Repetitive transcranial magnetic stimulation (rTMS) for depression: outcomes in a United Kingdom (UK) clinical practice

Objective: The aim of this paper is to present the outcomes data from the largest United Kingdom’s (UK) National Health Service (NHS) clinical rTMS service treating treatment resistant depression (TRD).

Methods: The study was a retrospective investigation of routinely collected data on patients receiving rTMS between 2015 and 2017. Measures used were the clinician-rated Clinical Global Impression (CGI) and Hamilton Depression Rating Scale (HAM-D), and patient rated Beck Depression Inventory (BDI). The outcome data of 73 patients with TRD were analysed. The sample included patients with co-morbid psychiatric diagnosis.

Results: Response and remission rates, respectively, were 40.4% and 25.5% for the HAM-D; 35.6% and 20.8% for the BDI; and 51.1% and 52.1% for the CGI. Effect sizes were medium (0.54, 0.52 and 0.56, respectively).

Conclusions: The results show that a UK-based clinical service achieves similar results to those published internationally and that clinical rTMS can have significant impact on symptoms of depression in many patients with TRD. Health services are under pressure to make financial savings, investment in rTMS could reduce the long-term treatment costs associated with TRD.     

Choosing among second-generation antidepressant treatments for depressed patients with cardiac diseases

Objectives: The present paper aimed to assist physicians in the accurate choice among second-generation agents (SGAs) for patients with cardiovascular disease (CVD).

Methods: We reviewed the published pharmacokinetic (PK) and pharmacodynamic (PD) clinical data that report potential -or absence of- drug interactions between second-generation agents (SGAs) and CVD drugs most commonly used in cardiology, including antiplatelet drugs and anticoagulants, statins, beta-blockers, angiotensin-converting enzyme inhibitors, calcium channel blockers, diuretics and the antiarrhythmic drugs amiodarone and digoxin.

We also reviewed the cardiovascular safety profile that has been published for each class of SGAs and side effects reported by patients with CVD.

Results: Most relevant PK/PD data about SGAs and CVD drugs are based on small studies or detailed case reports. In many cases, the drug interactions are at most assessed in healthy volunteers so that the clinical relevance of findings needs further investigation in patients with CVD. Case reports of serious, sometimes fatal reactions due to concomitant administration of certain drugs require careful consideration.

The major cardiac side effects of SGAs include HR increase, postural hypotension and slight prolongation of the intraventricular conduction time and QT interval. On normal dosage of antidepressants, both advanced heart block and ventricular arrhythmias could occur in patients with severe heart disease, together with clinically important loss of myocardial contractile force.

Conclusions: Data reported in the present review should help physicians about their decision-making processes that govern SGAs use in CVD patients.     

Oral health of patients with special needs requiring treatment under general anaesthesia

Background: General anaesthesia (GA) remains a vital modality to facilitate dental treatment for patients with special needs but there is limited literature to describe the types of patients requiring this form of care and the treatment they receive.

Method: A cross-sectional clinical audit was conducted of patients treated under GA at the Day Surgery Unit of the Royal Dental Hospital of Melbourne during August 2015.

Results: The majority of patients had an intellectual disability and were referred due to their inability to tolerate conventional dental treatment. These patients demonstrated high levels of treatment need requiring an average of two fillings and six extractions.

Conclusions: Although these results demonstrate the value of GA in treating patients with intellectual disabilities, the level of treatment need identified raises concerns about current approaches to oral health for this cohort. Greater efforts are required towards preventive oral care for patients with special needs.     

Acute aseptic meningitis during isotretinoin treatment for nodular acne solely presenting with headache: case report and brief review of the literature

Purpose/aim: We describe, in detail, the first case of isotretinoin-induced aseptic meningitis. A brief summary of the literature on drug-induced aseptic meningitis (DIAM) is also presented.

Materials and methods: A 20-year old female patient with probable (Naranjo adverse reaction probability score of 7) DIAM during treatment with isotretinoin therapy for nodular acne solely, presenting with headache. Pseudotumor cerebri was appropriately ruled-out.

