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Transactive response (TAR) DNA-binding protein 43 kDa (TDP-43) pathology is a hallmark of limbic-predominant age-related TDP-43 encephalopathy (LATE). The amygdala is affected early in the evolution of LATE neuropathologic change (LATE-NC), and heterogeneity of LATE-NC in amygdala has previously been observed. However, much remains to be learned about how LATE-NC originates and progresses in the brain. To address this, we assessed TDP-43 and other pathologies in the amygdala region of 184 autopsied subjects (median age = 85 years), blinded to clinical diagnoses, other neuropathologic diagnoses, and risk genotype information. As previously described, LATE-NC was associated with older age at death, cognitive impairment, and the TMEM106B risk allele. Pathologically, LATE-NC was associated with comorbid hippocampal sclerosis (HS), myelin loss, and vascular disease in white matter (WM). Unbiased hierarchical clustering of TDP-43 inclusion morphologies revealed discernable subtypes of LATE-NC with distinct clinical, genetic, and pathologic associations. The most common patterns were: Pattern 1, with lamina II TDP-43 + processes and preinclusion pathology in cortices of the amygdala region, and frequent LATE-NC Stage 3 with HS; Pattern 2, previously described as type-β, with neurofibrillary tangle-like TDP-43 neuronal cytoplasmic inclusions (NCIs), high Alzheimer’s disease neuropathologic change (ADNC), frequent APOE ε4, and usually LATE-NC Stage 2; Pattern 3, with round NCIs and thick neurites in amygdala, younger age at death, and often comorbid Lewy body disease; and Pattern 4 (the most common pattern), with tortuous TDP-43 processes in subpial and WM regions, low ADNC, rare HS, and lower dementia probability. TDP-43 pathology with features of patterns 1 and 2 were often comorbid in the same brains. Early and mild TDP-43 pathology was often best described to be localized in the “amygdala region” rather than the amygdala proper. There were also important shared attributes across patterns. For example, all four patterns were associated with the TMEM106B risk allele. Each pattern also demonstrated the potential to progress to higher LATE-NC stages with confluent anatomical and pathological patterns, and to contribute to dementia. Although LATE-NC showed distinct patterns of initiation in amygdala region, there was also apparent shared genetic risk and convergent pathways of clinico-pathological evolution.

•Controversial registration of aducanumab for Alzheimer's Disease•Aducanumab is the subject of post-licensing observational studies aiming to follow the effects of the drug•Given the high prevalence of cerebrovascular pathology it is important that these studies do not ignore vascular cognitive disorders•The studies may give detailed phenotyping data that may lead to knowledge of targets for treatments of patients with vascular cognitive disorders.

Background: Ventriculoperitoneal shunt (VPS) insertion is one of the most common neurosurgical procedures done around the world to treat hydrocephalus. The occurrence of spontaneous migration of the peritoneal shunt catheter into the thoracic cavity is a very rare complication; we report here case number 27 of respiratory complications of a VPS in a patient with normal-pressure hydrocephalus (NPH). Case Description: A 76-year-old woman with Alzheimer’s disease and anosognosia was diagnosed idiopathic NPH treated surgically with a VPS. Pleural effusion and pulmonary complications occurred 4 weeks after the insertion of the shunt due to the spontaneous migration of the peritoneal catheter of the VPS into the thoracic cavity. The hydrothorax of cerebrospinal fluid was drained and the distal catheter was removed and replaced. The patient made an uneventful recovery. Conclusion: Due to the rarity of this complication, there are no standard corrective procedures. Some of the methods used to diagnose and successfully treat this rare complication of the VPS are presented.

