Cognitive Behavioral Therapy for Anxiety Disorders: Outcomes From a Multi-State,Multi-Site Primary Care Practice

BackgroundAnxiety disorders are among the most common mental health conditions. Individuals with anxiety typically seek services in primary, rather than specialty, care. While there is significant evidence supporting the efficacy and effectiveness of cognitive behavioral therapy (CBT) for anxiety disorders, there have been no naturalistic studies reporting anxiety-specific treatment outcomes in primary care.MethodsParticipants (N = 1,589) were recruited from a multi-state, multi-site primary care practice, with 491 participants endorsing moderate to severe anxiety at baseline and engaging in at least one CBT session. Data was drawn from a psychotherapy tracking database.ResultsAmong participants with moderate to severe anxiety who engaged in CBT, a significant decrease in anxiety and depression symptoms was observed over the course of psychotherapy (p < .001, d = 0.57-0.95). Rates of reliable change, response, and remission varied across diagnostic categories. The use of CBT interventions also varied across diagnoses in line with evidence-based treatment recommendations.DiscussionShort-term CBT delivered in primary care is associated with significant improvements in anxiety and depression symptoms among participants with anxiety disorders. These findings support the use of a population-based approach to anxiety disorders treatment and suggest that evidence-based CBT can be implemented in the real-world setting.     

Is there a link between headache and cognitive disorders? A systematic review

BackgroundThe overall prevalence of headaches decreases with age; however headaches remain frequent in aged individuals who are also affected by other disorders such as cognitive decline. Despite the high frequency of both conditions in these persons, the association between headaches and cognitive decline is underexplored, underdiagnosed and poorly understood.ObjectiveIn the present article, we aim to provide a comprehensive review of existing data concerning the link between headache and cognitive decline.MethodsWe undertook a systematic literature review to report articles that focus on headaches (including all types of headaches) and neurocognitive disorders of degenerative causes.ResultsOnly 9 studies have explored the association between headaches and neurocognitive decline. Methods were highly variable from population-based study to short series of patients using either database or questionnaire during consultation. Studies focusing on Familial Alzheimer's Disease revealed a very high prevalence of headaches in mutation carrier patients compared to non-carrier patients.ConclusionThe association between headaches and cognitive decline is underexplored. Future studies are needed to address the pathophysiological mechanisms to improve the treatment of these underestimated headaches.     

Consensus Guidelines of the French Society of Neuroradiology (SFNR) on the use of Gadolinium-Based Contrast agents (GBCAs) and related MRI protocols in Neuroradiology

Gadolinium-based contrast agents (GBCAs) are used in up to 35% of magnetic resonance imaging (MRI) examinations and are associated with an excellent safety profile. Nevertheless, two main issues have arisen in the last two decades: the risk of nephrogenic systemic fibrosis and the risk of gadolinium deposition and retention. As a first step, this article reviews the different categories of GBCAs available in neuroradiology, their issues, and provides updates regarding the use of these agents in routine daily practice. Recent advances in MRI technology, as well as the development of new MRI sequences, have made GBCA injection avoidable in many indications, especially in patients with chronic diseases when iterative MRIs are required and when essential diagnostic information can be obtained without contrast enhancement. These recent advances also lead to changes in recommended MRI protocols. Thus, in a second step, this review focuses on consensus concerning brain MRI protocols in 10 common situations (acute ischemic stroke, intracerebral hemorrhage, cerebral venous thrombosis, multiple sclerosis, chronic headache, intracranial infection, intra- and extra-axial brain tumors, vestibular schwannoma and pituitary adenoma). The latter allowing the standardization of practices in neuroradiology. Recommendations were also made concerning the use of GBCAs in neuroradiology, based on evidence in the literature and/or by consensus between the different coauthors.     

