Rafael Stryjer

Diagnostic value of vestibular evoked myogenic potentials in cerebellar and lower-brainstem strokes

BACKGROUND Vestibular evoked myogenic potentials (VEMPs) provide assessment of vestibular function. They consist in picking up compound muscle action potentials in the sternocleidomastoid (SCM) muscles in response to auditory stimulation of the vestibulum. VEMP testing has found application mainly in peripheral vestibular disorders, whereas reports about VEMPs in central vestibular lesions are rather scarce. AIMS OF THE STUDY Based on the physiological connections between the cerebellum and the vestibular nuclei, we investigated the influence on VEMPs of cerebellar and lower-brainstem strokes. We examined whether or not this method may be suitable as a clinical tool for the evaluation of the extent of cerebellar strokes. PATIENTS AND METHODS Nineteen patients with cerebellar ischemic stroke and 15 patients with lower-brainstem ischemic stroke (11 in the pons, four in the medulla) were included. The latencies and amplitudes of P13 and N23 in both groups of patients were compared with those obtained in a control group of 53 normal individuals. RESULTS VEMP responses were obtained in all patients and controls. At the group level, mean peak latencies and amplitudes, and the number of subjects with significantly deviant values did not differ between patients and controls. There were no latency or amplitude differences ipsilaterally or contralaterally to the lesion. At the individual level, there was no correlation between laterality of lesion and that of P13 or N23 abnormalities in patients with cerebellar strokes; however, there were two patients (one pontine, one medullar stroke) who presented P13 and N23 latency abnormalities ipsilaterally to the lesion. CONCLUSION Cerebellar strokes do not influence VEMPs. Moreover, despite previous reports, we were unable to find at a group level any statistically significant VEMP changes in patients with lower-brainstem strokes as compared with controls. Therefore, VEMPs do not appear a suitable tool for assessment of brainstem integrity in patients with posterior fossa strokes. However, they could constitute a sensitive method for documentation of involvement of the central vestibular pathways in patients with brainstem stroke.

Polymorphism screening of PIP5K2A: a candidate gene for chromosome 10p-linked psychiatric disorders.

Lithium is a potent noncompetitive inhibitor of inositol monophosphatases, enzymes involved in phosphoinositide (PI) and inositol phosphate metabolism. A critical component of the PI pathway is phosphatidylinositol 4,5‐bisphosphate (PtdIns(4,5)P2), which is hydrolyzed to second messengers and has a direct role in synaptic vesicle function. Interestingly, a number of genes involved in the synthesis and dephosphorylation of PtdIns(4,5)P2 are found in regions of the genome previously mapped in bipolar disorder (BD) including 10p12, 21q22, and 22q11, among others. Some of these regions overlap with loci mapped in schizophrenia (SZ). One gene involved in PI metabolism that maps to a region of interest is 10p12‐linked PIP5K2A, a member of the phosphatidylinositol 4‐phosphate 5‐kinase family. Polymorphism screening revealed the existence of an imperfect CT repeat polymorphism located near the exon 9‐intron 9 splice donor site. A modest difference was found in the distribution of alleles from this highly polymorphic variant when bipolar and schizophrenic subjects were compared with controls; relatively rare short repeat variants were found more commonly in patients and homozygosity for a common long repeat variant was found more commonly in controls. These data suggest that the imperfect CT repeat in PIP5K2A intron 9 should be further investigated as a possible candidate allele for 10p12‐linked psychiatric disorders.

Response to deep TMS in depressive patients with previous electroconvulsive treatment

