Clinical predictors of therapeutic response to clozapine in a sample of Turkish patients with treatment-resistant schizophrenia

BACKGROUND: Several lines of evidence suggest that clozapine is more effective than both first- and second-generation antipsychotic drugs in treatment-resistant schizophrenia (TRS). However, clinicians appear to be hesitant to prescribe this drug. It would therefore be extremely valuable if predictors of response to clozapine could be identified. The aim of this study was to evaluate the predictive factors of clinical responses to clozapine in a group of Turkish patients with TRS. METHODS: This was a 16-week uncontrolled open study carried out among 97 TRS patients (80 males and 17 females; DSM-IV diagnosis). All patients fulfilled the criteria for refractory schizophrenia according to the UK guidelines for the National Institute of Clinical Excellence (NICE). After all previous antipsychotic medications had run their course, the patients were started on clozapine according to a standardized titration and dosage schedule. Psychopathology was evaluated before the initiation of clozapine therapy and once every 4 weeks using the Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessment for Positive Symptoms, and the Scale for the Assessment of Negative Symptoms. RESULTS: Of the TRS patients on clozapine, 55.7% achieved a clinical response, defined as at least a 20% decrease in BPRS. We observed a favorable effect of clozapine on both positive and negative symptoms. Logistic regression analysis showed that a good clozapine response was more likely when schizophrenia began at a later age, when negative symptoms were severe, and when patients had an early response at 4 weeks. CONCLUSION: A combination of demographic, baseline clinical, and acute treatment response variables may accurately predict response to clozapine in TRS. Priority should be given to initiating clozapine at the earliest phase of TRS, especially for patients with evident negative symptoms.     

Retinal ganglion cell toxicity due to oxcarbazepine and valproic acid treatment in rat

PurposeTo evaluate and to compare the possible toxic effects of oxcarbazepine (OXC) and valproic acid (VPA) on retinal ganglion cells (RGCs) in rat.MethodsForty female Wistar rats (21–24 days old and weighted between 44.6 and 57.3 g) were divided equally into 4 experimental groups which were applied tap water (group 1), 300 mg/(kg day) VPA (group 2), 100 mg/(kg day) OXC (group 3), and both VPA and OXC (group 4) via gavage for 90 days. Enucleation was performed for histopathologic analysis. RGCs were counted under the light microscopic examination.ResultsRGC numbers in OXC and combined OXC-VPA groups were found to be lower than those of control group. On the other hand RGC number was comparable with those of control group in VPA group.ConclusionOXC seems to be toxic to RGCs at 100 mg/kg dose when it is been given as a monotherapy or combined with VPA. Single VPA treatment has no effect on RGC number.     

HMGB‐1, TLR4, IL‐1R1, TNF‐α, and IL‐1β: novel epilepsy markers?

Aim: The purpose of this study was to compare HMGB‐1, TLR4, IL‐1β, IL‐1R1, and TNF‐α levels in patients with mild and severe epilepsy with those in a healthy control group. Methods: Children aged 4–17 years, diagnosed with epilepsy for at least three years and with no progressive neurological disease, metabolic disease or infection, were selected for the study. The severe epilepsy group consisted of 28 children with at least one episode a week despite receiving three or more antiepileptic drugs. The mild epilepsy group consisted of 29 children with no seizures in the previous year, receiving only one antiepileptic drug, while 27 healthy children were selected as the control group. HMGB‐1, TLR4, IL‐1R1, TNF‐α and IL‐1β levels were investigated in these three groups. The MRI findings and clinical characteristics of the patients in the epilepsy group were also compared with these markers. Results: HMGB‐1, TLR4, TNF‐α, and IL‐1β levels in the severe epilepsy group were higher than in the control group and the mild epilepsy group (p<0.05), and were higher in the mild epilepsy group than in the control group (p<0.05). IL‐1R1 was also higher in the severe epilepsy group than in the control group (p<0.05). Conclusion: In this first report to identity a possible correlation between HMGB‐1, TLR4, IL‐1β, IL‐1R1, and TNF‐α levels and severity of epilepsy, our data demonstrates that the serum level of these cytokines is higher in cases of drug‐refractory epilepsy.     

