Neuropsychological Side Effects Research Articles

Longitudinal Effects of Elexacaftor/Tezacaftor/Ivacaftor: Multidimensional Assessment of Neuropsychological Side Effects and Physical and Mental Health Outcomes in Adolescents and Adults

Italy initiated elexacaftor/tezacaftor/ivacaftor (ETI) for people with cystic fibrosis (pwCF) in July 2021. It has led to dramatic improvements in lung function, BMI, sweat chloride, and respiratory symptoms. However, few data are available on side effects or effects on a broad range of outcomes. How does ETI affect mental health, cognitive processing, neuropsychological side effects, GI symptoms, and health-related quality of life over time? This was a prospective, "real-world" longitudinal study. Participants were recruited consecutively and evaluated at initiation (T0) and after 1month, 3months, and 6months of starting treatment. Assessments included depression (nine-item Patient Health Questionnaire), anxiety (seven-item Generalized Anxiety Disorder), cognition (Symbol Digit Modalities Test), GI Symptom Tracker, and health-related quality of life (Cystic Fibrosis Questionnaire-Revised). Based on literature, an ad hoc questionnaire was developed to assess side effects: insomnia, headache, memory problems, "brain fog," and concentration problems. Following descriptive analyses, longitudinal data were analyzed by using mixed models for repeated measures, controlling for age and sex when appropriate. Ninety-two consecutive pwCF (female/male, 46/46; mean age, 25.4 years) participated. FEV1 increased initially and then remained stable. BMI also increased significantly from T0 to 6months (P< .01). Depression improved from T0 to 1month (P< .001); however, no changes in anxiety were found. Cognitive processing improved from T0 to subsequent assessments. Positive changes were reported on the GI Symptom Tracker for stools and adherence challenges, although no changes were found for abdominal pain and digestion. Side effects occurred in 10%to 29%, with no reduction over time; insomnia increased significantly across time. Female participants reported more side effects than male participants (ie, insomnia, headache, concentration problems, brain fog). This prospective study evaluated the effects of ETI using multiple measures. Significant improvements were found in many domains; however, side effects were reported by a substantial proportion of pwCF, with no improvements over time. Female participants reported more side effects than male participants. pwCF should be followed up systematically to assess the frequency of side effects after starting this new modulator.

501 Longitudinal prevalence and type of neuropsychological side-effects after starting ETI: Are women at greater risk?

501 Longitudinal prevalence and type of neuropsychological side-effects after starting ETI: Are women at greater risk?

Neuropsychological side effects of anti-epileptic drugs in epilepsy patients: a cross sectional study

Background: Epilepsy is the fourth most common neurological disorder in world. Managing an epilepsy with anti-epileptic drugs (AEDs) either as monotherapy or polytherapy is necessary to reduce the deleterious effect of the disease and to provide neuroprotection. AEDs exert their negative effects on cognition by suppressing neuronal excitability or enhancing inhibitory neurotransmission. These neuropsychological side effects are found to be modest when the drug level is within the therapeutic concentration and used as monotherapy. Objectives were to assess the prevalence of neuropsychological side effects among epilepsy patients who were on antiepileptic drug therapy. Methods: An open label, cross-sectional, clinical study was conducted at a tertiary care hospital, 126 participants were recruited. Participants demographic data, detailed medical and seizure history followed by neuropsychological tests was performed. The prevalence was assessed based on the number of participants scoring &lt;15th percentile in one or more tests. Results: Out of 126 participants who were recruited, 82 participants were on monotherapy and 44 participants were on polytherapy. Levetiracetam was the most commonly prescribed drug as monotherapy, followed by phenytoin, carbamazepine and valproate; whereas in polytherapy levetiracetam, clobazam followed by phenytoin were the commonly prescribed AED. The most common adverse effect was drowsiness, followed by headache, hypersensitivity reaction, giddiness, tremors, anxiety etc. The prevalence of neuropsychological side effects was 77.8%. The prevalence of impairment between monotherapy and polytherapy was statistically insignificant (p=0.727). Conclusions: In this study, levetiracetam was the most commonly prescribed drug and the most common adverse effect was drowsiness due to AEDs. The subgroup analyses between monotherapy and polytherapy did not show any statistically significant neuropsychological impairment when compared based on the gender, age groups, duration of epilepsy with medication and duration of current therapy.