Melatonin (MEL) and its use in neurological diseases and insomnia: Recommendations of the French Medical and Research Sleep Society (SFRMS)

The French Medicine and Research Sleep Society had organized a consensus conference about sleep/wake circadian rhythms and their disorders. During this conference a subgroup of 11 sleep doctors/researchers looked specifically at the use of MEL in different pathologies. This article gives a summary of the main results of MEL therapy in some neurological diseases and insomnia approved by this consensus group. Exogenous MEL, which crosses the blood-brain barrier, has been used as a treatment in its two available forms: an immediate release form that principally shows a chronobiotic action and a long release form that mimics the physiological MEL secretion rhythm and is used to replace reduced physiological secretion. MEL secretion decreases frequently with age, mostly in elderly insomniacs and dementia patients. Results of level A studies show that MEL therapy, used as an add-on treatment, has beneficial effects in mild cognitive impairment (MCI) and Alzheimer patients with sleep disorders in improving sleep quality and in regulating the sleep/wake rhythm. MEL has to be prescribed as early as possible and for a long period, at a dose of 2 to 5 or 10 mg. It may have a beneficial effect on cognitive function in MCI but shows no effect in moderate to severe Alzheimer's disease. It should be emphasized that there are no serious side effects with MEL treatment. In these diseases, light therapy used 12 hours before melatonin treatment has a positive synergic effect. In REM sleep behavior disorder, immediate release MEL should be prescribed first as its side effect profile is much better than clonazepam shortly before bedtime. MEL has a good efficacy on clinical symptoms and PSG REM sleep without atonia episodes and is well tolerated. In Parkinson disease with sleep disorders and without REM sleep behavior disorder, MEL seems to improve subjective sleep quality but no conclusions can be drawn. There is insufficient scientific proof for using MEL as a prophylactic treatment in primary headache, migraine and cluster headache. In epileptic patients, MEL can be safely used to regulate the sleep/wake rhythm and to improve insomnia but more randomized controlled studies are necessary. In primary or no-comorbid insomnia, only a 2 mg dose of slow release MEL, 1 to 2 hours before bedtime, over a period of 3 to 12 weeks, is recommended. It decreases sleep onset latency, improves quality of sleep, morning alertness and quality of life without serious side effects and without withdrawal symptoms.     

Thalamic deep brain stimulation for Tourette Syndrome: A naturalistic trial with brief randomized,double-blinded sham-controlled periods

BackgroundThere is still a lack of controlled studies to prove efficacy of thalamic deep brain stimulation for Tourette's Syndrome.ObjectivesIn this controlled trial, we investigated the course of tic severity, comorbidities and quality of life during thalamic stimulation and whether changes in tic severity can be assigned to ongoing compared to sham stimulation.MethodsWe included eight adult patients with medically refractory Tourette's syndrome. Bilateral electrodes were implanted in the centromedian-parafascicular-complex and the nucleus ventro-oralis internus. Tic severity, quality of life and comorbidities were assessed before surgery as well as six and twelve months after. Short randomized, double-blinded sham-controlled crossover sequences with either active or sham stimulation were implemented at both six- and twelve-months’ assessments. The primary outcome measurement was the difference in the Yale Global Tic Severity Scale tic score between active and sham stimulation. Adverse events were systematically surveyed for all patients to evaluate safety.ResultsActive stimulation resulted in significantly higher tic reductions than sham stimulation (F = 79.5; p = 0.001). Overall quality of life and comorbidities improved significantly in the open-label-phase. Over the course of the trial two severe adverse events occurred that were resolved without sequelae.ConclusionOur results provide evidence that thalamic stimulation is effective in improving tic severity and overall quality of life. Crucially, the reduction of tic severity was primarily driven by active stimulation. Further research may focus on improving stimulation protocols and refining patient selection to improve efficacy and safety of deep brain stimulation for Tourette's Syndrome.     

The Arousal Disorders Questionnaire: a new and effective screening tool for confusional arousals,Sleepwalking and Sleep Terrors in epilepsy and sleep disorders units

