Stimulation Parameters for Sacral Neuromodulation on Lower Urinary Tract and Bowel Dysfunction–Related Clinical Outcome: A Systematic Review

ObjectiveSacral neuromodulation (SNM) has been used to treat patients with lower urinary tract dysfunction and bowel dysfunction for many years. Success rates vary between 50% and 80%, indicating that there is much room for improvement. Altering stimulation parameters may result in improved outcome. This paper reports a systematic review of the clinical efficacy of nonconventional stimulation parameters on urinary tract and bowel dysfunction.Materials and MethodsThree databases were used for the literature search: Ovid (Medline, Embase) and PubMed. Papers were screened by two independent reviewers, who also extracted data from these papers. Clinical papers studying SNM stimulation parameters, that is, intermittent stimulation, frequency, pulse width, and amplitude, in urinary tract and bowel dysfunction were included. Quality of included papers was assessed using standardized guidelines.ResultsOut of 5659 screened papers, 17 papers, studying various stimulation parameters, were included. Overall quality of these papers differed greatly, as some showed no risk of bias, whereas others showed high risk of bias.Stimulation parameters included intermittent stimulation, frequency, pulse width, amplitude, and unilateral vs. bilateral stimulation. Especially high frequency SNM and either a narrow or wide pulse width seem to improve efficacy in patients with bowel dysfunction. Additionally, implementation of short cycling intervals is promising to improve quality of life for patients with urinary tract or bowel dysfunction.ConclusionThe results of our systematic review indicate that stimulation parameters may improve efficacy of SNM in treatment of both urinary tract dysfunction and bowel dysfunction.     

Does Analgesic Overuse Contribute to Chronic Post-traumatic Headaches in Adolescent Concussion Patients?

BackgroundThe causes of persistent headache following concussion are poorly understood. The objective of this study is to explore analgesic overuse as a potential cause of chronic post-traumatic headache among adolescents referred to a headache clinic following concussion.MethodsA retrospective chart review was conducted of all adolescent concussion patients referred to our pediatric headache clinic over the 16-month period between August 1, 2011, and November 30, 2012. Those patients with chronic post-traumatic headaches of 3-12 months' duration who also met International Headache Society criteria for probable medication-overuse headache were identified. Demographic data, concussion symptoms, and headache features were characterized from the initial evaluation and from follow-up visits.ResultsOf 104 adolescent concussion patients referred during the study period, 77 had chronic post-traumatic headache of 3-12 months' duration. Fifty-four of 77 (70.1%) met criteria for probable medication-overuse headache. Only simple analgesics were overused. Thirty-seven patients (68.5%) had resolution of headaches or improvements to preconcussion headache patterns after discontinuing analgesics; seven (13%) had no change in headaches or worsening of headaches after discontinuing analgesics and 10 (18.5%) did not discontinue analgesics or were lost to follow-up.ConclusionExcessive use of analgesics postconcussion may contribute to chronic post-traumatic headaches in some adolescents. Management of patients with chronic post-traumatic headache should include analgesic detoxification when medication overuse is suspected.     

Genomic Disorders in Psychiatry—What Does the Clinician Need to Know?

Purpose of Review

The purpose of this review is to summarize the role of genomic disorders in various psychiatric conditions and to highlight important recent advances in the field that are of potential clinical relevance.

Recent Findings

Genomic disorders are caused by large rare recurrent deletions and duplications at certain chromosomal “hotspots” (e.g., 22q11.2, 16p11.2, 15q11-q13, 1q21.1, 15q13.3) across the genome. Most overlap multiple genes, affect development, and are associated with variable cognitive and other neuropsychiatric expression. Although individually rare, genomic disorders collectively account for a significant minority of intellectual disability, autism spectrum disorder, and schizophrenia.

Summary

Genome-wide chromosomal microarray analysis is capable of detecting all genomic disorders in a single test, offering the first opportunity for routine clinical genetic testing in psychiatric practice.