Questionnaire-Based Analysis of Adverse Events and Compliance with Malaria Chemoprophylaxis in Taiwan

Malaria was eradicated in Taiwan in 1952; however, imported malaria cases are reported every year. The subtropical climate in Taiwan permits mosquito propagation and possible outbreaks of mosquito-borne diseases. The aim of this study was to investigate travelers' compliance and side effects of malaria prophylaxis to prevent a malaria outbreak in Taiwan. In this prospective study, we enrolled travelers who visited our travel clinic before going to malarious areas. A total of 161 questionnaires were collected and analyzed. Associations between the occurrence of side effects and compliance with antimalarial drugs were analyzed. Adjusted odds ratios were calculated after adjusting for potential risk factors in multiple logistic regression analysis. Of the 161 enrolled travelers, 58 (36.0%) reported side effects. Insomnia, somnolence, irritability, nausea, and anorexia were associated with poor compliance. Mefloquine was not associated with more neuropsychological side effects than doxycycline. Multiple logistic regression analysis showed that chemoprophylaxis compliance was affected by a younger age, visiting friends and relatives, visiting the travel clinic more than 1 week before the trip, and preferring to use the same antimalarial regimen on the next trip. Our findings could provide information to travelers besides labeled side effects to improve compliance with malaria prophylaxis and consequently help to prevent malaria outbreaks in Taiwan.

Neuropsychological side effects of combined hormonal contraceptives for the treatment of mild symptoms. Bioethical assessment of its adequacy

Since the beginning of the commercialization, in 1960, of combined estrogen-progestin hormonal contraceptives (CHCs), their use has become widespread for other non-contraceptive indications: dysmenorrhea, irregular cycle length, hypermenorrhea and acne, among others (Lete, 2009; Barranco, 2016). In all cases, these are mild pathologies or minor symptoms for which there are effective therapeutic alternatives. Millions of women in the world receive this treatment, which acts by inhibiting the hypothalamic-pituitary-ovarian hormonal axis (HHO Axis), the central axis and regulator of the entire sexual and reproductive physiology of women. Despite the existence of an enormous number of women subjected to this inhibition (ACHs are currently used by some 214 million women around the world, with an annual market of close to 18 billion dollars), very little research has been done on the consequences of suppressing the HHO axis. Only in recent years, and in parallel to the demonstration of the existence of functional receptors for gonadotropins at different levels in the central and peripheral nervous systems, have publications on the neuropsychological effects of HCAs begun to appear. It is also striking that, despite being the most widely used drugs and for the longest time for the treatment of functional gynecological disorders, their use is outside the technical data sheet (i.e., they are used for purposes other than those listed in the official indication approved in their technical data sheet and which appear in the package insert). Although the use of these hormonal products causes a wide variety of side effects, which have been widely studied in the medical literature, the present study proposes, after an exposition of the different aspects of the use of HCAs, a detailed review of the available literature on the neuropsychological effects due to the annulment of the HHO axis. This in order to, after a biological analysis, subsequently establish whether there is an ethical appropriateness in the use that concerns us.

Antiseizure medication use and medical resource utilization after resective epilepsy surgery in children in the United States: A contemporary nationwide cross-sectional cohort analysis.