BackgroundArousal Disorders (DoA) include Confusional Arousals, Sleepwalking and Sleep Terrors. DoA diagnosis is mainly clinical but no validated questionnaires exist for DoA screening according to the criteria of the International Classification of Sleep Disorders, Third Edition. Recently our group proposed the Arousal Disorders Questionnaire (ADQ) as a new diagnostic tool for DoA diagnosis. The objective of this study was to evaluate the diagnostic accuracy of the ADQ in a sleep and epilepsy center.MethodsOne interviewer blinded to clinical and video-polysomnographic (VPSG) data administered the ADQ to 150 patients consecutively admitted to our Sleep and Epilepsy Centers for a follow-up visit. The final diagnosis, according to VPSG recordings of at least one major episode, classified patients either with DoA (DoA group) or with other sleep-related motor behaviors confounding for DoA (nDoA group).Results47 patients (31%) composed the DoA group; 56 patients with REM sleep behavior disorder, 39 with sleep-hypermotor epilepsy, six with night eating syndrome, and two with drug-induced DoA composed the nDoA group. The ADQ had a sensitivity of 72% (95% CI: 60–82) and a specificity of 96% (95% CI: 89–98) for DoA diagnosis; excluding the items regarding consciousness and episode recall, sensitivity was 83% (95% CI: 71–90) and specificity 93% (95% CI: 86–97).ConclusionsThe ADQ showed good accuracy in screening patients with DoA in a sleep and epilepsy center setting. Diagnostic criteria related to cognition and episode recall reduced ADQ sensitivity, therefore a better definition of these criteria is required, especially in adults.     

Review of synthetic MRI in pediatric brains: Basic principle of MR quantification,its features,clinical applications,and limitations

Quantitative magnetic resonance imaging (MRI) with multislice, multi-echo, and multi-delay acquisition enables simultaneous quantification of R₁ and R₂ relaxation rates, proton density, and the B₁ field in a single acquisition, and requires only about 6 minutes for full-head coverage. Using dedicated SyMRI software, radiologists can generate any contrast-weighted image by manipulating the acquisition parameters, including repetition time, echo time, and inversion time. Moreover, automatic brain tissue segmentation, volumetry, and myelin measurement can also be performed. Using the SyMRI approach, a shorter scan time, an objective examination, and personalized MR imaging parameters can be obtained in daily clinical pediatric imaging. Here we summarize and review the use of SyMRI in imaging of the pediatric brain, including the basic principles of MR quantification along with its features, clinical applications, and limitations.     

Cognitive effort decreases beta,alpha, and theta coherence and ends afterdischarges in human brain

ObjectiveMental activation has been reported to modify the occurrence of epileptiform activity. We studied its effect on afterdischarges.MethodIn 15 patients with implanted electrodes we presented cognitive tasks when afterdischarges occurred. We developed a wavelet cross-coherence function to analyze the electrocorticography before and after the tasks and compared findings when cognitive tasks did or did not result in afterdischarge termination. Six patients returned for functional MRI (fMRI) testing, using similar tasks.ResultsCognitive tasks often could terminate afterdischarges when direct abortive stimulation could not. Wavelet cross-coherence analysis showed that, when afterdischarges stopped, there was decreased coherence throughout the brain in the 7.13–22.53 Hz frequency ranges (p values 0.008–0.034). This occurred a) regardless of whether an area activated on fMRI and b) regardless of whether there were afterdischarges in the area.ConclusionsIt is known that cognitive tasks can alter localized or network synchronization. Our results show that they can change activity throughout the brain. These changes in turn can terminate localized epileptiform activity.SignificanceCognitive tasks result in diffuse brain changes that can modify focal brain activity. Combined with a seizure detection device, cognitive activation might provide a non-invasive method of terminating or modifying seizures.     

Cognitive deficits and rehabilitation mechanisms in mild traumatic brain injury patients revealed by EEG connectivity markers

ObjectiveTo explore the multiple specific biomarkers and cognitive compensatory mechanisms of mild traumatic brain injury (mTBI) patients at recovery stage.MethodsThe experiment was performed in two sections. In Section I, using event-related potential, event-related oscillation and spatial phase-synchronization, we explored neural dynamics in 24 volunteered healthy controls (HC) and 38 patients at least 6 months post-mTBI (19 with epidural hematoma, EDH; 19 with subdural hematoma, SDH) during a Go/NoGo task. In Section II, according to the neuropsychological scales, patients were divided into sub-groups to assess these electroencephalography (EEG) indicators in identifying different rehabilitation outcomes of mTBI.ResultsIn Section I, mean amplitudes of NoGo-P3 and P3d were decreased in mTBI patients relative to HC, and NoGo-theta power in the non-injured hemisphere was decreased in SDH patients only. In Section II, patients with chronic neuropsychological defects exhibited more serious impairments of intra-hemispheric connectivity, whereas inter-hemispheric centro-parietal and frontal connectivity were enhanced in response to lesions.ConclusionsEEG distinguished mTBI patients from healthy controls, and estimated different rehabilitation outcomes of mTBI. The centro-parietal and frontal connectivity are the main compensatory mechanism for the recovery of mTBI patients.SignificanceEEG measurements and network connectivity can track recovery process and mechanism of mTBI.     