Relationship of olfactory function with olfactory bulbus volume,disease duration and Unified Parkinson’s disease rating scale scores in patients with early stage of idiopathic Parkinson’s disease

We aimed to investigate the relationship between olfactory function and olfactory bulbus (OB) volume, disease duration and Unified Parkinson’s disease rating scale (UPDRS) scores in early stage idiopathic Parkinson’s disease patients. The University of Pennsylvania Smell Identification Test (UPSIT) was used for the evaluation of olfactory function. UPSIT scores for patients with Parkinson’s disease were significantly lower than controls. There was no significant difference between stage 1 and stage 2 patients. OB volumes were higher in stage 1 and 2 patients than controls, but there was no statistical difference between the three groups. No significant correlation was found between UPSIT and UPDRS total scores, nor between UPSIT scores and disease duration in stage 1 and 2 patients. According to our results, we propose UPSIT be used as a screening test to diagnose presymptomatic patients, but not OB volumes.     

Assessment of atherosclerosis risk due to the homocysteine–asymmetric dimethylarginine–nitric oxide cascade in children taking antiepileptic drugs

PurposeThe aim of this study was to assess the atherogenicity risk of antiepileptics in children by investigating the cascade, “hyperhomocysteinemia (HHcy) → asymmetric dimethylarginine (ADMA) increase → nitric oxide (NO) decrease”, which is thought to contribute to the developmental process of atherosclerosis.MethodsThe participants included 53 epilepsy patients who received either valproic acid (VPA, n = 26) or oxcarbazepine (OXC, n = 27). Twenty-four healthy sex- and age-matched children served as controls. Fasting plasma total homocysteine (tHcy), ADMA and NO levels were measured.ResultsThe differences in Hcy, ADMA, NO, vitamin B₁₂ and folate levels between VPA, OXC and control groups were all insignificant (p > 0.05 for all). In the patient group (VPA and OXC groups), 22.6% of the children (12/53) had tHcy levels above the normal cutoff (13.1 μmol/l) for children and 17% of the children (9/53) had tHcy levels of greater than 15 μmol/l which is accepted as the critical value for an increased atherosclerosis risk (p < 0.05 for both). The difference in rate of HHcy between VPA and OXC groups was statistically insignificant (p > 0.05, for both cut off levels of HHCy). There was a positive correlation of tHcy levels and antiepileptic drug treatment duration in the patient group (r = +0.276, p < 0.05).ConclusionHHcy may develop in patients using OXC. Contrary to some previous publications, our data do not suggest that OXC is safer than VPA in terms of HHcy risk. Further prospective, large scale and longer term studies investigating all suggested pathways responsible for development of atherosclerosis due to HHcy should be conducted to define the exact mechanism responsible for AEDs related atherosclerosis.     

Predictors of Intractable Childhood Epilepsy

Our study sought to identify early predictive factors of medically intractable childhood epilepsy. A cohort of epileptic children from the city of Mersin was retrospectively investigated. All patients received care from the same Department of Pediatric Neurology. The epileptic cohort was divided into a drug-responsive epilepsy group and an intractable epilepsy group. Intractable epilepsy is defined as continued seizures in children despite adequate therapy with two or more antiepileptic drugs for more than 18 months. Strong univariate association was observed between intractability and several factors: age of onset, high initial seizure frequency, symptomatic etiology, mixed seizure types, previous history of status epilepticus, febrile and neonatal seizures, mental and motor developmental delay, multiple seizures in 1 day, electroencephalogram abnormalities, magnetic resonance imaging findings, and specific epileptic syndromes. Logistic regression analysis revealed that a previous history of epilepticus status, abnormal electroencephalogram results, and multiple seizures in 1 day comprise independent predictors of medically intractable childhood epilepsy. We suggest that medical intractability in childhood epilepsy can be predicted by monitoring these factors. Along with early prediction, alternative therapies may be designed to provide patients better seizure control and quality of life.     