Antiseizure drug (ASD) therapy can significantly impact quality of life for pediatric patients whose epilepsy remains refractory to medications and who experience neuropsychological side effects manifested by impaired cognitive and social development. Contemporary patterns of ASD reduction after pediatric epilepsy surgery across practice settings in the United States are sparsely reported outside of small series. We assessed timing and durability of ASD reduction after pediatric epilepsy surgery and associated effects on health care utilization. We performed a retrospective analysis of 376 pediatric patients who underwent resective epilepsy surgery between 2007 and 2016 in the United States using the Truven MarketScan database. Filled ASD prescriptions during the pre- and postoperative periods were compared. Univariate and multivariate analyses identified factors associated with achieving a stable discontinuation of or reduction in number of ASDs. Health care utilization and costs were systematically compared. One hundred seventy-one patients (45.5%) achieved a >90-day ASD-free period after surgery, and 84 (22.3%) additional patients achieved a stable reduction in number of ASDs. Achieving ASD freedom was more common in patients undergoing total hemispherectomy (n=21, p=.002), and less common in patients with tuberous sclerosis (p=.003). A higher number of preoperative ASDs was associated with a greater likelihood of achieving ASD reduction postoperatively (hazard ratio [HR]: 1.85, 95% confidence interval [CI]: 1.50-2.28), but was not associated with a significant difference in the likelihood of achieving ASD freedom (0.83, 95% CI: 0.49-1.39). Achieving an ASD-free period was associated with fewer hospital readmissions within the first year after surgery. Patterns of ASD use and discontinuation after pediatric epilepsy surgery provide an unbiased surgical outcome endpoint extractable from administrative databases, where changes in seizure frequency are not captured. This quantitative measure can augment traditional surgical outcome scales, incorporating a significant clinical parameter associated with improved quality of life.

Psychological Distress in Intracranial Neoplasia: A Comparison of Patients With Benign and Malignant Brain Tumours.

Objective: We aimed to assess psychological distress in patients with intracranial neoplasia, a group of patients who suffer from severe functional, neurocognitive and neuropsychological side effects, resulting in high emotional distress.Methods: We conducted a cross-sectional study, including inpatients with brain tumours. Eligible patients completed validated self-report questionnaires measuring depression, anxiety, distress, symptoms of posttraumatic stress disorder (PTSD), fear of progression and health-related quality of life. The questionnaire set was completed after brain surgery and receiving diagnosis and before discharge from hospital.Results: A total of n = 31 patients participated in this survey. Fourteen of them suffered from malignant (n = 3 metastatic neoplasia) and 17 from benign brain tumours. Mean values of the total sample regarding depression (M = 9.28, SD = 6.08) and anxiety (M = 6.00, SD = 4.98) remained below the cut-off ≥ 10. Mean psychosocial distress (M = 16.30, SD = 11.23, cut-off ≥ 14) and posttraumatic stress (M = 35.10, SD = 13.29, cut-off ≥ 32) exceeded the clinically relevant cut-off value in all the patients with intracranial tumours. Significantly, more patients with malignant (79%) than benign (29%) brain tumours reported PTSD symptoms (p = 0.006).Conclusion: Distress and clinically relevant PTSD symptoms in patients with intracranial neoplasia should be routinely screened and treated in psycho-oncological interventions immediately after diagnosis. Especially, neuro-oncological patients with malignant brain tumours or metastases need targeted support to reduce their emotional burden.

Use of proton-pump inhibitors is associated with depression: a population-based study.

Treatment with proton-pump inhibitors (PPIs) might be associated with neuropsychological side effects. We examined the association between use of PPIs and depressive symptoms in an elderly population. Mood was assessed by the 30-item Geriatric Depression Scale (GDS) in all 344 inhabitants of Tuscania (Italy) aged 75 years and over, without exclusion criteria; depression was defined by a GDS score ≥11. Use of PPIs was associated with a higher GDS score in linear regression analysis (B = 2.43; 95% CI = 0.49-4.38; p = 0.014) after adjusting; also, use of PPIs was associated with increased adjusted probability of depression in logistic regression (OR = 2.38; 95% CI = 1.02-5.58; p = 0.045). Higher PPIs dosages were associated with increased probability of depression (p for trend = 0.014). This association was independent of the diagnosis of peptic disease, as well as the use of antidepressant medications. No association was found between use of H2-blockers or antacids and the GDS score. Calculation of the population attributable risk indicated that 14% of depression cases could be avoided by withdrawal of PPIs. Use of PPIs might represent a frequent cause of depression in older populations; thus, mood should be routinely assessed in elderly patients on PPIs.