H. Jokinen työryhmän jäsenenä. Introduction: Numerous diagnostic criteria have tried to tackle the variability in clinical manifestations and problematic diagnosis of vascular cognitive impairment (VCI) but none have been universally accepted. These criteria have not been readily comparable, impacting on clinical diagnosis rates and in turn prevalence estimates, research, and treatment. Methods: The Vascular Impairment of Cognition Classification Consensus Study (VICCCS) involved participants (81% academic researchers) from 27 countries in an online Delphi consensus study. Participants reviewed previously proposed concepts to develop new guidelines. Results: VICCCS had a mean of 122 (98-153) respondents across the study and a 67% threshold to represent consensus. VICCCS redefined VCI including classification of mild and major forms of VCI and subtypes. It proposes new standardized VCI-associated terminology and future research priorities to address gaps in current knowledge. Discussion: VICCCS proposes a consensus-based updated conceptualization of VCI intended to facilitate standardization in research. (C) 2016 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Cerebral vascular disease (CVD) represents the second cause in years of life lost, according to the Global Burden of Disease Study 2015 study. The global report on Alzheimer's disease 2015 estimates that in Latin America there are 9.2 million cases of dementia, with a prevalence of 8.2%. Undoubtedly, Alzheimer's disease is the most frequent cause, followed by vascular dementia (VD) with 15% of the cases, although global data are unknown in Latin America. Objective: To analyze and present the current evidence on the classification, pathophysiology, diagnosis and treatment of vascular cognitive impairment. Methodology: A group of experts met in Miami, Florida, in April 2016. The group included Neurologists, Geriatricians and Psychiatrists from the following countries: Mexico, Guatemala, El Salvador, Costa Rica, Peru, Spain, Bolivia, Chile, Paraguay, Colombia, Panama, Venezuela, Italy, the United States, Dominican Republic, Honduras and Nicaragua. The Delphi method was used to review available information (provided months before the meeting), in relation to assigned topics: definition of Cognitive Vascular Impairment (CVI), risk factors, pathophysiology, diagnosis (neuropsychological and imaging) and treatment. For the allocation of evidence and recommendation of available treatments, the GRADE system was used. The working groups analyzed and discussed available evidence on CVI concerning proposed definitions, risk factors and diagnostic elements. Subsequently, the conclusions of each of the working groups were drafted, which were reviewed by each of the authors and by the rest of the study groups until a global consensus was reached. Once this process was completed, the process of external validation and preparation of the final document was carried out. The results of this consensus allow the incorporation of the opinion and experience of physicians of different specialties in Latin America regarding the vascular cognitive impairment.

Author(s): Sachdev, Perminder; Kalaria, Raj; O'Brien, John; Skoog, Ingmar; Alladi, Suvarna; Black, Sandra E; Blacker, Deborah; Blazer, Dan G; Chen, Christopher; Chui, Helena; Ganguli, Mary; Jellinger, Kurt; Jeste, Dilip V; Pasquier, Florence; Paulsen, Jane; Prins, Niels; Rockwood, Kenneth; Roman, Gustavo; Scheltens, Philip; Internationlal Society for Vascular Behavioral and Cognitive Disorders | Abstract: BackgroundSeveral sets of diagnostic criteria have been published for vascular dementia since the 1960s. The continuing ambiguity in vascular dementia definition warrants a critical reexamination.MethodsParticipants at a special symposium of the International Society for Vascular Behavioral and Cognitive Disorders (VASCOG) in 2009 critiqued the current criteria. They drafted a proposal for a new set of criteria, later reviewed through multiple drafts by the group, including additional experts and the members of the Neurocognitive Disorders Work Group of the fifth revision of Diagnostic and Statistical Manual (DSM-5) Task Force.ResultsCognitive disorders of vascular etiology are a heterogeneous group of disorders with diverse pathologies and clinical manifestations, discussed broadly under the rubric of vascular cognitive disorders (VCD). The continuum of vascular cognitive impairment is recognized by the categories of Mild Vascular Cognitive Disorder, and Vascular Dementia or Major Vascular Cognitive Disorder. Diagnostic thresholds are defined. Clinical and neuroimaging criteria are proposed for establishing vascular etiology. Subtypes of VCD are described, and the frequent cooccurrence of Alzheimer disease pathology emphasized.ConclusionsThe proposed criteria for VCD provide a coherent approach to the diagnosis of this diverse group of disorders, with a view to stimulating clinical and pathologic validation studies. These criteria can be harmonized with the DSM-5 criteria such that an international consensus on the criteria for VCD may be achieved.