Results: Summary of data altogether lead us suggest that isotretinoin triggered DIAM, possible due to a delayed hypersensitivity mechanism type III or IV.

Conclusion: We highlight a quite uncommon cause of DIAM that may be increasing in frequency due to the current increasing use of isotretinoin against nodular acne.     

Noninvasive brain stimulation combined with other therapies improves gait speed after stroke: a systematic review and meta-analysis

Background: Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) are noninvasive brain stimulation (NIBS) techniques able to modulate cortical excitability.

Objective: To determine the effects of NIBS combined with other therapies on gait speed after stroke.

Methods: Electronic databases searched were PUBMED, EMBASE, COCHRANE, SCOPUS, SCIELO and PEDro. Eligibility criteria were randomized controlled trials that reported the effects of tDCS and rTMS combined with other therapies for improving gait speed, walking cadence, functional ambulation category (FAC) and motricity index (MI-LE) after stroke. Risk of bias was assessed by Cochrane risk of bias assessment tool. Mean differences (MD) and 95% confidence intervals were calculated. Quality of evidence was assessed by Grades of Researches, Assessment, Development and Evaluation approach.

Results: Ten studies (226 subjects) were included in the meta-analysis. NIBS combined with other therapies was effective for improving gait speed (MD 0.09 m/s [95% CI, 0.05 to 0.13; I² 0%, p < 0.0001]). Gait speed improved in both acute/subacute (MD 0.08 m/s [95% CI, 0.02 to 0.14]) and chronic phases (MD 0.08 m/s [95% CI, 0.03 to 0.13]). Furthermore, inhibitory (MD 0.09 m/s [95% CI, 0.04 to 0.14]) and excitatory (MD 0.07 m/s [95% CI, 0.02 to 0.12]) protocols were effective to improve gait speed. NIBS was also effective to improve walking cadence but was unable to modify other outcomes (FAC and MI-LE).

Conclusions: This systematic review with meta-analysis synthesizes moderate-quality evidence that NIBS combined with other therapies are effective to improve gait speed after stroke.

Systematic Review registration number: PROSPERO registration number CDR42015024237.     

Long-term cardiovascular safety of psychostimulants in children with attention deficit hyperactivity disorder

Objective: Side effects are a concern during psychostimulant treatment. Unfortunately, many previous studies only investigated short-term effects of psychostimulants in laboratory settings which lack clinical daily routines.

Methods: We examined 1042 patient records of patients with attention deficit hyperactivity disorder (ADHD) who were referred to a pediatric-psychiatry practice over 12?years. Data analysis was based on 466 children with ADHD who were newly treated with psychostimulants and who were not in treatment for elevated blood pressure. We analysed blood pressure percentiles, heart rate and BMI percentiles.

Results: There was a decrease in systolic and diastolic blood pressure percentiles. Heart rate was not affected. BMI slightly declined in girls.

Conclusions: In general psychostimulants were safe. To further elucidate negative effects of psychostimulants, long-term controlled and randomized studies in naturalistic settings are of interest.     

Estimation of skeletal muscle mass in patients with spinocerebellar ataxia type 3 and 10

Background: Neurodegenerative diseases may progress to a level in which patients present spontaneous weight loss, resulting in increased falls and functional disabilities when the disease is associated with muscle mass depletion.

Objective: Evaluate the muscle compartment in patients presenting spinocerebellar ataxia (SCA) type 3 and 10.

Methods: Forty-six patients presenting SCA type 3 and 10 were assessed and 76 volunteers were selected to the control group. In order to evaluate the muscle compartment, muscle mass anthropometric measurements were assessed and total skeletal muscle mass calculated through a predictive equation.

Results: Women with SCA3 presented greater weight loss and muscle mass reduction compared to those with SCA10 and the control group. Among the predictive measurements, calf muscle circumference showed a more significant correlation with total skeletal muscle mass (p = 0.718).

