Does sleep relate to next-day cannabis use during treatment? Findings from an adolescent and young adult motivational enhancement and cognitive behavioral therapy plus topiramate intervention.

BACKGROUND: Interventions for youth cannabis use have limited efficacy. Sleep is likely to affect treatment response, as sleep difficulties are cross-sectionally associated with use and common during treatment. This analysis examined how sleep duration and subjective trouble sleeping related to next-day cannabis use among youth during cannabis treatment. METHOD: Participants (N=64) received a psychosocial intervention plus topiramate versus placebo while completing a 6-week ecological momentary assessment study. Time-varying effect modeling (TVEM) examined within- and between-person associations between sleep and cannabis use and how the strength of within-person associations varied over the course of treatment. RESULTS: TVEM resvealed that, between-participants, youth with longer average sleep duration used cannabis less often controlling for baseline cannabis use, topiramate, and weekend status. Daily within-person fluctuations in sleep duration and trouble were not associated with use. CONCLUSIONS: Findings suggest regularly shorter sleep may impede treatment outcomes. Adolescents who regularly have insufficient sleep durations likely need additional intervention to improve sleep difficulties in tandem with cannabis use reduction.

2022 Taiwan Guidelines for Preventive Treatment of Migraine.

The Treatment Guideline Subcommittee of the Taiwan Headache Society evaluated the medications currently used for migraine prevention in Taiwan. The subcommittee assessed the results of recently published trials, meta-analyses, and guidelines. After expert panel discussions, the subcommittee reached a consensus on the preventive treatment of migraine in Taiwan, which includes recommendation levels, the strength of evidence, and essential prescription information (i.e., dosage and adverse effects) . The recent introduction of CGRP monoclonal antibodies has had a substantial effect on migraine treatment. Thus, the subcommittee updated the previous version of the treatment guideline published in 2017. Preventive medications for migraines can be divided into the following categories: ß-blockers, anticonvulsants, calcium channel blockers, antidepressants, onabotulinumtoxinA, anti-CGRP monoclonal antibodies, and complementary and alternative medicine. For episodic migraine prevention, propranolol, flunarizine, and topiramate are recommended as the first-line medications. Second-line medications for episodic migraine prevention include valproic acid, amitriptyline, and anti-CGRP monoclonal antibodies. Other treatment options could be used as third-line treatments. For chronic migraine prevention, topiramate, flunarizine, onabotulinumtoxinA, and anti-CGRP monoclonal antibodies are recommended as first-line therapies. Preventive medications for episodic migraine can also be used as second-line treatments for chronic migraine. For menstrual migraines, nonsteroidal anti-inflammatory drugs and triptans can be used for short-term prophylaxis. Indications for starting preventive treatment include a headache frequency of ≥4 days per month, profound disabilities, failure of or contraindication to acute therapies, a complicated migraine with debilitating (e.g., hemiplegic) auras, and migrainous brain infarction. The general principle for oral preventives is to "start low and go slow" while monitoring for adverse events and comorbid conditions. Physicians could consider gradually tapering the medications in patients with sustained improvement over 3 to 6 months in episodic migraine and 6 to 12 months in chronic migraine. Education about not overusing acute medications is also essential for all patients with migraine. Key words: migraine, preventive treatment, evidence-based medicine, guidelines, CGRP monoclonal antibodies, onabotulinumtoxinA, neuromodulation.

The interplay of epilepsy with impaired mitophagy and autophagy linked dementia (MAD): A review of therapeutic approaches.

The duration and, age of dementia have been linked to a higher risk of seizures. The exact mechanism that drives epileptogenesis in impaired mitophagy and autophagy linked dementia (MAD) is fully defined after reviewing the Scopus, Publon, and Pubmed databases. The epileptogenesis in patients with Alzheimer's disease dementia (ADD) and Parkinson's disease dementia (PDD) is due to involvement of amyloid plaques (Aß), phosphorylated tau (pTau), Parkin, NF-kB and NLRP3 inflammasome. Microglia, the prime protective and inflammatory cells in the brain exert crosstalk between mitophagy and inflammation. Several researchers believed that the inflammatory brain cells microglia could be a therapeutic target for the treatment of a MAD associated epilepsy. There are conventional antiepileptic drugs such as gabapentin, lamotrigine, phenytoin sodium, carbamazepine, oxcarbazepine, felbamate, lamotrigine, valproate sodium, and topiramate are prescribed by a psychiatrist to suppress seizure frequency. Also, the conventional drugs generate serious adverse effects and synergises dementia characteristics. The adverse effect of carbamazepine is neurotoxic and also, damages haemopoietic system and respiratory tract. The phenytoin treatment causes cerebellar defect and anemia. Dementia and epilepsy have a complicated relationship, thus targeting mitophagy for cure of epileptic dementia makes sense. Complementary and alternative medicine (CAM) is one of the rising strategies by many patients of the world, not only to suppress seizure frequency but also to mitigate dementia characteristics of patients. Therefore our present review focus on the interplay between epilepsy and MAD and their treatment with CAM approaches.

