Comparison of Partial (.6 mg/kg) versus Full‐Dose (.9 mg/kg) Intravenous Recombinant Tissue Plasminogen Activator Followed by Endovascular Treatment for Acute Ischemic Stroke: A Meta‐Analysis

ABSTRACT

BACKGROUND

In the treatment of acute ischemic stroke, intravenous (IV) recombinant tissue plasminogen (rt‐PA) and intraarterial (IA) interventions are often combined. However, the optimal dose of IV rt‐PA preceding endovascular treatment has not been established.

METHODS

Studies that used combined IV and IA thrombolysis were identified from a search of the MEDLINE, PubMed, and Cochrane databases. We compared the rates of angiographic recanalization, symptomatic intracerebral hemorrhage (sICH), and favorable functional outcome between patients who had been treated with .6 mg/kg IV rt‐PA and those who had received .9 mg/kg rt‐PA.

RESULTS

Eleven studies met our criteria. In 7 studies, .6 mg/kg IV rt‐PA had been administered to 317 patients, whereas 140 patients in 4 studies had received .9 mg/kg of IV rt‐PA. The weighted mean of median National Institutes of Health Stroke Scale score at presentation was 18.3 in the .6 mg/kg group (median range 9‐34), and 17.3 in the .9 mg/kg group (median range 4‐39). Patients in the .9 mg/kg group had higher rates of favorable outcome [odds ratio (OR) = 1.60, 95% confidence interval (CI) = (1.07‐2.40), P= .022] and similar rates of sICH [OR = .86 (95% CI .41‐1.83), P= .70]. Depending on the statistics used, the higher angiographic recanalization rate among patients treated with .9 mg/kg was significant (P= .03, events/trial syntax logistic regression) or borderline significant (P= .07, random effects model).

CONCLUSION

Our analysis suggests that using .9 mg/kg IV rt‐PA prior to IA thrombolysis is safe and may be associated with higher recanalization rates and better functional outcome at 3 months.

     

Reward learning impairment and avoidance and rumination responses at the end of Engage therapy of late‐life depression

Objectives

This study examined the association between reward processing, as measured by performance on the probabilistic reversal learning (PRL) task and avoidance/rumination in depressed older adults treated with Engage, a psychotherapy that uses “reward exposure” to increase behavioral activation.

Methods

Thirty older adults with major depression received 9 weeks of Engage treatment. At baseline and treatment end, the 24‐item Hamilton Depression Rating Scale (HAM‐D) was used to assess depression severity and the Behavioral Activation for Depression Scale (BADS) to assess behavioral activation and avoidance/rumination. Participants completed the PRL task at baseline and at treatment end. The PRL requires participants to learn stimulus‐reward contingencies through trial and error, and switch strategies when the contingencies unexpectedly change.

Results

At the end of Engage treatment, the severity of depression was lower (HAM‐D: t(19) = ?7.67, P < .001) and behavioral activation was higher (BADS: t(19) = 2.23, P = .02) compared to baseline. Response time following all switches (r(19) = ?0.63, P = .003) and error switches (r(19) = ?0.57, P = .01) at baseline was negatively associated with the BADS avoidance/rumination subscale score at the end of Engage treatment.

Conclusions

Impaired reward learning, evidenced by slower response following all switches and error switches, contributes to avoidant, ruminative behavior at the end of Engage therapy even when depression improves. Understanding reward processing abnormalities of avoidance and rumination may improve the timing and targeting of interventions for these symptoms, whose persistence compromises quality of life and increases the risk of depression relapse.

     

Characteristic Neuroimaging in Patients with Tumefactive Demyelinating Lesions Exceeding 30 mm

ABSTRACT

BACKGROUND AND PURPOSE

Features of tumefactive demyelinating lesion (TDL) on magnetic resonance imaging (MRI) can facilitate the differential diagnosis of TDL and neoplastic lesions, but vary considerably among patients. The larger TDL grows, the more difficult it becomes to differentiate TDL from neoplastic lesions. The purpose of this study was to elucidate typical MRI features in 12 patients with large TDL (>30 mm in diameter).