     

Does Switching Antipsychotics Ameliorate Weight Gain in Patients With Severe Mental Illness? A Systematic Review and Meta-analysis

ObjectiveObesity and adverse metabolic outcomes in patients with severe mental illness are clinically significant but potentially preventable. Importantly, the evidence for switching to antipsychotics to reduce cardiometabolic burden is unclear.MethodPubMED, Embase, PsycINFO, and Cochrane were searched from inception to March 8, 2020. Articles reporting weight and metabolic changes after antipsychotic switching vs staying on the previous antipsychotic were meta-analyzed both across and within group.ResultsOf 61 identified studies, 59 were meta-analyzed (40% rated high quality). In the switch-vs-stay pairwise meta-analyses, only aripiprazole significantly reduced weight (−5.52 kg, 95% CI −10.63, −0.42, P = .03), while olanzapine significantly increased weight (2.46 kg, 95% CI 0.34, 4.57, P = .02). Switching to aripiprazole also significantly improved fasting glucose (−3.99 mg/dl, 95% CI −7.34, −0.64, P = .02) and triglycerides (−31.03 mg/dl, 95% CI −48.73, −13.34, P = .0001). Dropout and psychosis ratings did not differ between switch and stay groups for aripiprazole and olanzapine. In before-to-after switch meta-analyses, aripiprazole (−1.96 kg, 95% CI −3.07, −0.85, P < .001) and ziprasidone (−2.22 kg, 95% CI −3.84, −0.60, P = .007) were associated with weight loss, whereas olanzapine (2.71 kg, 95% CI 1.87, 3.55, P < .001), and clozapine (2.80 kg, 95% CI 0.26, 5.34, P = .03) were associated with weight gain. No significant weight or other cardiometabolic changes were observed when switching to amisulpride, paliperidone/risperidone, quetiapine, or lurasidone.ConclusionsSwitching antipsychotics to agents with lower weight gain potential, notably to aripiprazole and ziprasidone, can improve weight profile and other cardiometabolic outcomes. When choosing switch agents, both the weight gain potential of the pre- and post-switch antipsychotic must be considered. Antipsychotic switching in psychiatrically stable patients must be weighed against the risk of psychiatric worsening.     

Can Latent Class Analysis Be Used to Improve the Diagnostic Process in Pediatric Patients with Chronic Ataxia?

Chronic ataxia is a relatively common symptom in children. There are numerous causes of chronic ataxia, making it difficult to derive a diagnosis in a timely manner. We hypothesized that the efficiency of the diagnostic process can be improved with systematic analysis of clinical features in pediatric patients with chronic ataxia. Our aim was to improve the efficiency of the diagnostic process in pediatric patients with chronic ataxia. A cohort of 184 patients, aged 0–16 years with chronic ataxia who received medical care at Winnipeg Children’s Hospital during 1991–2008, was ascertained retrospectively from several hospital databases. Clinical details were extracted from hospital charts. The data were compared among the more common diseases using univariate analysis to identify pertinent clinical features that could potentially improve the efficiency of the diagnostic process. Latent class analysis was then conducted to detect unique patterns of clinical features and to determine whether these patterns could be associated with chronic ataxia diagnoses. Two models each with three classes were chosen based on statistical criteria and clinical knowledge for best fit. Each class represented a specific pattern of presenting symptoms or other clinical features. The three classes corresponded to a plausible and shorter list of possible diagnoses. For example, developmental delay and hypotonia correlated best with Angelman syndrome. Specific patterns of presenting symptoms or other clinical features can potentially aid in the initial assessment and diagnosis of pediatric patients with chronic ataxia. This will likely improve the efficiency of the diagnostic process.     

Does the Use of Intraoperative Microelectrode Recording Influence the Final Location of Lead Implants in the Ventral Intermediate Nucleus for Deep Brain Stimulation?