Digoxin at sub-cardiotonic dose modulates the anticonvulsive potential of valproate, levetiracetam and topiramate in experimental primary generalized seizures.

The prevalence of epilepsy in the world population together with a high percentage of patients resistant to existing antiepileptic drugs (AEDs) stimulates the constant search for new approaches to the treatment of the disease. Previously a significant anticonvulsant potential of cardiac glycoside digoxin has been verified by enhancing a weak activity of AEDs in low doses under screening models of seizures induced by pentylenetetrazole and maximal electroshock. The aim of the present study is to investigate the influence of digoxin at a sub-cardiotonic dose on the anticonvulsant activity of valproate, levetiracetam, and topiramate in models of primary generalized seizures with different neurochemical mechanisms. A total of 264 random-bred male albino mice have been used. AEDs were administered 30 min before seizure induction once intragastrically at conditionally effective (ED50) and sub-effective (½ ED50) doses: sodium valproate and topiramate - at doses of 300 and 150 mg/kg; levetiracetam - at doses of 100 and 50 mg/kg. Digoxin was administered once subcutaneously at a dose of 0.8 mg/kg body weight (1/10 LD50) 10-15 min before seizure induction. Picrotoxin (aqueous solution 2.5 mg/kg, subcutaneously), thiosemicarbazide (aqueous solution 25 mg/kg, intraperitoneally), strychnine (aqueous solution 1.2 mg/kg, subcutaneously), camphor (oil solution 1000 mg/kg, intraperitoneally) have been used as convulsive agents for seizure induction. It was found that under the conditions of primary generalized seizures induced by picrotoxin, thiosemicarbazide, strychnine, and camphor, digoxin not only shows its own strong anticonvulsant activity but also significantly enhances the anticonvulsant potential of classical AEDs sodium valproate, levetiracetam, and topiramate. The obtained results substantiate the expediency of further in-depth study of digoxin as an anticonvulsant drug, in particular, the in-depth study of neurochemical mechanisms of its action.

Association of topiramate prescribed for any indication with reduced alcohol consumption in electronic health record data.

BACKGROUND AND AIMS: Topiramate is a medication that is widely prescribed to treat a variety of conditions, including alcohol use disorder (AUD). We used electronic health record (EHR) data to measure topiramate's effects on drinking in individuals differentiated by a history of AUD. DESIGN: Parallel-groups comparison of patients prescribed topiramate and a propensity score-matched comparison group. SETTING: A large US integrated health-care system. PARTICIPANTS: Patients with Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) scores prior to and after a minimum of 180 days of topiramate prescription for any indication and a propensity score-matched group. The sample included 5918 patients with an electronic health record diagnosis of alcohol use disorder at any time (AUD-hx-pos) (1738 topiramate-exposed and 4180 controls) and 23 614 patients with no EHR diagnosis of AUD (AUD-hx-neg) (6324 topiramate-exposed and 17 290 controls). MEASUREMENTS: Regression analyses compared difference-in-difference (DiD) estimates, separately by AUD history. DiD estimates represent exposure-group (i.e. topiramate versus control) differences on the pre-post difference in AUDIT-C score. Effects of baseline AUDIT-C score and daily topiramate dosage were also tested. FINDINGS: AUD-hx-neg patients who received topiramate had a greater reduction in AUDIT-C score (-0.11) than matched controls (-0.04). This yielded a DiD score of -0.07 [95% confidence interval (CI) = -0.11,-0.03; P = 0.002], with the greatest effect among AUD-hx-neg patients with a baseline AUDIT-C score of 4+ (DiD = -0.35, 95% CI = -0.49, -0.21; P < 0.0001) and those prescribed > 150 mg/day of the medication (DiD = -0.15, 95%CI = -0.23, -0.07; P < 0.001). DISCUSSION: Among individuals with no history of alcohol use disorder, topiramate appears to be associated with reduced drinking. This small effect is most evident among patients with higher baseline drinking levels and at a higher average daily topiramate dosage.