&lt;b&gt;Motivation Exercise and Feedback - Virtual Reality and Robotics in Physical Medicine and Rehabilitation&lt;/b&gt;

There exist new technologies as Robotics and Prosthetics, Functional Electrical Stimulations, Brain Computer Interfaces and Virtual Reality with the problems associated with cost reduction for diffusion in medical hospitals and home daily use and neuropsychological negative side effects in connection with new using technologies.Motivation exercise and feedback, virtual reality and robotics must be applied in PM & RM in concordance with the status of the patient and in relation with functional capabilities.

Cognitive impairment with interferon treatment in patients with chronic hepatitis C.

Interferon (IFN) has various side effects, including psychiatric symptoms. Event-related potentials are used as an electrophysiologic index of cognitive disorders. Auditory event-related potentials (P300) are often used in conditions in which cognitive ability is affected. In this study, we evaluated the association between P300, used to assess cognitive impairment, and neuropsychological side effects of IFN treatment in patients with chronic hepatitis C. Subjects were 20 patients with chronic hepatitis C; 13 patients were treated with peg IFN-α2b and ribavirin (riba group), and 7 patients were treated with peg IFN-α2a (alone group). P300 was performed on all patients before treatment and after 1 week, 4 weeks, 2 months, and 3 months of treatment. In addition, 10 patients of them completed the self-rating depression scale (SDS). P300 latency was significantly prolonged at all points of measurement during IFN treatment. No correlation between the change of SDS score and the change rate of P300 latency was shown. Six patients with neuropsychological symptom had a significantly increased change rate of P300 latency compared with patients without neuropsychological symptoms (P < 0.05). Based on P300 findings, this study suggests that patients with chronic hepatitis C treated with IFN may experience significant cognitive impairment.

A Double Blind Randomised Clinical Trial to Prevent Serious Side Effects of Dexamethasone during Pediatric Acute Lymphoblastic Leukemia Treatment

Background/Objectives: Dexamethasone is highly effective in the treatment of pediatric acute lymphoblastic leukemia (ALL), but can induce serious metabolic and neuropsychological side effects. Recent studies have led to the hypothesis that neuropsychological side effects could be due to cortisol depletion of the cerebral mineralocorticoid receptor. We therefore studied whether adding a physiological dose of hydrocortisone to dexamethasone treatment reduces neuropsychological and metabolic side effects in children with ALL.Design/Methods: We performed a multicentre double-blind, randomised controlled trial with a crossover design. Patients (3-16 years) treated with dexamethasone pulses according to the DCOG ALL protocols were included. Patients received hydrocortisone 10 mg/m2/day in a circadian rhythm during one dexamethasone course and placebo during another dexamethasone course in a randomised order. The primary outcome measures were mood and behavior (parent-reported Strenght and Difficulties Questionnaire- Dut (SDQ)). Secondary outcome measures included sleep (Sleep Disturbance Scale for Children (SDSC)), neurocognitive function, and metabolic parameters.Results: 50 subjects were enrolled, of which 48 patients completed both courses. For the total group no significant effects were found. However, in the subgroup of children with clinically significant behavioral side effects, adding hydrocortisone resulted in a significant reduction of side effects on overall stress (-4.9 (=0.9 SD), P =0.00), mood (-1.8 (=0.9 SD), P =0.03), behavior (-1.0 (=0.7 SD), P =0.01), and impact (P <0.05). The subgroup with dexamethasone-related sleeping problems did benefit on total sleeping problems (-4.3, P< 0.05). In contrast, hydrocortisone addition did not affect metabolic parameters.Conclusion: This randomised controlled trial provides evidence that addition of a physiological dose of hydrocortisone in circadian rhythm during dexamethasone treatment in pediatric ALL patients reduces side effects on behavior, mood and sleep. This novel and simple intervention may be valuable for all patients on high-dose dexamethasone treatment. DisclosuresNo relevant conflicts of interest to declare.