METHODS

We identified 12 patients with large TDL (six men, six women; age range 17‐64 years, median age 27 years) and studied the clinical histories and the results of laboratory and various radiological studies in these patients. All cases of clinically definite multiple sclerosis were diagnosed in accordance with McDonald's revised criteria.

RESULTS

Common MRI features of large TDLs included variable degrees of mass effect (71%) and edema (100%), a T2 hypointense rim (79%), venular enhancement (57%), and peripheral restriction on diffusion‐weighted images (50%). Ring enhancement (38%), open‐ring enhancement (31%), or decreased N‐acetylaspartate ratios on magnetic resonance spectroscopy (22%) were less frequently observed. Brain angiography demonstrated venous dilatations on and around the TDL.

CONCLUSIONS

The diagnosis of large TDL is challenging. Our findings suggest that multiple venous dilatations on and around TDLs on angiography can facilitate diagnosis.

     

Recognition of Human Emotions from Cerebral Blood Flow Changes in the Frontal Region: A Study with Event‐Related Near‐Infrared Spectroscopy

ABSTRACT

BACKGROUNDS AND PURPOSE

The aim of this study is to develop a near‐infrared spectroscopy (NIRS)‐based system that recognizes pleasant and unpleasant human emotions based on cerebral blood flow (CBF) in order to understand the minds of patients whose brain function is severely impaired. The forehead region is easily accessible to NIRS measurements, whereas the role of the anterior prefrontal cortex (PFC) in the processing of emotion remains to be elucidated.

METHODS

Initially, using event‐related NIRS we examined changes in oxygenated hemoglobin (oxy‐Hb) as an indicator of regional CBF changes, which reflect brain activity directly related to emotions, but not to cognitive operations in the anterior frontal regions, during viewing affective pictures. The event‐related potentials (ERPs), systemic blood pressure, and pulse rate were also measured simultaneously.

RESULTS

The event‐related analysis of changes in oxy‐Hb for a 6 s‐picture presentation period showed that very unpleasant emotion was accompanied by an increase in oxy‐Hb in the bilateral ventrolateral PFCs, while very pleasant emotion was accompanied by a decrease in oxy‐Hb in the left dorsolateral PFC. There were no significant differences in either ERPs or autonomic nervous system activities between the two emotional states.

CONCLUSION

These findings suggest the possibility of recognizing patients’ emotions from CBF changes.

     

Is transcranial sonography useful to distinguish scans without evidence of dopaminergic deficit patients from Parkinson's disease?

Background:

Approximately 10% of patients clinically diagnosed with early Parkinson's disease (PD) subsequently have normal dopaminergic functional imaging. Transcranial sonography (TCS) has been shown to detect midbrain hyperechogenicity in approximately 90% of Parkinson's disease (PD) patients and 10% of the healthy population. The aim of this study was to investigate the prevalence of midbrain hyperechogenicity in patients with suspected parkinsonism and scans without evidence of dopaminergic deficit (SWEDD), in comparison to PD patients.

Methods:

TCS was performed in 14 patients with SWEDD and 19 PD patients.

Results:

There was a significantly increased area of echogenicity in the PD group (0.24 ± 0.06 cm²), compared to the group of patients with SWEDD (0.13 ± 0.06 cm²; P < 0.001). One (9.1%) of these patients, compared to 14 (82.5%) of the PD patients, was found to have hyperechogenicity (P < 0.001).

Conclusions:

We conclude that TCS is useful to distinguish PD patients from patients with suspected parkinsonism and SWEDD. © 2012 Movement Disorder Society

     

Disagreeing about development: An analysis of parent‐teacher agreement in ADHD symptom trajectories across the elementary school years

Objectives

It is well‐known that in cross‐sectional analyses, agreement between informants is modest as best when rating attention‐deficit/hyperactivity disorder and other disruptive behaviour disorder symptoms. We here aimed to develop recommendations for the use of multi‐informant data in the context of longitudinal developmental analyses that examine symptom trajectories over time.

