Safety and Efficacy of Continuous Theta Burst "Intensive" Stimulation in Acute-Phase Bipolar Depression: A Pilot, Exploratory Study.

OBJECTIVES: Repetitive transcranial magnetic stimulation efficacy in unipolar depression is known, but its efficacy in acute-phase bipolar depression is at best modest. Citing differential right dorsolateral prefrontal cortex hyperconnectivity implicated in BD, we aimed to study the effect of novel continuous theta burst stimulation (cTBS) targeting right dorsolateral prefrontal cortex in a randomized rater blinded placebo control design. MATERIAL AND METHODS: Nineteen patients aged 18 to 59 years (baseline Hamilton Depression Rating Scale [HAM-D] 17 severity score >18) were randomly allocated to active cTBS (n = 11) and sham cTBS (n = 9) groups using block randomization method. They received 15 cTBS sessions (burst of 3 pulses delivered at 50 Hz, repeated every 200 ms at 5 Hz, 600 pulses per session), 3 sessions per day (total of 1800 pulses) for 5 days in a week at 80% resting motor threshold. The HAM-D, Beck Depression Inventory, Hamilton Anxiety Rating Scale, World Health Organization's abbreviated quality of life assessment, and Changes in Sexual Functioning Questionnaire were assessed at baseline, after the last session, and at 2 weeks after repetitive transcranial magnetic stimulation. Intention-to-treat analysis was conducted and missing values (2 patients) were replaced using the last observation carried forward method. RESULTS: On repeated measures analysis of variance, a significant within-group time effect (from pretreatment to 2 weeks after TBS) for HAM-D ( F = 15.091, P < 0.001), Beck Depression Inventory ( F = 22.376, P < 0.001), Hamilton Anxiety Rating Scale ( F = 18.290, P < 0.001), Changes in Sexual Functioning Questionnaire ( F = 9.281, P = 0.001), and World Health Organization's abbreviated quality of life assessment ( F = 24.008, P < 0.001). The integrity of the blind assessed by the guess matrix was good. When significant between group*time effect was compared, none of the variables retained statistical significance. No major adverse effects were reported, and none of the patients discontinued the trial because of adverse effects. CONCLUSIONS: Our trial concludes that although safe and well tolerated, the therapeutic efficacy of intensive intermittent TBS in acute-phase bipolar depression is inconclusive. Choice of lower total number to sessions and smaller intersession interval along with small sample size limit the study findings.

"Efficacy of intensive bilateral Temporo-Parietal Continuous theta-burst Stimulation for Auditory VErbal hallucinations (TPC-SAVE) in schizophrenia: A randomized sham-controlled trial"☆.

Transcranial magnetic stimulation (TMS) is a non-invasive tool that moderates specific brain regions to ameliorate auditory verbal hallucinations (AVH) in schizophrenia. Citing the critical involvement of temporoparietal cortex (TPC) in AVH, our study aimed to evaluate the effect of continuous theta burst stimulation (cTBS) targeting bilateral TPC in schizophrenia subjects with AVH, on a randomized rater blinded placebo control trial. 59 patients were randomly allocated to active and sham groups. They received 20 cTBS sessions (2 per day: first right TPC, then left TPC) 5 days a week for 2 weeks. PANSS (Positive and Negative Syndrome Scale), AVHRS (Auditory vocal hallucination rating scale), PSYRAT-AH (Psychiatric symptoms rating scale- Auditory hallucinations scale), CDSS (Calgary depression scale for schizophrenia), SCoRS (Schizophrenia cognition rating scale) and CGI-S (Clinical global impression-severity) were rated at baseline, immediately post 20th session and 2 weeks post-TBS. 50 patients (25-active, 25-sham) completed the study. Conducting an intention to treat analysis, we found a significant group*time effect for PANSS, AVHRS, PSYRAT-AH, CDSS, SCoRS, CGI-S but when controlled for confounding variables and multiple comparisons, only PANSS-PS (F=26.617, p < 0.001), PANSS-TOTAL (F=23.671, p < 0.001), AVHRS (F=17.779, p < 0.001), PSYRAT-AH (F=11.385, p < 0.001) and CGI-S (F=28.462, p < 0.001) retained significance. We conclude that cTBS over TPC is safe and has efficacy in treating AVH in schizophrenia. Limited sample size and lack of integrity assessment for blinding in the study participants are major limitations of the study.

