Showing papers in "Acta Neurologica Scandinavica in 2000"

Neurological findings in complex regional pain syndromes--analysis of 145 cases.

Abstract: Early diagnosis is a prerequisite for a successful treatment of complex regional pain syndrome (CRPS). In order to describe neurological symptoms which characterize CRPS, we evaluated 145 patients prospectively. Two-thirds of these were women, the mean age at time of investigation was 50.4 years. CRPS followed limb trauma, surgery and nerve lesion. Employing the current IASP criteria 122 patients were classified as CRPS I and 23 as CRPS II. All patients were assessed clinically pain was quantified using the McGill pain questionnaire, skin temperature was measured by an infrared thermometer and a subgroup of 57 patients was retested in order to determine thermal thresholds (QST). Of our patients 42% reported stressful life events in a close relationship to the onset of CRPS and 41% had a history of chronic pain before CRPS. The latter group of patients gave a higher rating of CRPS pain (P<0.05). The major symptoms were pain at rest in 77% and hyperalgesia in 94%. Typical pain was deep in the limb having a tearing character. Patients getting physical therapy had significantly less pain than those without (P<0.04). Autonomic signs were frequent (98%) and often changed with the duration of CRPS. Skin temperature was warmer in acute and colder in chronic stages (P<0.001). Likewise edema had a higher incidence in acute stages (P<0.001). We found no correlation between pain and autonomic dysfunction. Motor dysfunction (present in 97%) included weakness, tremor, exaggerated tendon reflexes, dystonia or myoclonic jerks. QST revealed increased warm perception thresholds (P<0.02) and decreased cold pain thresholds (P<0.03) of the affected limb. The detailed knowledge of clinical features of CRPS could help physicians early to recognize the disease and thus to improve therapy outcome.

Sleep and quality of life in the Austrian population

Abstract: Purpose– To compare the self-reported estimation of sleep quality evaluated by the Pittsburgh Sleep Quality Index (PSQI) and life quality assessed by the Quality of Life Index (QLI) Background– The PSQI comprised 19 questions and assessed a wide variety of factors relating to sleep quality The QLI consisted of 10 items for self assessment of different dimensions of life quality Subjects– A representative Austrian sample (n=1049) aged above 15 years Procedure– Interviews in the homes of the participants Results– 321% could be classified as poor sleepers (37% females, 265% males) Sleep quality decreased with increasing age, especially in women Overall quality of life was highest in younger (15–29 years) and lowest in elderly subjects (over 50 years) Life quality decreased with increasing age Between subjective sleep quality and quality of life a moderate, significant correlation was found (r2=06721) Conclusions– Complaints about a bad quality of sleep could be used as a screening method in the exploration of patients' quality of life (QoL)

Visual neglect as a predictor of functional outcome one year after stroke

Abstract: Objectives: The aim was to study the role of visual neglect in acute right hemisphere brain infarct as a predictor of poor functional outcome during the first year after stroke. In particular, we were interested in the additional value of neglect measures besides hemiparesis, hemianopia, cognitive deficits and age. Patients and methods: A consecutive series of 57 patients with a neuroradiologically verified right hemisphere infarct was examined within 10 days of the stroke. Fifty patients were followed up for 1 year. Neglect was measured with the Conventional and the Behavioural subtests of the Behavioural Inattention Test (BITC and BITB, respectively). The predictors were determined at the 10-day examination. Functional outcome was assessed 3, 6 and 12 months after the onset with the Frenchay Activities Index. Results: Neglect in BITB was the best single predictor, which together with high age formed the best combination of predictors for poor functional outcome at each follow-up. Hemiparesis was also included in this prediction model at the 3-month follow-up, but hemianopia, BITC, or visuoconstructional and memory deficits showed no additional predictive value. However, neglect usually recovered soon. When neurological and cognitive deficits were assessed at the same time as the outcome, hemiparesis rather than neglect was the strongest correlate of poor outcome. Conclusion: Neglect in acute stroke is an important predictor of poor functional recovery. Residual neglect, which could be compensated in the follow-up tests, may nevertheless restrict patients' real-life activities and hobbies.

Training-induced changes of motor cortex representations in stroke patients.

