Amyloid-β oligomers in cerebrospinal fluid are associated with cognitive decline in patients with Alzheimer's disease

Oligomers of the amyloid-β peptide (Aβ) are thought to be the most toxic form of Aβ and are linked to the development of Alzheimer's disease (AD). Here, we used a flow cytometric approach for the detection and assessment of oligomers in cerebrospinal fluid (CSF) from AD patients and other neurological disorders. 30 CSF samples from patients suffering from AD (n = 14), non-demented controls (n = 12), and other neurological disorders (dementia with Lewy bodies, n = 2; vascular dementia, n = 1; primary progressive aphasia, n = 1) were analyzed for the presence of Aβ-oligomers by flow cytometry. The CSF levels of total tau (t-tau), phosphorylated tau (p-tau), and amyloid-β (Aβ)42 were determined using ELISA. CSF Aβ-oligomer levels in AD patients were elevated in comparison to the non-AD group (p = 0.073). The ratio Aβ-oligomers/Aβ42 was significantly elevated in AD subjects compared to non-AD subjects (p = 0.001). Most important, there was a negative correlation between the amount of Aβ-oligomers and the Mini-Mental Status Exam score (r = -0.65; p = 0.013) in AD patients. The detection of Aβ-oligomers using flow cytometry analysis seems to be useful in assessing the stage of AD. This is a novel and important finding as none of the currently used CSF biomarkers are clearly associated with dementia severity.     

α-Synuclein Interacts with Lipoproteins in Plasma

Parkinson’s disease (PD) is an age-related neurodegenerative disorder characterized by dopaminergic neural cell death in the substantia nigra of the brain and α-synuclein (α-syn) accumulation in Lewy bodies. α-Syn can be detected in blood and is a potential biomarker for PD. It has been shown recently that α-syn can pass through the blood-brain barrier (BBB), but the mechanism is not yet understood. We hypothesized that α-syn could interact with lipoproteins, and in association with these particles, could pass through the BBB. Here, we show that apoE, apoJ, and apoA1, but not apoB, were co-immunocaptured along with α-syn from human blood plasma, suggesting that α-syn is associated with high-density lipoproteins (HDL). This association was also supported by experiments involving western blotting of plasma fractions separated by gel filtration, which revealed that α-syn was found in fractions identified as HDL. Interestingly, we could also detect α-syn and ApoJ in the intermediate fraction between HDL and LDL, referred to as lipoprotein (a) (Lp(a)), which has an important role in cholesterol metabolism. Overall, the results provide best support for the hypothesis that α-syn interacts with HDL, and this has potential implications for transport of α-syn from the brain to peripheral blood, across the BBB.     

Is treatment with growth hormone effective in children with cerebral palsy?

Children with cerebral palsy (CP) often have poor linear growth during childhood, resulting in a diminished final adult height. Here we report a female with CP and short stature but without growth hormone (GH) deficiency who exhibited increased growth during treatment with GH. We also report two other children with CP who were treated with GH: one female with a history of leukemia, and a male with Klinefelter syndrome. These two children were both found to be GH-deficient by insulin provocative GH testing and responded to treatment with increased growth rate. Growth improved to a greater extent in the two children with apparent GH deficiency. In summary, it is felt that GH therapy might be beneficial for children with CP and warrants further investigation.     

Does the risk of developing dementia increase with the number of episodes in patients with depressive disorder and in patients with bipolar disorder?

OBJECTIVE: Several findings suggest that some patients with depressive or bipolar disorder may be at increased risk of developing dementia. The present study aimed to investigate whether the risk of developing dementia increases with the number of affective episodes in patients with depressive disorder and in patients with bipolar disorder. METHODS: This was a case register study including all hospital admissions with primary affective disorder in Denmark during 1970-99. The effect of the number of prior episodes leading to admission on the rate of readmission with a diagnosis of dementia following the first discharge after 1985 was estimated. A total of 18,726 patients with depressive disorder and 4248 patients with bipolar disorder were included in the study. RESULTS: The rate of a diagnosis of dementia on readmission was significantly related to the number of prior affective episodes leading to admission. On average, the rate of dementia tended to increase 13% with every episode leading to admission for patients with depressive disorder and 6% with every episode leading to admission for patients with bipolar disorder, when adjusted for differences in age and sex. CONCLUSION: On average, the risk of dementia seems to increase with the number of episodes in depressive and bipolar affective disorders.     

