seen in absence status. The example shown in the authors’ figure 3 is much less convincing. This pattern, which could be variably described as rhythmic sharp waves, slow spike-wave complexes, periodic pattern, triphasic waves, or generalized periodic epileptiform discharges (GPED), is not as specific for status epilepticus as implied by the authors. In fact, it is extremely common in nonepileptic encephalopathies, especially anoxic …

Prevalence and risk factors of RLS in an elderly population: The MEMO Study

Abstract: Objective: To evaluate prevalence, sociodemographic characteristics, and risk factors of restless legs syndrome (RLS) in a population-based survey of the elderly, using standard diagnostic criteria. Background: Population-based studies of RLS are rare and have not yet used standard definition criteria. Methods: The Memory and Morbidity in Augsburg Elderly (MEMO) Study is a follow-up project of the World Health Organization Monitoring Trends and Determinants in Cardiovascular Disease (MONICA) Survey–Augsburg, Germany, 1989–1990, evaluating neurologic diseases and their risk factors in a German population 65 to 83 years of age. Two RLS-trained physicians assessed the prevalence of RLS based on the four minimal standard criteria (International Restless Legs Syndrome Study Group, 1995) using standardized questions in face-to-face interviews. They also obtained information on medical history, medications, depression (Center of Epidemiologic Studies Depression Scale), and quality of life (Short Form 36) and performed a standardized neurologic examination for each participant. Results: The study population included 369 participants (173 women and 196 men). The overall prevalence of RLS was 9.8% (n = 36) and higher in women (13.9% versus 6.1%; p = 0.02). In women, the prevalence did not change with age, whereas men showed a nonsignificant inverse trend with increasing age. RLS-positive individuals took more benzodiazepines and estrogen compared with non-RLS cases, but the differences were not statistically significant. Participants with RLS had higher incidence of depression ( p = 0.012) and lower self-reported mental health scores ( p = 0.029) than did non-RLS cases. Conclusions: RLS is a frequent syndrome in the elderly with considerable impact on self-perceived mental health, affecting women about twice as often as men.

A novel approach to stroke rehabilitation Robot-aided sensorimotor stimulation

Abstract: Objective: In patients with stroke, the authors tested whether additional sensorimotor training of the paralyzed or paretic upper limb delivered by a robotic device enhanced motor outcome. Methods: Fifty-six patients with stroke and hemiparesis or hemiplegia received standard poststroke multidisciplinary rehabilitation, and were randomly assigned either to receive robotic training (at least 25 hours) or exposure to the robotic device without training. Outcomes were assessed by the same masked raters, before treatment began and at the end of treatment, with the upper extremity component of the Fugl-Meyer Motor Assessment, the Motor Status score, the Motor Power score, and Functional Independence Measurement. Result: The robot treatment and control group had comparable clinical characteristics, lesion size, and pretreatment impairment scores. By the end of treatment, the robot-trained group demonstrated improvement in motor outcome for the trained shoulder and elbow (Motor Power score, p p p Conclusion: Robot-delivered quantitative and reproducible sensorimotor training enhanced the motor performance of the exercised shoulder and elbow. The robot-treated group also demonstrated improved functional outcome. When added to standard multidisciplinary rehabilitation, robotics provides novel therapeutic strategies that focus on impairment reduction and improved motor performance.

Transplantation of cultured human neuronal cells for patients with stroke

Abstract: Transplantation of cultured neuronal cells is safe in animal models and improves motor and cognitive deficits in rats with stroke. The authors studied the safety and feasibility of human neuronal cellular transplantation in patients with basal ganglia stroke and fixed motor deficits, including 12 patients (aged 44 to 75 years) with an infarct 6 months to 6 years previously (stable for at least 2 months). Serial evaluations (12 to 18 months) showed no adverse cell-related serologic or imaging-defined effects. The total European Stroke Scale score improved in six patients (3 to 10 points), with a mean improvement 2.9 points in all patients (p = 0. 046). Six of 11 PET scans at 6 months showed improved fluorodeoxyglucose uptake at the implant site. Neuronal transplantation is feasible in patients with motor infarction.

