Sinus Sigmoideus Thrombosis Secondary to Graves' Disease: A Case Description

Cerebral venous thrombosis (CVT) is a distinct cerebrovascular condition that represents 0.5-1% of all strokes in the general population. Because of its procoagulant and antifibrinolytic effects [Horne et al.: J Clin Endocrinol Metab 2004;89:4469-4473], hyperthyroidism has been proposed as a predisposing factor for CVT [Saposnik et al.: Stroke 2011;42:1158-1192]. For the first time, we describe a 22-year-old right-handed woman with a sinus sigmoideus thrombosis due to Graves' disease. Although subclinical hyperthyroidism had been detected 2 years before the onset of neurological symptoms, she did not receive any medical follow-up. Early recognition, diagnosis and treatment are of crucial importance, as Graves' disease is a risk factor for CVT and stroke

Choroidal Proteins Involved in Cerebrospinal Fluid Production may be Potential Drug Targets for Alzheimer’s Disease Therapy

Alzheimer’s disease is known to be the most common form of dementia in the elderly. It is clinically characterized by impairment of cognitive functions, as well as changes in personality, behavioral disturbances and an impaired ability to perform activities of daily living. To date, there are no effective ways to cure or reverse the disease. Genetic studies of early-onset familial Alzheimer’s disease cases revealed causative mutations in the genes encoding β-amyloid precursor protein and the γ-secretase-complex components presenilin-1 and presenilin-2, supporting an important role of β-amyloid in the pathogenesis of Alzheimer’s disease. Compromised function of the choroid plexus and defective cerebrospinal fluid production and turnover, with diminished clearance of β-amyloid, may play an important role in late-onset forms of Alzheimer’s disease. If reduced cerebrospinal fluid turnover is a risk factor for Alzheimer’s disease, then therapeutic strategies to improve cerebrospinal fluid flow are reasonable. However, the role of deficient cerebrospinal fluid dynamics in Alzheimer’s disease and the relevance of choroidal proteins as potential therapeutic targets to enhance cerebrospinal fluid turnover have received relatively little research attention. In this paper, we discuss several choroidal proteins, such as Na+-K+ ATPase, carbonic anhydrase, and aquaporin 1, that may be targets for pharmacological up-regulation of cerebrospinal fluid formation. The search for potentially beneficial drugs useful to ameliorate Alzheimer’s disease by facilitating cerebrospinal fluid production and turnover may be an important area for future research. However, the ultimate utility of such modulators in the management of Alzheimer’s disease remains to be determined. Here, we hypothesize that caffeine, the most commonly used psychoactive drug in the world, may be an attractive therapeutic candidate for treatment of Alzheimer’s disease since long-term caffeine consumption may augment cerebrospinal fluid production. Other potential mechanisms of cognitive protection by caffeine have been suggested by recent studies

Guanidino compounds that are increased in cerebrospinal fluid and brain of uremic patients inhibit GABA and glycine responses on mouse neurons in cell culture

Four guanidino compounds that have been found to be markedly increased in cerebrospinal fluid and brain tissue of uremic patients, namely, guanidine, methylguanidine, creatinine, and guanidinosuccinic acid, were applied to mouse spinal cord neurons in primary dissociated cell culture to evaluate their effects on postsynaptic responses to gammaaminobutyric acid (GABA) and glycine. Intracellular microelectrode recording techniques were used. Guanidine, methylguanidine, creatinine, and guanidinosuccinic acid reversibly and in a dose-dependent manner inhibited both GABA and glycine responses. Guanidinosuccinic acid was the most potent inhibitor of the amino acid responses, followed in decreasing potency by methylguanidine, guanidine, and creatinine. Guanidinosuccinic acid inhibited responses to GABA and glycine, at concentrations similar to those found in cerebrospinal fluid and brain tissue of patients with terminal renal insufficiency. The other guanidino compounds tested exerted their effects only at concentrations higher than those found in uremic biological fluids and tissues. The inhibitory effect of guanidine and methylguanidine on responses to GABA was additive. The effect of the guanidino compounds on GABA responses was not antagonized by coapplication of the benzodiazepine-receptor antagonist CGS 9896. The results suggest that guanidine, methylguanidine, creatinine, and guanidinosuccinic acid inhibited responses to the inhibitory neurotransmitters GABA and glycine by blocking the chloride channel. The observed action of the studied guanidino compounds might contribute to the pathogenesis of the complex neurological symptomatology encountered in uremia.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/50338/1/410280505_ftp.pd

Increased Cerebrospinal Fluid Production as a Possible Mechanism Underlying Caffeine's Protective Effect against Alzheimer's Disease

Alzheimer's disease (AD), the most common type of dementia among older people, is characterized by the accumulation of β-amyloid (Aβ) senile plaques and neurofibrillary tangles composed of hyperphosphorylated tau in the brain. Despite major advances in understanding the molecular etiology of the disease, progress in the clinical treatment of AD patients has been extremely limited. Therefore, new and more effective therapeutic approaches are needed. Accumulating evidence from human and animal studies suggests that the long-term consumption of caffeine, the most commonly used psychoactive drug in the world, may be protective against AD. The mechanisms underlying the suggested beneficial effect of caffeine against AD remain to be elucidated. In recent studies, several potential neuroprotective effects of caffeine have been proposed. Interestingly, a recent study in rats showed that the long-term consumption of caffeine increased cerebrospinal fluid (CSF) production, associated with the increased expression of Na+-K+ ATPase and increased cerebral blood flow. Compromised function of the choroid plexus and defective CSF production and turnover, with diminished clearance of Aβ, may be one mechanism implicated in the pathogenesis of late-onset AD. If reduced CSF turnover is a risk factor for AD, then therapeutic strategies to improve CSF flow are reasonable. In this paper, we hypothesize that long-term caffeine consumption could exert protective effects against AD at least in part by facilitating CSF production, turnover, and clearance. Further, we propose a preclinical experimental design allowing evaluation of this hypothesis

The 10-word learning task in the differential diagnosis of early Alzheimer's disease and elderly depression: a cross-sectional pilot study

Objectives: Identification of early Alzheimer's disease (AD) has become very important. Episodic memory tasks appear to have predictive power for indicating early AD. Deficits in encoding and storage processes that are characteristic of AD, however, must be distinguished from non-AD deficits that can also affect memory, including difficulties that may be present in depression. This pilot study was set up to ascertain whether a 10-word-list-learning task (delayed recognition and rate of forgetting) may be useful in making the differentiation between mild AD and depression. Method: A Dutch version of Rey's auditory verbal learning test was administered to 36 mild AD patients, 41 depressed patients, and 47 healthy controls. Data were analyzed in a cross-sectional manner. Results: Receiver operating characteristic analyses showed that for differentiating mild AD and depression, both delayed recognition and percentage of forgetting have sufficient diagnostic accuracy. Conclusion: Percentage of forgetting had the highest diagnostic accuracy for differentiating mild AD and depressed patients and may be useful in the early detection of AD