Showing papers in "Neurology in 2002"
TL;DR: Aβ-deposition in the entire brain follows a distinct sequence in which the regions are hierarchically involved and expands anterogradely into regions that receive neuronal projections from regions already exhibiting Aβ.
Abstract: Background: The deposition of the amyloid β protein (Aβ) is a histopathologic hallmark of AD. The regions of the medial temporal lobe (MTL) are hierarchically involved in Aβ-deposition. Objective: To clarify whether there is a hierarchical involvement of the regions of the entire brain as well and whether there are differences in the expansion of Aβ-pathology between clinically proven AD cases and nondemented cases with AD-related pathology, the authors investigated 47 brains from demented and nondemented patients with AD-related pathology covering all phases of β-amyloidosis in the MTL (AβMTL phases) and four control brains without any AD-related pathology. Methods: Aβ deposits were detected by the use of the Campbell-Switzer silver technique and by immunohistochemistry in sections covering all brain regions and brainstem nuclei. It was analyzed how often distinct regions exhibited Aβ deposits. Results: In the first of five phases in the evolution of β-amyloidosis Aβ deposits are found exclusively in the neocortex. The second phase is characterized by the additional involvement of allocortical brain regions. In phase 3, diencephalic nuclei, the striatum, and the cholinergic nuclei of the basal forebrain exhibit Aβ deposits as well. Several brainstem nuclei become additionally involved in phase 4. Phase 5, finally, is characterized by cerebellar Aβ-deposition. The 17 clinically proven AD cases exhibit Aβ-phases 3, 4, or 5. The nine nondemented cases with AD-related Aβ pathology show Aβ-phases 1, 2, or 3. Conclusions: Aβ-deposition in the entire brain follows a distinct sequence in which the regions are hierarchically involved. Aβ-deposition, thereby, expands anterogradely into regions that receive neuronal projections from regions already exhibiting Aβ. There are also indications that clinically proven AD cases with full-blown β-amyloidosis may be preceded in early stages by nondemented cases exhibiting AD-related Aβ pathology.
2,576 citations
2,428 citations
TL;DR: In this article, a case definition of minimally conscious states (MCS) was presented. But, there were insufficient data to establish evidence-based guidelines for diagnosis, prognosis, and management of MCS, therefore, a consensus-based case definition with behaviorally referenced diagnostic criteria was formulated to facilitate future empirical investigation.
Abstract: Objective: To establish consensus recommendations among health care specialties for defining and establishing diagnostic criteria for the minimally conscious state (MCS). Background: There is a subgroup of patients with severe alteration in consciousness who do not meet diagnostic criteria for coma or the vegetative state (VS). These patients demonstrate inconsistent but discernible evidence of consciousness. It is important to distinguish patients in MCS from those in coma and VS because preliminary findings suggest that there are meaningful differences in outcome. Methods: An evidence-based literature review of disorders of consciousness was completed to define MCS, develop diagnostic criteria for entry into MCS, and identify markers for emergence to higher levels of cognitive function. Results: There were insufficient data to establish evidence-based guidelines for diagnosis, prognosis, and management of MCS. Therefore, a consensus-based case definition with behaviorally referenced diagnostic criteria was formulated to facilitate future empirical investigation. Conclusions: MCS is characterized by inconsistent but clearly discernible behavioral evidence of consciousness and can be distinguished from coma and VS by documenting the presence of specific behavioral features not found in either of these conditions. Patients may evolve to MCS from coma or VS after acute brain injury. MCS may also result from degenerative or congenital nervous system disorders. This condition is often transient but may also exist as a permanent outcome. Defining MCS should promote further research on its epidemiology, neuropathology, natural history, and management.
1,843 citations
Journal Article•
TL;DR: MCS is characterized by inconsistent but clearly discernible behavioral evidence of consciousness and can be distinguished from coma and VS by documenting the presence of specific behavioral features not found in either of these conditions.
Abstract: Objective: To establish consensus recommendations among health care specialties for defining and establishing diagnostic criteria for the minimally conscious state (MCS) Background: There is a subgroup of patients with severe alteration in consciousness who do not meet diagnostic criteria for coma or the vegetative state (VS) These patients demonstrate inconsistent but discernible evidence of consciousness It is important to distinguish patients in MCS from those in coma and VS because preliminary findings suggest that there are meaningful differences in outcome Methods: An evidence-based literature review of disorders of consciousness was completed to define MCS, develop diagnostic criteria for entry into MCS, and identify markers for emergence to higher levels of cognitive function Results: There were insufficient data to establish evidence-based guidelines for diagnosis, prognosis, and management of MCS Therefore, a consensus-based case definition with behaviorally referenced diagnostic criteria was formulated to facilitate future empirical investigation Conclusions: MCS is characterized by inconsistent but clearly discernible behavioral evidence of consciousness and can be distinguished from coma and VS by documenting the presence of specific behavioral features not found in either of these conditions Patients may evolve to MCS from coma or VS after acute brain injury MCS may also result from degenerative or congenital nervous system disorders This condition is often transient but may also exist as a permanent outcome Defining MCS should promote further research on its epidemiology, neuropathology, natural history, and management
1,181 citations
TL;DR: Frontotemporal dementia is a more common cause of early-onset dementia than previously recognized and appears to be more common in men.