To determine if the use of intraoperative microelectrode recording (MER) influences the final location of lead implant in deep brain stimulation (DBS) of the ventral intermediate nucleus (VIM), and to evaluate the incidence of associated complications. The usefulness of intraoperative MER in DBS is debated, some centers suggesting it increases complications without additional benefit. We conducted a retrospective chart review of all patients who underwent VIM DBS with MER at the University of Texas Health Science Center in Houston from June 1, 2009 to October 1, 2013. Initial (MRI determined) and final (intraoperative MER determined) coordinates of implant were compared. To assess incidences of hemorrhagic and infectious complications, we reviewed postoperative CT scans and follow-up notes. Forty-five lead implants on 24 patients were reviewed. The mean age at implantation was 62.42 years (range 18–83). The average duration from diagnosis to surgery was 21.5 years (range 1–52). A statistically significant mean difference was observed in the superior-inferior plane (0.52 ± 0.80 mm inferiorly, p < 0.05) and the anterior-posterior plane (0.45 ± 0.86 mm posteriorly, p < 0.05). A non-statistically significant difference was also observed in the medial-lateral plane (0.02± 0.15 mm, p > 0.05). One patient developed an infectious complication (4.2 %) that required removal of leads; two patients had minimal asymptomatic intra-ventricular bleeding (8.3 %). In our DBS center, intraoperative MER in VIM DBS implant does not seem to have a higher rate of surgical complications compared to historical series not using MER, and might also be useful in determining the final lead location.     

What Happens After the First Episode? A Review of Progressive Brain Changes in Chronically Ill Patients With Schizophrenia

Numerous imaging studies have revealed structural brain changes in schizophrenia. Decreases in brain tissue are accompanied by increases in ventricle volumes and cerebrospinal fluid. Whether or not these brain changes are progressive beyond the first episode is subject to debate. To assess if progressive brain changes occur in chronically ill patients, 11 longitudinal magnetic resonance imaging and computed tomography studies were reviewed. Patients were ill for on average 10 years at their initial scan. Follow-up intervals varied between 1 and 10 years. Overall, the findings suggest continuous progressive brain tissue decreases and lateral ventricle volume increases in chronically ill patients, up to at least 20 years after their first symptoms. The extent of progressive brain tissue decrease in patients (-0.5% per year) is twice that of healthy controls (-0.2% per year). These findings are consistent with the extent of postmortem brain tissue loss in schizophrenia. Progressive volume loss seems most pronounced in the frontal and temporal (gray matter) areas. Progressive lateral ventricle volume increases are also found. More pronounced progressive brain changes in patients is associated with poor outcome, more negative symptoms, and a decline in neuropsychological performance in one or some of the studies, but not consistently so. Higher daily cumulative dose of antipsychotic medication intake is either not associated with brain volume changes or with less prominent brain volume changes. The progressive brain changes present in chronic schizophrenia may represent a continuous pathophysiological process taking place in the brains of these patients that warrants further study.     

Does the severity of the LGMD2A phenotype in compound heterozygotes depend on the combination of mutations?

Introduction: Limb‐girdle muscular dystrophy type 2A (LGMD2A) is caused by a deficiency of calpain‐3/p94. Although the symptoms in most LGMD2A patients are generally homogeneous, some variation in the severity and progression of the disease has been reported. Methods: We describe 2 patients who carry the same combination of compound heterozygous mutations (pG222R/pR748Q) and whose symptoms are exceptionally benign compared to homozygotes with each missense mutation. Results: The benign phenotype observed in association with the combined pG222R and pR748Q mutations suggested that it may result from a compensatory effect of compound heterozygosity rather than the individual mutations themselves. Our analyses revealed that these two mutations exert different effects on the protease activity of calpain‐3, suggesting “molecular complementation” in these patients. Conclusion: We propose several hypotheses to explain how this specific combination of mutations may rescue the normal proteolytic activity of calpain‐3, resulting in an exceptionally benign phenotype. Muscle Nerve, 2011     

Does prenatal nicotine exposure alter the brain's response to nicotine in adolescence? A neuroanatomical analysis