Abstract: Objective - To study changes in motor cortex representations after a single session of physiotherapy in stroke patients Methods - TMS mapping was used to evaluate the motor output map of the abductor pollicis brevis (APB) in both hemispheres Stroke patients (4-8 weeks after the infarction) were studied prior to a training session aimed at improving dexterity and 1 h and 1 day after the training Results - Prior to the training, the APB representation area in the affected hemisphere was significantly smaller than on the non-affected side After therapy, the cortical motor output to the paretic APB was significantly enlarged, and motor function was improved One day later, these effects were partially reversed Motor thresholds remained significantly increased in the affected hemisphere before and after the therapy Conclusion - A single session of physiotherapy produces a use-dependent enlargement of motor cortex representations paralleled by an improvement of motor function in stroke patients

Gabapentin use in neuropathic pain syndromes.

Abstract: The development of neuropathic pain involves a series of changes including primary and secondary hyperalgesia, peripheral and central sensitization, and wind-up phenomena. Neurotransmitters play a critical role in this process. For example, glutaminergic subtypes of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and neurokinin prime the N-methyl-D-aspartate (NMDA) receptor by triggering the release of intracellular calcium ions, thus unblocking the magnesium ion plug on the NMDA receptor and allowing Ca2+ influx into the cell. Ca2+ ions acting as secondary messengers initiate protein kinase C activation, phospholipase C and nitric oxide synthetase production, and proto-oncogene expression. The activation of the NMDA receptor thereby increases the responsiveness of the nociceptive system. Anticonvulsant drugs--including carbamazepine, phenytoin, and felbamate--have been used to treat neuropathic pain. Gabapentin is a novel anticonvulsant that may have a unique effect on voltage-dependent Ca2+ channel currents at postsynaptic dorsal horn neurons. Thus, gabapentin may interrupt an entire series of events, not just a single process, that lead to the development of neuropathic pain. Preclinical models of anti-inflammatory and neuropathic pain indicate that gabapentin effectively antagonizes the maintenance of this pain. Additionally, in preemptive surgical models, gabapentin has been shown to prevent the induction of pain. Gabapentin has been shown to be efficacious in numerous smaller clinical studies, case reports, and chart reviews in a variety of neuropathic pain syndromes. Two large multicenter studies, one in postherpetic neuralgia (PHN) and one in diabetic peripheral neuropathy (DPN), support preclinical findings. In the PHN study, patients treated with gabapentin demonstrated a significant difference (P<0.001) in their average daily pain score at endpoint compared to placebo patients. In the DPN trial, mean weekly pain was significantly (P<0.001) different for gabapentin-treated patients compared to placebo-treated patients at endpoint. Consistent with the known side-effect profile of gabapentin, the most common adverse events noted in both studies were dizziness and somnolence. Gabapentin should be considered an important addition to the management of neuropathic pain syndromes.

Effect of dietary advice and n-3 supplementation in newly diagnosed MS patients.

Abstract: Objective - To investigate whether supplementation with fish oil given together with dietary advice and vitamin supplementation influenced the clinical outcome in newly diagnosed multiple sclerosis (MS) patients. Material and methods - Sixteen consecutive, newly diagnosed patients with multiple sclerosis were recruited to an open intervention study. They were given dietary advice and supplemented with 0.9 g/day of long-chain marine fatty acids and vitamins. The patients were followed for 2 years with respect to dietary habits, blood parameters and neurological assessment including exacerbation rate. Results - There was a significant reduction in the mean annual exacerbation rate and the mean Expanded Disability Status Scale (EDSS) as compared to pre-study values. The plasma total phospholipid n-3 fatty acids increased and n-6 fatty acids decreased significantly. Conclusions - The results suggest that fish oil supplementation given together with vitamins and dietary advice can improve clinical outcome in patients with newly diagnosed MS.

Gender differences in Parkinson's disease symptom profile

Abstract: Gender symptom differences were studied in 948 subjects with Parkinson's disease (PD) using a questionnaire covering the most common symptoms associated with PD at debut (SP-1) and at present (SP-2). The symptoms most frequently reported by both genders were: tremor, fumblingness, writing problems, rigidity and fatigue. At SP-1 females reported neck-pain and low back pain more frequently than males. At SP-2 subjects reported an increased number of symptoms. The following symptoms were more frequent among males than females: writing difficulties, fumblingness, gait problems, speech problems, increased flow of saliva, lack of initiative. Sleep problems were common in both sexes with inability to turn in bed and calf muscle cramps in a high percentage. A majority of female subjects find their symptoms (e.g. depression) constantly distressing. Although depression is not one of primary reported symptoms (36%) attention is called for, due to the problem with compliance to treatment regimes. About 30% do not report having tremor and rigidity. This study indicates the usefulness of a symptom profile instrument capable of capturing the many symptoms involved in PD. Such an instrument could be used to detect apparent mistakes in medication and thereby increase the function and quality of life for the individual.