Is Taste Altered in Patients with ALS?

Amyotrophic lateral sclerosis (ALS) is a degenerative neurological disease that affects the motor systems in patients but also may affect some sensory systems. Some ALS patients report taste changes that may decrease their oral intake and nutritional status. This study examined whether focal taste damage occurs in ALS patients compared to age/gender-matched adult healthy controls. An abbreviated Spatial Taste Test was administered to the fungiform and circumvallate papillae. Compared to healthy controls, ALS patients exhibited significantly lower taste intensities across the four basic tastes and significantly lower taste intensities at both the fungiform and vallate papillae, but no significant difference in whole mouth taste intensities. Seven out of nine ALS patients with self reported altered taste had tongue fasciculations, involuntary movements within the tongue dorsum due to lower motor neuron impairment (a common sign of bulbar ALS). Additionally, for patients taking riluzole taste perception at the fungiform papillae appears to be further reduced relative to the vallate papillae. This study suggests ALS decreases taste at both the fungiform and vallate papillae. In addition, riluzole may further damage the chorda tympani. Further studies need to be conducted to examine the etiology for taste loss.     

Heatstroke in patients with Parkinson’s disease

We present two Parkinson's disease (PD) patients, who experienced heatstroke. Both patients manifested central nervous system dysfunction with elevated core temperature. Despite adequate lowering of the body temperature, multiorgan-dysfunction syndrome including encephalopathy, rhabdomyolysis, acute renal failure, acute respiratory failure, and disseminated intravascular coagulopathy was noted in one patient, leading to permanent neurologic damage. Because the ensuing multiorgan dysfunction could determine the functional prognosis in heatstroke patients, it is important to provide information about the prevention of heatstroke to patients, who are isolated or are severely disabled in the advanced stages of PD.     

Is EEG useful in assessing patients with acute encephalitis treated with acyclovir?

EEG has been used widely in diagnosing encephalitis, as it demonstrates rather typical abnormalities, especially in herpes simplex virus encephalitis (HSVE). We analysed 204 EEG recordings from 98 consecutive acyclovir-treated patients with acute encephalitis between 1984 and 1994. Periodic complexes (PC) in the acute phase predicted poor outcome (Kendall tau 0.40, P<0.001). However, unlike in many other diseases, e.g. stroke and intracerebral haemorrhage, the diffuse slowing of the background activity at acute phase did not predict outcome (Kendall tau −0.6, P=0.35). At follow-up, the emergence of diffuse slow background activity was significantly associated with a less favourable outcome (Kendall tau 0.33, P=0.0016). Among clinical variables, only epileptic seizures early during the course of the disease correlated significantly with outcome. EEG does have value as a prognostic indicator in acute encephalitides, but it seems that diffuse slowing of background activity or irritative features acutely are not as important as previously thought, based on the experiences of the pre-acyclovir era.     

Predictors of treatment outcome in adults with ADHD treated with OROS® methylphenidate

Background

We conducted a post-hoc analysis of the Long-Acting MethylpheniDate in Adult attention-deficit hyperactivity disorder (LAMDA) study to investigate predictors of response in adults with ADHD randomly assigned to Osmotic Release Oral System (OROS)^®-methylphenidate hydrochloride (MPH) 18, 36 or 72 mg or placebo.

Methods

LAMDA comprised a 5-week, double-blind (DB) period, followed by a 7-week, open-label (OL) period. A post-hoc analysis of covariance and a logistic regression analysis were undertaken to detect whether specific baseline parameters or overall treatment compliance during the double-blind phase contributed to response. The initial model included all covariates as independent variables; a backward stepwise selection method was used, with stay criteria of p < 0.10. Six outcomes were considered: change from baseline CAARS:O-SV (physician-rated) and CAARS:S-S (self-report) scores at DB and OL end points, and response rate (≥ 30% decrease in CAARS:O-SV score from baseline) and normalization of CAARS:O-SV score at DB end point.