Antipsicóticos: aspectos neurocognitivos

Cognitive function has received particular interest due its potential impact on the daily functioning of patients with bipolar disorder. It is currently well known that cognitive disorders could be present from the onset of the illness. The various pharmacological treatments that patients receive may not be free of neuropsychological side effects, from both positive and negative points of view. The cognitive side effects that are associated with the most commonly prescribed antipsychotic drugs to patients with bipolar disorder are then reviewed. Very few studies have been conducted specifically with this population, with most data coming from research into schizophrenia and, in some cases, from studies on healthy subjects. At present, we cannot conclude that an atypical antipsychotic is better than others with regard to its cognitive profile. In clinical practice, when prescribing a specific drug, clinicians should take its cognitive profile into consideration in the same way that its potential adverse effects are considered.

The treatment of Parkinson's disease with deep brain stimulation: current issues.

Deep brain stimulation has become a well-established symptomatic treatment for Parkinson's disease during the last 25 years. Besides improving motor symptoms and long-term motor complications, positive effects on patients’ mobility, activities of daily living, emotional well-being and health-related quality of life have been recognized. Apart from that, numerous clinical trials analyzed effects on non-motor symptoms and side effects of deep brain stimulation. Several technical issues and stimulation paradigms have been and are still being developed to optimize the therapeutic effects, minimize the side effects and facilitate handling. This review summarizes current therapeutic issues, i.e., patient and target selection, surgical procedure and programming paradigms. In addition it focuses on neuropsychological effects and side effects of deep brain stimulation.

Hydrocortisone does Not Influence in Vitro Glucocorticoid Sensitivity of Acute Lymphoblastic Leukemia Blasts

Introduction: Dexamethasone-induced neuropsychological side effects on mood, behavior and cognition seriously affect quality of life in children with acute lymphoblastic leukemia (ALL) during a long treatment period. Based on recent studies in animals, we hypothesized that these neuropsychological side effects are mediated by dexamethasone-induced cortisol depletion of the mineralocorticoid receptor (MR) in the brain. Therefore, we hypothesize that these side effects could be ameliorated by an intervention with hydrocortisone. For clinical application settings however, an absolute prerequisite is that MR activation does not interfere with the efficacy of the glucocorticoids, dexamethasone and prednisolone, on ALL cells.Materials and Methods: To investigate responsiveness of leukemic cell lines and fresh patients’ leukemic cells to dexamethasone and prednisolone in the presence of hydrocortisone, MTT-assays were performed. In addition MR and the glucocorticoid receptor (GR) expression on leukemic cells of different ALL subtypes was studied with a microarray-based gene expression profiling and validated by quantitative real-time PCR.Results: Leukemic cells expressed the MR at a very low level with a significantly higher (P≤0.001) expression in ETV6-RUNX1+ patients (median: 160.7 [AU] of fluorescence intensity, range: 38.1 - 760.6 [AU]) versus other ALL subtypes (median: 41.8 [AU] of fluorescence intensity, range: 25.1 - 276.2 [AU]). MR expression did not differ between glucocorticoid resistant and sensitive patients’ cells. Hydrocortisone addition did not affect glucocorticoid sensitivity of leukemic cell lines and patients’ leukemic cells of different leukemic subtypes also including ETV6-RUNX1+. Glucocorticoid sensitive patients’ cells became significantly more sensitive by hydrocortisone addition (prednisolone: P≤0.01, dexamethasone: P≤0.05).Conclusion: This present study shows that hydrocortisone does not interfere with efficacy of dexamethasone and prednisolone in vitro. These findings support a clinical randomized trial to study whether addition of hydrocortisone decreases the neuropsychological side effects of dexamethasone in children with ALL.Acknowledgments: The financial support of the KiKa® (Kinderen Kankervrij) foundation is highly appreciated. DisclosuresNo relevant conflicts of interest to declare.