BACKGROUND The efficacy of transcranial magnetic stimulation (TMS) in the treatment of major depression has already been shown. Novel TMS coils allowing stimulation of deeper brain regions have recently been developed and studied. OBJECTIVE Our study is aimed at exploring the possible efficacy of deep TMS in patients with resistant depression, who previously underwent electroconvalsive therapy (ECT). METHODS Using Brainsways deep TMS H1 coil, six patients who previously underwent ECT, were treated with 120% power of the motor threshold at a frequency of 20 Hz. Patients underwent five sessions per week, up to 4 weeks. Before the study, patients were evaluated using the Hamilton depression rating scale (HDRS, 24 items), the Hamilton anxiety scale, and the Beck depression inventory and were again evaluated after 5, 10, 15, and 20 daily treatments. Response to treatment was considered a reduction in the HDRS of at least 50%, and remission was considered a reduction of the HDRS-24 below 10 points. RESULTS Two of six patients responded to the treatment with deep TMS, including one who achieved full remission. CONCLUSIONS Our results suggest the possibility of a subpopulation of depressed patients who may benefit from deep TMS treatment, including patients who did not respond to ECT previously. However, the power of the study is small and similar larger samples are needed.

Treatment of neuroleptic-induced akathisia with the 5-HT2A antagonist trazodone.

Akathisia is a common and distressful extrapyramidal adverse side effect usually resulting from the use of antipsychotic medications. Early management of akathisia is important because it may be associated with poor treatment response and medication noncompliance. Unfortunately many patients fail to respond to standard management of akathisia. In addition to dopaminergic mechanisms, it has been hypothesized that serotonin may play a prominent role in the pathophysiology of akathisia. Trazodone is an antidepressant agent demonstrating prominent serotonergic antagonistic properties. This open-label pilot study investigates the efficacy of trazodone in the management of akathisia. Nine female patients with a score of at least “mild akathisia” on the Barnes Akathisia Scale, and receiving a stable dose of antipsychotic medication, were administered trazodone, titrated up to a dosage of 100 mg/day over a period of 5 days. The patients demonstrated marked improvement in symptoms of akathisia. In addition, some improvement was noted in symptomatology of anxiety, depression, and psychosis. These observations suggest the use of trazodone as a beneficial and relatively safe medication for the treatment of antipsychotic medication-induced akathisia. Further study in the context of a double-blind, placebo-controlled trial is mandated to substantiate these preliminary findings.

Trazodone for the Treatment of Neuroleptic-Induced Acute Akathisia: A Placebo-Controlled, Double-Blind, Crossover Study

Introduction:Neuroleptic-induced acute akathisia (NIA) is a common and distressing extrapyramidal symptom usually resulting from the use of antipsychotic medication.Despite its high incidence (20%-45%), the underlying mechanism of NIA has not yet been adequately explained. Although treatment strategies for NIA have traditionally included anticholinergic agents, &ggr;-aminobutyric acid agents, dopamine enhancers, and the &bgr;-adrenergic antagonists, many patients fail to respond. Trazodone (Trz) is an antidepressant agent demonstrating prominent serotonergic antagonistic properties. In a recent pilot open-label trial, Trz demonstrated to be strongly effective in the treatment of NIA in 9 female schizophrenic patients. Objective:On the basis of the results of this pilot study, we investigate further the efficacy of Trz in the treatment of NIA in a double-blind, placebo (Pla)-controlled, crossover design. Methods:Thirteen inpatients with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition schizophrenia or schizo-affective disorder and with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition NIA with a severity of at least mild akathisia according to the Barnes Akathisia Rating Scale participated in the study. Patients were randomly assigned to either the order Trz-Pla or the order Pla-Trz in the treatment periods. Each period lasted for 3 consecutive days (days 1-3 and 4-6). Eight patients were treated with the Trz-Pla order (100 mg/d before bedtime); and 5, with the opposite order (Pla-Trz). Results:Statistically significant improvement in most symptoms of NIA, as measured by the Barnes Akathisia Rating Scale, was detected with Trz compared with Pla treatment. Conclusions:The findings of this double-blind, placebo-controlled, crossover study indicate the efficacy of Trz in the management of NIA, corroborating the results of a preliminary pilot study. We suggest that Trzs property of serotonin 2A postsynaptic receptor antagonism may be its principal mechanism for the improvement of NIA.

Escitalopram in the treatment of patients with schizophrenia and obsessive-compulsive disorder: an open-label, prospective study.