An unusual cause of allergy: Case report of normal saline solution allergy

Anaphylaxis and acute allergic reactions may sometimes be fatal. They occur within minutes in a sensitized individual. So quick diagnosis and management are necessary issues. In the literature, cases are widely reported against allergens found in drugs, foods and their additives, radiocontrast material, bee stings, and many other materials. Here, we present a 37-year-old woman who developed an anaphylactic reaction to normal saline infusion during evaluation for her acute abdominal pain. We found only one report about normal saline allergy in the literature (Litvin ME, Shemchuck AS, Lisetskii VA. Anaphylactic shock caused by intravenous injection of isotonic solution of sodium chloride. Klin Khir 1976;(7):59-61).     

Nightmare disorder, dream anxiety, and subjective sleep quality in patients with borderline personality disorder

Aims:  The aims of the present study were to examine the rate of nightmare disorder (ND) and to determine the levels of dream anxiety and subjective sleep quality in patients with borderline personality disorder (BPD). Another aim was to determine whether dream anxiety was associated with childhood trauma, dissociative experiences, and subjective sleep disturbance in BPD patients. Finally, the hypothesis as to whether BPD patients with ND exhibited a more severe clinical profile than those without ND, was also tested.
Methods:  A total of 88 borderline patients and 100 age- and sex-matched healthy control subjects were assessed using the Structured Clinical Interview for DSM-III-R Personality Disorders, Structured Clinical Interview for DSM-IV Axis I Disorders, Van Dream Anxiety Scale, Pittsburgh Sleep Quality Index, Dissociative Experiences Scale, and Traumatic Experiences Checklist. Subjects with codiagnoses that could affect sleep were not included.
Results:  BPD patients suffered a significantly greater rate of nightmares, elevated levels of dream anxiety, and disturbed sleep quality than did controls. In the borderline group, heightened dream anxiety was correlated with higher rates of early traumatic experiences and dissociative symptoms, and impaired sleep quality. Furthermore, borderline patients with ND exhibited greater psychopathology as compared to those without ND in terms of several clinical characteristics.
Conclusions:  The present study provides support for a strong association between BPD, distressing nightmares, and subjective sleep quality. Recognition and management of dream and sleep disturbances in BPD patients might lead to improvements in their global clinical picture.     

The management of carpal tunnel syndrome in pregnancy.

OBJECTIVES: To determine the prevalence of carpal tunnel syndrome (CTS) after delivery and its relationship to individual factors. STUDY DESIGN: A cohort of 46 pregnant women, aged 15-48 years, who had suffered from CTS during pregnancy and who had delivered at Aydin Maternity Hospital, Turkey was selected. They had been followed up through pregnancy and 12 months postpartum and filled out a questionnaire. The data were analysed statistically. RESULTS: Follow up showed that CTS at 6 and 12 months post partum was reported by 10.9% and 4.3% of the women, respectively. The difference in prevalence of CTS between young women and older women was statistically significant (P= 0.005). The history of diabetes mellitus and infant birth weight were similar in the two groups. However, patient weight gain during pregnancy increased the risk of CTS (P= 0.000). On the other hand, there was no difference in the number of previous pregnancies between women with CTS and without CTS during pregnancy (P= 0.210). Furthermore, affected and unaffected groups required Caesarean section in nine and 248 patients during pregnancy, respectively. CONCLUSION: These results indicate that, in most pregnant patients with CTS, the symptoms are present in both hands and are first noted during the third trimester. The majority of patients with CTS obtain spontaneous relief in the immediate postpartum period.