Method

Using parallel process modelling, we estimated parent–teacher agreement in inattention and hyperactivity/impulsivity symptom initial levels and slopes across the elementary school years (ages 7, 9, and 11) for a community sample of n = 1,388 youth. We also used these models to examine whether initial levels and slopes differed significantly across informants.

Results

Informant agreement was low to moderate and higher for inattention slopes (r = .47) than for hyperactivity/impulsivity slopes (r = .23). Parents and teachers reported opposite developmental trends for inattention with teachers reporting declines and parents reporting increases over time. Parents reported overall higher levels of hyperactivity/impulsivity, but there were no average informant differences in slopes.

Conclusion

Of the options available, we recommend specifying separate but correlated factors for different informants in developmental analyses of attention‐deficit/hyperactivity disorder. This can be achieved within latent growth curve and growth mixture models.

     

Changes in resting-state brain networks in writer's cramp

Objectives:

Writer's cramp (WC) is characterized by excessive cocontractions of agonist and antagonist hand and forearm muscles during writing. Changes in functional magnetic resonance imaging activation patterns in such conditions can be ambiguous as they might either reflect some aspect of the primary pathophysiological mechanism or, alternatively, may be the result of adaptive actions during task execution. To circumvent this problem, we examined WC patients during rest, i.e., without a task, using independent component analysis (ICA) applied to the blood oxygen level‐dependent time series.

Methods:

Functionally connected brain networks during rest were defined by ICA to assess differences between WC patients (n = 16) and healthy controls (n = 16). Analysis was carried out using FMRIB's Software Library.

Results:

Two functional networks showed between‐group differences, the sensorimotor network and the default‐mode network. In WC patients, the connectivity was reduced in the left postcentral area and increased in basal ganglia in contrast to healthy controls. These changes were not reversed after treatment with botulinum toxin.

Conclusions:

In line with other studies, the results show a dysfunction in cortico‐subcortical circuits in WC involving somatosensory cortex, areas interfacing the sensory and motor systems, and putamen contralateral to symptomatic hand. Hum Brain Mapp, 2012. © 2011 Wiley Periodicals, Inc.

     

Adenosine A2A receptor antagonist istradefylline (KW-6002) reduces "off" time in Parkinson's disease: a double-blind, randomized, multicenter clinical trial (6002-US-005)

Objective

Based on new understanding of nondopaminergic pathways involved in Parkinson's disease (PD) pathophysiology, a selective adenosine A_2A receptor antagonist, istradefylline, shows promise for the treatment of PD.

Methods

Istradefylline (40mg/day) was studied in levodopa‐treated PD subjects experiencing prominent wearing‐off motor fluctuations. At 23 North American sites, 196 subjects were randomized in a double‐blind, 12‐week outpatient clinical trial of istradefylline (114 completing the trial) or placebo (58 completing the trial). The primary efficacy measure was change from baseline to end point in the percentage of daily awake “off” time, recorded by subjects using a patient PD diary. Secondary end points evaluated “on” time (including “on time with dyskinesia”), the Unified Parkinson's Disease Rating Scale, and a Clinical Global Impression–Improvement of Illness score. Clinical laboratory, electrocardiograms, vital signs, and adverse event monitoring comprised the safety monitoring.

Results

After randomization, approximately 88% of subjects completed the double‐blind period. Compared with baseline, the decrease of daily awake “off” time for istradefylline was a mean (± standard deviation) of ?10.8 ± 16.6% (95% confidence interval, ?13.46 to ?7.52) and for placebo, ?4.0 ± 15.7% (95% confidence interval, ?7.73–0.31; p = 0.007 using two‐way analysis of variance). This effect corresponded to changes from baseline in total daily awake “off” time of ?1.8 ± 2.8 hours for istradefylline and ?0.6 ± 2.7 hours for placebo (p = 0.005). Treatment‐emergent adverse effects with istradefylline were generally mild.

