Leonardo Baldaçara

Is cerebellar volume related to bipolar disorder

BACKGROUND Recent data suggest that cerebellum influences emotion modulation in humans. The findings of cerebellar abnormalities in bipolar disorder (BD) are especially intriguing given the link between the cerebellum emotional and behavioral regulation. The purpose of this study was to evaluate cerebellar volume in patients with euthymic BD type I compared to controls. Moreover, we investigated the possible relationship between cerebellar volume and suicidal behavior. METHODS Forty-patients with euthymic BD type I, 20 with and 20 without history of suicide attempt, and 22 healthy controls underwent an MRI scan. The participants were interviewed using the Structured Clinical Interview with the DSM-IV axis I (SCID-I), the Hamilton Depression Rating Scale (HDRS), the Young Mania Rating Scale (YMRS) and the Barratt Impulsiveness Scale (BIS-11). RESULTS Groups were age, gender and years of schooling-matched. The left cerebellum (p=0.02), right cerebellum (p=0.02) and vermis (p<0.01) were significantly smaller in the BD group; however, there were no volumetric differences between the BD subjects with and without suicidal attempt. There was no correlation between cerebellar measurements and clinical variables. LIMITATIONS The main strength is that our sample consisted of patients with euthymic BD type I without any comorbidities, however, these results cannot establish causality as the cross-sectional nature of the study. CONCLUSIONS Our findings suggest that the reduction in cerebellar volumes observed in BD type I might be a trait-related characteristic of this disorder. Additional studies with larger samples and subtypes of this heterogeneous disorder are warranted to determine the possible specificity of this cerebellar finding.

Rapid tranquilization for agitated patients in emergency psychiatric rooms: a randomized trial of olanzapine, ziprasidone, haloperidol plus promethazine, haloperidol plus midazolam and haloperidol alone.

OBJECTIVE To compare the effectiveness of intramuscular olanzapine, ziprasidone, haloperidol plus promethazine, haloperidol plus midazolam and haloperidol alone as the first medication(s) used to treat patients with agitation and aggressive behavior. METHOD One hundred fifty patients with agitation caused by psychotic or bipolar disorder were randomly assigned under double-blind conditions to receive olanzapine, ziprasidone, haloperidol plus midazolam, haloperidol plus promethazine or haloperidol alone. The Overt Agitation Severity Scale, Overt Aggression Scale and Ramsay Sedation Scale were applied within 12 hours after the first dosage. RESULTS All medications produced a calming effect within one hour of administration, but only olanzapine and haloperidol reduced agitation by less than 10 points, and only olanzapine reduced aggression by less than four points in the first hour. After twelve hours, only patients treated with haloperidol plus midazolam had high levels of agitation and aggression and also more side effects. Ziprasidone, olanzapine and haloperidol alone had more stable results for agitation control, while ziprasidone, haloperidol plus promethazine and olanzapine had stable results for aggression control. CONCLUSION Olanzapine, ziprasidone, haloperidol plus promethazine, haloperidol plus midazolam and haloperidol were effective in controlling agitation and aggression caused by mental illness over 12 hours. Although all the drugs had advantages and disadvantages, haloperidol plus midazolam was associated with the worst results in all the observed parameters.OBJETIVO: Comparar a eficacia da olanzapina, ziprasidona, haloperidol associado ao midazolam, haloperidol associado a prometazina e haloperidol isoladamente por via intramuscular como primeira escolha no tratamento de pacientes em agitacao e agressividade. METODO: Cento e cinquenta pacientes com agitacao psicomotora por transtorno psicotico ou transtorno bipolar foram recrutados para estudo duplo-cego e receberam olanzapina, ziprasidona, haloperidol associado a midazolam, haloperidol associado a prometazina ou haloperidol isoladamente. Foram aplicadas as escalas Overt Agitation Severity Scale, Overt Aggression Scale e Ramsay Sedation Scale no periodo de 12 horas apos a primeira aplicacao. RESULTADOS: Todas as medicacoes foram capazes de acalmar os pacientes apos uma hora da administracao. Apenas a olanzapina e o haloperidol reduziram a agitacao para menos de 10 pontos e apenas a olanzapina reduziu a agressividade para menos de quatro pontos nesse periodo. Doze horas depois, apenas o haloperidol com midazolam apresentou valores altos para a agitacao e agressividade, e tambem esteve relacionado com maior proporcao de efeitos colaterais. A ziprasidona, a olanzapina e o haloperidol apresentaram resultados mais estaveis para o controle da agitacao e a ziprasidona, haloperidol associado a prometazina e olanzapina para o controle da agressividade. CONCLUSAO: A olanzapina, a ziprasidona, o haloperidol associado a prometazina, o haloperidol associado ao midazolam e o haloperidol isoladamente foram efetivos no controle da agitacao e da agressividade secundaria a transtornos mentais dentro de 12 horas. Todas as drogas apresentaram vantagens e desvantagens, exceto pela associacao haloperidol e midazolam que demonstrou os piores resultados em todos os parâmetros.