Abstract: Objective: To estimate the prevalence of frontotemporal dementia (FTD) and other degenerative early-onset dementias in a geographically defined population. Background: Early-onset dementia (at age Methods: Case ascertainment was by review of case records of three specialist clinic databases and inpatient admissions at a university hospital in Cambridge, United Kingdom, for patients with dementia who were Results: A total of 108 patients (66 men and 42 women) with dementia with onset before they were 65 years of age were identified, of whom 60 were Conclusions: Frontotemporal dementia is a more common cause of early-onset dementia than previously recognized and appears to be more common in men.
1,032 citations
TL;DR: It is proposed that the cortex degenerates early in disease and that regionally selective cortical degeneration may explain the heterogeneity of clinical expression in HD, and these measures might provide a sensitive prospective surrogate marker for clinical trials of neuroprotective medications.
Abstract: Background: Huntington’s disease (HD) is a fatal and progressive neurodegenerative disease that is accompanied by involuntary movements, cognitive dysfunction, and psychiatric symptoms. Although progressive striatal degeneration is known to occur, little is known about how the disease affects the cortex, including which cortical regions are affected, how degeneration proceeds, and the relationship of the cortical degeneration to clinical symptoms. The cortex has been difficult to study in neurodegenerative diseases primarily because of its complex folding patterns and regional variability; however, an understanding of how the cortex is affected by the disease may provide important new insights into it. Methods: Novel automated surface reconstruction and high-resolution MR images of 11 patients with HD and 13 age-matched subjects were used to obtain cortical thickness measurements. The same analyses were performed on two postmortem brains to validate these methods. Results: Regionally specific heterogeneous thinning of the cortical ribbon was found in subjects with HD. Thinning occurred early, differed among patients in different clinical stages of disease, and appeared to proceed from posterior to anterior cortical regions with disease progression. The sensorimotor region was statistically most affected. Measurements performed on MR images of autopsy brains analyzed similarly were within 0.25 mm of those obtained using traditional neuropathologic methods and were statistically indistinguishable. Conclusions: The authors propose that the cortex degenerates early in disease and that regionally selective cortical degeneration may explain the heterogeneity of clinical expression in HD. These measures might provide a sensitive prospective surrogate marker for clinical trials of neuroprotective medications.
1,031 citations
TL;DR: New diagnostic criteria for IIH are described that may be used for routine patient management and for research purposes and not addressed in the Modified Dandy Criteria.
Abstract: The syndrome of increased intracranial pressure without hydrocephalus or mass lesion and with normal CSF composition, previously referred to as pseudotumor cerebri, is a diagnosis of exclusion now termed idiopathic intracranial hypertension (IIH). Diagnostic criteria of this disorder have not been updated since the Modified Dandy Criteria were articulated in 1985. Since then, new developments, including advances in neuroimaging technology and recognition of additional secondary causes of intracranial hypertension, have further enhanced the ability to diagnose conditions that may mimic IIH. These factors are not addressed in the Modified Dandy Criteria. This report describes updated diagnostic criteria for IIH that may be used for routine patient management and for research purposes.
934 citations
TL;DR: Structural findings suggest abnormal brain developmental processes early in the clinical course of autism, and research currently is underway to better elucidate mechanisms underlying mechanisms underlying these structural abnormalities and their longitudinal progression.
Abstract: Objective: To explore the specific gross neuroanatomic substrates of this brain developmental disorder, the authors examine brain morphometric features in a large sample of carefully diagnosed 3- to 4-year-old children with autism spectrum disorder (ASD) compared with age-matched control groups of typically developing (TD) children and developmentally delayed (DD) children. Methods: Volumes of the cerebrum, cerebellum, amygdala, and hippocampus were measured from three-dimensional coronal MR images acquired from 45 children with ASD, 26 TD children, and 14 DD children. The volumes were analyzed with respect to age, sex, volume of the cerebrum, and clinical status. Results: Children with ASD were found to have significantly increased cerebral volumes compared with TD and DD children. Cerebellar volume for the ASD group was increased in comparison with the TD group, but this increase was proportional to overall increases in cerebral volume. The DD group had smaller cerebellar volumes compared with both of the other groups. Measurements of amygdalae and hippocampi in this group of young children with ASD revealed enlargement bilaterally that was proportional to overall increases in total cerebral volume. There were similar findings of cerebral enlargement for both girls and boys with ASD. For subregion analyses, structural abnormalities were observed primarily in boys, although this may reflect low statistical power issues because of the small sample (seven girls with ASD) studied. Among the ASD group, structural findings were independent of nonverbal IQ. In a subgroup of children with ASD with strictly defined autism, amygdalar enlargement was in excess of increased cerebral volume. Conclusions: These structural findings suggest abnormal brain developmental processes early in the clinical course of autism. Research currently is underway to better elucidate mechanisms underlying these structural abnormalities and their longitudinal progression.
916 citations
TL;DR: Mild cognitive impairment is associated with an increased risk of death and incident AD, and a greater rate of decline in selected cognitive abilities.