Interpretation

Istradefylline was safe, well tolerated, and offered a clinically meaningful reduction in “off” time without increased troublesome dyskinesia. Ann Neurol 2008

     

Hippocampal atrophy patterns in mild cognitive impairment and Alzheimer's disease

Background:

Histopathological studies and animal models suggest that hippocampal subfields may be differently affected by aging, Alzheimer's disease (AD), and other diseases. High‐resolution images at 4 Tesla depict details of the internal structure of the hippocampus allowing for in vivo volumetry of different subfields. The aims of this study were as follows: (1) to determine patterns of volume loss in hippocampal subfields in normal aging, AD, and amnestic mild cognitive impairment (MCI). (2) To determine if measurements of hippocampal subfields provide advantages over total hippocampal volume for differentiation between groups.

Methods:

Ninety‐one subjects (53 controls (mean age: 69.3 ± 7.3), 20 MCI (mean age: 73.6 ± 7.1), and 18 AD (mean age: 69.1 ± 9.5) were studied with a high‐resolution T2 weighted imaging sequence aimed at the hippocampus. Entorhinal cortex (ERC), subiculum, CA1, CA1‐CA2 transition zone (CA1‐2), CA3 & dentate gyrus (CA3&DG) were manually marked in the anterior third of the hippocampal body. Hippocampal volume was obtained from the Freesurfer and manually edited.

Results:

Compared to controls, AD had smaller volumes of ERC, subiculum, CA1, CA1‐2, and total hippocampal volumes. MCI had smaller CA1‐2 volumes. Discriminant analysis and power analysis showed that CA1‐2 was superior to total hippocampal volume for distinction between controls and MCI.

Conclusion:

The patterns of subfield atrophy in AD and MCI were consistent with patterns of neuronal cell loss/reduced synaptic density described by histopathology. These preliminary findings suggest that hippocampal subfield volumetry might be a better measure for diagnosis of early AD and for detection of other disease effects than measurement of total hippocampus. Hum Brain Mapp, 2010. © 2010 Wiley‐Liss, Inc.

     

Association of antidiabetic medication use,cognitive decline,and risk of cognitive impairment in older people with type 2 diabetes: Results from the population‐based Mayo Clinic Study of Aging

Objective

To determine the cross‐sectional and longitudinal associations between diabetes treatment type and cognitive outcomes among type II diabetics.

Methods

We examined the association between metformin use, as compared to other diabetic treatment (ie, insulin, other oral medications, and diet/exercise) and cognitive test performance and mild cognitive impairment (MCI) diagnosis among 508 cognitively unimpaired at baseline type II diabetics enrolled in the Mayo Clinic Study of Aging. We created propensity scores to adjust for treatment effects. We used multivariate linear and logistic regression models to investigate the cross‐sectional association between treatment type and cognitive test z scores, respectively. Mixed effects models and competing risk regression models were used to determine the longitudinal association between treatment type and change in cognitive test z scores and risk of developing incident MCI.

Results

In linear regression analyses adjusted for age, sex, education, body mass index, APOE ε4, insulin treatment, medical comorbidities, number of medications, duration of diabetes, and propensity score, we did not observe an association between metformin use and cognitive test performance. Additionally, we did not observe an association between metformin use and cognitive test performance over time (median = 3.7‐year follow‐up). Metformin was associated with an increased risk of MCI (subhazard ratio (SHR) = 2.75; 95% CI = 1.64, 4.63, P < .001). Similarly, other oral medications (SHR = 1.96; 95% CI = 1.19, 3.25; P = .009) and insulin (SHR = 3.17; 95% CI = 1.27, 7.92; P = .014) use were also associated with risk of MCI diagnosis.

Conclusions

These findings suggest that metformin use, as compared to management of diabetes with other treatments, is not associated with cognitive test performance. However, metformin was associated with incident MCI diagnosis.

     

The Clinical and Radiological Spectrum of Posterior Reversible Encephalopathy Syndrome: A Retrospective Series of 24 Patients

ABSTRACT

BACKGROUND AND PURPOSE

Some patients with posterior reversible encephalopathy syndrome (PRES) present with atypical clinical and neuroimaging findings. The purpose of this study is to review the clinical and neuroimaging findings in patients diagnosed with PRES.