Ultrasound contrast enhancing agents in neurosonology: principles, methods, future possibilities.

Abstract: The various factors which determine brain weight and volume of the lateral ventricles were studied in an autopsy material of 467 cases. The material consisted of 64 men and 17 women between 45-54 years and 196 men and 190 women between 70-79 years. The weights of the cerebral hemispheres and of the cerebellum and brainstem were determined separately. The volume of the lateral ventricles was determined by weighing the hemispheres with and without water in the lateral ventricles. The recorded variables were age, sex, body length, body weight, cerebral atherosclerosis, Alzheimer changes and alcoholism. Cerebral atherosclerosis and Alzheimer changes were quantitated by morphometric methods. The results were analysed by conventional and multivariate statistical methods. The following observations were made: In normal brains there was a significant correlation between the weight of the supra- and infratentorial parts. Similarly, there was a significant correlation between the size of the lateral ventricles and the weight of the cerebral hemispheres. Women had smaller brains than men even when the difference in body length was taken into account. The difference was approximately 110-115 g for the whole brain after correction for other variables. Women had also smaller lateral ventricles than men, but this difference was in proportion to the smaller size of their hemispheres. There was a physiologic decline in brain weight and a widening of the lateral ventricles with increasing age. This shrinkage probably started after the age of 55. There was a clear correlation between body length and brain weight. The estimated increase in brain weight was approximately 3 g per cm body length. There was a decreasing brain weight and an increasing ventricular size with a decreasing body mass index. This shows that emaciation leads to a decrease in brain size. Severe Alzheimer changes caused a statistically significant enlargement of the lateral ventricles both in men and women. There was a general trend for brain weight reduction in cases with severe Alzheimer changes but the decrease was statistically significant only in old women, and it could not be entirely excluded that the weight reduction in part was due to a concurrent emaciation rather than to the Alzheimer changes per se. In the majority of the cases, the Alzheimer changes were mild and had probably progressed slowly with age. A few cases had very severe changes.(ABSTRACT TRUNCATED AT 400 WORDS)

Galantamine is an allosterically potentiating ligand of the human alpha4/beta2 nAChR.

Abstract: Galantamine (ReminyI ) is a novel drug treatment for mild to moderate Alzheimer's disease (AD). Originally established as a reversible inhibitor of the acetylcholine-degrading enzyme acetylcholinesterase (AChE), galantamine also acts as an allosterically potentiating ligand (APL) on nicotinic acetylcholine receptors (nAChR). Having previously established this second mode of action on nAChRs from murine brain, we demonstrate here the same action of galantamine on the most abundant nAChR in the human brain, the α4/β2 subtype. This nAChR-sensitizing action is not a common property of all, or most, AChE inhibitors, as is shown by the absence of this effect for other therapeutically applied AChE inhibitors including tacrine, metrifonate, rivastigmine and donepezil. The possible benefits for therapy of AD of an APL action on nicotinic receptors is discussed.

Neuropsychological disturbances in cerebellar infarcts.

Abstract: Background– Recent clinical and research reports suggest that the cerebellum may contribute to the modulation of higher cognitive functions. Material and methods– We included 15 consecutive patients with isolated cerebellar infarcts (4 superior cerebellar artery territory infarcts, 1 anterior inferior cerebellar artery territory infarct and 10 posterior inferior cerebellar artery territory infarcts), all confirmed by magnetic resonance imaging. These subjects plus 15 controls matched for age, sex, and educational level underwent a neuropsychological test battery including vocabulary, similarities and block design subtests of the Wechsler Adult Intelligence Scale Revised (WAIS-R); verbal fluency tests (categorial, phonemic, and alternate categorial fluency tests); Rey's 15 auditory word learning list; the paced auditory serial addition task; the Stroop test and the Zerssen Rating Scale. One year after the cerebellar infarct, each subject with cerebellar infarct was asked to undergo a second neuropsychological examination with the same test battery. Results– Patients with cerebellar infarcts exhibited significantly lower neuropsychological performances compared to those of the control group without any obvious difference between the different vascular cerebellar territories. After 1 year of follow-up, this neuro-psychological impairment tended to improve. Conclusions– The pattern of deficits observed in isolated cerebellar infarcts highlights the non-motor functions of the cerebellum and functional relationship between the cerebral cortex and the cerebellum.