Cerebellar volume in patients with dementia

OBJECTIVE The aim of this study was to examine the cerebellar volume of subjects at different stages of Alzheimers disease and to investigate whether volume reductions in this structure are related to cognitive decline. METHOD Ninety-six subjects from an epidemiological study were submitted to a magnetic resonance imaging scan and evaluated using the Mini-Mental State Examination and the Functional Activities Questionnaire. Subjects were divided into five groups according to the Clinical Dementia Rating scale. Twenty-six subjects from the original group who had no dementia diagnosis at baseline were re-evaluated for the onset of dementia after two years. RESULTS The volumes of the cerebellar hemispheres, posterior cerebellar lobe, vermis and temporal lobe were found to be reduced as a function of the severity of the disease. There were significant positive correlations between the volume of the temporal lobe and cerebellum and the language, attention, and total scores in the Mini-Mental State Examination and the Functional Activities Questionnaire. A logistic regression analysis demonstrated that reduced temporal lobe, posterior cerebellar lobe and vermal volume at baseline is a risk factor for the onset of dementia. CONCLUSION This is the first study demonstrating that reduced cerebellar volume is already apparent at the predementia stage. The results of this study support the involvement of the cerebellum in the progression of dementia. Whereas the cerebellum might not be directly associated with the origin of Alzheimers disease, it may provide useful information related to its prognosis.

Reduction of anterior cingulate in adults with urban violence- related PTSD

BACKGROUND To evaluate differences in limbic structure volume of subjects exposed to urban violence during adulthood, between those who developed posttraumatic stress disorder (with PTSD) and resilient matched controls (without PTSD). METHODS Limbic volumetric measures of 32 subjects with PTSD and 32 subjects without PTSD who underwent brain MRI were analyzed in an epidemiological study in the city of Sao Paulo. The hippocampus, amygdala, cingulate, and parahipocampal gyri volumes were estimated using FreeSurfer software. We also investigated the association between limbic volumetric measurements, symptom´s severity, and early life stress history (measure by Early Trauma Inventory - ETI). RESULTS Subjects with PTSD presented reduced volume of the right rostral part of the anterior cingulate, compared to subjects without PTSD, after controlling for intracranial volume, ETI, and depressive symptoms. Subjects with PTSD presented larger bilateral hippocampus and right amygdala, but secondary to the higher ETI. In PTSD group there was a positive correlation between ETI with bilateral hippocampus, bilateral amygdala, and left parahippocampus. LIMITATIONS First, the cross-sectional study design precludes causal interpretation of limbic structure reduction in PTSD, consequence of PTSD, or other life events. Finally, since the sample size was not sufficiently large, we could not observe whether or not limbic structure volume could be related to the type of trauma. CONCLUSIONS The present study provides evidence of a reduced anterior cingulate volume in subjects with PTSD than in resilient subjects exposed to urban violence. Enlargement of hippocampus and amygdala volume was observed in subjects with PTSD, however secondary to early trauma experience.

Hiperlexia em um caso de autismo e suas hipóteses

CONTEXTO: Pouco se sabe sobre os mecanismos neurais precoces da leitura. Criancas com doencas do espectro do autismo, em raras ocasioes, apresentam avancadas habilidades de leitura. Apesar de suas serias dificuldades na expressao e recepcao da linguagem, essas criancas podem identificar palavras impressas tao jovens quanto aos 18 meses de idade sem nenhuma instrucao explicita. RELATO DE CASO: Relatamos aqui um caso de uma crianca de seis anos com historia de autismo e que embora apresentasse dificuldades na comunicacao, comecou a ler aos tres anos. Em seguida, discutimos algumas teorias sobre essa associacao. CONCLUSAO: Deficiencias no desenvolvimento da linguagem e na comunicacao sao criterios definidores do autismo; ja a hiperlexia, apesar de incomum, quando presente deve ser levada em conta para o diagnostico. Seus mecanismos ainda sao pouco compreendidos, mas diversos estudos feitos associados a outros que estao em andamento poderao elucidar melhor esse sintoma.