Objective To determine the long-term tolerability and efficacy of donepezil in patients with vascular dementia (VaD). Methods International, multicentre, open-label, 30-week extension study of two 24-week, randomised, double-blind, placebo-controlled studies. Participants were ambulatory adults (59% female; mean age, 74.7 ± 0.3) with a diagnosis of possible or probable VaD and without a diagnosis of Alzheimer's disease, who were medically stable and had completed one of two double-blind studies. All patients received donepezil 5 mg/day for the first 6 weeks, then 10 mg/day (clinician approval required). Assessments were performed at week 6 and every 12 weeks thereafter. The main outcome measure was the Alzheimer's disease Assessment Scale-cognitive subscale (ADAS-cog). Safety/tolerability measures included adverse events (AEs) and physical and laboratory evaluations. Results Of 1219 eligible patients, 885 (72.6%) were enrolled, of which 707 (79.9%) completed the study; 127 (14.4%) patients discontinued due to AEs. A mean reduction (0.6–1.15 points) from double-blind study baseline score to week 54 (end of open-label study) on the ADAS-cog was observed for patients who received donepezil continuously for 54 weeks. ADAS-cog scores remained stable in the group that initiated donepezil treatment during the extension study. Most common donepezil-related AEs were nausea (occurring in 5.3%) and diarrhoea (8.8%); no unexpected AEs attributable to donepezil occurred. Conclusion These data suggest that donepezil improves cognition for up to 54 weeks in patients with VaD. Patients initiating donepezil in this extension study did not perform as well on the primary outcome measure as those initiating donepezil in the double-blind study. Copyright © 2009 John Wiley & Sons, Ltd.

The incidence and prevalence of autism have increased during the past two decades. Despite comprehensive genetic studies the cause of autism remains unknown. This review emphasizes the potential importance of environmental factors in its causation. Alterations of cortical neuronal migration and cerebellar Purkinje cells have been observed in autism. Neuronal migration, via reelin regulation, requires triiodothyronine (T3) produced by deiodination of thyroxine (T4) by fetal brain deiodinases. Experimental animal models have shown that transient intrauterine deficits of thyroid hormones (as brief as 3 days) result in permanent alterations of cerebral cortical architecture reminiscent of those observed in brains of patients with autism. I postulate that early maternal hypothyroxinemia resulting in low T3 in the fetal brain during the period of neuronal cell migration (weeks 8-12 of pregnancy) may produce morphological brain changes leading to autism. Insufficient dietary iodine intake and a number of environmental antithyroid and goitrogenic agents can affect maternal thyroid function during pregnancy. The most common causes could include inhibition of deiodinases D2 or D3 from maternal ingestion of dietary flavonoids or from antithyroid environmental contaminants. Some plant isoflavonoids have profound effects on thyroid hormones and on the hypothalamus-pituitary axis. Genistein and daidzein from soy (Glycine max) inhibit thyroperoxidase that catalyzes iodination and thyroid hormone biosynthesis. Other plants with hypothyroid effects include pearl millet (Pennisetum glaucum) and fonio millet (Digitaria exilis); thiocyanate is found in Brassicae plants including cabbage, cauliflower, kale, rutabaga, and kohlrabi, as well as in tropical plants such as cassava, lima beans, linseed, bamboo shoots, and sweet potatoes. Tobacco smoke is also a source of thiocyanate. Environmental contaminants interfere with thyroid function including 60% of all herbicides, in particular 2,4-dichlorophenoxyacetic acid (2,4-D), acetochlor, aminotriazole, amitrole, bromoxynil, pendamethalin, mancozeb, and thioureas. Other antithyroid agents include polychlorinated biphenyls (PCBs), perchlorates, mercury, and coal derivatives such as resorcinol, phthalates, and anthracenes. A leading ecological study in Texas has correlated higher rates of autism in school districts affected by large environmental releases of mercury from industrial sources. Mercury is a well known antithyroid substance causing inhibition of deiodinases and thyroid peroxidase. The current surge of autism could be related to transient maternal hypothyroxinemia resulting from dietary and/or environmental exposure to antithyroid agents. Additional multidisciplinary epidemiological studies will be required to confirm this environmental hypothesis of autism.

We report a case of subcortical vascular dementia in a young Hispanic woman, without vascular risk factors, who was found to have extensive ischemic brain lesions due to bilateral intracranial carotid artery occlusions (Moyamoya disease). A combination of ECIC surgeries, donepezil and antiplatelet therapy resulted in increased cerebral perfusion, improvement of cognitive deficits, and prevention of further ischemic or hemorrhagic strokes. Moyamoya disease has been rarely described as a cause of vascular dementia. Differential diagnosis includes atherosclerotic disease, multiple sclerosis, and CADASIL.