Transient global amnesia: a review emphasizing pathogenic aspects.

Abstract: The transitory memory disturbance known as transient global amnesia (TGA) remains an enigma from a pathogenic point of view. In spite of its typical benign prognosis, TGA is a frightening experience for patients and their relatives. Moreover, a TGA episode usually leads to extensive investigation of patients in search of organic alterations that might be responsible for the event. Finally, TGA generates queries about therapeutic choices. In this review, we critically re-evaluate the evidence in support of and against the three main pathogenic hypotheses (i.e. ischemia, seizure discharge, and migraine), and we conclude that none of these appears completely convincing. Given the good prognosis and the lack of association with organic and instrumental abnormalities, we advance the hypothesis that TGA may be related to psychological disturbances causing transient alteration in brain metabolism and, consequently, amnesia. Our conclusion has relevant consequences in the evaluation of patients with TGA.

Adaptive electric field control of epileptic seizures

Abstract: Epilepsy is a dynamical disease - symptoms are produced by aberrant dynamics of neuronal networks. Although numerous attempts have been made to suppress epileptic seizures in human patients by stimulating sites remote from the epileptic focus, the efficacy of doing this without taking the dynamics of the seizures into account have been unimpressive.

Different vascular risk factor profiles in ischemic stroke subtypes: a study from the "Sagrat Cor Hospital of Barcelona Stroke Registry"

Abstract: Objectives To characterize the vascular risk factor profiles in different subtypes of ischemic stroke. Material and methods The study population consisted of 1473 consecutive ischemic stroke patients collected in a prospective stroke registry. The prevalence of vascular risk factors in each stroke subtype was analyzed independently and in comparison with other subtypes of stroke pooled together by means of univariate analysis and logistic regression models. Results Hypertension was present in 52% of patients followed by atrial fibrillation in 27% and diabetes in 20%. The pattern of risk factors associated with atherothrombotic stroke included chronic obstructive pulmonary disease (COPD) (odds ratio [OR] = 2.63), hypertension (OR = 2.55), diabetes (OR = 2.26), transient ischemic attack (OR = 1.61), and age (OR = 1.03). Previous cerebral hemorrhage (OR = 4.72), hypertension (OR = 4.29), obesity (OR = 2.45), and diabetes (OR = 1.73) were strong predictors of lacunar stroke. In the case of cardioembolic stroke, atrial fibrillation (OR = 22.24), valvular heart disease (OR = 10.97), and female gender (OR = 1.66) occurred more frequently among patients with this stroke subtype than among the other stroke subtypes combined. Conclusion Different potentially modifiable vascular risk factor profiles were identified for each subtype of ischemic stroke, particularly COPD in the case of atherothrombotic stroke and previous cerebral hemorrhage and hypertension in the case of lacunar infarction.

Internal carotid artery dissection.

Abstract: The purpose of this review is to increase the awareness of internal carotid artery dissection (ICAD), a potentially serious and probably underdiagnosed condition. ICAD is a not uncommon cause of stroke in young patients. ICAD may occur spontaneously or as a result of trauma. However, the "spontaneous" dissection is often preceded by a trivial trauma. The typical patient presents with ipsilateral headache or neck pain, ipsilateral Horner's syndrome and delayed ischemic symptoms from the ipsilateral hemisphere or retina. Conventional angiography, the gold standard for diagnosis, tends to be replaced by non-invasive diagnostic methods. There are no evidence-based guidelines for therapy although anticoagulation is most commonly used. The references are selected from the Medline database for the years 1966-1997.

Cardiovascular dysfunction in multiple sclerosis.

Abstract: Cardiovascular dysfunction (CD) in multiple sclerosis (MS) is related to involvement of reflex pathways in the brainstem. The battery of CD tests was applied to a group of 40 healthy subjects and 40 patients with MS, divided in 2 subgroups according to the expanded disability status scale (EDSS). The tests included: 1) postural blood pressure changes, 2) postural heart rate changes, 3) heart rate changes on inspiration/forced expiration and 4) ECG R-R interval measurement on the Valsalva maneuver. Both groups were subjected to the functional independence scale (FIM). Imaging studies were reviewed and autonomic dysfunction at other levels was explored. The results showed a statistically significant difference (P < 0.05) in all tests when comparing patients to controls. Tests 1 and 4 had the highest significance, with findings of more severe involvement in patients with a higher EDSS and lower FIM. A correlation was also found between CD and brainstem lesions on MRI (P < 0.01). A significant number of MS patients had evidence of CD. Test 1 may be considered a simple marker, in daily clinical practice, to detect subclinical CD. Subclinical CD is a cause of disability in this group of patients.