Abstract: Background: Cognitive abilities of older persons range from normal, to mild cognitive impairment, to dementia. Few large longitudinal studies have compared the natural history of mild cognitive impairment with similar persons without cognitive impairment. Methods: Participants were older Catholic clergy without dementia, 211 with mild cognitive impairment and 587 without cognitive impairment, who underwent annual clinical evaluation for AD and an assessment of different cognitive abilities. Cognitive performance tests were summarized to yield a composite measure of global cognitive function and separate summary measures of episodic memory, semantic memory, working memory, perceptual speed, and visuospatial ability. The authors compared the risk of death, risk of incident AD, and rates of change in global cognition and different cognitive domains among persons with mild cognitive impairment to those without cognitive impairment. All models controlled for age, sex, and education. Results: On average, persons with mild cognitive impairment had significantly lower scores at baseline in all cognitive domains. Over an average of 4.5 years of follow-up, 30% of persons with mild cognitive impairment died, a rate 1.7 times higher than those without cognitive impairment (95% CI, 1.2 to 2.5). In addition, 64 (34%) persons with mild cognitive impairment developed AD, a rate 3.1 times higher than those without cognitive impairment (95% CI, 2.1 to 4.5). Finally, persons with mild cognitive impairment declined significantly faster on measures of episodic memory, semantic memory, and perceptual speed, but not on measures of working memory or visuospatial ability, as compared with persons without cognitive impairment. Conclusions: Mild cognitive impairment is associated with an increased risk of death and incident AD, and a greater rate of decline in selected cognitive abilities.
902 citations
TL;DR: Neurologic benefit resulting from hMSC treatment of stroke in rats may derive from the increase of growth factors in the ischemic tissue, the reduction of apoptosis in the penumbral zone of the lesion, and the proliferation of endogenous cells in the subventricular zone.
Abstract: Objective: To test the effect of IV-injected human bone marrow stromal cells (hMSC) on neurologic functional deficits after stroke in rats. Methods: Rats were subjected to transient middle cerebral artery occlusion and IV injected with 3 × 10 6 hMSC 1 day after stroke. Functional outcome was measured before and 1, 7, and 14 days after stroke. Mixed lymphocyte reaction and the development of cytotoxic T lymphocytes measured the immune rejection of hMSC. A monoclonal antibody specific to human cellular nuclei (mAb1281) was used to identify hMSC and to measure neural phenotype. ELISA analyzed neurotrophin levels in cerebral tissue from hMSC-treated or nontreated rats. Bromodeoxyuridine injections were used to identify newly formed cells. Results: Significant recovery of function was found in rats treated with hMSC at 14 days compared with control rats with ischemia. Few (1 to 5%) hMSC expressed proteins phenotypic of brain parenchymal cells. Brain-derived neurotrophic factor and nerve growth factor significantly increased, and apoptotic cells significantly decreased in the ischemic boundary zone; significantly more bromodeoxyuridine-reactive cells were detected in the subventricular zone of the ischemic hemisphere of rats treated with hMSC. hMSC induced proliferation of lymphocytes without the induction of cytotoxic T lymphocytes. Conclusion: Neurologic benefit resulting from hMSC treatment of stroke in rats may derive from the increase of growth factors in the ischemic tissue, the reduction of apoptosis in the penumbral zone of the lesion, and the proliferation of endogenous cells in the subventricular zone.
890 citations
TL;DR: Although FTD and SemD are associated with different overall patterns of brain atrophy, regions of gray matter tissue loss in the orbital frontal, insular, and anterior cingulate regions are present in both groups and are suggested to underlie some the behavioral symptoms seen in the two disorders.
Abstract: Objective: To identify and compare the patterns of cerebral atrophy associated with two clinical variants of frontotemporal lobar degeneration (FTLD): frontotemporal dementia (FTD) and semantic dementia (SemD). Methods: Twenty patients with FTLD were classified as having FTD (N = 8) or SemD (N = 12) based on current clinical criteria. Both groups showed a similar spectrum of behavioral abnormalities, as indicated by the neuropsychiatric inventory. T1-weighted MRI was obtained for each patient and 20 control subjects. The regions of focal gray matter tissue loss associated with both FTD and SemD, as well as those differing between the two groups were examined using voxel-based morphometry. Results: Regions of significant atrophy seen in both groups were located in the ventromedial frontal cortex, the posterior orbital frontal regions bilaterally, the insula bilaterally, and the left anterior cingulate cortex. The FTD, but not the SemD, group showed atrophy in the right dorsolateral frontal cortex and the left premotor cortex. The SemD, but not the FTD, group showed tissue loss in the anterior temporal cortex and the amygdala/anterior hippocampal region bilaterally. Conclusions: Although FTD and SemD are associated with different overall patterns of brain atrophy, regions of gray matter tissue loss in the orbital frontal, insular, and anterior cingulate regions are present in both groups. The authors suggest that pathology in the areas of atrophy associated with both FTD and SemD may underlie some the behavioral symptoms seen in the two disorders.
TL;DR: Clinical trials study patients for only short periods of time (2 or 3 years) and, therefore, use only short-term outcome measures to assess efficacy, and evaluation of the relative effectiveness of different therapies requires consideration of which outcome measure or measures are relevant to the goals of therapy.
Abstract: MS is a chronic recurrent inflammatory disorder of the CNS. The disease results in injury to the myelin sheaths, the oligodendrocytes, and, to a lesser extent, the axons and nerve cells themselves.1-5⇓⇓⇓⇓ The symptoms of MS vary, depending in part on the location of plaques within the CNS. Common symptoms include sensory disturbances in the limbs, optic nerve dysfunction, pyramidal tract dysfunction, bladder or bowel dysfunction, sexual dysfunction, ataxia, and diplopia.5 Four different clinical courses of MS have been defined.6 The first, relapsing–remitting MS (RRMS), is characterized by self-limited attacks of neurologic dysfunction. These attacks develop acutely, evolving over days to weeks. Over the next several weeks to months, most patients experience a recovery of function that is often (but not always) complete. Between attacks the patient is neurologically and symptomatically stable. The second clinical course, secondary progressive MS (SPMS), begins as RRMS, but at some point the attack rate is reduced and the course becomes characterized by a steady deterioration in function unrelated to acute attacks. The third clinical type, primary progressive MS (PPMS), is characterized by a steady decline in function from the beginning without acute attacks. The fourth type, progressive–relapsing MS (PRMS), also begins with a progressive course although these patients also experience occasional attacks.