This article reviews the piperidine derivative, donepezil hydrochloride (E2020, Aricept), a reversible central acetylcholinesterase inhibitor currently approved for treatment of mild-to-moderate Alzheimer's disease. Donepezil is well absorbed orally, unaffected by food or by time of administration; it reaches therapeutic levels in doses of 5-10 mg/day and peak plasma concentrations are obtained 3-4 h after oral administration. A single bedtime dose is recommended due to the long elimination half-life of the drug (70 h). Donepezil does not cause liver toxicity or significant drug interactions and is relatively well-tolerated. Initial side effects include nausea, vomiting, diarrhoea, insomnia, muscle cramps, fatigue, anorexia and syncope. Caution is advised in patients with bradycardia. Long-term use of donepezil in AD has been found to delay nursing-home placement and to result in caregiver respite. Donepezil also slows deterioration of cognition and global function in patients with moderate-to-severe AD, with improvement of abnormal behaviours. In addition to AD, donepezil demonstrates significant improvement in cognition, global function and activities of daily living in comparison with placebo-treated patients with vascular dementia and has potential therapeutic benefit for other neurological conditions.

Objectives: To investigate the relationship between metabolic markers of cobalamin deficiency and cognitive function in normal older adults. Design: Cross-sectional study. Setting: Queen's University and St. Mary's of the Lake Hospital, Kingston, Ontario, Canada. Participants: Two hundred eighty-one cognitively normal, community-dwelling participants aged 65 and older. Measurements: Serum cobalamin, red blood cell folate, methylcitric acid, homocysteine, and methylmalonic acid were determined. Cognitive instruments included the California Verbal Learning Test, Mattis Dementia Rating Scale, and the Stroop Neuropsychological Screening Inventory (Stroop). Results: Serum levels of methylcitric acid had a significant negative correlation with recall, learning, and discriminability (factor 1) of the California Verbal Learning Test after adjusting for age and sex (β=−0.138, P=.019). Subjects with elevated methylcitric acid had significantly lower scores (factor 1) than subjects with normal methylcitric acid (P

Vascular dementia (VaD) is the second-most-common cause of dementia in the elderly, after Alzheimer's disease (AD). VaD is defined as loss of cognitive function resulting from ischemic, hypoperfusive, or hemorrhagic brain lesions due to cerebrovascular disease or cardiovascular pathology. Diagnosis requires the following criteria: cognitive loss, often predominantly subcortical; vascular brain lesions demonstrated by imaging; a temporal link between stroke and dementia; and exclusion of other causes of dementia. Poststroke VaD may be caused by large-vessel disease with multiple strokes (multiinfarct dementia) or by a single stroke (strategic stroke VaD). A common form is subcortical ischemic VaD caused by small-vessel occlusions with multiple lacunas and by hypoperfusive lesions resulting from stenosis of medullary arterioles, as in Binswanger's disease. Unlike with AD, in VaD, executive dysfunction is commonly seen, but memory impairment is mild or may not even be present. The cholinesterase inhibitors used for AD are also useful in VaD. Prevention strategies should focus on reduction of stroke and cardiovascular disease, with attention to control of risk factors such as hypertension, diabetes mellitus, hypercholesterolemia, and hyperhomocysteinemia.

Cerebrovascular lesions, mainly lacunes and white matter ischemia, are common in elderly patients with dementia. Vascular dementia (VaD) is the second most common cause of dementia, after Alzheimer's disease (AD). However, lacunar strokes have become an important factor in the clinical expression of AD. Also, population-based studies indicate that vascular risk factors increase the risk of developing AD. It is postulated here that the two main causes of VaD—stroke and ischemic heart disease (IHD)—may be responsible for the majority of cases of dementia in the elderly. Stroke-related VaD : Cerebrovascular disease (CVD) is the second leading cause of death worldwide. About 1/3 of stroke survivors [range: 25–41%] 65 years old and above develop VaD within 3 months following the ictus. In the USA alone, 125,000 new cases/year of VaD occur after ischemic stroke (about 1/3 of the 360,000 incident cases of AD). Therefore, more than 1 million elderly people are currently affected by poststroke VaD in the USA. Since current criteria identify "pure" cases of AD and VaD, it is likely that "AD plus CVD" ("mixed" dementia) could be responsible for a large number of cases currently diagnosed as probable AD. Cardiogenic VaD : By 2020, IHD leading to congestive heart failure (CHF) will become the leading cause of disability worldwide. Vascular cognitive impairment occurs in 26% of patients discharged from hospitals after treatment for CHF. Cognitive dysfunction correlates with left ventricular dysfunction and systolic blood pressure below 130 mm Hg. CHF is a leading cause of hospital admissions in Western nations (4.5 million cases in the USA alone) and is a growing problem in developing countries. Furthermore, over 800,000 patients/year undergo coronary artery bypass graft (CABG) surgery worldwide, including 300,000 patients in the USA. Measurable cognitive dysfunction occurs post-CABG in 80–90% of patients at hospital discharge. Long-term (5 years) incidence of cognitive defects is 42%. Finally, an international study found short-term postoperative cognitive dysfunction in 26% of patients (>60 years) after abdominal or orthopedic surgery; most of them may be instances of VaD. In conclusion, VaD may be the most underdiagnosed and undertreated form of dementia in the elderly.