Alpha-synuclein cortical Lewy bodies correlate with dementia in Parkinson’s disease

Abstract: Background: Dementia is a frequent complication of idiopathic parkinsonism or PD, usually occurring later in the protracted course of the illness. The primary site of neuropathologic change in PD is the substantia nigra, but the neuropathologic and molecular basis of dementia in PD is less clear. Although Alzheimer’s pathology has been a frequent finding, recent advances in immunostaining of α-synuclein have suggested the possible importance of cortical Lewy bodies (CLBs) in the brains of demented patients with PD. Methods: The brains of 22 demented and 20 nondemented patients with a clinical and neuropathologic diagnosis of PD were evaluated with standard neuropathologic techniques. In addition, CLBs and dystrophic neurites were identified immunohistochemically with antibodies specific for α-synuclein and ubiquitin; plaques and tangles were identified by staining with thioflavine S. Associations between dementia status and pathologic markers were tested with logistic regression. Results: CLBs positive for α-synuclein are highly sensitive (91%) and specific (90%) neuropathologic markers of dementia in PD and slightly more sensitive than ubiquitin-positive CLBs. They are better indicators of dementia than neurofibrillary tangles, amyloid plaques, or dystrophic neurites. Conclusion: CLBs detected by α-synuclein antibodies in patients with PD are a more sensitive and specific correlate of dementia than the presence of Alzheimer’s pathology, which was present in a minority of the cases in this series.

Abnormalities in CSF concentrations of ferritin and transferrin in restless legs syndrome

Abstract: CSF and serum were obtained from 16 patients with idiopathic restless legs syndrome (RLS) and 8 age-matched healthy control subjects. Patients with RLS had lower CSF ferritin levels (1. 11 +/- 0.25 ng/mL versus 3.50 +/- 0.55 ng/mL; p = 0.0002) and higher CSF transferrin levels (26.4 +/- 5.1 mg/L versus 6.71 +/- 1.6 mg/L; p = 0.018) compared with control subjects. There was no difference in serum ferritin and transferrin levels between groups. The presence of reduced ferritin and elevated transferrin levels in CSF is indicative of low brain iron in patients with idiopathic RLS.

Estrogen for Alzheimer’s disease in women Randomized, double-blind, placebo-controlled trial

Abstract: Background: AD, the most prevalent cause of dementia, affects twice as many women as men. Therapeutic options are limited, but results of prior studies support the hypothesis that estrogen treatment may improve symptoms of women with this disorder. Methods: Forty-two women with mild-to-moderate dementia due to AD were enrolled into a randomized, double-blind, placebo-controlled, parallel-group trial of unopposed conjugated equine estrogens (1.25 mg/day) for 16 weeks. Results: Outcome data were available for 40 women at 4 weeks and 36 women at 16 weeks. At both 4 and 16 weeks, there were no significant differences or statistical trends between treatment groups on the primary outcome measure (the cognitive subscale of the Alzheimer’s Disease Assessment Scale), clinician-rated global impression of change, or caregiver-rated functional status. Exploratory analyses of mood and specific aspects of cognitive performance also failed to demonstrate substantial group differences. Conclusions: Although conclusions are limited by small sample size and the possibility of a type II error, results suggest that short-term estrogen therapy does not improve symptoms of most women with AD. These findings do not address possible long-term effects of estrogen in AD, possible interactions between estrogen and other treatment modalities, or putative effects of estrogen in preventing or delaying onset of this disorder.

Practice parameter: Thymectomy for autoimmune myasthenia gravis (an evidence-based review) Report of the Quality Standards Subcommittee of the American Academy of Neurology

Abstract: The Quality Standards Subcommittee of the American Academy of Neurology is charged with developing practice parameters for neurologists for diagnostic procedures, treatment modalities, and clinical disorders. The selection of topics for which practice parameters are used is based on prevalence, frequency of use, economic impact, membership involvement, controversy, urgency, external constraints, and resources required. This paper addresses the role of thymectomy in the treatment of nonthymomatous autoimmune MG. In 1939, Blalock et al.1 reported the remission of generalized MG in a 21-year-old woman after removal of a cystic thymic tumor. Subsequently, Blalock et al.2,3 performed thymectomy on MG patients without thymoma, found hyperplasia in the thymus glands, and reported improvement in at least half of their patients. Since these reports, thymectomy, with or without the presence of thymoma, has gained widespread acceptance as a form of treatment for MG. Because a definitive study of the effectiveness of thymectomy has never been done,4,5 the role of thymectomy in the management of MG remains uncertain. Nevertheless, physicians have to advise their patients regarding the benefits of thymectomy based on the existing literature. Our goal is to develop evidence-based recommendations for clinicians considering thymectomy for patients with nonthymomatous autoimmune MG by performing a systematic review and analysis of the literature. ### Identification and selection of studies. We searched the National Library of Medicine’s Medline database from 1966 to February 1998 using the medical subject headings “myasthenia gravis” (restricted to the surgery subheading) and “thymectomy.” To identify articles published before 1966, or missed by our original search strategy, we reviewed the references of the identified articles. We classified the resulting articles into the following categories: Class II, controlled but nonrandomized studies describing outcomes in MG patients with and without thymectomy; and Class III, uncontrolled case series describing outcomes in patients with or without …