Efficacy of Topiramate in the Treatment of Crack Cocaine Dependence: A Double-Blind, Randomized, Placebo-Controlled Trial

OBJECTIVE We performed a double-blind, randomized, placebo-controlled trial to assess the efficacy of topiramate in the treatment of crack cocaine dependence. METHOD Sixty men who were dependent on cocaine (DSM-IV) (exclusive use of crack cocaine) were selected. The subjects were randomly assigned to either a topiramate group (subjects received 50-200 mg of topiramate per day for 12 weeks) or a control group (subjects received placebo). The initial daily treatment dose was 50 mg, and this dose was increased weekly at increments of 25 to 50 mg, based on the subjects tolerability, to a maximum of 200 mg. All of the subjects also participated in motivational interviews and group therapy. The primary outcome measures were detection of benzoylecgonine in the urine, study retention, frequency of cocaine smoking, amount of cocaine use, and mean amount of money spent on cocaine per week. The study was conducted from February 2013 to February 2014. RESULTS Twenty-nine subjects in the topiramate group and 29 subjects in the control group completed the study. Longitudinal assessment revealed that retention was not significant (odds ratio [OR] = 1.072, P = .908) between the 2 groups. Negative results from a urine test for benzoylecgonine (a cocaine metabolite), which is a measure of cocaine abstinence, were more frequently obtained from the topiramate group (OR = 8.687, P < .001). Topiramate reduced the quantity of cocaine used (mean reduction = -3.108 g, P < .001), the frequency of cocaine use (mean = -0.784 times per week, P = .005), and the amount of money spent on cocaine (mean [US dollars] = -

Relationship between structural abnormalities in the cerebellum and dementia, posttraumatic stress disorder and bipolar disorder

25.38, P = .015; this variable did not achieve statistical significance after Bonferroni correction) compared with the placebo during the 12 weeks (or 84 days) of the assessment. However, the differences in reductions between the 2 groups in the quantity of cocaine used, the frequency of cocaine use, and money spent on cocaine over time (time × group interaction) were present only during the first 4 weeks, and none of these variables by 12 weeks. The studied groups did not differ with regard to secondary end points, such as study dropout and the number of subjects who reported side effects. CONCLUSIONS The present findings indicate that topiramate is effective and safe and thus reinforce previous data suggesting that topiramate is a potentially useful treatment for crack cocaine dependence. However, we found that topiramate is only useful as an adjunctive treatment during the first 4 weeks of the treatment. Future studies with larger samples are needed to confirm these results. TRIAL REGISTRATION Registro Brasileiro de Ensaios Clínicos (ReBEC) RBR-3vwfjs and UTN: U1111-1131-4443.

Hippocampal volume and CDR-SB can predict conversion to dementia in MCI patients

New evidence suggests that the cerebellum has structural and functional abnormalities in psychiatric disorders. Objective In this research, the goal was to measure the volume of the cerebellum and its subregions in individuals with psychiatric disorders and to relate these findings to their symptoms. Methods Patients with different degrees of cognitive impairment (Epidemiology of the Elderly - UNIFESP) and patients with post-traumatic stress disorder (PTSD) from population studies were analyzed. Also, patients with bipolar disorder from an outpatient clinic (Center for the Study of Mood and Anxiety Disorders, Universidade Federal da Bahia) were recruited for this study. All subjects underwent a 1.5T structural magnetic resonance scan. Volumetric measures and symptom measurements, by psychometric scales, were performed and compared between patients and controls. Results The cerebellum volume was reduced in patients with cognitive impairment without dementia and with dementia, in patients with PTSD, and in patients with bipolar disorder compared to controls. In dementia and PTSD, the left cerebellar hemisphere and vermis volume were reduced. In bipolar disorder, volumes of both hemispheres and the vermis were reduced. In the first two studies, these cerebellar volumetric reductions correlated with symptoms of the disease. Conclusion The exact nature of cerebellar involvement in mental processes is still not fully understood. However, abnormalities in cerebellar structure and its functions have been reported in some of these diseases. Future studies with larger samples are needed to clarify these findings and investigate whether they are important for treatment and prognosis.

Alterações cutâneas com ziprasidona

OBJECTIVE To evaluate the combination of two factors: clinical dementia rating sum of boxes scores (CDR-SB) and hippocampal volume (HV) as predictors of conversion from mild cognitive impairment (MCI) to dementia. METHODS Twenty-eight individuals (9 normal and 19 with MCI) were classified according to their CDR sum of boxes scores into 3 groups. RESULTS The hippocampal volume was significantly lower in the high-risk group and in those who developed dementia after two years. The rate of conversion was crescent among the three groups. CONCLUSION We were proposed an additional measurement of the hippocampal volume which may be helpful in the prognosis. However, we noted that the CDR-SB is a method as efficient as neuroimaging to predict dementia with the advantage of being a procedure for low cost and easy implementation, more consistent with public policy.

Organic mental disorder after pneumococcal meningoencephalitis with autism-like symptoms

There are descriptions of skin reactions secondary to antipsychotic use. We reported a case of erythema multiform associated with ziprasidone use in a 47-year-old female patient diagnosed with schizophrenia. The patient was receiving the medication (80 mg/day) for seven weeks, and the dose was increased to 120 mg/day. Seven days after the dose change, the patient presented pruritus and erythematosus lesions in trunk, upper and lower members. The medication was discontinued and there was a complete improvement of the lesions. We were unable to find previous reports of association between erythema multiform and ziprasidone.