An interesting neurological syndrome, characterized by recurrent optic neuritis, cervical myelopathy from syringomyelia, paraparesis, amenorrhea-galactorrhea, and other endocrine problems, has been described among young black women in the French West Indies. The etiology remains unknown, but possible links with Devic's disease, acute disseminated encephalomyelitis, and neurotoxicity from quinolines in Annona muricata teas have been postulated. The largest epidemic of neuropathy in this century occurred in Cuba in 1991-1994. Clinical features and etiologic studies are reviewed. Its primary cause was nutritional. A similar epidemic was recently described in Tanzania. A number of infectious neuropathies and myopathies are reviewed, including leprosy, tuberculosis, hemorrhagic fevers (Ebola and Marburg filoviruses, Lassa, Argentinean and Bolivian arenaviruses), the human retrovirus human T-cell lymphotropic virus type I, Lyme disease and postimmunization neuropathies. The tropics continue to contribute interesting and important clinical conditions that may illuminate the etiopathiogenesis of other common disorders.

In 1992, the USA embargo on Cuba was tightened through the passage of the Cuban Democracy Act (CDA) that explicitly restricts food and medical supplies. The embargo has contributed to cause a number of public health problems in Cuba including: (1) an epidemic of more than 50,000 cases of optic and peripheral neuropathies in 1992–1993, resulting from dietary deficiency; (2) an epidemic of esophageal stenoses in toddlers who inadvertently drank liquid lye as a result of a soap shortage for which liquid lye was substituted; (3) an outbreak of Guillain-Barré syndrome in Havana, in June and July 1994, resulting from water contamination due to lack of chemicals for water treatment to eliminate Campylobacter sp.; (4) outbreaks of self-inflicted disease and injuries caused by rioting among Cubans detained at the US Naval base at Guantánamo Bay, and (5) a decline in medical practice standards and public health indicators in Cuba resulting from the enactment of the CDA, documented by the American Public Health Association in 1993 and confirmed in March 1997 by the American Association for World Health. Despite this evidence, the Cuban embargo remains a politically sensitive subject in the USA, resistant to public health concerns, as evidenced by the recent passage of the Helms-Burton Act. The public health effects of the CDA need to be reviewed with possible revocation or at least modification.

Cerebrovascular disease (CVD), as well as secondary ischemic brain injury from cardiovascular disease, are common causes of dementia and cognitive decline in the elderly. In addition, CVD frequently contributes to cognitive loss in patients with Alzheimer's disease (AD). Progress in understanding the pathogenetic mechanism involved in vascular cognitive impairment (VCI) and vascular dementia (VaD) has resulted in promising treatments of these conditions. Cholinergic deficits in VaD are due to ischemia of basal forebrain nuclei and of cholinergic pathways and can be treated with the use of the cholinesterase inhibitor agents used in AD. Controlled clinical trials with donepezil, galantamine and rivastigmine in VaD, as well as in patients with AD plus CVD, have demonstrated improvements in cognition, behavior and activities of daily living.

Nucleus pulposus embolism causing spinal cord infarction is exceptional. A 16-year-old girl was seen with sudden onset of interscapular pain and paraplegia from fatal ischemic transverse myelopathy due to arterial and venous occlusions by fibrocartilaginous embolism. In 32 cases of nucleus pulposus embolism, females predominated (69%) and age distribution was bimodal with peaks at 22 and 60 years (median, 38.5). Embolization was either arterial and venous (50%) or purely arterial (50%). Myelopathy predominated in cervical (69%) and lumbosacral (22%) segments. Schmorl's nodes, larger volume and vascularization of nucleus pulposus in the young, and spinal arteriovenous communications, trauma, and degenerative changes in older patients could be important pathogenetic factors. Diagnosis requires histopathologic confirmation. Nucleus pulposus embolism may be an underlying cause in cases diagnosed as transverse myelitis and ischemic infarction of spinal cord.