Ischemic stroke in Korean young adults

Abstract: Objectives To evaluate the characteristics of ischemic stroke in Korean young adults. Material and methods We prospectively studied 149 consecutive patients with acute ischemic stroke aged between 15 to 44 years who were admitted to Asan Medical Center. All patients underwent brain CT/MRI and the majority of them underwent cerebral anglogram, echocardiography and laboratory studies for coagulopathy and vasculitis. Stroke subtypes were classified according to TOAST criteria. Results In our study, men (75.2%) significantly outnumbered women. Stroke subtypes were: large artery atherosclerosis 20.8%), small artery occlusive disease 17.4%), cardioembolism 18.1%, undetermined causes 16.8%, and other determined etiologies 26.8%. The prevalence of hypertension, cigarette smoking and habitual alcohol consumption was significantly higher in men than in women. Conclusions Compared to the western studies, the deviation of sex ratio and the relative proportion of large artery atherosclerosis/small artery occlusion was higher. Heavy exposure to risk factors such as hypertension and cigarette smoking in Korean young men may explain these differences.

Is there any change of stroke incidence during Ramadan

Abstract: Ramadan is a special month for Muslims, as fasting during Ramadan is a religious duty In this study we investigated whether stroke incidence differs during Ramadan compared to other months All patients with stroke admitted to any hospital in the Isparta Province between 1991-1995 were included in this study Patients were divided into 2 groups according to the month of onset of stroke The first group included patients with strokes that occurred in Ramadan and the second group strokes with onset in other months The stroke incidence of Isparta has been found to be 137 per 100,000 for people older than 25 years There were no statistically significant differences between the age and sex distribution of patients and the incidences of strokes in both groups We concluded that fasting during Ramadan has no affect on stroke occurrence in the Isparta Province

Transient autonomic nervous system dysfunction during hyperacute stroke.

Abstract: Forty-four patients suffering a stroke for the first time were examined within 10 h of the onset of symptoms; the tests performed on their admission to hospital, and thereafter on the third and seventh day, were 24-h Holter EKG with spectral analysis of heart rate variability, evaluation of arterial blood pressure and the levels of catecholamine in the blood and 24-h urine. The dynamic EKG on admission revealed that 31 (70.5%) out of the 44 patients already had arrhythmia. These alterations were observed in 9 (75%) out of 12 haemorrhagic patients with a significant (P < 0.05) prevalence compared to 22 (68.8%) of the 32 ischaemic ones. Arrhythmia showed up in 16 (76.2%) out of 21 cases with right hemisphere lesions and in 12 (63.2%) out of 19 cases of left hemisphere lesions; this difference was also significant (P<0.05). Arrhythmia was still present in 19 (43.2%) patients after 3 days and only in 2 (6.5%) patients after 7 days. The spectral analysis parameters on admission and after 3 days were significantly (P < 0.05) modified in patients with stroke plus arrhythmia, compared to patients with stroke alone and to control subjects, whereas no further differences were observed on the seventh day. Moreover, the percentage of patients with arterial hypertension and high levels of catecholamine greatly decreased from the third day onwards. A transient autonomic nervous system imbalance with prevalent sympathetic activity may justify this cardiovascular impairment during the hyperacute phase of stroke.

Cerebrospinal fluid C3 and C4 indexes in immunological disorders of the central nervous system.

Abstract: Objectives - Validation of cerebrospinal fluid (CSF) indexes as a measure for intrathecal C3 and C4 production. Examination of their role in differential diagnosis of immunological disorders of the central nervous system (CNS). Material and methods - Correlative study in controls (low back pain without disk herniation) between the CSF/serum ratio (Q) for albumin, and Q C3 and Q C4. Comparative study of C3 and C4 indexes in patients with CNS dysfunction due to relapsing-remitting (RR) multiple sclerosis (MS), secondary progressive (SP) MS, systemic lupus erythematosus (SLE), and human immunodeficiency virus (HIV) infection. Results - Strong and statistically highly significant correlations between Q albumin and Q C3 (r=0.89, P=0.0001), and Q C4 (r=0.68, P=0.0001). In MS patients decreased mean values for serum (RR, SP) and CSF (RR) C3, and increased C3 index mean value (RR, SP). In CNS SLE increase of mean C3 and C4 index values. In CNS HIV increase of mean C3 and C4 index values, and CSF C3 and C4 concentrations. Most individual index values were within the reference range. Conclusion -CSF index is a valid tool to detect intrathecal C3 or C4 production. C3 or C4 index contributes little to the differential diagnosis of immunological CNS disorders. C3 might play a pathogenic role in various immunological CNS disorders.