Results

Taking into account a significant effect of OROS^®-MPH treatment versus placebo in the original analysis (p ≤ 0.015), across the outcomes considered in this post-hoc analysis, higher baseline CAARS scores were most strongly predictive of superior outcomes. Male gender and lower academic achievement were also predictive for improved results with certain outcomes.

Conclusions

Several baseline factors may help to predict better treatment outcomes in adults receiving OROS^®-MPH; however, further research is required to confirm these findings and examine their neurobiological underpinnings.     

Is depression associated with microvascular disease in patients with type 2 diabetes?

We hypothesize that late-life depression is a manifestation of microvascular disease in patients with type 2 diabetes. We conducted a clinic-based cross-sectional study, comparing retinal vascular caliber, a marker of microvascular disease, in participants with type 2 diabetes with major depression (n=34), without depression (n=27) and healthy non-diabetic controls (n=38). Retinal vascular caliber was measured from digital retinal photographs using a validated computer-assisted method. After adjusting for age and gender, there was a trend of increasing retinal arteriolar caliber from healthy controls (132.6 microm), to diabetic patients without depression (139.2 microm), and diabetic patients with major depression (145.3 microm, P=0.008). The trend in retinal arteriolar caliber remains significant after adjusting for duration of diabetes, but not after further adjusting for vascular risk factors. Our findings suggest that there is variation in the retinal vascular caliber between type 2 diabetic patients with and without major depression and non-diabetic controls. This variation was largely related to poorer diabetes control and a higher frequency of vascular risk factors in diabetic patients, particularly those with depression. Studies with larger sample size may provide further insights into this association.     

Is hyperlipidemia correlated with longer survival in patients with amyotrophic lateral sclerosis?

Amyotrophic lateral sclerosis (ALS) is the most serious form of degenerative motor neuron disease in adults, whose relentless course leads to death within 2-5 years, generally due to respiratory failure. Apart from the age and site of onset, no other factors have consistently demonstrated to be related to the ALS outcome. The aim of the study was to investigate the influence of fasting serum lipid levels (cholesterol and triglycerides) and the body mass index (BMI) at the time of diagnosis on survival in ALS patients. The study included 82 patients with ALS residing in the Belgrade area who were diagnosed with ALS over a time period of 4 years (2006-2009). Survival was assessed by the Kaplan-Meier method. In this retrospective study, 39 (47.56%) patients had normal values of lipids and 43 (52.43%) patients had hyperlipidemia. The mean survival time from the onset of symptoms for patients with normal lipidemia was 4.21 ± 0.5 years, while the mean survival time from the onset of symptoms for patients with hyperlipidemia was 5.0 ± 0.67 years (P = 0.36). We also did not register a significant difference in survival in relation to gender, the site or age of onset, even though we noticed a longer survival in patients with hyperlipidemia in all of the examined groups, especially in the group of younger patients, with the onset of the disease before the age of 45 years. If we take into account the fact that BMI is pathophysiologically associated with cholesterol and triglyceride serum levels, the results in our study complement each other showing that patients with a higher BMI, registered in 28.8% of the cases, do not live longer. Our findings show that hyperlipidemia, which we found in 52.43% of our ALS patients, at the time of diagnosis, is not related to significantly longer survival.     

Correlation of glucose metabolism in brain cells and brain morphological changes with clinical typing in children with cerebral palsy

INTRODUCTION Cerebral palsy of children is a non-processing brain injury which is caused by various factors before and 1 month after birth. The main symptoms are central motor disorder and postural abnormality, which are always combined with dysnoesia and…     

Intravenous immunoglobulin in children with Guillain-Barré syndrome

We report our experience with intravenous immunoglobulin (IVIG), plasmapheresis and supportive care in 13 patients with the Guillain-Barré syndrome. Seven of 13 patients received IVIG, 2 plasmapheresis and 4 supportive care. At 15th day after IVIG administration, all patients in this group had improved at least one disability grade. In the plasmapheresis group, 1 improved at 5th day after the procedure. Two of the 4 patients that received supportive care improved at 20th day of evaluation. In the IVIG group, the final scores were lower and had no relapses. These results suggest faster clinical improvement with IVIG when compared with supportive measures.     