METHODS

We retrospectively included all patients diagnosed with PRES between January 2005 and March 2009. We reviewed demographic, clinical and laboratory data, neuroimaging findings, and prognosis.

RESULTS

Twenty‐four patients were included with a median age of 19 years. The clinical presentations included seizures (91.7%), headache (83.3%), visual disturbance (62.5%), encephalophathy (29.2%), and paralysis (8.3%). Co‐morbidities included systemic lupus erythematous (29.2%), kidney disease (20.8%), eclampsia (20.8%), renal artery stenosis (12.5%), Takayasu arteritis (4.2%), Sheehan's syndrome (4.2%), allergic purpura (4.2%), and acute intermittent porphyria (4.2%). Acute elevation of blood pressure was found in 22 patients (91.7%). Ten patients (41.7%) used steroids or immunosuppressants, three (12.5%) had acute renal failure before the symptoms. Atypical neuroimaging features included involvement of the frontal lobe (54.2%), basal ganglia (4.2%) or cortex (8.3%), and irreversible lesions (3/18, 16.7%).

CONCLUSIONS

A large proportion of patients with PRES may present with atypical neuroimaging findings. Apart from the known risk factors, such as hypertension, immunosuppressants, and renal failure of various etiologies may be the precipitants of PRES.

     

Recurrent spreading depolarizations after subarachnoid hemorrhage decreases oxygen availability in human cerebral cortex

Objective

Delayed ischemic neurological deficit (DIND) contributes to poor outcome in subarachnoid hemorrhage (SAH) patients. Because there is continuing uncertainty as to whether proximal cerebral artery vasospasm is the only cause of DIND, other processes should be considered. A potential candidate is cortical spreading depolarization (CSD)‐induced hypoxia. We hypothesized that recurrent CSDs influence cortical oxygen availability.

Methods

Centers in the Cooperative Study of Brain Injury Depolarizations (COSBID) recruited 9 patients with severe SAH, who underwent open neurosurgery. We used simultaneous, colocalized recordings of electrocorticography and tissue oxygen pressure (p_tiO₂) in human cerebral cortex. We screened for delayed cortical infarcts by using sequential brain imaging and investigated cerebral vasospasm by angiography or time‐of‐flight magnetic resonance imaging.

Results

In a total recording time of 850 hours, 120 CSDs were found in 8 of 9 patients. Fifty‐five CSDs (∼46%) were found in only 2 of 9 patients, who later developed DIND. Eighty‐nine (∼75%) of all CSDs occurred between the 5th and 7th day after SAH, and 96 (80%) arose within temporal clusters of recurrent CSD. Clusters of CSD occurred simultaneously, with mainly biphasic CSD‐associated p_tiO₂ responses comprising a primary hypoxic and a secondary hyperoxic phase. The frequency of CSD correlated positively with the duration of the hypoxic phase and negatively with that of the hyperoxic phase. Hypoxic phases significantly increased stepwise within CSD clusters; particularly in DIND patients, biphasic p_tiO₂ responses changed to monophasic p_tiO₂ decreases within these clusters. Monophasic hypoxic p_tiO₂ responses to CSD were found predominantly in DIND patients.

Interpretation

We attribute these clinical p_tiO₂ findings mainly to changes in local blood flow in the cortical microcirculation but also to augmented metabolism. Besides classical contributors like proximal cerebral vasospasm, CSD clusters may reduce O₂ supply and increase O₂ consumption, and thereby promote DIND. ANN NEUROL 2010;67:607–617

     

Depression and anxiety in chronic heart failure and chronic obstructive pulmonary disease: prevalence,relevance, clinical implications and management principles

Objective

To review evidence regarding the prevalence, causation, clinical implications, aspects of healthcare utilisation and management of depression and anxiety in chronic heart failure and chronic obstructive pulmonary disease.

Design

A critical review of the literature (1994–2009).