Evaluation of the relative effectiveness of different therapies requires consideration of which outcome measure or measures are relevant to the goals of therapy. Clearly, the most important therapeutic aim of any disease-modifying treatment of MS is to prevent or postpone long-term disability. However, long-term disability in MS often evolves slowly over many years.1-3⇓⇓ Clinical trials, by contrast, study patients for only short periods of time (2 or 3 years) and, therefore, use only short-term outcome measures to assess efficacy. As a result, …
TL;DR: Major differences between brains of autistic patients and controls in the number of minicolumns, in the horizontal spacing that separates cell columns, and in their internal structure are found.
Abstract: Objective: To determine whether differences exist in the configuration of minicolumns between the brains of autistic and control patients. Background: Autism is a severe and pervasive developmental disturbance of childhood characterized by disturbances in both social interactions and communication, as well as stereotyped patterns of interests, activities, and behaviors. Postmortem neuropathologic studies remain inconclusive. Methods: The authors used a computerized imaging program to measure details of cell column morphologic features in area 9 of the prefrontal cortex and areas 21 and posterior 22 (Tpt) within the temporal lobe of nine brains of autistic patients and controls. Results: The authors found significant differences between brains of autistic patients and controls in the number of minicolumns, in the horizontal spacing that separates cell columns, and in their internal structure, that is, relative dispersion of cells. Specifically, cell columns in brains of autistic patients were more numerous, smaller, and less compact in their cellular configuration with reduced neuropil space in the periphery. Conclusions: In autism, there are minicolumnar abnormalities in the frontal and temporal lobes of the brain.
TL;DR: Patients with frontotemporal dementia with no known diagnosis of ALS or family history of ALS were clinically and electrophysiologically assessed for the presence of ALS and two had EMG findings suggestive of denervation in one limb.
Abstract: Patients with frontotemporal dementia (FTD) with no known diagnosis of ALS or family history of ALS were clinically and electrophysiologically assessed for the presence of ALS. Of 36 patients studied, five met criteria for a definite diagnosis of ALS and two had EMG findings suggestive of denervation in one limb. An additional five patients had prominent fasciculations and six other patients had trouble swallowing but all had normal results on EMG studies. One of the patients with fasciculations and a normal EMG study progressed to definite ALS over the course of 1 year.
TL;DR: MCI was a good predictor of AD with an annual conversion rate of 8.3% and a good specificity, but it was very unstable over time: Within 2 to 3 years, only 6% of the subjects continued to have MCI, whereas >40% reverted to normal.
Abstract: Objective: To estimate the age-specific incidence rate of mild cognitive impairment (MCI) according to sex and educational level and to explore the course of MCI, particularly its progression to AD, in a population-based cohort. Methods: A community-based cohort of nondemented elderly people (Personnes Agees QUID [PAQUID]) was followed longitudinally for 5 years. MCI was defined as memory complaints with objective memory impairment, without dementia, impairment of general cognitive functioning, or disability in activities of daily living. Incidence rates were calculated using the person–years method. A descriptive analysis at the different follow-up times was performed to study the course of MCI. Results: At baseline, there were 58 prevalent cases of MCI (2.8% of the sample). During a 5-year follow-up, 40 incident cases of MCI occurred in 1,265 subjects at risk. The global incidence rate of MCI was 9.9/1,000 person–years. MCI was a good predictor of AD with an annual conversion rate of 8.3% and a good specificity, but it was very unstable over time: Within 2 to 3 years, only 6% of the subjects continued to have MCI, whereas >40% reverted to normal. Conclusions: Conventionally defined MCI has reasonable predictive value and specificity for AD. However, MCI was very unstable across time in this study. Furthermore, the definition of MCI seems to be too restrictive and should probably be extended to other categories of individuals also at high risk of developing AD.
TL;DR: This document defines the standards, guidelines, and options for EDX studies of CTS based on a critical review of the literature published in 19931 and recently updated by a review ofThe literature through the year 2000.
Abstract: Carpal tunnel syndrome (CTS) is a common clinical problem and frequently requires surgical therapy. The results of electrodiagnostic (EDX) studies have been found to be highly sensitive and specific for the diagnosis of CTS. This document defines the standards, guidelines, and options for EDX studies of CTS based on a critical review of the literature published in 19931 and recently updated by a review of the literature through the year 2000.2 The reader is referred to the updated review2 for a detailed discussion of the literature and the EDX techniques for the assessment of CTS that are summarized here. Both reviews addressed the following key clinical questions:
1. In patients clinically suspected of having CTS, what are the best EDX studies to confirm the diagnosis?
2. How can future clinical research studies be improved to evaluate the usefulness of laboratory studies, including EDX studies, to confirm the diagnosis of CTS?
