Can electromyography objectively detect voluntary movement in disorders of consciousness?

Determining conscious processing in unresponsive patients relies on subjective behavioural assessment. Using data from hand electromyography, the authors studied the occurrence of subthreshold muscle activity in response to verbal command, as an objective indicator of awareness in 10 disorders of consciousness patients. One out of eight vegetative state patients and both minimally conscious patients (n = 2) demonstrated an increased electromyography signal specifically linked to command. These findings suggest electromyography could be used to assess awareness objectively in pathologies of consciousness.     

Characterization of antibodies that selectively detect α-synuclein in pathological inclusions

Sensitive detection of alpha-synuclein (alpha-syn) pathology is important in the diagnosis of disorders like Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy and in providing better insights into the etiology of these diseases. Several monoclonal antibodies that selectively react with aggregated alpha-syn in pathological inclusions and reveal extensive and underappreciated alpha-syn pathology in the brains of diseased patients were previously reported by Duda et al. (Ann Neurol 52:205-210, 2002). We sought to characterize the specificity of some of these antibodies (Syn 505, Syn 506 and Syn 514); using C-terminal and N-terminal truncations of alpha-syn, all three antibodies were determined to require N-terminal epitopes that minimally comprise amino acids 2-4, but possibly extend to amino acid 12 of alpha-syn. The selectivity of these antibodies was further assessed using biochemical analysis of human brains and reactivity to altered recombinant alpha-syn proteins with duplication variants of amino acids 1-12. In addition, by expressing wild-type or a double mutant (E46K/A53T) of alpha-syn in cultured cells and by comparing their immunoreactivities to another antibody (SNL-4), which has a similar primary epitope, it was determined that Syn 505, Syn 506 and Syn 514 recognize conformational variants of alpha-syn that is enhanced by the presence of the double mutations. These studies indicate that antibodies Syn 505, Syn 506 and Syn 514 preferentially recognize N-terminal epitopes in complex conformations, consistent with the dramatic conformational change associated with the polymerization of alpha-synuclein into amyloid fibrils that form pathological inclusions.     

How to detect cognitive dysfunction at early stages of multiple sclerosis?

Detecting cognitive dysfunction may be clinically important during the early stages of multiple sclerosis (MS). We assessed a self-report questionnaire on cognitive complaints and individual neuropsychological tests to select patients with early relapsing-remitting MS (RRMS) who needed comprehensive cognitive testing. Fifty-seven patients underwent neurological and neuropsychological assessment, including Rao's Brief Repeatable Battery (BRB) and the complete SEP-59 Questionnaire, a French adaptation of the MSQOL-54, which contains four specific questions about self-perception of cognitive functions. Predictive values, specificity, sensitivity and accuracy of five individual neuropsychological tests--Selective Reminding Test, Symbol Digit Modalities Test (SDMT), Similarities Subtest, PASAT and Stroop Test--were calculated to predict cognitive impairment. Only 10.5% of patients did not report any cognitive complaint, while most reported complaints. On the basis of cognitive performances, 59.7% of patients were classified as cognitively impaired, although only one cognitive score was correlated with cognitive complaints. Depressive symptoms and fatigue were associated with more cognitive complaints. Sensitivity of the SDMT to predict cognitive impairment was 74.2%, specificity was 76.9% and accuracy was 75.4%. Since, at this stage, patients' cognitive complaints are already influenced by depression and fatigue and do not accurately reflect cognitive performances, the SDMT may help to select patients for testing with a more complete cognitive battery.     

Use of an immunocapture device to detect cytokine release in discrete brain regions

<正>Production of proinfla mmatory cytokines in the central nervous system is a key process in the neuroinfla mmatory response to trauma,infection,and neurodegenerative diseases(Kumar,2019).These intercellular signaling molecules play multiple roles in the central nervous system immune response including the orchestration of the sickness response to innate immune perturbations in the brain (Dantzer et al.,2008).     

Can IQCODE detect poststroke dementia?

BACKGROUND: Little is known about the performance of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) in the screening of post-stroke dementia (PSDE). METHODS: At 3 months after the index stroke, a research assistant administered the IQCODE to relatives of 189 Chinese patients with acute stroke who were consecutively admitted to a general hospital. A psychiatrist, who was blind to the IQCODE scores, interviewed all 189 patients and made DSM-IV diagnosis of dementia, which served as the benchmark for judging the performance of IQCODE in screening PSDE. RESULTS: The optimal cut-off point of IQCODE was 3.40. The sensitivity, specificity, and positive and negative predictive values of IQCODE, and the area under the receiver operating characteristic curve, were 88%, 75%, 33%, 98%, and 0.88, respectively. CONCLUSIONS: When used as a sole instrument, IQCODE does not appear to be useful in screening PSDE in Chinese elderly.     