Validation of the Japanese version of the Sleep Hygiene Practice Scale

ObjectiveThis study sought to validate the Japanese version of the Sleep Hygiene Practices Scale (SHPS-J).Patients/methodsA cross-sectional questionnaire-based study was conducted via the internet. In total, 854 participants (435 men, 419 women; mean age, 42.91 ± 11.54 years) were asked to complete all scales, and 283 of them were asked to complete the same scales two weeks later. The survey consisted of the SHPS-J, the Japanese version of the Insomnia Severity Index (ISI-J), and the Japanese version of the Pittsburgh Sleep Quality Index (PSQI-J). The SHPS-J was developed according to the International Society for Pharmacoeconomics and Outcomes Research Task Force for Translation and Cultural Adaption. For the analysis, participants were divided into three groups: insomnia syndrome, insomnia symptoms, and good sleep groups.ResultsThe SHPS-J had good test-retest reliability (ICC: 0.55–0.76) and adequate internal consistency (α = 0.54–0.74), except with regard to eating/drinking behaviors. The factorial validity of the four-factor structure was confirmed through a confirmatory factor analysis; however, one item related to eating/drinking behaviors had no significant factor loading. The construct validity was confirmed through a correlation analysis between each domain of the SHPS-J and ISI-J (r = 0.19–0.60, p < 0.01). The results of clinical validation confirmed that all domains of the SHPS-J were significantly higher for individuals with insomnia than for good sleepers.ConclusionsThis study confirmed both the reliability and validity of the SHPS-J.     

High frequency oscillations relate to cognitive improvement after epilepsy surgery in children

ObjectiveTo investigate how high frequency oscillations (HFOs; ripples 80–250 Hz, fast ripples (FRs) 250–500 Hz) and spikes in intra-operative electrocorticography (ioECoG) relate to cognitive outcome after epilepsy surgery in children.MethodsWe retrospectively included 20 children who were seizure free after epilepsy surgery using ioECoG and determined their intelligence quotients (IQ) pre- and two years postoperatively. We analyzed whether the number of HFOs and spikes in pre- and postresection ioECoGs, and their change in the non-resected areas relate to cognitive improvement (with ≥ 5 IQ points increase considered to be clinically relevant (=IQ+ group) and < 5 IQ points as irrelevant (=IQ− group)).ResultsThe IQ+ group showed significantly more FRs in the resected tissue (p = 0.01) and less FRs in the postresection ioECoG (p = 0.045) compared to the IQ− group. Postresection decrease of ripples on spikes was correlated with postoperative cognitive improvement (correlation coefficient = −0.62 with p = 0.01).ConclusionsPostoperative cognitive improvement was related to reduction of pathological HFOs signified by removing FR generating areas with subsequently less residual FRs, and decrease of ripples on spikes in the resection edge of the non-resected area.SignificanceHFOs recorded in ioECoG could play a role as biomarkers in the prediction and understanding of cognitive outcome after epilepsy surgery.     

Primary Lateral Sclerosis: Clinical,radiological and molecular features

Primary Lateral Sclerosis (PLS) is an uncommon motor neuron disorder. Despite the well-recognisable constellation of clinical manifestations, the initial diagnosis can be challenging and therapeutic options are currently limited. There have been no recent clinical trials of disease-modifying therapies dedicated to this patient cohort and awareness of recent research developments is limited. The recent consensus diagnostic criteria introduced the category ‘probable’ PLS which is likely to curtail the diagnostic journey of patients. Extra-motor clinical manifestations are increasingly recognised, challenging the view of PLS as a 'pure' upper motor neuron condition. The post mortem literature of PLS has been expanded by seminal TDP-43 reports and recent PLS studies increasingly avail of meticulous genetic profiling. Research in PLS has gained unprecedented momentum in recent years generating novel academic insights, which may have important clinical ramifications.     