The Impact of Vitamin D3 Supplementation to Topiramate Therapy on Pediatric Migraine Prophylaxis.

Background:There is still a need for more studies to evaluate the role of vitamin D3 in pediatric migraine prophylaxis. Objectives: We aimed to evaluate the effects and safety of vitamin D3 supplementation to topiramate on pediatric migraine. Methods: A double-blinded prospective clinical trial was conducted on 5- to 14-year-old children with migraine. They were randomly assigned in a 1:1 ratio into 2 groups, one with vitamin D3 supplementation (the supplementation group) and the other without vitamin D supplementation (the placebo group). The supplementation group received topiramate plus one 5000-IU dose of vitamin D3 daily for 4 months. The placebo group received topiramate with a placebo capsule without any effective substances. The primary outcomes were a monthly frequency of headache attacks, a good response to intervention, and reduction in migraine severity, duration, and disability before and after treatment. Fifty-six children completed the trial. Vitamin D3 supplementation to topiramate was more effective than the placebo group in the reduction of monthly frequency (6231.31 vs 9792.24 times, P = .01) and disability score for migraines (17 566.43 vs 25 187.65, P = .04). A good response was observed in 76.13% of patients in the vitamin D3 supplementation group and 53.5% of patients in the placebo group, and vitamin D3 supplementation was significantly more effective than placebo (P = .01). Side effects were observed in 13.3% and 20% of the intervention group and placebo groups, respectively, P = .5. Conclusion: Vitamin D3 supplementation in pediatric migraine prophylaxis could be a well-tolerated, safe, and effective strategy.

Topiramate, acupuncture, and BoNT-A for chronic migraine: a network meta-analysis.

BACKGROUND: Botulinum neurotoxin A (BoNT-A) was the primary choice for preventive treatment of chronic migraine. Topiramate and acupuncture showed promising effect for chronic migraine, but their effectiveness relative to BoNT-A was rarely studied. We aimed to perform a network meta-analysis to compare the effectiveness and acceptability between topiramate, acupuncture, and BoNT-A. METHODS: We searched OVID Medline, Embase, the Cochrane register of controlled trials (CENTRAL), the Chinese Clinical Trial Register, and clinicaltrials.gov for randomized controlled trials (RCTs) that compared topiramate, acupuncture, and BoNT-A with any of them or placebo in the preventive treatment of chronic migraine. A network meta-analysis was performed by using a frequentist approach and a random-effects model. The primary outcomes were reduction in monthly headache days and monthly migraine days at week 12. Acceptability was defined as the number of dropouts owing to adverse events. RESULTS: We included 15 RCTs (n = 2545). Eleven RCTs were at low risk of bias. The network meta-analyses (n = 2061) showed that acupuncture (2061 participants; standardized mean difference [SMD] -1.61, 95% CI: -2.35 to -0.87) and topiramate (582 participants; SMD -0.4, 95% CI: -0.75 to -0.04) ranked the most effective in the reduction of monthly headache days and migraine days, respectively; but they were not significantly superior over BoNT-A. Topiramate caused the most treatment-related adverse events and the highest rate of dropouts owing to adverse events. CONCLUSIONS: Topiramate and acupuncture were not superior over BoNT-A; BoNT-A was still the primary preventive treatment of chronic migraine. Large-scale RCTs with direct comparison of these three treatments are warranted to verified the findings.

Efficacy, Safety, and Acceptability of Pharmacologic Treatments for Pediatric Migraine Prophylaxis: A Systematic Review and Network Meta-analysis.