Despite intensive evaluation of acute stroke patients, perhaps only half of the attributable stroke risk is usually identified. In addition to traditional and non-traditional vascular risk factors-including most recently homocysteine, inflammation, and alterations of coagulation-a number of environmental risk factors for stroke have been identified in the last decade. In this update we review the following: lower education and poor socioeconomic status (probable surrogates for exposure to traditional high-risk behaviors such as smoking, poor nutrition, lack of prenatal control, absence of preventive medical and dental care, and non-compliance of treatment of conditions such as hypertension); depression, stress and affective disorders; obstructive sleep apnea; passive smoking and environmental pollution; infections, in particular periodontal diseases that increase C-reactive protein (CRP); raised body mass index (obesity); exercise, and diet. The possible role of high-fructose corn syrup in the epidemic of obesity in the USA is reviewed. Protective diets include higher consumption of fish, olive oil, grains, fruits and vegetables (Mediterranean diet), as well as probiotic bacteria in yogurt and dairy products. Careful attention should be given to the patient's environment looking for modifiable factors. The effects of clean environmental air and water, adequate diet and appropriate nutrition, healthy teeth, exercise, and refreshing sleep in the prevention of stroke and cardiovascular disease appear to be quite compelling. Although some of these modifiable risk factors lack evidence-based information, judicious clinical sense should be used to counteract the potentially damaging effects of adverse environmental vascular risk factors.

A cross-sectional prevalence study of Parkinson's disease in China was undertaken in 1997-98. We assessed 29?454 residents agedor =55 years from 79 rural and 58 urban communities in Beijing, Xian, and Shanghai, who were selected through stratified, multistage, cluster sampling. With a standardised diagnostic protocol, we identified 277 people with the disease. Prevalence of Parkinson's disease for those agedor =65 years was 1.7% (95% CI 1.5-1.9). We estimate that 1.7 million people in China have the disease (agedor =55 years). Our findings suggest that prevalence of Parkinson's disease in China is similar to that in developed countries.

Vascular cognitive impairment (VCI) was proposed as an umbrella term to include subjects affected with any degree of cognitive impairment resulting from cerebrovascular disease (CVD), ranging from mild cognitive impairment (MCI) to vascular dementia. VCI may or may not exclude the host of "focal" circumscribed impairments of specialized functions such as language (aphasia), intentional gesture (apraxia), or categorical recognition (agnosia), among others, that may result from a stroke. Therefore, there are no universally accepted diagnostic criteria for VCI. We conclude that this concept could be more useful if it were to be limited to cases of vascular MCI without dementia, by analogy with the concept of amnestic MCI, currently considered the earliest clinically diagnosable stage of Alzheimer disease (AD). In agreement with our view,the Canadian Study on Health and Aging successfully implemented a restricted definition of VCI, excluding cases of dementia (i.e., vascular cognitive impairment no dementia, VCI-ND). The Canadian definition and diagnostic criteria could be utilized for future studies of VCI. This definition excludes isolated impairments of specialized cognitive functions. Vascular dementia (VaD): The main problem of this diagnostic category stems from the currently accepted definition of dementia that requires memory loss as the sine qua non for the diagnosis. This may result in over-sampling of patients with AD worsened by stroke (AD+CVD). This problem was minimized in controlled clinical trials of VaD by excluding patients with a prior diagnosis of AD, those with pre-existing memory loss before the index stroke, and those with amnestic MCI. We propose a definition of dementia in VaD based on presence of abnormal executive control function, severe enough to interfere with social or occupational functioning. Vascular cognitive disorder (VCD): This term, proposed by Sachdev [P. Sachdev, Vascular cognitive disorder. Int J Geriat Psychiatry 14 (1999)402-403.] would become the global diagnostic category for cognitive impairment of vascular origin, ranging from VCI to VaD. It would include specific disease entities such as post-stroke VCI, post-stroke VaD, CADASIL, Binswanger disease, and AD plus CVD. This category explicitly excludes isolated cognitive dysfunctions such as those mentioned above.