Conclusion: Patients presenting both types of ataxia did not show severe depletion in their nutritional status; however, those with SCA3 displayed greater weight loss and muscle mass reduction compared to the SCA10 group.     

Low-frequency rTMS stimulation over superior parietal cortex medially improves time reproduction and increases the right dorsolateral prefrontal cortex predominance

Aim of the study: Previous studies have shown that several cortical regions are involved in temporal tasks in multiple timescales. However, the hemispheric predominance of the dorsolateral prefrontal cortex (DLPFC) during time reproduction after repetitive low-frequency transcranial magnetic stimulation (rTMS) is relatively unexplored. Here, we study the effects of 1?Hz rTMS and sham stimulation applied medially over the superior parietal cortex (SPC) on the DLPFC alpha and beta band asymmetry and on time reproduction.

Materials and methods: For this purpose, we have combined rTMS with electroencephalography in 20 healthy subjects who performed the time reproduction task in two conditions (sham and 1?Hz).

Results: The worst performance was observed in sham and 1Hz conditions for longer time intervals (p?<?.05), with the 1Hz condition subjects sub-reproducing the time interval, closer to the target interval (p?<?.05). The right DLPFC hemispheric predominance was found in both conditions, but after low-frequency rTMS, the right hemisphere predominance increased in the 1Hz condition (p?<?.05).

Conclusions: Results of this study suggest that rTMS applied over the SPC influences time interval interpretation and the DLPFC functions. Future studies would explore the effects of the rTMS application to other cortical areas, and study how it influences time interval interpretation.     

Moderators,mediators and nonspecific predictors of outcome after cognitive rehabilitation of executive functions in a randomised controlled trial

Moderators, mediators and nonspecific predictors of treatment after cognitive rehabilitation of executive functions in a randomised controlled trial

Objective: To explore moderators, mediators and nonspecific predictors of executive functioning after cognitive rehabilitation in a randomised controlled trial, comparing Goal Management Training (GMT) with an active psycho-educative control-intervention, in patients with chronic acquired brain injury.

Methods: Seventy patients with executive dysfunction were randomly allocated to GMT (n?=?33) or control (n?=?37). Outcome measures were established by factor-analysis and included cognitive executive complaints, emotional dysregulation and psychological distress.

Results: Higher age and IQ emerged as nonspecific predictors. Verbal memory and planning ability at baseline moderated cognitive executive complaints, while planning ability at six-month follow-up mediated all three outcome measures. Inhibitory cognitive control emerged as a unique GMT specific mediator. A general pattern regardless of intervention was identified; higher levels of self-reported cognitive—and executive–symptoms of emotional dysregulation and psychological distress at six-month follow-up mediated less improvement across outcome factors.

Conclusions: The majority of treatment effects were nonspecific to intervention, probably underscoring the variables’ general contribution to outcome of cognitive rehabilitation interventions. Interventions targeting specific cognitive domains, such as attention or working memory, need to take into account the patients’ overall cognitive and emotional self-perceived functioning. Future studies should investigate the identified predictors further, and also consider other predictor candidates.     

French translation and validation of a fragile X syndrome screening checklist

Background: Fragile X syndrome (FXS) is the most common cause of inherited intellectual disability among men. This syndrome is frequently underdiagnosed in adults. The aim of this study was to develop and validate a French translation of the screening checklist Fragiele-X screeningslijst.

Method: The validation sample for the translated checklist included 22 pairs of men between the ages of 18 and 52, matched by age and degree of intellectual impairment.

Results: The translated checklist achieved coefficients of 0.92 for internal consistency, 0.90 for test-retest reliability and 0.65 for inter-rater reliability. These psychometric properties are commensurate with those of the original checklist.

Conclusion: Therefore, the translated checklist developed in this study can be considered a valid screening instrument for the detection of FXS in men with intellectual disabilities.

Abbreviations: FXS: fragile X syndrome; FMR1: fragile X mental retardation 1 (gene)