What is the minimum duration of head-up tilt necessary to detect orthostatic hypotension?

Abstract Objective There is uncertainty as to the minimum duration of head-up tilt (HUT) needed to detect orthostatic hypotension (OH). The orthostatic duration has variably been recommended to be 1, 2, 3, and 5 minutes. The purpose of the current study was 1) to determine the minimum duration of HUT necessary to detect OH and 2) to identify different patterns of orthostatic blood pressure (BP) response in patients with OH. Design/methods We evaluated the medical records of 66 consecutive patients (mean age 70.0±10.1 years; 64% male) seen at Mayo Clinic-Rochester from 2000–2001 who fulfilled the criteria for OH (systolic blood pressure [SBP] reduction 20mm Hg within 3 minutes of HUT) during routine clinical autonomic studies. All patients completed an autonomic reflex screen with continuous monitoring of heart rate and BP during supine rest and 5 minutes of 70 degree HUT. Severity of autonomic deficits was quantified with the Composite Autonomic Severity Score (CASS). Results Overall, BP was the lowest at 1 minute with gradual and partial recovery over the following 4 minutes. Eighty-eight percent of patients (N=58) developed OH by 1 minute of HUT, with an additional 11% (N=7) developing OH by 2 minutes and the remaining 1% (N=1) developing OH by 3 minutes. We identified two broad patterns of SBP response to HUT. Forty-eight percent (N=32) of patients demonstrated an initial drop in SBP ( 20 mm Hg),which remained stable until tilt-back. Thirty-six percent (N=24) demonstrated an initial drop ( 20mm Hg) followed by a progressive decline in SBP until tilt-back. Repeated measures analysis of variance confirmed that the SBP change in response to HUT differed significantly among patients with a stable vs. progressive pattern [F(3,32)=25.1, p<0.001). Patients with the progressive pattern also had more severe adrenergic impairment on the CASS (p=0.03) and were more likely to have their tilt test terminated early (prior to 5minutes) due to presyncope (p<0.0001) than patients with the stable pattern. Conclusions One minute of HUT will detect OH in the great majority (88%) of patients and three minutes will detect the balance. Orthostatic stress beyond 2 minutes is necessary to detect the pattern of progressive OH. Since this group has more severe adrenergic deficits than the group with stable OH, we suggest that the progressive pattern is due to greater impairment of compensatory reflexes. Recognition of the group with progressive fall in BP is important since this group may be at greater risk of orthostatic syncope.     

How well do neural signatures of resting-state EEG detect consciousness? A large-scale clinical study

The assessment of consciousness states, especially distinguishing minimally conscious states (MCS) from unresponsive wakefulness states (UWS), constitutes a pivotal role in clinical therapies. Despite that numerous neural signatures of consciousness have been proposed, the effectiveness and reliability of such signatures for clinical consciousness assessment still remains an intense debate. Through a comprehensive review of the literature, inconsistent findings are observed about the effectiveness of diverse neural signatures. Notably, the majority of existing studies have evaluated neural signatures on a limited number of subjects (usually below 30), which may result in uncertain conclusions due to small data bias. This study presents a systematic evaluation of neural signatures with large-scale clinical resting-state electroencephalography (EEG) signals containing 99 UWS, 129 MCS, 36 emergence from the minimally conscious state, and 32 healthy subjects (296 total) collected over 3 years. A total of 380 EEG-based metrics for consciousness detection, including spectrum features, nonlinear measures, functional connectivity, and graph-based measures, are summarized and evaluated. To further mitigate the effect of data bias, the evaluation is performed with bootstrap sampling so that reliable measures can be obtained. The results of this study suggest that relative power in alpha and delta serve as dependable indicators of consciousness. With the MCS group, there is a notable increase in the phase lag index-related connectivity measures and enhanced functional connectivity between brain regions in comparison to the UWS group. A combination of features enables the development of an automatic detector of conscious states.     