Efficacy of intensive orbitofrontal continuous Theta Burst Stimulation (iOFcTBS) in Obsessive Compulsive Disorder: A Randomized Placebo Controlled Study.

Transcranial magnetic stimulation (TMS) can non-invasively modulate specific brain regions in Obsessive-compulsive disorder (OCD). Citing orbito-frontal cortex (OFC) hyper-connectivity with striatum as the most consistent finding implicated in patho-physiologically of OCD, we aimed to study the effect of novel continuous Theta Burst Stimulation (cTBS) targeting OFC in OCD subjects on a randomized placebo control design. Thirty-three patients were randomly allocated to active cTBS (n= 18) and sham (n= 15) groups. They received 10 TBS sessions, 2 per day (total of 1200 pulses; intensive protocol) for 5 days in a week. The Yale Brown Obsessive Compulsive Scale (Y-BOCS), Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Rating Scale (HAM-A), and Clinical Global Impression-Severity (CGI-S) scores were assessed at baseline, after last session and at 2 weeks post-rTMS. On repeated measures-ANOVA, a significant group*time effect (from pretreatment to 2 weeks post TBS) for obsessions, compulsions, HAM-A, HAM-D, and CGI scores was found. But when controlled for confounding variables, only HAM-A scores and CGI effect retained statistical significance. We conclude that intensive OFC cTBS (iOFcTBS) in OCD is well tolerated with clinically significant improvements in anxiety symptoms and global severity. This improvement in anxiety symptoms could be due to modulations of state dependent dysregulation in OCD.

Serum Interleukin-6 is Not Linked with Sleep-Quality, Restless Legs Syndrome, and Depression, But with 6-Month Survival in Hematological Malignancies.

BACKGROUND: Serum interleukin (IL)-6 has been found to be associated with sleep quality, mood, and survival in patients with solid tumors. Results in these studies were confounded by knowledge of diagnosis to study subjects. Moreover, such data among subjects with hematological malignancies and data regarding restless legs syndrome is limited. The present study was, therefore, conducted to assess the sleep quality, depression, and restless leg syndrome in hematological malignancies and to study if there is any role of IL6 associated with it. METHODS: Sixty-six subjects having hematological malignancy were included in this study after excluding the potential confounders. Sleep quality was examined using Pittsburg Sleep Quality Index, depression by the Patient Health Questionnaire-9. Diagnosis of RLS was made through clinical examination. Serum for measurement of IL-6 was collected at baseline and after 1 month of initiation of chemotherapy. Patients were followed up for 6 months. RESULTS: Average age of study subjects was 50.16 years with male predominance. Nearly 22.7% had clinical depression, 28.8% had poor quality sleep, and restless legs syndrome (RLS) was reported in 6.1% cases. Nearly 22.7% patients died at 6 months. Disturbed sleep at baseline was associated with depression (odds ratio [OR] =7.89) and poor 6 months survival. Serum IL-6 did not show any association with sleep quality, restless-legs-syndrome, and depression. However, baseline high level of serum IL-6 (OR = 26.06) and low level after chemotherapy (OR = 0.03) were associated with poor survival at 6 months. CONCLUSION: Poor quality sleep, depression, and RLS are prevalent among adult subjects with hematological malignancies. Sleep disturbance, high pretreatment inflammatory and lowering of inflammatory load after chemotherapy increase likelihood for poor prognosis. Serum IL-6 did not show any association with sleep quality, restless legs syndrome and depression.

Study of Sleep Disorders among Young Children Using Hindi Translated and Validated Version of Pediatric Sleep Questionnaire.