Does dexamethasone induce more neuropsychological side effects than prednisone in pediatric acute lymphoblastic leukemia? A systematic review

Steroid-induced neuropsychological side effects impact quality of life in children with acute lymphoblastic leukemia. Dexamethasone induces more metabolic side effects than prednisone. To evaluate whether dexamethasone also leads to more neuropsychological side effects, we reviewed all available literature. Randomized controlled trials with neuropsychological function as the primary or secondary outcome did not show clinically meaningful differences between dexamethasone and prednisone on cognition, mood or behavior.

High‐dose busulfan–thiotepa with autologous stem cell transplantation followed by posterior fossa irradiation in young children with classical or incompletely resected medulloblastoma

The aim of the study is to evaluate the outcome of young children with high risk localized medulloblastomas (newly diagnosed classical or incompletely resected) treated by high-dose busulfan-thiotepa with autologous stem cell rescue (ASCT) followed by focal radiation therapy (RT). Between September 1994 and January 2010, 19 children younger than 5 years old at diagnosis fulfilling the above inclusion criteria were treated at the Institute Gustave Roussy. After conventional chemotherapy, they received busulfan at a dose of 600 mg/m(2) and thiotepa at a dose of 900 mg/m(2) followed by ASCT. Focal RT was delivered at least 70 days after ASCT. The median follow-up was 40.5 months (range, 14.5-191.2 months). The 3-year event-free survival (EFS) and OS were 68% (95% CI 45-84%) and 84% (95% CI 61-94%), respectively. Acute toxicity consisted mainly in hepatic veno-occlusive disease (6/19 patients) and bone marrow aplasia (all patients). No toxic death occurred. The Full Scale Intellectual Quotient tended to decrease over time at a mean rate of 0.9 point per year from the date of diagnosis. This intensive treatment resulted in a high overall survival rate in young children with newly diagnosed non-metastatic classic or incompletely resected MB. In spite of a high incidence of hepatic veno-occlusive disease (32%), the acute toxicity was manageable. Delayed neuropsychological side effects remain main concerns. These results should to be confirmed in a larger cohort.

EPA-0030 – The effects of bilateral subthalamic nucleus stimulation on cognitive and neuropsychiatric functions in parkinson's disease: a case-control study

Introduction Parkinson's disease is one of the most disabling neurological diseases; however much progress has been made in the treatment of drug resistant patients through electrode implantation and stimulation of the subthalamic nucleus (STN). This new neurosurgical method may lead to some neuropsychological side effects in patients. The main aim of this study was to evaluate the neuropsychiatric effects of this treatment. Method This case-control study was designed to compare two groups of patients with Parkinson's disease. Thirty patients who underwent electrode implantation and deep brain stimulation were compared with 60 patients treated with antiparkinson drugs. These two groups were matched for age, sex, duration and severity of Parkinson's disease. Measurements The UPDRS was used to assess the severity of Parkinson's disease. The Beck Depression Inventory questionnaire and the Hamilton Anxiety Rating Scale were used to evaluate depression and anxiety as a consequence of DBS. The Mini Mental Status Examination and Clock Drawing Test (CDT) were used to evaluate the cognitive and executive function. Results Thirty months after STN stimulation, a lower level of anxiety and depression were seen in the DBS patients compared with drug treated subjects, but the differences were not significant. However, cognitive status deteriorated to a greater extent in study subjects compared to the control group. The MMSE results were not significantly different, but the differences in CDT scores were significant. Conclusion Patients who have undergone DBS surgery must be followed up for neuropsychiatric symptoms, particularly for subcortical cognitive deterioration in the long term.