This study examined changes in dendritic morphology and spine density in multiple brain regions [Zilles' areas: (i) the Cg3 region of the anterior cingulate cortex or the medial prefrontal cortex, layer III (Cg3); (ii) the dorsal agranular insular cortex, layer III (AID); (iii) the PAR I region of the parietal cortex, layer III (Par1) and (iv) the nucleus accumbens (NAc)]of Long–Evans rats following exposure to nicotine prenatally, in late adolescence, or both prenatally and in adolescence. Prenatal nicotine exposure induced enduring changes in neuroanatomical organisation that varied between male and female offspring, with males exhibiting increased dendritic complexity of neurons in AID and NAc whereas females experienced increased dendritic complexity in Par1 but decreased dendritic complexity of neurons in NAc. Similarly, nicotine given in late adolescence dramatically reorganised neural circuitry of both male and female offspring, with males exhibiting decreased dendritic complexity of neurons in Par1 and Cg3 but increased dendritic complexity in AID, and females exhibiting decreased dendritic complexity in Cg3 and NAc but increased complexity in AID. Exposure to nicotine both prenatally and in adolescence produced few neuroanatomical parameters that demonstrated a prenatal experience × adolescent drug administration interaction. Females showed additive effects in Par1, Cg3 and NAc whereas males demonstrated additive effects only in AID. Thus, the timing of nicotine exposure produced differential effects on cerebral organisation in a regionally specific manner.     

Taking Back the Brain: Could Neurofeedback Training Be Effective for Relieving Distressing Auditory Verbal Hallucinations in Patients With Schizophrenia?

Progress in identifying the neural correlates of auditory verbal hallucinations (AVHs) experienced by patients with schizophrenia has not fulfilled its promise to lead to new methods of treatments. Given the existence of a large number of such patients who have AVHs that are refractory to traditional treatments, there is the urgent need for the development of new effective interventions. This article proposes that the technique of neurofeedback may be an appropriate method to allow the translation of pure research findings from AVH-research into a clinical intervention. Neurofeedback is a method through which individuals can self-regulate their neural activity in specific neural regions/frequencies, following operant conditioning of their intentional manipulation of visually presented real-time feedback of their neural activity. Four empirically testable hypotheses are proposed as to how neurofeedback may be employed to therapeutic effect in patients with AVHs.     

Does strategy instruction on the Rey-Osterrieth Complex Figure task lead to transferred performance improvement on the Modified Taylor Complex Figure task? A randomized controlled trial in school-aged children

Objective: Providing children with organizational strategy instruction on the Rey Osterrieth Complex Figure (ROCF) has previously been found to improve organizational and accuracy performance on this task. It is unknown whether strategy instruction on the ROCF would also transfer to performance improvement on copying and the recall of another complex figure. Methods: Participants were 98 typically developing children (aged 9.5–12.6 years, M = 10.6). Children completed the ROCF (copy and recall) as a pretest. Approximately a month later, they were randomized to complete the ROCF with strategy instruction in the form of a stepwise administration of the ROCF or again in the standard format. All children then copied and recalled the Modified Taylor Complex Figure (MTCF). All productions were assessed in terms of organization, accuracy and completion time. Results: Organization scores for the MTCF did not differ for the two groups for the copy production, but did differ for the recall production, indicating transfer. Accuracy and completion times did not differ between groups. Performance on all measures, except copy accuracy, improved between pretest ROCF and posttest MTCF production for both groups, suggesting practice effects. Conclusion: Findings indicate that transfer of strategy instruction from one complex figure to another is only present for organization of recalled information. The increase in RCF-OSS scores did not lead to a higher accuracy or a faster copy or recall.     

Does depression in patients with known or suspected cerebral disease contribute to impairment on the Luria-Nebraska Neuropsychological Battery?

Both the Luria-Nebraska Neuropsychological Battery (LNNB) and the Beck Depression Inventory (BDI) were administered to 48 consecutively referred patients. These consecutively seen patients comprised 25 cases of confirmed brain damage and 23 cases of "suspected" or questionable damage. Product-moment correlations were calculated between the BDI and three LNNB-derived indices of impairment. No relationship was found between depression and any of the LNNB performance indicators, indicating that the battery may be robust in the presence of depression. Necessary constraints on this implication were discussed and explicated in light of the concurrent need to evaluate new neuropsychological instruments in realistic clinical contexts.