Quality of life and memory performance in patients with temporal lobe epilepsy

Abstract: Objective - To explore the contribution of memory performance to quality of life (QOL) in patients with left or right temporal lobe epilepsy (TLE). Subjects and methods - Sixty-five patients with left or right TLE compiled the QOL in Epilepsy-89 Inventory (QOLIE-89), the State-Trait Anxiety Inventory (STAI) and the Hopelessness Scale (BDI) for self-evaluation of QOL and mood. Memory was assessed by tests of verbal and non-verbal memory and the Questionnaire of Memory Efficiency (QME). A neuropsychological battery was also administered to assess general intelligence, attention, visual perception, language, set shifting, word fluency and conceptual-motor tracking. Results - On factor analysis, the neuropsychological battery and mood scales consisted of six factors (Memory, Mental Speed, Mood, Praxis, Sorting and Perception), while the QOLIE-89 consisted of five factors (Psychosocial Satisfaction, Epilepsy-Related Effects, Role, Physical Performance, Cognition). On regression analysis, overall QOLIE-89 score was predicted by the factor Mood and QME score. The QOLIE-89 factor Cognition was predicted by QME score and the Memory, Mental Speed, Perception and Praxis factors of the neuropsychological battery. Conclusion - In TLE patients self-reported memory, as assessed by QME, is an important predictor of QOL, and also correlates with performance on memory tests. This suggests that memory improvement by specific training may help to improve QOL in these patients.

Cholinesterase inhibitors, β‐amyloid precursor protein and amyloid β‐peptides in Alzheimer's disease

Abstract: The extracellular deposition of amyloid beta-peptide (Abeta) in the form of cerebrovascular amyloid and extracellular plaques is one of the major neuropathological manifestations of Alzheimer's disease (AD). Abeta is generated proteolytically from the large beta-amyloid precursor protein (APP). APP is cleaved by a group of proteases called "secretase" to generate soluble derivatives of APP (sAPP), which are secreted in human plasma, CSF and cultured cells. Neurochemically, there is a severe loss of cholinergic neurons and a decreased synthesis of acetylcholine in neocortex in AD. Current approved AD drugs, such as aricept and tacrine, are based on the use of cholinesterase inhibitors (ChEIs) and have been reported to improve memory deficits and cognitive decline in some patients with AD. To compare the effects of ChEIs on APP processing, we have tested a series of ChEIs such as tacrine, physostigmine, metrifonate, phenserine and cymserine in cultured human neuroblastoma cells. We analyzed levels of sAPP by immunochemical techniques with APP-specific antibodies and assayed levels of Abeta by a sensitive sandwich ELISA. Based on these results, ChEIs can be divided into three groups: the first group of ChEIs had no effect on sAPP secretion, the second decreased the sAPP secretion only, and third group affected the secretion of sAPP and Abeta. The difference in the action of metrifonate, physostigmine, phenserine and tacrine on APP processing is independent of their selectivity for the cholinesterase enzymes. This possibly is due to the different targets that are used by ChEIs. Studying the effects of ChEIs on different targets is useful to maximize the benefit of ChEIs for the treatment of AD subjects.

High suicidal ideation in persons testing for Huntington's disease.

Abstract: This study examined the first participants who registered for the Huntington's disease predictive testing program 1990-1995 in Stockholm, Sweden. A psychosocial investigation was performed to evaluate potential effects of the presymptomatic testing. The results showed no significant differences between 13 gene carriers and 21 noncarriers in pretest attitudes, expectations, general well-being, life satisfaction and lifestyle, the need for support, estimated sense of wellbeing or degree of health. However, both groups showed high suicidal ideation and self-injurious behavior. Noncarriers had a very high frequency of attempted suicide, and both groups had similarly pronounced psychiatric dysfunction. Their relatives also had high frequencies of psychiatric diseases, suicide or suicidal attempts. Most of the participants had a desire to meet a psychologist or a social worker. The need for counseling, using a well designed protocol, and the importance of focusing on suicide risk of participants in predictive testing programs is emphasized.

Postural disturbance in patients with normal pressure hydrocephalus.