Findings

The prevalence of depression and anxiety is high in both chronic obstructive pulmonary disease (8–80% depression; 6–74% anxiety) and chronic heart failure (10–60% depression; 11–45% anxiety). However, methodological weaknesses and the use of a wide range of diagnostic tools make it difficult to reach a consensus on rates of prevalence. Co‐morbid depression and anxiety are associated with increased mortality and healthcare utilisation and impact upon functional disability and quality of life. Despite these negative consequences, the identification and management of co‐morbid depression and anxiety in these two diseases is inadequate. There is some evidence for the positive role of pulmonary/cardiac rehabilitation and psychotherapy in the management of co‐morbid depression and anxiety, however, this is insufficient to guide recommendations.

Conclusions

The high prevalence and associated increase in morbidity and mortality justifies future research regarding the management of anxiety and depression in both chronic heart failure and chronic obstructive pulmonary disease. Current evidence suggests that multi‐faceted interventions such as pulmonary and cardiac rehabilitation may offer the best hope for improving outcomes for depression and anxiety. Copyright © 2009 John Wiley & Sons, Ltd.

     

Predicting health‐related quality of life 2 years after moderate‐to‐severe traumatic brain injury

Aims

To describe health‐related quality of life (HRQL) 2 years after moderate‐to‐severe traumatic brain injury (TBI) and to assess predictors of HRQL.

Materials and methods

A prospective cohort study of 91 patients, aged 16–55 years, admitted with moderate‐to‐severe TBI to a trauma referral centre between 2005 and 2007, with follow‐up at 1 and 2 years. Mean age was 31.1 (SD = 11.3) years, and 77% were men. Injury severity was evaluated by the Glasgow Coma Scale (GCS), head CT scan (using a modified Marshall Classification), Injury Severity Score (ISS) and post‐traumatic amnesia (PTA). The Functional Independence Measure (FIM), Community Integration Questionnaire (CIQ), Beck Depression Inventory (BDI) and Medical Outcomes 36‐item Short Form Health Survey (SF‐36) were administered at follow‐up visits. The main outcome measures were the Physical Component Summary (PCS) and Mental Component Summary (MCS) of the SF‐36.

Results

HRQL appears to be relatively stable between 1 and 2 years after injury. In the multivariate linear regression, younger age (β = ?0.20, P = 0.032), more severe TBI (β = 0.28, P = 0.016), more severe overall trauma (β = 0.22, P = 0.026), higher levels of community integration (β = 0.36, P = 0.019) and higher positive change in PCS scores from 1 to 2 years (β = 0.41, P < 0.001) predicted better self‐reported physical health 2 years post‐TBI. Lower scores for depression (β = ?0.70, P < 0.001) and a higher positive change in MCS scores (β = 0.62, P < 0.001) predicted better self‐reported mental health.

Conclusions

Future interventions should focus on aspects related to HRQL that are more easily modified, such as physical functioning, home and social integration, productivity, and mental and emotional status.

     

An entorhinal cortex sulcal pattern is associated with Alzheimer's disease

Objectives:

Magnetic resonance (MRI) studies rely on sulcal boundaries to delineate the human entorhinal cortex (EC) and typically show that EC size is reduced in Alzheimer's disease (AD) and a predictor of future dementia. However, it is unknown if variations in the EC sulcal patterns are associated with AD. We classified the lateral EC sulcal boundary as either a rhinal or collateral pattern and tested the hypotheses that the rhinal pattern was (1) more common in AD and (2) associated with a smaller EC size.

Experimental Design:

MRI was used to determine the prevalence of the rhinal and collateral EC patterns in 421 subjects (212 AD, 107 old normal (ONL), and 102 young NL (YNL). Anatomical validation studies of normal subjects were conducted at postmortem in 34 brain hemispheres and in vivo with 21 MRI volume studies. EC pattern reliability was studied with MRI in both cross‐sectional and longitudinal designs.