Levetiracetam for partial seizures Results of a double-blind, randomized clinical trial

Abstract: Objective: To evaluate the efficacy and safety of 500 mg bid and 1500 mg bid levetiracetam as adjunctive therapy for refractory partial seizures in a double-blind, randomized, placebo-controlled, parallel-group, multicenter trial. Methods: The authors studied patients with uncontrolled partial seizures (minimum 12 per 12 weeks), regardless of whether they became secondarily generalized, for 38 weeks. A 12-week baseline was followed by random assignment to adjunctive therapy with placebo (n = 95), levetiracetam 1000 mg/day (n = 98), or levetiracetam 3000 mg/day (n = 101). Upward titration over 4 weeks was followed by 14 weeks of fixed dose treatment, and concluded with an 8-week medication withdrawal period or entering a follow-up study. Results: Of 294 patients randomized, 268 completed the study. Partial seizure frequency during the entire evaluation period (primary efficacy variable) was lower with levetiracetam compared to placebo ( p ≤ 0.001 for both groups). More patients responded (defined as minimum 50% reduction in partial seizure frequency) to levetiracetam than placebo, with rates of 33.0% in the 1000 mg/day and 39.8% in the 3000 mg/day group, compared to 10.8% in the placebo group ( p Conclusion: Adjunctive therapy with levetiracetam was effective and well tolerated in controlling partial seizures.

Iatrogenic Creutzfeldt-Jakob disease at the millennium.

Abstract: The causes and geographic distribution of 267 cases of iatrogenic Creutzfeldt-Jakob disease (CJD) are here updated at the millennium. Small numbers of still-occurring cases result from disease onsets after longer and longer incubation periods following infection by cadaveric human growth hormone or dura mater grafts manufactured and distributed before the mid-1980s. The proportion of recipients acquiring CJD from growth hormone varies from 0.3 to 4.4% in different countries, and acquisition from dura mater varies between 0.02 and 0.05% in Japan (where most cases occurred). Incubation periods can extend up to 30 years, and cerebellar onsets predominate in both hormone and graft recipients (in whom the site of graft placement had no effect on the clinical presentation). Homozygosity at codon 129 of the PRNP gene is over-represented in both forms of disease; it has no effect on the incubation period of graft recipients, but may promote shorter incubation periods in hormone cases. Knowledge about potential high-risk sources of contamination gained during the last quarter century, and the implementation of methods to circumvent them, should minimize the potential for iatrogenic contributions to the current spectrum of CJD.

Head injury and the risk of AD in the MIRAGE study

Abstract: Objectives: It has been suggested in some studies that head injury is a risk factor for AD, and that this risk is heightened among carriers of the APOE -e4 allele. We examined the effects of head injury and APOE genotype on AD risk in a large family study. Subjects: A total of 2,233 probands who met criteria for probable or definite AD and their 14,668 first-degree family members (4,465 parents, 7,694 siblings, and 2,509 spouses) were ascertained at 13 centers in the United States, Canada, and Germany participating in the MIRAGE (Multi-Institutional Research in Alzheimer Genetic Epidemiology) project. Information on head injury was collected by interview of multiple informants and review of medical records. Nondemented relatives and spouses served as control subjects for this study. Methods: Odds of AD for head trauma with or without loss of consciousness were computed by comparing probands with unaffected spouses using conditional logistic regression analysis. To account for the unique biologic relationship between probands and their parents and siblings, odds of AD were computed using a generalized estimating equation (GEE) Poisson regression approach. GEE logistic regression was used to examine the joint effects of APOE genotype and head injury on the odds of AD in probands and a control group comprised of unaffected siblings and spouses. Results: Comparison of probands with their unaffected spouses yielded odds ratios for AD of 9.9 (95% CI, 6.5 to 15.1) for head injury with loss of consciousness and 3.1 (2.3 to 4.0) for head injury without loss of consciousness. The corresponding odds derived from the comparison of probands with their parents and sibs were 4.0 (2.9 to 5.5) for head injury with loss of consciousness and 2.0 (1.5 to 2.7) for head injury without loss of consciousness. Head injury without loss of consciousness did not significantly increase the risk of AD in spouses (OR = 1.3; 95% CI, 0.4 to 4.1). The joint effects of head injury and APOE genotype were evaluated in a subsample of 942 probands and 327 controls (spouses and siblings). Head injury increased the odds of AD to a greater extent among those lacking e4 (OR = 3.3) than among e4 heterozygotes (OR = 1.8) or homozygotes (OR = 1.3). Conclusion: Head injury is a risk factor for AD. The magnitude of the risk is proportional to severity and heightened among first-degree relatives of AD patients. The influence of head injury on the risk of AD appears to be greater among persons lacking APOE -e4 compared with those having one or two e4 alleles, suggesting that these risk factors may have a common biologic underpinning.