Importance: Migraine is one of the most common neurologic disorders in children and adolescents. However, a quantitative comparison of multiple preventive pharmacologic treatments in the pediatric population is lacking. Objective: To examine whether prophylactic pharmacologic treatments are more effective than placebo and whether there are differences between drugs regarding efficacy, safety, and acceptability. Data Sources: Systematic review and network meta-analysis of studies in MEDLINE, Cochrane, Embase, and PsycINFO published through July 2, 2018. Study Selection: Randomized clinical trials of prophylactic pharmacologic treatments in children and adolescents diagnosed as having episodic migraine were included. Abstract, title, and full-text screening were conducted independently by 4 reviewers. Data Extraction and Synthesis: Data extraction was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis network meta-analysis guidelines. Quality was assessed with the Cochrane Risk of Bias tool. Effect sizes, calculated as standardized mean differences for primary outcomes and risk ratios for discontinuation rates, were assessed in a random-effects model. Main Outcomes and Measures: Primary outcomes were efficacy (ie, migraine frequency, number of migraine days, number of headache days, headache frequency, or headache index), safety (ie, treatment discontinuation owing to adverse events), and acceptability (ie, treatment discontinuation for any reason). Results: Twenty-three studies (2217 patients) were eligible for inclusion. Prophylactic pharmacologic treatments included antiepileptics, antidepressants, calcium channel blockers, antihypertensive agents, and food supplements. In the short term (<5 months), propranolol (standard mean difference, 0.60; 95% CI, 0.03-1.17) and topiramate (standard mean difference, 0.59; 95% CI, 0.03-1.15) were significantly more effective than placebo. However, the 95% prediction intervals for these medications contained the null effect. No significant long-term effects for migraine prophylaxis relative to placebo were found for any intervention. Conclusions and Relevance: Prophylactic pharmacologic treatments have little evidence supporting efficacy in pediatric migraine. Future research could (1) identify factors associated with individual responses to pharmacologic prophylaxis, (2) analyze fluctuations of migraine attack frequency over time and determine the most clinically relevant length of probable prophylactic treatment, and (3) identify nonpharmacologic targets for migraine prophylaxis.

Anti-epileptic drug and folic acid usage during pregnancy, seizure and malformation outcomes: Changes over two decades in the Kerala Registry of Epilepsy and Pregnancy.

BACKGROUND: This study was carried out to determine changes over time in use of folic acid, anti-epileptic drugs (AED), seizures during pregnancy and malformation rate over two decades in women with epilepsy enrolled in the Kerala registry of Epilepsy and Pregnancy (KREP). METHODS: All completed pregnancies with known outcome between 1998 and 2017 (n = 1962) were analyzed for the use of folic acid and AEDs in the first trimester, seizure count for the entire pregnancy and the presence of major congenital malformation (MCM). The results were presented for three epochs (1998-2004, 2005-2011 and 2012-2017). RESULTS: There was significant increase (p = .001) in the use of folic acid 5 mg/day or more in pre-pregnancy month (43.9 to 81 %) and first trimester (52.7 to 86.6 %). Occurrence of seizures during pregnancy had declined significantly (57.2 to 32.9 %, p = 0.001) over time. Those who were off AEDs during pregnancy declined from 17.4 to 8.5 % (p = .001). Newer AEDs - lamotrigine, levetiracetam, oxcarbazepine and topiramate) were increasingly preferred in the last seven years instead of older AEDs (phenobarbitone, phenytoin and clonazepam). There was no significant change in the use of carbamazepine or valproate. MCM rates did not show any significant change (7.5 to 7.3 %). CONCLUSION: Seizure control and high dose folic acid usage during pregnancy had improved over two decades. Despite the changes in the AED usage over time the MCM rates had remained unchanged probably due to continued use of valproate, increased use of topiramate and clobazam that are associated with higher MCM rates and lack of reduction in polytherapy.

Migraine patients' journey until a tertiary headache center: an observational study.

BACKGROUND: Migraine diagnosis is based on clinical aspects and is dependent on the experience of the attending physician. This study aimed to describe the patients journey profile until they start their experience in a tertiary headache center. METHODS: In a cross-sectional study, medical charts from migraine patients were reviewed to describe which treatments, procedures and follow-up strategies are performed until the first appointment with a headache specialist. Patients from both sexes, ≥18 years old, which came to their first visit from March to July 2017 were included. Sociodemographic information, headache characteristics, diagnostic methods previously used, clinical history, family history and the treatments previously used were assessed in the first appointment with a specialist. Patient Health Questionnaire-9 and General Anxiety Disorder-7 were also applied. Descriptive analyses were performed to describe the sample profile and statistical tests were used to evaluate factors associated with the type of migraine (chronic or episodic). RESULTS: The sample consisted of 465 patients. On average, the pain started 17.1 (SD = 11.4) years before the first appointment with a headache specialist. Most of patients were classified as having chronic migraine (51.7%), with an average frequency of 15.5 (SD = 9.9) days per month. Regarding patients' journey until a specialist, most patients were submitted to laboratory tests (74.0%), cranial tomography (66.8%) and magnetic resonance imaging (66.8%) as diagnostic methods, and preventive drugs (70.2%) and acupuncture (61.0%) as treatments. After stratification by migraine type as episodic or chronic, patients with chronic migraine were submitted to more magnetic resonance imaging test, acupuncture, psychotherapy, used preventive drugs, and reported to have used topiramate without beneficial effects. CONCLUSIONS: Brazilian patients with migraine experiment a long journey until getting to a headache specialist and are submitted to a great number of unnecessary exams, especially those with chronic migraine.