The source of the articles for the first CTS Literature Review1 published in 1993 was a Medline search for literature in English from January 1, 1986 through May 1991. The Medical Subject Headings searched were 1) wrist injuries or wrist joint, 2) nerve compression syndrome, and 3) carpal tunnel syndrome. The search identified 488 articles. Based on a review of the abstracts, 81 articles describing EDX studies were chosen for this review. An additional 78 reports were identified from the bibliographies of these 81 articles and American Academy of Electrodiagnostic Medicine (AAEM) consultants recommended six others. Of the total of 165 articles reviewed, 20 were classified as background references.
The source of the articles for the second CTS Literature Review2 was a Medline search for literature in English through December 2000. The Medical Subject Headings (MeSH) searched were 1) carpal tunnel syndrome and diagnosis or 2) carpal …
TL;DR: Even in relapsing cases, the distinction between acute disseminated encephalomyelitis and MS was possible on the basis of long-term clinical and neuroimaging follow-up and the absence of oligoclonal bands in CSF.
Abstract: Background: Acute disseminated encephalomyelitis (ADEM) is an inflammatory demyelinating disease of the CNS. Few pediatric series have been published, with retrospective and short-term follow-up studies. Objectives : To describe a cohort of pediatric patients with ADEM and to determine whether clinical and neuroimaging findings predict outcome. Methods: A prospective study was conducted between March 1988 and July 2000 on 84 consecutive children with ADEM at the National Pediatric Hospital “Dr. J. P. Garrahan.” Results: Mean age at onset was 5.3 ± 3.9 years, with a significant male predominance. Sixty-two patients (74%) had a preceding viral illness or vaccination. Acute hemiparesis (76%), unilateral or bilateral long tract signs (85%), and changes in mental state (69%) were the most prominent presenting features. Four MRI groups were identified: ADEM with small lesions (62%), with large lesions (24%), with additional bithalamic involvement (12%), and acute hemorrhagic encephalomyelitis (2%). Of the 54 children whose CSF samples were analyzed, none showed intrathecal oligoclonal bands. The use of high-dose corticosteroid treatment, particularly IV methylprednisolone, was associated with good recovery and resolution of MRI lesions. After a mean follow-up of 6.6 ± 3.8 years, 90% of children showed a monophasic course, and 10% a biphasic disease. Eighty-nine percent of patients show at present Expanded Disability Status Scale scores of 0 to 2.5. Eleven percent have disability scores of 3 to 6.5. Conclusions: Childhood acute disseminated encephalomyelitis is a benign condition, affecting boys more frequently. No association was found between MRI groups and disability. Disability was related to optic nerve involvement at presentation. Even in relapsing cases, the distinction between acute disseminated encephalomyelitis and MS was possible on the basis of long-term clinical and neuroimaging follow-up and the absence of oligoclonal bands in CSF.
TL;DR: IFNβ-1a 44 μg subcutaneously tiw was more effective than IFNβ -1a 30 μg IM qw on all primary and secondary outcomes investigated after 24 and 48 weeks of treatment.
Abstract: Background: Interferon β (IFNβ) reduces relapses and MRI activity in relapsing-remitting MS (RRMS), with variable effects on disability. The most effective dose regimen remains controversial. Methods: This randomized, controlled, multicenter trial compared the efficacy and safety of IFNβ-1a (Rebif®) 44 μg subcutaneously three times weekly (tiw), and IFNβ-1a (Avonex®) 30 μg IM once weekly (qw) in 677 patients with RRMS. Assessors blinded to treatment performed neurologic and MRI evaluations. The primary endpoint was the proportion of patients who were relapse free at 24 weeks; the principal MRI endpoint was the number of active lesions per patient per scan at 24 weeks. Results: After 24 weeks, 74.9% (254/339) of patients receiving IFNβ-1a 44 μg tiw remained relapse free compared with 63.3% (214/338) of those given 30 μg qw. The odds ratio for remaining relapse free was 1.9 (95% CI, 1.3 to 2.6; p = 0.0005) at 24 weeks and 1.5 (95% CI, 1.1 to 2.1; p = 0.009) at 48 weeks, favoring 44 μg tiw. Patients receiving 44 μg tiw had fewer active MRI lesions ( p p p = 0.002) and altered leukocyte counts (11% vs 5%, p = 0.003) compared with the 30 μg qw dosage. Neutralizing antibodies developed in 25% of 44 μg tiw patients and in 2% of patients receiving 30 μg qw. Conclusions: IFNβ-1a 44 μg subcutaneously tiw was more effective than IFNβ-1a 30 μg IM qw on all primary and secondary outcomes investigated after 24 and 48 weeks of treatment.
TL;DR: Incapacity resulting from the dysautonomic fluctuations was also significantly correlated with levodopa treatment, and the total number of NMF was found to be correlated with the motor disability.
Abstract: Objective : To assess the frequency and disability caused by nonmotor fluctuations (NMF) in PD. Methods : A structured questionnaire was administered to 50 patients with PD with motor fluctuations (MF), focused on 54 nonmotor symptoms classified in three subgroups: 26 dysautonomic, 21 cognitive and psychiatric, and seven pain/sensory NMF. The link between each NMF and the motor state was determined. Patients were asked to grade their disability from 0 (no disability) to 4 (maximum discomfort) and to specify which kind of fluctuation subgroup (motor or nonmotor) was the most incapacitating. A statistical analysis was performed to determine the frequency of each NMF and to determine whether the level of disability resulting from NMF could be correlated to the main characteristics of the population. Results : All patients had had at least one type of NMF, most of which were associated with the “off” state. Anxiety (66%), drenching sweats (64%), slowness of thinking (58%), fatigue (56%), and akathisia (54%) were the most frequent NMF. Some symptoms such as anxiety or dyspnea correlated with a greater level of disability. The total number of NMF was found to be correlated with the motor disability. Incapacity resulting from the dysautonomic fluctuations was also significantly correlated with levodopa treatment. Surprisingly, 28% of the patients stated that NMF involved a greater degree of disability than MF. Conclusion : Nonmotor fluctuations are frequent and debilitating in PD.