1024 – Prospective analysis of STN DBS in parkinson's disease: motor and non-motor symptoms evolution link to electrodes localization

Even if evidence suggests that Deep Brain Stimulation (DBS) of the Subthalamic Nucleus (STN) provides a beneficial clinical effect in Parkinson's disease (PD) for up to 10 years there are also several potential risks among them psychiatrics complications. The aim of this study was to identify the patient-related, medicosurgical, and psychosocial factors that influence PD patient's evolution in STN DBS. Method We investigate, in 36 STN DBS PD patients, depression, anxiety and mania at baseline, 3-mounth post-surgery and 6-mounth post-surgery. At baseline, demographic data and clinical characteristics (duration of disease, PD medication, past psychiatric history were also collected. Scores at motor section of the unified Parkinson disease rating scale and PD medication were evaluated at baseline, 3-mounth post-surgery and 6-mounth post-surgery. A multivariate analysis and a factorial discriminant analysis (FDA) were considered to study differences between surgical outcomes considering an adjustment on disease duration. Results Thirty six patients with Parkinson's disease treated with STN-DBS were analyzed considering stimulating electrodes localization (‘in’, ‘frontier’, ‘out’ of STN). Concerning the pre-surgical parameters, no configuration was found. Considering only 3-mounth post-surgery parameters (electrodes localization, motor scores, psychiatric data, PD medication) patients differ according to surgical positioning: ‘frontier’/’out’ and ‘in’ but the best separation between the 3 groups of localization was obtain including pre-surgical post-surgery parameters. This segregation was maintained at 6-mounth postsurgery. Conclusions Our work provides preliminary answer to the question of impact of the exact electrode position on neuropsychological side effects of STN-DBS and enhances the importance of combining pychiatrico-neuro-surgical data.

Anatomo-clinical atlases correlate clinical data and electrode contact coordinates: Application to subthalamic deep brain stimulation

For patients suffering from Parkinson's disease with severe movement disorders, functional surgery may be required when medical therapy is not effective. In Deep Brain Stimulation (DBS), electrodes are implanted within the brain to stimulate deep structures such as SubThalamic Nucleus (STN). The quality of patient surgical outcome is generally related to the accuracy of nucleus targeting during surgery. In this paper, we focused on identifying optimum sites for STN DBS by studying symptomatic motor improvement along with neuropsychological side effects. We described successive steps for constructing digital atlases gathering patient's location of electrode contacts automatically segmented from postoperative images, and clinical scores. Three motor and five neuropsychological scores were included in the study. Correlations with active contact locations were carried out using an adapted hierarchical ascendant classification. Such analysis enabled the extraction of representative clusters to determine the optimum site for therapeutic STN DBS. For each clinical score, we built an anatomo-clinical atlas representing its improvement or deterioration in relation with the anatomical location of electrodes and from a population of implanted patients. To the best of our knowledge, we reported for the first time a discrepancy between a very good motor improvement by targeting the postero-superior region of the STN and an inevitable deterioration of the categorical and phonemic fluency in the same region. Such atlases and associated analysis may help better understanding of functional mapping in deep structures and may help pre-operative decision-making process and especially targeting.

A review of ultrabrief pulse width electroconvulsive therapy

The effect of shortening the pulse width of the electrical stimulus when administering electroconvulsive therapy (ECT) has recently been systematically studied with promising results. This review examines reported outcomes from three randomized controlled trials which compared ultrabrief (≤0.3 ms) with brief (0.5-1.5 ms) pulse width ECT, and other recent clinical trials of ultrabrief pulse width ECT. The emerging evidence for ultrabrief pulse right unilateral (RUL) ECT suggests clinically meaningful efficacy and substantially reduced neuropsychological side effects compared with standard (brief) pulse ECT; this may represent a generational advance in the ECT technique. However, it is unclear if patients receiving ultrabrief pulse RUL ECT may have a slower speed of response and require additional treatments compared with brief pulse ECT. Therefore, until further data are available, clinicians may be well advised to use brief pulse ECT in situations requiring an urgent clinical response. The evidence base for ultrabrief bilateral ECT is limited, with findings that efficacy may be reduced compared with brief pulse width ECT. Thus ultrabrief bilateral ECT should not be used outside the research setting.