To investigate the relationship between metabolic markers of cobalamin deficiency and cognitive function in normal older adults.Cross-sectional study.Queen's University and St. Mary's of the Lake Hospital, Kingston, Ontario, Canada.Two hundred eighty-one cognitively normal, community-dwelling participants aged 65 and older.Serum cobalamin, red blood cell folate, methylcitric acid, homocysteine, and methylmalonic acid were determined. Cognitive instruments included the California Verbal Learning Test, Mattis Dementia Rating Scale, and the Stroop Neuropsychological Screening Inventory (Stroop).Serum levels of methylcitric acid had a significant negative correlation with recall, learning, and discriminability (factor 1) of the California Verbal Learning Test after adjusting for age and sex (beta=-0.138, P=.019). Subjects with elevated methylcitric acid had significantly lower scores (factor 1) than subjects with normal methylcitric acid (P.01). Bivariate analysis showed significant correlations between levels of homocysteine and the Stroop score and between cobalamin, methylmalonic acid, and homocysteine and some scores of the California Verbal Learning Test, but these relationships did not remain significant after multivariate analysis. Subjects with high homocysteine (tHcy) had lower Stroop scores than subjects with normal tHcy (P.05). No biochemical parameters were associated with the Mattis Dementia Rating Scale scores.This study indicates that, in normal elderly subjects, some cognitive scores are related to serum methylcitric acid and possibly homocysteine.

Summary Vascular dementia is the second most common type of dementia. The subcortical ischaemic form (SIVD) frequently causes cognitive impairment and dementia in elderly people. SIVD results from small-vessel disease, which produces either arteriolar occlusion and lacunes or widespread incomplete infarction of white matter due to critical stenosis of medullary arterioles and hypoperfusion (Binswanger's disease). Symptoms include motor and cognitive dysexecutive slowing, forgetfulness, dysarthria, mood changes, urinary symptoms, and short-stepped gait. These manifestations probably result from ischaemic interruption of parallel circuits from the prefrontal cortex to the basal ganglia and corresponding thalamocortical connections. Brain imaging (computed tomography and magnetic resonance imaging) is essential for correct diagnosis. The main risk factors are advanced age, hypertension, diabetes, smoking, hyperhomocysteinaemia, hyperfibrinogenaemia, and other conditions that can cause brain hypoperfusion such as obstructive sleep apnoea, congestive heart failure, cardiac arrhythmias, and orthostatic hypotension. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) and some forms of cerebral amyloid angiopathy have a genetic basis. Treatment is symptomatic and prevention requires control of treatable risk factors.

Fibrocartilaginous embolism from the nucleus pulposus has been reported as a rare cause of spinal cord ischemia. We were unable to find previous reports of embolism from this source to cerebral arteries. A previously healthy 17-year-old girl fell during a basketball game. Left hemiparesis and unresponsiveness developed followed by signs of right uncal herniation and death over a 3-day period. There was no evidence of neck, head, or spine trauma, and cardiac evaluation was normal. Neuropathological examination showed extensive ischemic infarction of the right middle cerebral artery territory, brain edema, and herniation. Complete embolic occlusion of the right middle cerebral artery by fibrocartilaginous material, consistent with nucleus pulposus, was documented. Small, terminal coronary artery branches also showed embolism by the same material and limited areas of myocardial infarction. Acute cerebral embolism after minor trauma in a young patient may be rarely due to fibrocartilaginous embolism from the nucleus pulposus. The pathogenesis of this problem remains poorly understood, but systemic embolism appeared to have occurred in this case.

Vascular dementia (VaD) incorporate different vascular mechanisms and changes in the brain, and have different causes and clinical manifestations. Variation in defining the cognitive syndrome, in vascular etiologies, and allowable brain changes in current clinical definitions of VaD have resulted in variable estimates of prevalence, of groups of subjects, and of the types and distribution of putative causal brain lesions. Thus current criteria for VaD select an etiologically and clinically heterogeneous group. This definitional heterogeneity may have been a factor in “negative” clinical trials. An alternative for clinical drug trials is to focus on a more homogenous group, such as those with subcortical (ischemic) VaD. This designation incorporates two small vessel clinical entities “Binswanger’s disease” and “the lacunar state”. It comprises small vessel disease as the primary vascular etiology, lacunar infarct(s) and ischaemic white matter lesions as the primary type of brain lesions, and subcortical location as the primary location of lesions. The subcortical clinical syndrome is the primary clinical manifestation, a definition which still requires additional empirical data. We expect that subcortical VaD show a more predictable clinical picture, natural history, outcome, and treatment responses. We propose a modification of the NINDS-AIREN criteria as a new research criteria for subcortical VaD.