Survey of Child Neurologists on Management of Pediatric Post-traumatic Headache.

Traumatic brain injury causes significant morbidity in youth, and headache is the most common postconcussive symptom. No established guidelines exist for pediatric post-traumatic headache management. We aimed to characterize common clinical practices of child neurologists. Of 95 practitioners who completed our survey, most evaluate <50 pediatric concussion patients per year, and 38.9% of practitioners consistently use International Classification of Headache Disorders criteria to diagnose post-traumatic headache. Most recommend nonsteroidal anti-inflammatory drugs as abortive therapy, though timing after injury and frequency of use varies, as does the time when providers begin prophylactic medications. Amitriptyline, topiramate, and vitamins/supplements are most commonly used for prophylaxis. Approach to rest and return to activities varies; one-third recommend rest for 1 to 3 days and then progressive return, consistent with current best practice. With no established guidelines for pediatric post-traumatic headache management, it is not surprising that practices vary considerably. Further studies are needed to define the best, evidence-based management for pediatric post-traumatic headache.

Pharmacotherapies for co-occurring substance use and bipolar disorders: A systematic review.

OBJECTIVES: Substance use disorders (SUDs), including those for alcohol, stimulants, tobacco, opioids and cannabis, in patients with bipolar disorder are a major clinical and public health problem, and are present in the majority of these patients. Nonetheless, the development of effective pharmacological treatments for co-occurring SUDs in bipolar illness have not been well-developed and may be an important practical reason for the reduced effectiveness of these medications in community practice. METHODS: We conducted a systematic review of the literature (PubMed, Medline, Google Scholar), and identified N = 29 clinical studies, which evaluated both mental health and SUD outcomes in patients with co-occurring bipolar disorders and SUDs. RESULTS: Our findings suggest the potential of valproate sodium and lamotrigine as preferred pharmacological agents for the treatment of co-occurring psychiatric and substance use outcomes in these patients. However, many of the reviewed studies are of open-label designs and of modest sample sizes. CONCLUSIONS: Thus, given the gaps in our knowledge, recommendations for treatment of this common and important co-morbidity are preliminary. Accordingly, the conduct of larger, randomized controlled trials for this co-morbidity is clearly needed.

Antiepileptic Drug Treatment Patterns in Women of Childbearing Age With Epilepsy.

Importance: Limited population-based data are available on antiepileptic drug (AED) treatment patterns in women of childbearing age with epilepsy; the current population risk is not clear. Objectives: To examine the AED treatment patterns and identify differences in use of valproate sodium and topiramate by comorbidities among women of childbearing age with epilepsy. Design, Setting, and Participants: A retrospective cohort study used a nationwide commercial database and supplemental Medicare as well as Medicaid insurance claims data to identify 46 767 women with epilepsy aged 15 to 44 years. The eligible study cohort was enrolled between January 1, 2009, and December 31, 2013. Data analysis was conducted from January 1, 2017, to February 22, 2018. Exposures: Cases required an International Classification of Diseases, Ninth Revision, Clinical Modification-coded epilepsy diagnosis with continuous medical and pharmacy enrollment. Incident cases required a baseline of 2 or more years without an epilepsy diagnosis or AED prescription before the index date. For both incident and prevalent cases, focal and generalized epilepsy cohorts were matched by age, payer type, and enrollment period and then compared. Main Outcomes and Measures: Antiepileptic drug treatment pattern according to seizure type and comorbidities. Results: Of the 46 767 patients identified, there were 8003 incident cases (mean [SD] age, 27.3 [9.4] years) and 38 764 prevalent cases (mean [SD] age, 29.7 [9.0] years). Among 3219 women in the incident epilepsy group who received AEDs for 90 days or more, 3173 (98.6%) received monotherapy as first-line treatment; among 28 239 treated prevalent cases, 18 987 (67.2%) received monotherapy. In 3544 (44.3%) incident cases and 9480 (24.5%) prevalent cases, AED treatment was not documented during 180 days or more of follow-up after diagnosis. Valproate (incident: 35 [5.81%]; prevalent: 514 [13.1%]) and phenytoin (incident: 33 [5.48%]; prevalent: 178 [4.53%]) were more commonly used for generalized epilepsy and oxcarbazepine (incident: 53 [8.03%]; prevalent: 386 [9.89%]) was more often used for focal epilepsy. Levetiracetam (incident: focal, 267 [40.5%]; generalized, 271 [45.0%]; prevalent: focal, 794 [20.3%]; generalized, 871 [22.2%]), lamotrigine (incident: focal, 123 [18.6%]; generalized, 106 [17.6%]; prevalent: focal, 968 [24.8%]; generalized, 871 [22.2%]), and topiramate (incident: focal, 102 [15.5%]; generalized, 64 [10.6%]; prevalent: focal, 499 [12.8%]; generalized, 470 [12.0%]) were leading AEDs prescribed for both focal and generalized epilepsy. Valproate was more commonly prescribed for women with comorbid headache or migraine (incident: 53 of 1251 [4.2%]; prevalent: 839 of 8046 [10.4%]), mood disorder (incident: 63 of 860 [7.3%]; prevalent: 1110 of 6995 [15.9%]), and anxiety and dissociative disorders (incident: 57 of 881 [6.5%]; prevalent: 798 of 5912 [13.5%]). Topiramate was more likely prescribed for those with comorbid headache or migraine (incident: 335 of 1251 [26.8%]; prevalent: 2322 of 8046 [28.9%]). Conclusions and Relevance: Many women appear to be treated with valproate and topiramate despite known teratogenicity risks. Comorbidities may affect selecting certain AEDs despite their teratogenicity risks.