Principal Observations:

The rhinal pattern was more frequent in the right hemisphere in AD (47%) compared with ONL (28%, odds ratio = 2.25, P = 0.001). EC pattern was not related to ApoE genotype. The validations showed that the EC sulcal pattern was not associated with the neuronal number, surface area, or volume of the EC. In patients with antemortem MRI studied at postmortem it was equivalently determined, that EC patterns are reliably determined on MRI and do not change with the progressive atrophy of AD.

Conclusions:

The data indicate that the right hemisphere rhinal pattern is over represented in AD as compared with control. However, in normal subjects the EC rhinal pattern is not associated with a diminished EC tissue size. It remains to be demonstrated if the right EC rhinal sulcus pattern association with AD reflects genetic or developmental influences. Hum Brain Mapp, 2009. © 2008 Wiley‐Liss, Inc.

     

No cerebrocervical venous congestion in patients with multiple sclerosis

Objective:

Multiple sclerosis (MS) is characterized by demyelination centered around cerebral veins. Recent studies suggested this topographic pattern may be caused by venous congestion, a condition termed chronic cerebrospinal venous insufficiency (CCSVI). Published sonographic criteria of CCSVI include reflux in the deep cerebral veins and/or the internal jugular and vertebral veins (IJVs and VVs), stenosis of the IJVs, missing flow in IJVs and VVs, and inverse postural response of the cerebral venous drainage.

Methods:

We performed an extended extra‐ and transcranial color‐coded sonography study including analysis of extracranial venous blood volume flow (BVF), cross‐sectional areas, IJV flow analysis during Valsalva maneuver (VM), and CCSVI criteria. Fifty‐six MS patients and 20 controls were studied.

Results:

Except for 1 patient, blood flow direction in the IJVs and VVs was normal in all subjects. In none of the subjects was IJV stenosis detected. IJV and VV BVF in both groups was equal in the supine body position. The decrease of total jugular BVF on turning into the upright position was less pronounced in patients (173 ± 235 vs 362 ± 150ml/min, p < 0.001), leading to higher BVF in the latter position (318ml/min ± 242 vs 123 ± 109ml/min; p < 0.001). No differences between groups were seen in intracranial veins and during VM. None of the subjects investigated in this study fulfilled >1 criterion for CCSVI.

Interpretation:

Our results challenge the hypothesis that cerebral venous congestion plays a significant role in the pathogenesis of MS. Future studies should elucidate the difference between patients and healthy subjects in BVF regulation. ANN NEUROL 2010;68:173–183

     

Using spaced retrieval and Montessori‐based activities in improving eating ability for residents with dementia

Objectives

To construct a training protocol for spaced retrieval (SR) and to investigate the effectiveness of SR and Montessori‐based activities in decreasing eating difficulty in older residents with dementia.

Methods

A single evaluator, blind, and randomized control trial was used. Eighty‐five residents with dementia were chosen from three special care units for residents with dementia in long‐term care facilities in Taiwan. To avoid any confounding of subjects, the three institutions were randomized into three groups: spaced retrieval, Montessori‐based activities, and a control group. The invention consisted of three 30–40 min sessions per week, for 8 weeks.

Results

After receiving the intervention, the Edinburgh Feeding Evaluation in Dementia (EdFED) scores and assisted feeding scores for the SR and Montessori‐based activity groups were significantly lower than that of the control group. However, the frequencies of physical assistance and verbal assistance for the Montessori‐based activity group after intervention were significantly higher than that of the control group, which suggests that residents who received Montessori‐based activity need more physical and verbal assistance during mealtimes. In terms of the effects of nutritional status after intervention, Mini‐Nutritional Assessment (MNA) in the SR group was significantly higher than that of the control group.

Conclusion

This study confirms the efficacy of SR and Montessori‐based activities for eating difficulty and eating ability. A longitudinal study to follow the long‐term effects of SR and Montessori‐based activities on eating ability and nutritional status is recommended. Copyright © 2010 John Wiley & Sons, Ltd.