The current data suggest that up to 50% of patients with schizophrenia have obsessive–compulsive (OC) symptoms coexisting with psychosis and between 7.8 and 46% of schizophrenia patients also have full-blown obsessive–compulsive disorder (OCD). The aim of this study was to examine the efficacy of the most selective serotonin reuptake inhibitor escitalopram in the management of OCD in schizophrenia patients. The study was an open-label prospective trial of 12 weeks’ duration in which escitalopram at a dose of up to 20 mg/day was added to the existing antipsychotic drug regimen in schizophrenia patients with OCD. Fifteen patients (10 men/five women) with the diagnosis of schizophrenia and OCD were recruited for the study (mean age: 39±14, range 21–61 years) and received escitalopram according to the study design. A significant improvement was observed in the total Yale Brown Obsessive–Compulsive Scale (Y-BOCS) scores and in the scores of both the Y-BOCS-Obsession and the Y-BOCS-Compulsion subscale at the end point. In addition, a significant improvement was observed in the total scores of the Positive and Negative Syndrome Scale and particularly in scores of anxiety, tension, depression, and preoccupation items. No adverse effects of escitalopram were reported by patients during the trial. In our prospective 12-week open-label study, escitalopram 20 mg/day was well tolerated and improved OC symptoms in schizophrenia patients. Our preliminary results are encouraging and a double-blind randomized study is required to confirm our results.

Altered thermoregulation in ambulatory schizophrenia patients: A naturalistic study

Background. Schizophrenia patients may exhibit alterations in core/body temperature. Hence, we intended to examine the potential existence of thermoregulatory abnormalities in ambulatory schizophrenia patients. Methods. Anonymous electronic patient record data of the Leumit Health Fund (Israel) were screened for all schizophrenia patients who have no other apparent chronic co-morbidity (mental or non-mental) and had their oral temperature assessed during routine follow-ups (Schiz-rFUs) or for various transitory infectious/inflammatory processes (Schiz-Infect) during the years 1999–2005 (n = 535). The comparison group consisted of a comparable sample (n = 560) of healthy subjects (Control-rFUs and Control-Infect). Results. The sub-group of Schiz-rFUs (n = 216) exhibited significantly lower mean oral temperature compared to the matched group of Control-rFUs (n = 140) (36.72±0.54 vs. 36.94±0.64°C, respectively; P<0.05). There was no significant difference in mean oral temperatures between the Schiz-Infect (n = 319) and the Control-Infect (n = 420) (37.32±0.92 vs. 37.28±0.98°C, respectively; NS). Conclusions. Ambulatory schizophrenia patients without a concomitant infectious/inflammatory process exhibit altered thermoregulation manifested by a substantial (about 0.2°C) and significantly lower oral temperature compared to healthy comparison subjects as well as a potential exaggerated increase in oral temperature during transitory infectious/inflammatory processes. The relevance of these phenomena to the pathophysiology of schizophrenia as well as the potential immune-mediated pathologies in schizophrenia merit further investigation.

Zolmitriptan compared to propranolol in the treatment of acute neuroleptic-induced akathisia: A comparative double-blind study

Neuroleptic-induced akathisia (NIA) is a common, sometimes incapacitating adverse effect of anti-psychotic medication. Zolmitriptan is a selective 5-HT(1D) agonist. We aimed to determine its anti-NIA efficacy in comparison to propranolol. Thirty-three neuroleptic-treated patients were randomly allocated in a double-blind design to receive either 7.5 mg/d of zolmitriptan or 120 mg/d of propranolol for 3 consecutive days, followed by 3 days without any anti-NIA treatment. Patients were assessed at baseline and on days 3 and 7 by the Barnes Akathisia Rating Scale (BARS), PANSS, HAMD, HAMA, Pulse, and Blood Pressure. Both groups showed improvement of akathisia (BARS) along the treatment period, with significant effect for time but not for group. No significant differences were found between the groups in all other measurements. Taken together, zolmitriptan was found to be as effective as propranolol for the treatment of NIA. Further placebo-controlled studies are warranted.