Is dementia reversible in patients with neurocysticercosis?

OBJECTIVE: To determine the correlates and outcome of dementia in patients with neurocysticercosis (NCC). METHODS: Ninety consecutive patients with untreated NCC underwent a cognitive assessment (Mini-mental State Examination, Neurobehavioral Cognitive Status Examination, and IQCODE) and were classified as having or not having dementia according to DSM-IV criteria. Imaging and cerebrospinal fluid examination data were recorded. The cognitive measures were repeated six months after treatment with albendazole and steroids. RESULTS: At the initial evaluation 15.5% (n = 14) of the patients were classified as having dementia. Dementia was associated with older age, lower education level, increased number of parasitic lesions in the brain (mostly in the frontal, temporal, and parietal lobes). After six months, 21.5% of the patients from the dementia group continued to have a full dementia disorder and 78.5% no longer fulfilled the DSM-IV criteria for dementia, although some of these patients still showed mild cognitive decline. CONCLUSIONS: The results of this study suggest that dementia occurs frequently in patients with untreated NCC, and it is reversible in most cases.     

Electrophysiological evaluation in 4 patients with diabetic pseudotabes

BACKGROUND: Researches on diabetic nervous system lesion are mainly focus on peripheral nerve and vegetative nerve, so there are few investigations on diabetic pseudotabes. OBJECTIVE: To investigate the electrophysiological examinations on the diagnosis of diabetic pseudotabes. DESIGN: Case study. SETTING: Department of Electrophysiology and Department of Neurology, Zhongshan Hospital Affiliated to Xiamen University. PARTICIPANTS: A total of 4 patients with type 2 diabetes mellitus, including 3 males and 1 female aged from 50 to 72 years, were selected from Department of Neurology, Zhongshan Hospital Affiliated to Xiamen University from March 2002 to February 2005. All accepted subjects met the modified diagnostic criteria of diabetes mellitus, which was set by American Diabetes Mellitus Association (ADA) in 1997. Otherwise, the subjects had typical symptoms and physical signs of spinal posterior funiculus damage. However, patients with spinal cord lesion which was caused by other factors were excluded. All accepted subjects provided the confirmed consent. METHODS: Nicolet NT electromyography (EMG)/evoked potential meter (made in the USA) was used to detect spinal cord conduction velocity (SCCV), somatosensory evoked potential (SEP) of lower limbs, motor nerve conduction velocity (MNCV) and sensory nerve conduction velocity (SNCV) of extremities. Determining criteria: Measurements were performed based on the laboratory standards. SCCV, which was less than lower limit of normal value (T2–12: 40–55 m/s, T12–L4: 20–41 m/s, T2–L4: 36–45 m/s), was regarded as abnormal. SEP value of lower limbs: P40, P60 and PF, which were more than standard deviation of normal value (x(—)+2.5), were regarded as the abnormality. Normal value of P40, P60 and PF latencies (x(—)±s) in this study: P40, P60 and PF in males were (37.6±1.9) ms, (59.8±3.9) ms and (7.6±0.9) ms, respectively; meanwhile, those in females were (35.5±1.7) ms, (55.2±2.7) ms and (6.3±0.7) ms, respectively. MNCV and SNCV, which were less than 50 m/s in upper limbs and 40 m/s in lower limbs, were regarded as the abnormality. MAIN OUTCOME MEASURES: Electrophysiological examinations. RESULTS: All 4 patients with type 2 diabetes mellitus were involved in the final analysis. ① SCCV: Among 4 patients, SCCV of three patients was decreased in T2–12, T12–L4 and T2–L4, and that of the other one was decreased in T2–12 and T2–L4; however, SCCV in T12–L4 was normal. There was significant difference as compared with normal value (P < 0.01). ② SEP of lower limbs: SEP values of lower limbs were abnormal in all 4 patients. Among them, P40, P60 and PF latencies of two patients were delayed; P40 of one patient was delayed and PF was not drained out; P40 and P60 of the last one were delayed and PF was normal. ③ MNCV and SNCV: The MNCV and SNCV were normal in one patient and abnormal in three patients. The results demonstrated that MNCV and SNCV of extremities decreased; especially, sensory nerve action potential (SNAP) of both lower extremities of one patient were not drained out. CONCLUSION: Detections of SCCV, SEP of lower limbs, MNCV and SNCV of extremities are helpful to investigate whether peripheral nerve and deep sensory passage are damaged or not and determine whether deep sensory damage is caused by peripheral nerve and spinal posterior funiculus.     