TL;DR: Relative to prior cross-sectional surveys, epidemiologic profiles for migraine have remained stable in the United States over the last decade, although self-reported rates of current medical consultation have more than doubled.
Abstract: Objective: To determine the prevalence and distribution of migraine in the United States as well as current patterns of health care use. Methods: A random-digit-dial, computer-assisted telephone interview (CATI) survey was conducted in Philadelphia County, PA, in 1998. The CATI identifies individuals with migraine (categories 1.1 and 1.2) as defined by the diagnostic criteria of the International Headache Society with high sensitivity (85%) and specificity (96%). Interviews were completed in 4,376 subjects to identify 568 with migraine. Those with 6 or more attacks per year (n = 410) were invited to participate in a follow-up interview about health care utilization and family impact of migraine; 246 (60.0%) participated. Results: The 1-year prevalence of migraine was 17.2% in females and 6.0% in males. Prevalence was highest between the ages of 30 and 49. Whereas 48% of migraine sufferers had seen a doctor for headache within the last year (current consulters), 31% had never done so in their lifetimes and 21% had not seen a doctor for headache for at least 1 year (lapsed consulters). Of current or lapsed consulters, 73% reported a physician-made diagnosis of migraine; treatments varied. Of all migraine sufferers, 49% were treated with over-the-counter medications only, 23% with prescription medication only, 23% with both, and 5% with no medications at all. Conclusion: Relative to prior cross-sectional surveys, epidemiologic profiles for migraine have remained stable in the United States over the last decade. Self-reported rates of current medical consultation have more than doubled. Moderate increases were seen in the percentage of migraine sufferers who use prescription medications and in the likelihood of receiving a physician diagnosis of migraine.
TL;DR: Very heavy use of marijuana is associated with persistent decrements in neurocognitive performance even after 28 days of abstinence, and it is unclear if these decrements will resolve with continued abstinence or become progressively worse with continued heavy marijuana use.
Abstract: Background: Although about 7 million people in the US population use marijuana at least weekly, there is a paucity of scientific data on persistent neurocognitive effects of marijuana use. Objective: To determine if neurocognitive deficits persist in 28-day abstinent heavy marijuana users and if these deficits are dose-related to the number of marijuana joints smoked per week. Methods: A battery of neurocognitive tests was given to 28-day abstinent heavy marijuana abusers. Results: As joints smoked per week increased, performance decreased on tests measuring memory, executive functioning, psychomotor speed, and manual dexterity. When dividing the group into light, middle, and heavy user groups, the heavy group performed significantly below the light group on 5 of 35 measures and the size of the effect ranged from 3.00 to 4.20 SD units. Duration of use had little effect on neurocognitive performance. Conclusions: Very heavy use of marijuana is associated with persistent decrements in neurocognitive performance even after 28 days of abstinence. It is unclear if these decrements will resolve with continued abstinence or become progressively worse with continued heavy marijuana use.
TL;DR: RBD and REM sleep without atonia are frequent in PD as shown by PSG recordings, and their cases may represent preclinical forms of RBD associated with PD.
Abstract: Objective: To determine the frequency of REM sleep behavior disorder (RBD) among patients with PD using both history and polysomnography (PSG) recordings and to further study REM sleep muscle atonia in PD. Background: The reported occurrence of RBD in PD varies from 15 to 47%. However, no study has estimated the frequency of RBD using PSG recordings or analyzed in detail the characteristics of REM sleep muscle atonia in a large group of unselected patients with PD. Methods: Consecutive patients with PD (n = 33) and healthy control subjects (n = 16) were studied. Each subject underwent a structured clinical interview and PSG recording. REM sleep was scored using a method that allows the scoring of REM sleep without atonia. Results: One third of patients with PD met the diagnostic criteria of RBD based on PSG recordings. Only one half of these cases would have been detected by history. Nineteen (58%) of 33 patients with PD but only 1 of 16 control subjects had REM sleep without atonia. Of these 19 patients with PD, 8 (42%) did not present with behavioral manifestations of RBD, and their cases may represent preclinical forms of RBD associated with PD. Moreover, the percentage of time spent with muscle atonia during REM sleep was lower among patients with PD than among healthy control subjects (60.1% vs 93.2%; p = 0.003). Conclusions: RBD and REM sleep without atonia are frequent in PD as shown by PSG recordings.
TL;DR: Hippocampal atrophy, while not specific for AD, was a fairly sensitive marker of the pathologic AD stage (particularly among subjects with isolated AD pathology [r = −0.63, p = 0.001]) and consequent cognitive status.