Uncharted territory: The feasibility of serial computerised cognitive assessment the first week post-stroke

BackgroundCognitive impairment is common and problematic post-stroke, yet vital information to understand early cognitive recovery is lacking. To examine early cognitive recovery, it is first necessary to establish the feasibility of repeat cognitive assessment during the acute post-stroke phase.ObjectiveTo determine if serial computerised testing is feasible for cognitive assessment in an acute post-stroke phase, measured by assessment completion rates.MethodAn observational cohort study recruited consecutive stroke patients admitted to an acute stroke unit within 48 hours of onset. Daily assessment with the Cambridge Neuropsychological Test Automated Battery (CANTAB) was performed for seven days, and single Montreal Cognitive Assessment (MoCA).ResultsSeventy-one participants were recruited, mean age 74 years, with 67 completing daily testing. Participants had predominantly mild (85%; NIHSS ≤6), ischemic (90%) stroke, 32% demonstrated clinical delirium. The first day of testing, 76% of participants completed CANTAB batteries. Eighty-seven percent of participants completed MoCA a mean of 3.4 days post-stroke. The proportion of CANTAB batteries completed improved significantly from day 2 to day 3 post-stroke with test completion rates stabilizing ≥ 92% by day 4. Participants with incomplete CANTAB were older, with persisting delirium, and longer stay in acute care.ConclusionSerial computerised cognitive assessments are feasible the first week post-stroke and provide a novel approach to measuring cognitive change for both clinical and research purposes. Maximum completion rates by day four have clinical implications for optimal timing of cognitive testing.     

Association of lipid levels with motor and cognitive function and decline in advanced Parkinson's disease in the Mark-PD study

ObjectivesIn prospective cohort studies different blood lipid fractions have been identified as risk factors of Parkinson's disease (PD). However, data relating lipoproteins to disease phenotypes and progression in advanced PD patients are sparse. Therefore, we assessed the most common lipoproteins in a case-control design and evaluated their associations with motor and cognitive function and decline in PD patients.MethodsTriglycerides, LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C), apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), and lipoprotein a (Lp(a)) were analyzed in 294 PD patients of the MARK-PD study cohort and 588 controls matched for age, sex and cardiovascular risk factors. In PD patients, motor (MDS-UPDRS III, Hoehn-Yahr stage) and cognitive function (MoCA) were examined. In a sub-cohort (n = 98 patients), baseline lipid levels were correlated with motor and cognitive disease progression during a follow-up period of 523 ± 199 days.ResultsAt baseline, HDL-C levels were lower in PD patients compared to matched controls after adjustment. We observed a very weak association of Lp(a) levels with UDPRS III scores. In cross-sectional analyses, no other lipid fraction revealed a significant and consistent association with motor or cognitive function. During follow-up, no lipid fraction level was associated with motor or cognitive progression.ConclusionIn advanced PD, there is no strong and consistent association of lipid levels with motor or cognitive function and decline.     

Narcolepsy in Slovakia – Epidemiology,clinical and polysomnographic features,comorbid diagnoses: a case-control study