Prevalence of Parkinson's disease in Europe : A collaborative study of population-based cohorts

Abstract: Article abstract-The results of seven population-based studies were examined separately and pooled to obtain age- and sex-specific estimates of the prevalence of PD An in-person screening instrument and diagnostic clinical examination were used to detect potential PD cases The overall prevalence (per 100 population) in persons 65 years of age and older was 18, with an increase from 06 for those age 65 to 69 years to 26 for those 85 to 89 years There were no sex differences in prevalence of PD

Regional metabolic patterns in mild cognitive impairment and Alzheimer's disease: A 1H MRS study.

Abstract: Background: Mild cognitive impairment (MCI) is a recently described transitional clinical state between normal aging and AD. Assuming that amnestic MCI patients had pathologic changes corresponding to an early phase and probable AD patients to a later phase of the disease progression, the authors could approximate the temporal course of proton MR spectroscopic ( 1 H MRS) alterations in AD with a cross-sectional sampling scheme. Methods: The authors compared 1 H MRS findings in the superior temporal lobe, posterior cingulate gyri, and medial occipital lobe in 21 patients with MCI, 21 patients with probable AD, and 63 elderly controls. These areas are known to be involved at different neurofibrillary pathologic stages of AD. Results: The N -acetylaspartate (NAA)/creatine (Cr) ratios were significantly lower in AD patients compared to both MCI and normal control subjects in the left superior temporal and the posterior cingulate volumes of interest (VOI) and there were no between-group differences in the medial occipital VOI. Myoinositol (MI)/Cr ratios measured from the posterior cingulate VOI were significantly higher in both MCI and AD patients than controls. The choline (Cho)/Cr ratios measured from the posterior cingulate VOI were higher in AD patients compared to both MCI and control subjects. Conclusion: These findings suggest that the initial 1 H MRS change in the pathologic progression of AD is an increase in MI/Cr. A decrease in NAA/Cr and an increase in Cho/Cr develop later in the disease course.

Analysis of EEG and CSF 14-3-3 proteins as aids to the diagnosis of Creutzfeldt-Jakob disease.

Abstract: Objective: To improve diagnostic criteria for sporadic Creutzfeldt–Jakob disease (CJD). Methods: Pooled data on initial and final diagnostic classification of suspected CJD patients were accumulated, including results of investigations derived from a coordinated multinational study of CJD. Prospective analysis for a comparison of clinical and neuropathologic diagnoses and evaluation of the sensitivity and specificity of EEG and 14-3-3 CSF immunoassay were conducted. Results: Data on 1,003 patients with suspected CJD were collected using a standard questionnaire. After follow-up was carried out, complete clinical data and neuropathologic diagnoses were available in 805 cases. In these patients, the sensitivity of the detection of periodic sharp wave complexes in the EEG was 66%, with a specificity of 74%. The detection of 14-3-3 proteins in the CSF correlated with the clinical diagnosis in 94% (sensitivity). The specificity (84%) was higher than that of EEG. A combination of both investigations further increased the sensitivity but decreased the specificity. Conclusions: Incorporation of CSF 14-3-3 analysis in the diagnostic criteria for CJD significantly increases the sensitivity of case definition. Amended diagnostic criteria for CJD are proposed.