Abstract: Objectives: To assess the diagnostic specificity of MRI-defined hippocampal atrophy for AD among individuals with a variety of pathologically confirmed conditions associated with dementia as well as changes attributable to typical aging, and to measure correlations among premortem MRI measurements of hippocampal atrophy, mental status examination performance, and the pathologic stage of AD. Methods: An unselected series of 67 individuals participating in the Mayo Alzheimer’s Disease Research Center/Alzheimer’s Disease Patient Registry who had undergone a standardized antemortem MRI study and also postmortem examination were identified. Hippocampal volumes were measured from antemortem MRI. Each postmortem specimen was assigned a pathologic diagnosis and in addition, the severity of AD pathology was staged using the method of Braak and Braak. Results: Individuals with an isolated pathologic diagnosis of AD, hippocampal sclerosis, frontotemporal degeneration, and neurofibrillary tangle–only degeneration usually had substantial hippocampal atrophy, while those with changes of typical aging did not. Among all 67 subjects, correlations (all p r = −0.39), between hippocampal volume and Mini-Mental State Examination (MMSE) score ( r = 0.60), and between MMSE score and Braak and Braak stage ( r = −0.41). Conclusions: Hippocampal atrophy, while not specific for AD, was a fairly sensitive marker of the pathologic AD stage (particularly among subjects with isolated AD pathology [ r = −0.63, p = 0.001]) and consequent cognitive status.
TL;DR: The prevalence of NPSLE was high in this cohort of unselected patients with SLE and the lack of ethnicity and language-matched normative neuropsychological data may make comparisons of cognitive dysfunction in SLE populations difficult.
Abstract: Objective : The San Antonio Lupus Study of Neuropsychiatric Disease is a longitudinal study designed to characterize the spectrum of and important risk factors for specific neuropsychiatric systemic lupus erythematosus (NPSLE) syndromes. Methods : Subjects must meet criteria for SLE and must be at least 18 years of age. A standardized medical history, neurologic, rheumatologic, and psychiatric examinations, computerized neuropsychological evaluation, and serologic testing are performed. Results : This report is based on the first 128 subjects (120 women and 8 men) who completed the initial study visit. Data from this initial study visit were evaluated for the prevalence of NPSLE using the American College of Rheumatology case definitions for 19 NPSLE syndromes. One or more NPSLE syndromes were present in 80% of subjects: cerebrovascular disease (2, 2%; ischemic stroke); headaches (73, 57%); mononeuropathy (9, 8%; median 8, ulnar 1); movement disorder (1, 1%; chorea); neuropathy, cranial (2, 2%; trigeminal); polyneuropathy (29, 22%; sensorimotor); seizures (21, 16%; partial); anxiety disorder (27, 24%); major depressive-like episode (37, 28%); mood disorder with depressive features (21, 19%); mood disorder with manic features (3, 3%); mood disorder with mixed features (1, 1%); psychosis (6, 5%). In a subset of 67 patients who received standardized neuropsychological testing, 21% had normal results. In the remainder, the following levels of impairment were seen: 43% mild, 30% moderate, and 6% severe. Conclusions : The prevalence of NPSLE was high in this cohort of unselected patients with SLE. Headaches, cognitive dysfunction, and psychiatric disorders were the most common NPSLE syndromes seen. These results will be easily comparable to other studies also using standardized diagnostic criteria. However, the lack of ethnicity and language-matched normative neuropsychological data may make comparisons of cognitive dysfunction in SLE populations difficult.
TL;DR: The authors modified the adult RC diagnostic criteria to allow for pediatric clinical and histologic features and for more sensitive coding of RC enzyme and functional studies, which appear to improve the sensitivity of the adult criteria.
Abstract: Background: Respiratory chain (RC) disorders are clinically, biochemically, and molecularly heterogeneous. The lack of standardized diagnostic criteria poses difficulties in evaluating diagnostic methodologies. Objective: To assess proposed adult RC diagnostic criteria that classify patients into “definite,” “probable,” or “possible” categories. Methods: The authors applied the adult RC diagnostic criteria retrospectively to 146 consecutive children referred for investigation of a suspected RC disorder. Data were collected from hospital, genetics, and laboratory records, and the diagnoses predicted by the adult criteria were compared with the previously assigned assessments. Results: The authors identified three major difficulties in applying the adult criteria:lack of pediatric-specific criteria; difficulty in segregating continuous data into circumscribed major and minor criteria; and lack of additivity of clinical features or enzyme tests. They therefore modified the adult criteria to allow for pediatric clinical and histologic features and for more sensitive coding of RC enzyme and functional studies. Reanalysis of the patients’ data resulted in congruence between the diagnostic certainty previously assigned by the authors’ center and that defined by the new general RC diagnostic criteria in 99% of patients. Conclusions: These general diagnostic criteria appear to improve the sensitivity of the adult criteria. They need further assessment in prospective clinical and epidemiologic studies.
TL;DR: Findings are consistent with neuropathologic data showing substantial involvement of the entorhinal cortex in the preclinical phase of AD and suggest that, as the disease spreads, atrophic change develops within the hippocampus, which is measurable on MRI.