Abstract: The postural function in 52 patients with normal pressure hydrocephalus (NPH) and in 19 patients with subcortical arteriosclerotic encephalopathy (SAE) was analysed bedside and in 17 of the NPH, 10 of the SAE and 23 healthy individuals (HI) also examined with a force platform. At the bedside examination, no differences in postural functions between NPH and SAE patients were found. The NPH patients improved more in the postural than in motor functions after shunt surgery. The NPH patients had a larger sway area and a higher backward directed velocity of centre of pressure than HI. The direction of the inclination in the sagittal plane was neutral or forward in the NPH and the SAE patients while it was backward in HI. The postural function was better in positions with open eyes in all 3 groups, but significantly less in the NPH patients, indicating a misinterpretation of afferent visual stimuli in the brainstem postural centre.

Immediate causes of death of demented and non-demented elderly.

Abstract: Objective - To investigate the immediate causes of death, in autopsied demented and non-demented elderly. Design - Retrospective clinicopathologic correlations. Setting - Acute and intermediate care geriatric hospital. Participants - 342 hospitalized demented and non-demented elderly (mean age 84.94 ± 6.9 years) who underwent consecutive post-mortem examinations: 120 demented patients with either vascular dementia (VaD, n = 34), mixed dementia (MD, n = 65) or Alzheimer's disease (AD, n = 21) neuropathologically confirmed and 222 non-demented elderly. Results - Primary causes of death were similar in both demented and non-demented patients; the commonest were cardiovascular disease and bronchopneumonia. Cardiac causes of death and especially cardiac failure were more frequent in VaD than in AD or MD (respectively P = 0.027 and 0.005). Dementia was an underlying but never a primary cause of death, Conclusions - Immediate causes of death are similar in elderly demented and non-demented patients.

Unawareness of deficits after right hemisphere stroke: double-dissociations of anosognosias.

Abstract: Objectives - The aim was to study whether anosognosia for hemiparesis, anosognosia for neglect and general unawareness of illness double-dissociate, indicating that anosognosias are specific and independent impairments of awareness. On the other hand, anosognosias may be associated with one another and with general cognitive dysfunction, which decreases awareness of deficits. The persistence and predictive value of anosognosias was examined during a 1-year follow-up. Patients and methods - Fifty-seven consecutive patients with acute right hemisphere infarction underwent neurological and neuroradiological examinations, neuropsychological testing and an interview 10 days, 3 months and 1 year after onset. Results - Anosognosia for neglect and anosognosia for hemiparesis double-dissociated, as did unawareness of illness and anosognosia for neglect. Patients showing unawareness of illness or anosognosia for neglect and anosognosia for hemiparesis had poorer orientation and verbal memory than patients who were aware of these defects. Unawareness of illness and anosognosia for hemiparesis disappeared during 3-month follow-up. Conclusion - Double-dissociations demonstrate that anosognosias for different defects are independent and specific impairments of awareness, although general cognitive disorder may also reduce awareness of defects. Unawareness of illness and anosognosia for hemiparesis disappear rapidly and can hardly be direct causes of poor long-term recovery. However, transient anosognosia may be associated with persistent disorders which result in poor outcome.

Autoimmune diseases in families of French patients with multiple sclerosis.

Abstract: Multiple sclerosis (MS) is associated with autoimmune disorders (AIDs) in individual patients, and limited data suggest a possible familial association of MS and AIDs; however, no systematic study has been conducted on the occurrence of AIDs in the families of MS patients. Using a standardized interview focused on AIDs, we obtained the family histories of 357 consecutive patients from our MS clinic. Adequate information was obtained on 1971 first-degree relatives. Fifty-five patients (15.4%) had first-degree relatives with MS (n=22, 6.2%) another AID (n = 30, 8.4%), or both (n = 3, 0.8%). In 16 families (4.5%), at least 3 first-degree relatives had MS or another AID. MS, Grave's disease, rheumatoid arthritis, vitiligo, type 1 insulin-dependent diabetes mellitus, and uveitis, were the most common AIDs in these families. Such multiplex families (families with MS plus AID) are appropriate for identifying susceptibility genes that may be common to MS and other AIDs.

Cognitive outcome after bacterial meningitis.