A reproducible assay of polymerase chain reaction to detect trinucleotide repeat expansion of Huntington’s disease and senile chorea

Abstract

A simple and reproducible method of polymerase chain reaction (PCR) assay was established to detect trinucleotide repeat expansion for Huntington’s disease (HD) using a new DNA polymerase and buffer system. The system consists of an extremely heat stable DNA polymerase (Pfu), and a buffer supplemented with ammonium sulfate and dimethyl sulfoxide. Previous methods to amplify expanded alleles for HD have been very complex in PCR conditions; but the reproducibility was sometimes very low because of repetitive sequences around the primer sequences. With the present method’ strong bands for the disease alleles were reproducibly visible in a conventional agarose gel stained with ethidium bromide without using isotopes. Three cases with sporadic HD and a case with senile chorea showed expanded alleles for HD with smaller sizes of the expansion than cases with typical HD. These results showed that the present method provides a simple and reproducible way to detect HD allele, and some cases with sporadic HD and senile chorea had expanded HD alleles. [Neurol Res 1996; 18: 16–18]     

Quality of life measures in epilepsy: how well can they detect change over time?

OBJECTIVE: To evaluate the ability of health-related quality of life (HRQOL) measures to detect change over time in persons with epilepsy. BACKGROUND: The application of HRQOL measures in clinical trials has been limited by a dearth of information regarding their abilities to measure change over time (i.e., their responsiveness). To calculate responsiveness, one must categorize subjects as "changed" or "unchanged" by a priori criteria. METHODS: The authors analyzed data collected at baseline and at 28-week follow-up from an antiepileptic drug trial. Two different criteria for classifying subjects as changed or unchanged-one based on seizure frequency (where changed = attainment of seizure freedom) and one based on self-reported overall condition (where changed = improvement in overall condition)-were used. We compared responsiveness indices for two generic (Short Form [SF]-36 and SF-12) and two epilepsy-targeted (Quality of Life in Epilepsy [QOLIE]-89 and QOLIE-31) HRQOL measures. Two scoring procedures for the SF-36, one based on classic test theory and the other on item response theory (IRT), were compared. RESULTS: Effect sizes of the most responsive HRQOL measures were medium to large. The shorter epilepsy-targeted measure had similar responsiveness indices to those of the longer measure. Epilepsy-targeted measures were consistently more responsive than generic measures under the overall condition criterion, but for the seizure freedom criterion, IRT scoring of the SF-36 yielded responsiveness indices comparable to those of the epilepsy-targeted measures. CONCLUSION: Epilepsy-targeted health-related quality of life measures may be preferable to generic ones in longitudinal studies. Selection of a shorter epilepsy-targeted measure does not compromise responsiveness. Item response theory scoring should be applied to epilepsy-targeted HRQOL measures.     

Effects of elevated ICP on brain function: can the multiparametric monitoring system detect the 'Cushing Response'?

The 'Cushing Response' is a significant phenomenon associated with elevated ICP. The purpose of our study was to examine the effects of the intracranial hypertension level and duration on the cerebral tissue physiology, using a Multiprobe assembly (MPA). The parameters monitored simultaneously included ICP, CBF, mitochondrial NADH redox state, extracellular K+ and H+ levels, DC potential and ECoG, calculated CPP and blood pressure. Two groups of rats were used. In one group, ICP was elevated to 50-60 mmHg for 13-15 min and, in the second group, ICP was elevated to 20 mmHg for 30 min. The results show that ICP of 50-60 mmHg led to CPP reduction below the lower limits of autoregulation. However, ICP of 20 mmHg, even for a prolonged period of time is completely tolerated. Additionally, we found that the 'Cushing Response', developed in the moderate treatment (ICP = 20 mmHg) is beneficial, assuring high CBF levels under intracranial hypertension. Furthermore, CBF and CPP monitoring, apparently, are not sufficient for autoregulation assessment; more parameters are needed.     

How well do caregivers detect mild cognitive change in Parkinson's disease?

Using the Cambridge Behavior Inventory‐Revised, this study evaluated the relationship between caregiver ratings of cognitive change and neuropsychological performance. In sixty‐one nondemented patients with Parkinson's Disease (PD; mean age = 64.5 years, MMSE = 28.7), 62% met criteria for mild cognitive impairment. This group were rated as having more overall change as well as memory and behavior change. Caregiver ratings were related to poorer psychomotor speed, learning/memory, language, and executive functioning. The capacity for caregivers to rate mild cognitive change in PD may be useful to assist in early screening and intervention approaches. © 2010 Movement Disorder Society     

Seizure anticipation: are neurophenomenological approaches able to detect preictal symptoms?