OBJECTIVE: The objective of this study is to assess the prevalence of sleep disorders among children aging between 4 and 9 years using Hindi version of Pediatric Sleep Questionnaire (PSQ). METHODS: This study had two parts first, translation and validation of PSQ into Hindi language, and second, assessment of the prevalence of sleep disorders using PSQ Hindi version. Hindi PSQ was distributed in randomly chosen primary schools in a semi-urban area. The children were requested to get them filled by their parents. When the questionnaires were returned, responses were analyzed. RESULTS: Most of the items of the Hindi version had perfect agreement with original questionnaire in a bilingual population (κ =1). Totally, 435 children were included in the field study having average age of 6.3 years. Obstructive sleep apnea was reported in 7.5% children; symptoms suggestive of restless legs syndrome were reported by 2%-3%; teeth grinding by 13.9% and sleep talking by 22.6% children. CONCLUSION: PSQ Hindi version is a validated tool to screen for sleep disorders among children. Sleep disorders are fairly prevalent among young children in India.

Prevalence of Sleep Disorders Among Primary School Children.

OBJECTIVE: To screen symptoms of sleep disorders among primary school children. METHODS: Four schools from urban area and four rural schools were included in this study. Symptoms of sleep disorders were assessed using the validated Hindi version of Childhood Sleep Habit Questionnaire in 8-13 y old children. Comparison was made between urban and rural group and between boys and girls. Descriptive statistics was calculated. RESULTS: Mean age of the subjects included in this study was 8.9 ± 1.5 y. Boys and girls were equally distributed, however, rural sample was smaller. More than one awakening each night was found in 12.2 % children. In the whole group, prevalence of bed-wetting was 8.7 %, sleep-talking 20.9 %, sleep-walking 3.2 %, teeth grinding 15.4 % and night terrors 8.4 %. Daytime sleepiness was reported by 25.5 % and napping by 56.4 %. 17.3 % used to fall asleep in unusual circumstances and the teacher or the friend in 6.9 % students noticed it. Snoring was reported by 11.4 % children, and 6.3 % reportedly struggled to breathe during sleep. Domicile and gender did not affect prevalence of parasomnia, however, symptoms of sleep apnea were more frequent among rural children. Daytime sleepiness was more common among rural children as compared to urban. CONCLUSIONS: Symptoms of sleep disorders are prevalent among primary school children. Common disorders are parasomnia, sleep apnea and daytime sleepiness.

Hindi translation of Berlin questionnaire and its validation as a screening instrument for obstructive sleep apnea.

BACKGROUND: Obstructive sleep apnea (OSA) is a fairly common problem with adverse health consequences. However, any screening questionnaire is not available in Hindi to screen sleep apnea. MATERIALS AND METHODS: Subjects undergoing video-synchronized in laboratory attended polysomnography were requested to participate in this study. They were screened with the help of Hindi version of Berlin questionnaire (BQ). Outcome of the BQ was tested against the gold standard polysomnography. Descriptive statistics, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of Hindi version were calculated. RESULTS: 38 patients with polysomnography diagnosed OSA and 12 controls were included in this study. Average body mass index (BMI) in the OSA group was 33.12 + 6.66 kg/m(2) whereas in the control group BMI was 25.01 + 4.20 kg/m(2). Average age in the OSA group was 48.9 + 10.2 years whereas the control group was older (56.9 + 12.1 years). Hindi version had sensitivity of 89% and specificity of 58%. PPV of the instrument was 0.87 whereas NPV was 0.63. CONCLUSION: Hindi version of BQ is a valid tool for screening the OSA irrespective of the literacy status of the subjects.

Sleep-patterns, co-sleeping and parent's perception of sleep among school children: Comparison of domicile and gender.

This study was aimed at assessment of sleep schedule, pre-sleep behavior, co-sleeping and parent's perception of sleep of school going children. METHOD: Four schools each, from urban and rural area were included. Sleep patterns were assessed using the validated Hindi version of Childhood-Sleep-Habit-Questionnaire. Comparison was made between urban and rural group and between boys and girls. Interaction of gender, domicile and school-type was examined on the sleep patterns. RESULTS: This study included 831 school children with mean age of 8.9 years. Nearly half of the subjects were boys in this study. Urban children outnumbered those from rural area. Total sleep time on weekdays was 8.3 h that increased to 9.5 h on weekends. Rural children spent more time in sleep than urban children on weekdays and weekends. A higher proportion of urban children felt sleepy during the day. Television watching before bedtime was more common in urban settings. Room sharing was more common among rural children. Nearly 65% rural parents as compared to 77.5% urban parents reported that their child was sleeping sufficient enough. Gender did not affect sleep-schedule and parent's perception regarding their child's sleep. Interaction between gender, domicile and school-type did not have any significant effect on sleep patterns. CONCLUSION: Television watching before bedtime was more common among urban school children and they had shorter total sleep time. They had signs of sleep deprivation. Room sharing was more common among rural children. Despite longer sleep time, parents of rural children felt the need for more sleep.