Abstract: Background: MRI measures of the entorhinal cortex and the hippocampus have been used to predict which nondemented individuals with memory problems will progress to meet criteria for AD on follow-up, but their relative accuracy remains controversial. Objectives: To compare MRI measures of the entorhinal cortex and the hippocampus for predicting who will develop AD. Methods: MRI volumes of the entorhinal cortex and the hippocampus were obtained in 137 individuals comprising four groups: 1) individuals with normal cognition both at baseline and after 3 years of follow-up (n = 28), 2) subjects with memory difficulty but not dementia both at baseline and after 3 years of follow-up (n = 73), 3) subjects with memory difficulty at baseline who were diagnosed with probable AD within 3 years of follow-up (n = 21), and 4) patients with mild AD at baseline (n = 16). Results: Measures of both the entorhinal cortex and the hippocampus were different for each of the pairwise comparisons between the groups ( p p Conclusion: These findings are consistent with neuropathologic data showing substantial involvement of the entorhinal cortex in the preclinical phase of AD and suggest that, as the disease spreads, atrophic change develops within the hippocampus, which is measurable on MRI.
TL;DR: The authors reviewed 59 consecutive patients treated with plasma exchange for acute, severe attacks of CNS demyelination at Mayo Clinic from January 1984 through June 2000 to find that successfully treated patients improved rapidly following PE, and improvement was sustained.
Abstract: The authors reviewed 59 consecutive patients treated with plasma exchange (PE) for acute, severe attacks of CNS demyelination at Mayo Clinic from January 1984 through June 2000. Most patients had relapsing-remitting MS (n = 22, 37.3%), neuromyelitis optica (NMO) (n = 10, 16.9%), and acute disseminated encephalomyelitis (n = 10, 16.9%). PE was followed by moderate or marked functional improvement in 44.1% of treated patients. Male sex (p = 0.021), preserved reflexes (p = 0.019), and early initiation of treatment (p = 0.009) were associated with moderate or marked improvement. Successfully treated patients improved rapidly following PE, and improvement was sustained.
TL;DR: In this paper, the authors compared the analgesic and cognitive effects of opioids with those of tricyclic antidepressants (TCA) and placebo in the treatment of postherpetic neuralgia (PHN).
Abstract: Background: Tricyclic antidepressants (TCA) provide less than satisfactory pain relief for postherpetic neuralgia (PHN), and the role of opioids is controversial. Objective: To compare the analgesic and cognitive effects of opioids with those of TCA and placebo in the treatment of PHN. Methods: Seventy-six patients with PHN were randomized in a double-blind, placebo-controlled, crossover trial. Each subject was scheduled to undergo three treatment periods (opioid, TCA, and placebo), approximately 8 weeks’ duration each. Doses were titrated to maximal relief or intolerable side effects. The primary outcome measures were pain intensity (0 to 10 scale), pain relief (0 to 100%), and cognitive function. Analyses included patients who provided any pain ratings after having received at least a single dose of a study medication. Results: Fifty patients completed two periods, and 44 patients completed all three. Mean daily maintenance doses were morphine 91 mg or methadone 15 mg and nortriptyline 89 mg or desipramine 63 mg. Opioids and TCA reduced pain (1.9 and 1.4) more than placebo (0.2; p Conclusions: Opioids effectively treat PHN without impairing cognition. Opioids and TCA act via independent mechanisms and with varied individual effect.
TL;DR: It is confirmed that the most beneficial effects induced by STN stimulation are obtained at high frequencies and that voltage is the most critical factor to obtain adequate alteration in STN activity.
Abstract: Background: The main advantage of deep brain stimulation (DBS) in the treatment of PD is that the electrical settings can be adjusted to optimize benefits and minimize adverse effects. The main objective of this study was to discover how varying these electrical parameters impacted on parkinsonian motor signs. Methods: Twelve patients with PD with chronic bilateral subthalamic nucleus (STN) stimulation were selected. The authors evaluated the effects of a variation in the voltages, frequencies, and pulse widths on tremor, bradykinesia, and rigidity using two different paradigms: one in which the total electrical energy delivered was held constant, and one in which this was varied. Up to 26 parameter conditions were tested under double blind randomized conditions. Results: Voltages ≥3 V and frequencies ≥130 Hz led to the greatest improvement in all three parkinsonian signs. A rate of 5 Hz significantly worsened akinesia. The combination of the highest voltage with the narrowest pulse width was most effective. Conclusions: This study confirms that the most beneficial effects induced by STN stimulation are obtained at high frequencies and that voltage is the most critical factor to obtain adequate alteration in STN activity. The mechanisms by which STN DBS improves parkinsonism remain speculative.
TL;DR: It is shown that elderly subjects recruit additional cortical and subcortical areas even for the performance of a simple motor task, which may represent compensatory mechanisms invoked by the aging brain, such as reorganization and redistribution of functional networks to compensate for age-related structural and neurochemical changes.
Abstract: Background: There are well-defined and characteristic age-related deficits in motor abilities that may reflect structural and chemical changes in the aging brain. Objective: To delineate age-related changes in the physiology of brain systems subserving simple motor behavior. Methods: Ten strongly right-handed young ( 50 years of age) subjects with no evidence of cognitive or motor deficits participated in the study. Whole-brain functional imaging was performed on a 1.5-T MRI scanner using a spiral pulse sequence while the subjects performed a visually paced “button-press” motor task with their dominant right hand alternating with a rest state. Results: Although the groups did not differ in accuracy, there was an increase in reaction time in the elderly subjects (mean score ± SD, young subjects = 547 ± 97 ms, elderly subjects = 794 ± 280 ms, p right), and contralateral cerebellum of the elderly subjects. Conclusions: The results of this study show that elderly subjects recruit additional cortical and subcortical areas even for the performance of a simple motor task. These changes may represent compensatory mechanisms invoked by the aging brain, such as reorganization and redistribution of functional networks to compensate for age-related structural and neurochemical changes.