Analysis of electroencephalographic signals and several brain imaging studies suggest that a preictal state precedes the onset of seizures. In this study, we used phenomenological strategies to detect modifications in patients' experience before their seizures. We observed that patients with partial epilepsy feeling an aura (n=9) frequently experienced prodromes (n=6). Prodromes were subtle preictal symptoms, varying among patients and having common negative features. They were generally continuous before seizures and could last hours, whereas auras were sudden and intermittent. All patients were able to recognize facilitating factors. We also found that patients spontaneously develop cognitive countermeasures to avoid facilitating factors (n=6), to prevent a seizure (n=1) or to interrupt a seizure (n=5). Prodromes are not specific enough for clinical use, but could refine the behavioral strategies used in the treatment of epilepsy and the pathophysiology of the preictal state.     

Do F‐wave measurements detect changes in motor neuron excitability?

The use of F waves to assess motor neuron excitability in experimental paradigms has never been validated. Our objective was to determine whether F-wave area, amplitude, and persistence measurements change in response to manipulations known to alter the excitability of motor neurons. The effects of muscle vibration, contraction of a remote muscle, and high-intensity stimulation of ipsilateral or contralateral fingers were assessed in 12 healthy volunteers. F-wave area, amplitude, and persistence all declined with ipsilateral cutaneous stimulation. The other maneuvers facilitated some, but not all, of the F-wave measurements. Changes in F-wave area and amplitude were correlated, but neither correlated with changes in persistence. A sample size of 50-75 F waves was needed to approximate amplitude and area results from 100 F waves with an accuracy of +/- 25%. We conclude that changes in F waves are better at detecting inhibition than facilitation of motor neurons. F waves reflect motor neuron excitability in a general way but do not allow for accurate measures of short-term changes in excitability.     

Is the Addenbrooke’s Cognitive Examination effective to detect frontotemporal dementia?

We evaluated the Addenbrooke's cognitive examination (ACE), a simple instrument to differentiate frontotemporal dementia (FTD) from Alzheimer's disease (AD), in our dementia patients clinic population. The Verbal-Language/Orientation-Memory (VLOM) ratio, which compares its language and memory scores, determines whether FTD or AD is more likely. The ACE was translated into French with adaptation maintaining the number of words in the name and address learning and delayed recall test, and with cultural adaptation for the semantic memory. The 85 included subjects had no evidence of two or more organic pathologies, after at least six months of follow-up, and an MMSE score>or=20/30. Patients with cognitive impairment due to alcohol intake were excluded. The diagnosis of a specific dementing illness was based on the consensus of the neurologist and neuropsychologists in the team. Thereafter, another neurologist expert in dementia, blinded to the ACE result and to the diagnosis and treatment, reviewed all cases files and proposed a diagnosis. A diagnostic agreement was reached for 79 cases (92.9%) with 40 (50.6%) dementia: 25 AD (62.5 %), 9 FTD (22.5 %).We estimated that the sensitivity for detecting dementia of an ACE score3.2 was 72%,with a specificity of 69.4%. We conclude that, when used as originally proposed, ACE is very accurate for the detection of dementia, but much less effective in discriminating the most common frontal variant of FTD.     

Time series fMRI measures detect changes in pontine raphé following acute tryptophan depletion

Serotonin is synthesized from its precursor, tryptophan, by brainstem raphé neurons and their synaptic terminals in limbic regions. The omission of tryptophan from an Acute Tryptophan Depletion (ATD) diet transiently diminishes serotonin synthesis, alters raphé activity, and mimics symptoms of depression. Raphé functional magnetic resonance imaging (fMRI) poses challenges using signal-averaging analyses. Time-series properties of fMRI blood oxygenation level dependent (BOLD) signals may hold promise, so we analyzed raphé signals for changes with the ATD diet. Eleven remitted (previously depressed) patients were awake with eyes-closed during seven-minute resting scans with 0.5s(-1) sampling. BOLD signal time-series data were frequency-filtered using wavelet transforms, yielding three octave-width frequency bands from 0.25 to 0.03s(-1) and an unbounded band below 0.03s(-1). Spectral power, reflecting signal information, increased in pontine raphé at high frequencies (0.25 to 0.125s(-1)) during ATD (compared to control, balanced, diet, P<0.004) but was unchanged at other frequencies. Functional connectivity, the correlation between time-series data from pairs of regions, weakened between pontine raphé and anterior thalamus at low frequencies during ATD (P<0.05). This preliminarily supports using fMRI time-series features to assess pontine raphé function. Whether, and how, high frequency activity oscillations interfere with low frequency signaling requires further study.