β-Adrenergic Antagonists for the Treatment of Clozapine-Induced Sinus Tachycardia: A Retrospective Study

C lozapine is an atypical antipsychotic agent with well-documented superiority over other antipsychotics in the treatment of patients with treatment-resistant schizophrenia, reducing negative, affective symptoms and improving cognitive deficits. Because clozapine has no substitute in clinical psychiatry, its adverse effect management continues to pose an extraordinary medical challenge. One of the most important and least investigated clozapine adverse effects is sympathetic hyperactivity and decreased heart rate (HR) variability, which may account for the increased frequency of arrhythmias, myocarditis, cardiomyopathy, and sudden death observed in patients with clozapine treatment. For example, the rate of myocarditis in clozapine-treated patients seems to be 17 to 322 times greater than that of the general population, and it is associated with an increased risk of fatal myocarditis, that is, 14 to 161 times greater than that of the general population. The clinical features of myocarditis are varied. The spectrum includes asymptomatic patients who may show abnormalities in the electrocardiogram (ECG), patients with signs and symptoms of clinical heart failure and ventricular dilatation, and patients with symptoms of fulminant heart failure and severe left ventricular dysfunction, with or without cardiac dilatation. Patients may present with a history of a recent flulike syndrome accompanied by fever, arthralgias, and malaise. Laboratory tests may show leukocytosis, an elevated sedimentation rate, eosinophilia, or an elevation in the cardiac fraction of creatine kinase. The ECG may show ventricular arrhythmias or heart block, or it may mimic the findings in acute myocardial infarction or pericarditis. Tachycardia has been noted as a presenting sign of myocarditis and, along with low values of HR variability, may predict malignant arrhythmias such as sustained ventricular tachycardia and sudden death. Clozapine-induced sympathetic hyperactivity that usually presents with tachycardia is a significant clinical problem with no established pharmacological prevention and treatment. In many cases, clozapine-induced tachycardia results in discontinuation of clozapine, leaving those patients with treatment-resistant schizophrenia without the most effective pharmacological treatment of this devastating mental condition. A-Adrenergic antagonist agents (BAAA) are widely used for the prevention and treatment of the cardiovascular consequences of sympathetic hyperactivity. By blocking peripheral A receptors, A-adrenergic antagonists improve sympathetic balance by decreasing sympathetic nervous system activity and increasing parasympathetic activity, as well as increasing HR variability, conferring cardiac protection through the prevention of tachyarrhythmias, cardiomyopathies, and sudden death. We suggest that administration of A-adrenergic antagonists may reverse sinus tachycardia caused by clozapine treatment. To test this suggestion, we assessed retrospectively, by chart review, the efficacy of A-adrenergic antagonist administration on clozapine-induced sinus tachycardia in patients with schizophrenia.

Beliefs and emotional reactions in patients with benign paroxysmal positional vertigo: a longitudinal study ☆

OBJECTIVE Psychologic studies in patients with benign paroxysmal positional vertigo (BPPV) are scarce, considering the high frequency of the disorder. We performed a repeated-measures design questionnaire study in a cohort of patients with BPPV before and after treatment to investigate the dynamics of the psychologic findings and possible treatment consequences. METHODS Thirty-seven consecutive patients with idiopathic BPPV participated in the study. During the first visit and 2 to 3 months after therapy, the patients completed 4 questionnaires: the Dizziness Handicap Inventory, the Illness Perception Questionnaire-Revised, the Intolerance of Uncertainty Scale, and the State-Trait Anxiety Inventory. RESULTS The scores for all questioned items did not change before and after treatment except for the physical handicap scores. Correlation was found between the grade of functional and emotional impact of the disease and belief in consequences as well as anxiety levels of the patients. Moreover, uncertainty scores were in correlation with emotional impact, anxiety levels, and perceived consequences of the disease. The belief in personal control of the condition was correlated with the belief in treatment control and understanding of the disease. CONCLUSION The main finding in this study is the lack of a significant change in beliefs and emotional reactions in patients with BPPV after treatment of their condition. Physicians dealing with BPPV should be aware that the disease is not solely a somatic condition but has a serious impact on the patients mental state. Selected patients might benefit from anxiolytic medication.