Hindi translation and validation of Cambridge-Hopkins Diagnostic Questionnaire for RLS (CHRLSq).

BACKGROUND: Restless legs syndrome also known as Willis-Ekbom's Disease (RLS/WED) is a common illness. Cambridge-Hopkins diagnostic questionnaire for RLS (CHRLSq) is a good diagnostic tool and can be used in the epidemiological studies. However, its Hindi version is not available. Thus, this study was conducted to translate and validate it in the Hindi speaking population. MATERIALS AND METHODS: After obtaining the permission from the author of the CHRLSq, it was translated into Hindi language by two independent translators. After a series of forward and back translations, the finalized Hindi version was administered to two groups by one of the authors, who were blinded to the clinical diagnosis. First group consisted of RLS/WED patients, where diagnosis was made upon face to face interview and the other group - the control group included subjects with somatic symptoms disorders or exertional myalgia or chronic insomnia. Each group had 30 subjects. Diagnosis made on CHRLSq was compared with the clinical diagnosis. STATISTICAL ANALYSIS: Analysis was done using Statistical Package for Social Sciences (SPSS) v 21.0. Descriptive statistics was calculated. Proportions were compared using chi-square test; whereas, categorical variables were compared using independent sample t-test. Sensitivity, specificity, and positive predictive value of the translated version of questionnaire were calculated. RESULTS: Average age was comparable between the cases and control group (RLS/WED = 39.1 ± 10.1 years vs 36.2 ± 11.4 years in controls; P = 0.29). Women outnumbered men in the RLS/WED group (87% in RLS/WED group vs 57% among controls; χ(2) = 6.64; P = 0.01). Both the sensitivity and specificity of the translated version was 83.3%. It had the positive predictive value of 86.6%. CONCLUSION: Hindi version of CHRLSq has positive predictive value of 87% and it can be used to diagnose RLS in Hindi speaking population.

Headache secondary to sleep-related bruxism: A case with polysomnographic findings.

Sleep-related bruxism may present with headache. However, in clinical practice it may be difficult to differentiate from other causes of headache, especially in subjects with substance abuse. We are presenting a case of sleep-related bruxism that presented with headache and sleep-related symptoms in the presence of substance abuse. Polysomnography was used to ascertain cause of headache. How the other possible causes of headache ruled out is also discussed in report. In short, Sleep-related bruxism can cause headache that is worse in the morning. It is associated with poor quality sleep.

Head banging persisting during adolescence: A case with polysomnographic findings.

Head banging is a sleep-related rhythmic movement disorder of unknown etiology. It is common during infancy; however, available literature suggests that prevalence decreases dramatically after childhood. We report the case of a 16-year-old male who presented with head banging. The symptoms were interfering with his functioning and he had been injured because of the same in the past. We are presenting the video-polysomnographic data of the case. Possible differential diagnoses, etiology, and treatment modalities are discussed. The boy was prescribed clonazepam and followed up for 3 months. Parents did not report any episode afterward.

Kleine-Levin syndrome: a case report and review of literature.

BACKGROUND: Kleine-Levin syndrome presents with recurrent hypersomnia along with a number of other neuropsychiatric features, of which hyperorality has not been described frequently. METHOD: We report a male adolescent who presented with recurrent hypersomnia, hypersexuality, and hyperorality. Magnetic resonance imaging of the brain and overnight polysomnography followed by a multiple sleep latency tests were ordered. Excessive daytime sleepiness was assessed with the Epworth Sleepiness Scale. RESULTS: Magnetic resonance imaging of the brain did not reveal any abnormality. Overnight video-synchronized polysomnography and multiple sleep latency tests ruled out narcolepsy. Epworth Sleepiness Scale score at baseline was 22. He was prescribed lithium carbonate 300 mg twice a day. The symptoms improved within a week after starting lithium carbonate therapy. CONCLUSION: Kleine-Levin syndrome may present with hyperorality, and our patient responded well to lithium carbonate therapy.