Insight in adults with obsessive–compulsive disorder

The present study examined the clinical correlates of insight among adults with obsessive–compulsive disorder (OCD). One hundred and thirty treatment-seeking adults with a primary diagnosis of OCD, aged 18 to 68 years (mean 31.4 years) participated. Measures of clinical severity, obsessive–compulsive symptom dimensions, anxiety symptoms, depressive symptoms, and ability to resist and control OCD symptoms were obtained. Results indicated that poor insight was positively related to greater OCD symptom severity and poorer ability to resist and control OCD symptoms; this pattern of associations held when insight was examined continuously and categorically (i.e., high versus low insight). Insight was generally not associated with other clinical characteristics, except for a relationship with mental neutralizing behaviors. Insight did not mediate the relationship between the ability to resist and control OCD symptoms and obsessive–compulsive symptom severity. Overall, this study provides further information into the nature and role of insight in adults with OCD.     

Health-related quality of life of children with epilepsy in Hong Kong: How does it compare with that of youth with epilepsy in Canada?

OBJECTIVE: The primary aim of our study was to compare the health-related quality of life (HRQL) of children with epilepsy in Hong Kong with that of children with epilepsy in Canada, and to explore possible factors affecting these findings. A second interest was to determine agreement between proxy reports and self-ratings among children with epilepsy in Hong Kong, compare these with findings in Canada, and identify factors that influence the concordance. METHODS: Child self-report and parent-proxy questionnaires on an epilepsy-specific HRQL measure, appropriately translated and validated in Chinese, were administered to 266 Hong Kong children and their parents. An unpaired t test was used to compare the scores with published results from 381 Canadian children and their parents, who used the original English version of the measure. Demographic characteristics of the two groups were compared using t tests, chi2 tests, and Fisher's exact tests. Agreement between parents' and children's scores was evaluated with intraclass correlation coefficients (ICCs) and standardized response means (SRMs). The total HRQL score differences between parents and children in Hong Kong were compared with those in Canada using an unpaired t test. Factors that might affect the parent-child score difference were studied using Pearson correlation analysis, chi2 test, and analysis of variance. Factors studied included: sex, current age, age at diagnosis, duration of epilepsy, number of antiepileptic drugs used, type of seizure, seizure severity, cognition of the child, the type of school attended, presence of neurological problems, presence of behavioral problems, recent health care usage, education and employment status of both parents, housing status of the family, and relationship of the proxy respondent to the child. RESULTS: (1) In contrast to the Canadian sample, Hong Kong children with epilepsy were older (P<0.01), had a longer duration of epilepsy (P<0.01) and less severe seizures (P<0.01), and were more likely to attend normal schools (P<0.01). Children in Hong Kong reported more interpersonal/social difficulties (P<0.01), more worries (P<0.01), and more secrecy about their epilepsy (P<0.01). Parents in Hong Kong believed that their children perceived more worries (P<0.01) and were more secretive about their epilepsy (P<0.01). (2) Moderate to good agreement between parent-proxy response scores and child self-report scores was demonstrated (ICC=0.50-0.69, SRM=0.19-0.33). The total HRQL score differences between parent and child in Hong Kong were not different from those in Canada. None of the factors studied were related to the parent-child score difference. CONCLUSIONS: Youth with epilepsy in Hong Kong and their parents reported poorer quality of life than children with epilepsy in Canada. Further studies are necessary to identify the determinants of HRQL in children with epilepsy in different cultures. Acceptable agreement between the two ratings suggests that proxy reports can be used when child self-reports cannot be obtained.