A closed workshop on “Neurocysticercosis (NCC) and Epilepsy” was held in Tumbes, Peru, with support from the American Epilepsy Society (AES), the Universidad Peruana Cayetano Heredia, and the University of Western Ontario. The aim of the workshop was to develop the foundations for an international collaborative research network on this subject. The Neurocysticercosis and Epilepsy Research Network (NERN) will comprise a group of researchers with expertise in diverse related fields aiming to foster collaborative research in all aspects of epilepsy related to NCC. The ultimate goal is to better understand the epilepsy caused by NCC; its basic molecular and genetic mechanisms; as well as the medical, surgical, cognitive, and psychosocial aspects.

A 64-year-old man with a history of traumatic brain injury 4 years previously presented with progressive cognitive decline and gait abnormality. MRI revealed diffusion restriction in the bilateral centrum semiovale and multiple serpiginous flow voids. Cerebral angiogram revealed a total of six intracranial dural arteriovenous fistulas with separate fistulas of the right and left sphenoid bones, left clival plexus, right transverse sinus, right sigmoid sinus, and superior sagittal sinus. A diffuse pseudophlebitic pattern of venous drainage indicating severe venous hypertension was also observed. The patient underwent a series of endovascular treatments over the next 10 months to achieve resolution of all arteriovenous shunting. Repeat MRI showed resolution of the diffusion restriction and marked reduction in T2 vascular flow voids. The patient's clinical status improved significantly over the course of treatment, paralleling the improvement in venous hypertension.

Accepted approaches to therapy for the different forms of neurocysticercosis are reviewed. Therapy must be individualized according to the level of disease activity and the location of the parasite. Patients with inactive disease should receive only symptomatic treatment. In contrast, patients with parenchymal brain cysts must receive a course of anticysticercal drugs. Both albendazole and praziquantel are useful; however, recent evidence favors the former as the drug of choice for this form of the disease. Albendazole (but not praziquantel) is also effective in the treatment of giant subarachnoid cysts; such medical treatment obviates surgery in some cases. Patients with ventricular cysts may also benefit from medical therapy; however, surgery is the current approach to this type of lesion, as it is to spinal cysticercosis. Although intraocular cysts have classically been resected by surgery, a recent study indicates that albendazole is equally effective. For patients with mixed forms of neurocysticercosis, therapeutic measures related to--but not directly targeting--the disease (i.e., steroid administration for brain edema or shunt placement for hydrocephalus) should be contemplated before therapy with anticysticercal drugs is instituted.

To the Editor. —Dr Snowdon and colleagues 1 emphasized the important contribution of lacunar infarcts to cognitive decline in patients with AD. However, with few exceptions, no clear correlation exists between location or number of lacunar infarcts and development of vascular dementia. 2,3 More than a direct cause of dementia, lacunar infarcts per se probably represent a surrogate or a marker for small-vessel disease(arteriolosclerosis) leading also to periventricular ischemic white matter disease in the elderly. 4 These lesions, rediscovered by brain imaging techniques under the name leukoaraiosis, constitute the pathological substratum of Binswanger disease, 5 a vascular form of senile dementia. Moreover, Brun and Englund 6 demonstrated these lesions in about 60% of patients with AD. However, periventricular ischemic white matter lesions in the elderly may be undetectable to the naked eye examination of the brain

During 1992 to 1993, an epidemic of neurologic disease in Cuba affected 50,862 patients with optic neuropathy, sensorineural deafness, predominantly sensory peripheral neuropathy, and dorsolateral myelopathy. The clinical syndromes were identical to those of prisoners of war subjected to nutritional restriction in tropical prison camps during World War II (Strachan's disease). A dietary deficiency of group B vitamins and sulfur-containing amino acids appears to have been the primary cause of the epidemic. This was a consequence of economic and political events in Cuba linked to the collapse of the Soviet Union and socialist countries. The recently toughened 30-year-old US economic embargo on Cuba contributed to these problems and hampered the investigation, treatment, and prevention of the epidemic. A plea is made to the neurologic community to request the lifting of the trade blockade on a humanitarian basis.