Suicidal behaviour of Indian patients with obsessive compulsive disorder.

BACKGROUND SETTING AND DESIGN: The chronicity, distress, high rates of comorbidity and varying degree of non response to treatment in Obsessive Compulsive Disorder (OCD) may contribute to suicidal behavior. There is relatively little information on suicidal behavior in OCD subjects. Our study design is Single point non-invasive, cross sectional, clinical study of new and follow up cases. MATERIALS AND METHODS: Assessment of Suicidal Behavior in patients of OCD attending the adult Psychiatry O.P.D. of Chatrapati Shahuji Maharaj Medical University (CSMMU) U.P. Lucknow using (DSM-IV) criteria for diagnosis of Obsessive Compulsive Disorder, Structured Clinical Interview for DSM-IV Axis-I disorders, Yale Brown Obsessive Compulsive Rating Scale, Scale for Suicidal Ideation (SSI), Beck's Hopelessness Scale (BHS). STATISTICAL ANALYSIS: Mean standard deviation and t test for independent samples, Pearson's correlation coefficient. RESULTS: Statistically significant differences were seen in the SSI score between the "Clinical" and "Sub-Clinical" cases with Clinical group having higher scores. Value of correlation coefficient between YBOCS score and SSI and BHS score is positive and statistically significant (P<0.01). CONCLUSION: "Clinical" group of patients had significantly higher scores of suicidal ideation measured by Scale of Suicidal Ideation (SSI). There was a significantly positive correlation between disease severity (YBOCS Score) and degree of suicidal ideation (SIS Score).

Prevalence and correlates of insomnia and obstructive sleep apnea in chronic kidney disease.

BACKGROUND: Poor sleep quality, insomnia, and restless legs syndrome (RLS) and sleep apnea are common in patients with chronic kidney disease (CKD). Clinical correlates of these problems are poorly understood. AIMS: This study was to find out the prevalence and correlates of insomnia and subjects with 'high risk for obstructive sleep apnea (OSA)' in adults with chronic kidney disease. MATERIALS AND METHODS: One hundred and four adults with CKD were included. Their demographic data, details regarding kidney disease and hemodialysis (HD) were recorded. Presence of insomnia and its severity was assessed. They were screened for sleep apnea using a validated questionnaire. RESULTS: Average age was 54.17 (± 12.96) years. 89.4% had stage 5 nephropathy and 78.8% subjects were on regular HD. Males outnumbered females. Insomnia was reported by 35.5%. Among these, 50% had chronic insomnia. Insomnia subjects had higher prevalence of diabetes (P = 0.01) and depression (P < 0.001). Fifty-one percent subjects were at "high risk for sleep apnea". They had higher prevalence of diabetes (P < 0.001), coronary disease (P = 0.02), insomnia (P = 0.008), and experienced daytime symptoms of insomnia (P < 0.001). However, in the logistic regression, only male gender (odds ratio, OR = 13.59) and daytime symptoms of insomnia (OR = 7.34) were found to be associated with "higher risk for sleep apnea". CONCLUSION: Insomnia was prevalent in CKD. Nearly half of these patients are at high risk for sleep apnea and a third of them suffer from insomnia. Hence, these patients should be screened for sleep disorders.

Hindi translation and validation of dysfunctional beliefs and attitudes about sleep (DBAS - 16).

OBJECTIVES: The objective of this study is to translate and validate the Dysfunctional Beliefs and Attitudes about Sleep Brief Version (DBAS-16)) in Hindi language. MATERIALS AND METHODS: The scale was obtained online, and the permission for translation was obtained from the author. The translation of the scale was carried out following back translation method. The scale was applied on 63 participants attending the adult psychiatry OPD who were included in the study. RESULTS: Thirty-two patients were having insomnia, and 31 patients were controls without insomnia. The results show that the translated version had good reliability with internal consistency (Chronbach alpha = 0.901). CONCLUSION: The Hindi translation of DBAS-16 is a reliable tool for assessing the dysfunctional beliefs and attitude about sleep.