Abstract: Objective - To evaluate long-term cognitive deficits in unselected patients with previously diagnosed meningitis and to compare these deficits to neurologic and psychopathologic impairment. Patients and methods -Twenty-two unselected patients (mean age 52.5 ± 17.1 years) were examined neurologically, psychiatrically, and psychometrically 30 ± 11 months after the acute stage of bacterial meningitis. Results of psychometric tests were compared with clinical long-term deficits. Psychometric tests were additionally applied on 17 healthy controls (mean age 49.2 ± 14.2 years). Results - Neurologic or psychopathologic symptoms were found in 16 patients. Psychometrically, the speed of cognitive processes and psychomotor performance, concentration, visuoconstructive capacity, and memory functions were reduced significantly in patients as compared to controls. Verbal intelligence was less affected than performance efficiency. Patients with pneumococcal meningitis had significantly lower test results than patients with other pathogens. The psychometric test results were only slightly related with clinical findings of the follow-up examination. Conclusion -Psychometric deficits are frequent after bacterial meningitis, and their relation with neurologic and psychopathologic symptoms is loose. The pattern of neuropsychologic impairment accentuates psychomotor slowing combined with memory disturbances, and resembles features observed in subcortical cognitive impairment.

Effects of lamotrigine on nocturnal sleep, daytime somnolence and cognitive functions in focal epilepsy

Abstract: Objectives - The aim of our study was to evaluate possible changes in nocturnal sleep, daytime somnolence and cognitive functions induced by add-on therapy with lamotrigine (LTG). Material and methods -Thirteen patients affected by seizures resistant to common antiepileptic drugs (AEDs) underwent nocturnal polysomnographic monitorings, daytime somnolence evaluations and a neuropsychological battery before and after 3 months of treatment with LTG. Results - With LTG therapy we observed a significant increase in REM sleep and a significant reduction in the number of entries into REM and stage shifts. No significant correlation was observed between the decrease in nocturnal epileptiform activity and the increase in REM sleep. Other sleep parameters were unmodified. No significant changes were observed in daytime somnolence and in cognitive performances. Conclusion - LTG may produce positive effects on epileptic seizures and interictal abnormalities without interfering negatively on REM sleep, with improvement of sleep stability and without changes in daytime somnolence and neuropsychological performances. For these reasons it could be an important drug for improving epileptic patients' quality of life.

Motor and cognitive functions in newly diagnosed adult seizure patients before antiepileptic medication

Abstract: Objective– Motor and cognitive functions in patients with partial or generalized onset of seizures were evaluated prior to the adminstration of antiepileptic medication. Material and methods– Motor function, attention and memory of 52 consecutive newly diagnosed adult patients with partial or generalized seizures were assessed with neuropsychological tests. Results– Patients with partial onset of seizures did not differ from patients with generalized seizures in tests of motor function or attention, nor in tests of learning and memory. Compared to controls patients with epilepsy performed significantly worse on visual motor tasks, mental flexibily and in delayed visual memory. Within the patient group as a whole lower education, higher age and symptomatic epilepsy with more abnormal CT scan findings tended to associate with worse performance in tests of concentration and mental flexibility and tests of memory. Conclusion– These findings indicate that newly diagnosed adult patients with partial or generalized onset of seizures prior to treatment with antiepileptic medication experience some problems in visual motor tasks, mental flexibility and memory even without the numerous risk factors for cognitive deficits in epilepsy. In newly diagnosed patients with epilepsy as a whole symptomatic etiology was associated with somewhat more pronounced cognitive problems.

Acetylcholinesterase-amyloid-β-peptide interaction and Wnt signaling involvement in Aβ neurotoxicity

Abstract: Previous studies have indicated that acetylcholinesterase (AChE) promotes amyloid-β-peptide (Aβ) fibril formation and AChE-Aβ complexes increase Aβ-dependent neurotoxicity. Here we present evidence for the: i) identification of the AChE motif that promotes amyloid formation, ii) in vivo effect of AChE on brain plaque formation, and iii) connection between AChE-Aβ neurotoxicity and the Wnt signal transduction pathway. Computer modeling, stereotaxic infusions and cell biological techniques were used to study the above problems. Results indicated that a 3.4 kDa AChE peptide promotes Aβ fibril formation. AChE infusion into rat hippocampus determines the appearance of anti-Aβ and thioflavine-S positive plaques, and AChE-Aβ toxicity on hippocampal cultures was blocked by lithium, an activator of the Wnt cascade. We suggest that AChE-Aβ/Aβ dependent neurotoxicity may result in loss of function of Wnt signaling components, and open the possibility that lithium may be considered as a candidate for therapeutic intervention in Alzheimer's disease pathology.