ObjectiveAn increase in the incidence of narcolepsy after the pandemic influenza with the H1N1 vaccination in 2009 resulted in an interest in narcolepsy epidemiology. The aim of the study was to examine the incidence and prevalence rates of narcolepsy and to describe the associated characteristics in Slovakia.MethodsEpidemiology data were calculated for each year from 2000 to 2017 based on records found in specialized centres. In sum, 61 narcoleptic patients were diagnosed, of which 51 (84%) had narcolepsy type 1 (NT1). Clinical data and results of polysomnography (PSG), Human Leukocyte Antigen (HLA)-typing, hypocretin (HCRT)-1 levels and body mass index (BMI) were summarised and evaluated for NT1 and narcolepsy type2 (NT2). Later, 244 sex and age matched controls were chosen to evaluate the comorbid diagnoses.ResultsThe prevalence of narcolepsy in 2017 in Slovakia was 10.47 (CI 95% 8.26–14) cases/million inhabitants, and the mean incidence rate (2000–2017) was 0.57 (CI 95% 0.4–0.74) cases/million inhabitants.Narcoleptic patients were comorbid with arterial hypertension (17%), ischemic heart disease (8%), dyslipidaemia (18%), diabetes mellitus type 2 (10%), cardiac arrhythmia/atrial fibrillation (5%), autoimmune disorders (20%), allergy (11%), malignancy (3%), headache (15%) and mental disorders (20%). Patients with narcolepsy showed double the excess prevalence in mental disorders (OR 2.15, p < 0.05), and dyslipidaemia (OR 2.22, p < 0.05). The presence of autoimmune disorders and allergy showed a mild increase in the narcolepsy group (OR 1.46, resp. 1.63). Hashimoto thyroiditis (HT) was the most frequent autoimmune disorder.ConclusionsNarcolepsy is a rare disorder in Slovakia. From the phenotype, genetic characteristics and comorbidities the disorder does not vary from other European countries.     

Early life Adversity,functional connectivity and cognitive performance in Schizophrenia: The mediating role of IL-6

ObjectiveExposure to childhood trauma (CT) is associated with cognitive impairment in schizophrenia, and deficits in social cognition in particular. Here, we sought to test whether IL-6 mediated the association between CT and social cognition both directly, and sequentially via altered default mode network (DMN) connectivity.MethodsThree-hundred-and-eleven participants (104 patients and 207 healthy participants) were included, with MRI data acquired in a subset of n = 147. CT was measured using the childhood trauma questionnaire (CTQ). IL-6 was measured in both plasma and in toll like receptor (TLR) stimulated whole blood. The CANTAB emotion recognition task (ERT) was administered to assess social cognition, and cortical connectivity was assessed based on resting DMN connectivity.ResultsHigher IL-6 levels, measured both in plasma and in toll-like receptor (TLR-2) stimulated blood, were significantly correlated with higher CTQ scores and lower cognitive and social cognitive function. Plasma IL-6 was further observed to partly mediate the association between higher CT scores and lower emotion recognition performance (CTQ total: β_indirect −0.0234, 95% CI: −0.0573 to −0.0074; CTQ physical neglect: β_indirect = −0.0316, 95% CI: −0.0741 to −0.0049). Finally, sequential mediation was observed between plasma IL-6 levels and DMN connectivity in mediating the effects of higher CTQ on lower social cognitive function (β_indirect = −0.0618, 95% CI: −0.1523 to −0.285).ConclusionThis work suggests that previous associations between CT and social cognition may be partly mediated via an increased inflammatory response. IL-6′s association with changes in DMN activity further suggest at least one cortical network via which CT related effects on cognition may be transmitted.     

Motor dysfunction in mild cognitive impairment as tested by kinematic analysis and transcranial magnetic stimulation

ObjectivePrevious studies have demonstrated voluntary movement alterations as well as motor cortex excitability and plasticity changes in patients with mild cognitive impairment (MCI). To investigate the pathophysiology of movement abnormalities in MCI, we tested possible relationships between movement abnormalities and primary motor cortex alterations in patients.MethodsFourteen amnestic MCI (aMCI) patients and 16 healthy controls were studied. Cognitive assessment was performed using clinical scales. Finger tapping was recorded by a motion analysis system. Transcranial magnetic stimulation was used to test the input/output curve of motor evoked potentials, intracortical inhibition, and short-latency afferent inhibition. Primary motor cortex plasticity was probed by theta burst stimulation. We investigated correlations between movement abnormalities, clinical scores, and cortical neurophysiological parameters.ResultsMCI patients showed less rhythmic movement but no other movement abnormalities. Cortical excitability measures were normal in patients, whereas plasticity was reduced. Movement rhythm abnormalities correlated with frontal dysfunction scores.ConclusionOur study in MCI patients demonstrated abnormal voluntary movement and plasticity changes, with no correlation between the two. Altered rhythm correlated with frontal dysfunction.SignificanceOur results contribute to the understanding of pathophysiological mechanisms of motor impairment in MCI.