     

Hemispheric specialization during mental imagery of brisk walking

Objectives:

Brisk walking, a sensitive test to evaluate gait capacity in normal and pathological aging such as parkinsonism, is used as an alternative to classical fitness program for motor rehabilitation and may help to decrease the risk of cognitive deterioration observed with aging. In this study, we aimed to identify brain areas normally involved in its control.

Methods:

We conducted a block‐design blood oxygen level dependent function magnetic resonance imaging (BOLD fMRI) experiment in 18 young healthy individuals trained to imagine themselves in three main situations: brisk walking in a 25‐m‐long corridor, standing or lying. Imagined walking time (IWT) was measured as a control of behavioral performance during fMRI.

Results:

The group mean IWT was not significantly different from the actual walking time measured during a training session prior to the fMRI study. Compared with other experimental conditions, mental imagery (MI) of brisk walking was associated with stronger activity in frontal and parietal regions mainly on the right, and cerebellar hemispheres, mainly on the left. Presumed imagined walking speed (2.3 ± 0.4 m/s) was positively correlated with activity levels in the right dorsolateral prefrontal cortex and posterior parietal lobule along with the vermis and the left cerebellar hemisphere.

Interpretations:

A new finding in this study is that MI of brisk walking in young healthy individuals strongly involves processes lateralized in right fronto‐parietal regions along with left cerebellum. These results show that brisk walking might be a non automatic locomotor activity requiring a high‐level supraspinal control. Hum Brain Mapp, 2012. © 2011 Wiley Periodicals, Inc.

     

Phasic muscle activity in sleep and clinical features of Parkinson disease

Objective

To determine whether amyloid deposition is associated with impaired neuropsychological (NP) performance and whether cognitive reserve (CR) modifies this association.

Methods

In 66 normal elderly controls and 17 patients with Alzheimer disease (AD), we related brain retention of Pittsburgh Compound B (PiB) to NP performance and evaluated the impact of CR using education and American National Adult Reading Test intelligence quotient as proposed proxies.

Results

We found in the combined sample of subjects that PiB retention in the precuneus was inversely related to NP performance, especially in tests of memory function, but also in tests of working memory, semantic processing, language, and visuospatial perception. CR significantly modified the relationship, such that at progressively higher levels of CR, increased amyloid deposition was less or not at all associated with poorer neuropsychological performance. In a subsample of normal controls, both the main effect of amyloid deposition of worse memory performance and the interaction with CR were replicated using a particularly challenging memory test.

Interpretation

Amyloid deposition is associated with lower cognitive performance both in AD patients and in the normal elderly, but the association is modified by CR, suggesting that CR may be protective against amyloid‐related cognitive impairment. ANN NEUROL 2010;67:353–364

     

Axonal pathways linked to therapeutic and nontherapeutic outcomes during psychiatric deep brain stimulation

Objective:

The underlying hypothesis of our work is that specific clinical neuropsychiatric benefits can be achieved by selective activation of specific axonal pathways during deep brain stimulation (DBS). As such, the goal of this study was to develop a method for identifying axonal pathways whose activation is most likely necessary for achieving therapeutic benefits during DBS.

Experimental design:

Our approach combined clinical data, diffusion tensor tractography, and computer models of patient‐specific neurostimulation to identify particular axonal pathways activated by DBS and determine their correlations with individual clinical outcome measures. We used this method to evaluate a cohort of seven treatment‐resistant depression patients treated with DBS of the ventral anterior internal capsule and ventral striatum (VC/VS).

Principal observations:

Clinical responders exhibited five axonal pathways that were consistently activated by DBS. All five pathways coursed lateral and medial to the VS or dorsal and lateral to the nucleus accumbens; however, details of their specific trajectories differed. Similarly, one common pathway was identified across nonresponders.

Conclusions:

Our method and preliminary results provide important background for studies aiming to expand scientific characterization of neural circuitry associated with specific psychiatric outcomes from DBS. Furthermore, identification of pathways linked to therapeutic benefit provides opportunities to improve clinical selection of surgical targets and stimulation settings for DBS devices. Hum Brain Mapp, 2012. © 2011 Wiley Periodicals, Inc.