Disruption of the hippocampal and hypothalamic blood-brain barrier in a diet-induced obese model of type II diabetes: prevention and treatment by the mitochondrial carbonic anhydrase inhibitor, topiramate.

BACKGROUND: Type II diabetes is a vascular risk factor for cognitive impairment and increased risk of dementia. Disruption of the blood-retinal barrier (BRB) and blood-brain barrier (BBB) are hallmarks of subsequent retinal edema and central nervous system dysfunction. However, the mechanisms by which diet or metabolic syndrome induces dysfunction are not understood. A proposed mechanism is an increase in reactive oxygen species (ROS) and oxidative stress. Inhibition of mitochondrial carbonic anhydrase (mCA) decreases ROS and oxidative stress. In this study, topiramate, a mCA inhibitor, was examined for its ability to protect the BRB and BBB in diet-induced obese type II diabetic mice. METHODS: BBB and BRB permeability were assessed using 14C-sucrose and 99mTc-albumin in CD-1 mice fed a low-fat (control) or a high-fat diet. Topiramate administration was compared to saline controls in both preventative and efficacy arms examining BRB and BBB disruption. Body weight and blood glucose were measured weekly and body composition was assessed using EchoMRI. Metabolic activity was measured using a comprehensive laboratory animal monitoring system. Brain tissues collected from the mice were assessed for changes in oxidative stress and tight junction proteins. RESULTS: High-fat feeding caused increased entry of 14C-sucrose and 99mTc-albumin into the brains of diet-induced obese type II diabetic mice. Increased permeability to 14C-sucrose was observed in the hypothalamus and hippocampus, and attenuated by topiramate treatment, while increased permeability to 99mTc-albumin occurred in the whole brain and was also attenuated by topiramate. Treatment with topiramate decreased measures of oxidative stress and increased expression of the tight junction proteins ZO-1 and claudin-12. In the retina, we observed increased entry of 99mTc-albumin simultaneously with increased entry into the whole brain during the preventative arm. This occurred prior to increased entry to the retina for 14C-sucrose which occurred during the efficacy arm. Treatment with topiramate had no effect on the retina. CONCLUSIONS: Blood-brain barrier and blood-retinal barrier dysfunction were examined in a mouse model of diet-induced obese type II diabetes. These studies demonstrate that there are spatial and temporal differences in 14C-sucrose and 99mTc-albumin permeability in the brain and retina of diet-induced obese type II diabetic mice. Topiramate, a mitochondrial carbonic anhydrase inhibitor, is efficacious at both preventing and treating BBB disruption in this diet-induced obese type II diabetic mouse model.

Hipertensión endocraneana idiopática: respuesta al tratamiento Topiramato vs Acetazolamida / Endocranial idiopathic hypertension: response to treatment Topiramate vs. Acetazolamide

INTRODUCCIÓN: El término pseudotumorcerebri se reserva para denominar aquellas hipertensiones endocraneanas (HE) que clínicamente asemejan la existencia de un tumor cerebral, debido a la alteración de la circulación del líquido cefalorraquídeo (LCR). Para su diagnóstico se describen los criterios de Dandy-Smith. OBJETIVOS: Objetivo Primario: Determinar el beneficio del uso de Azetazolamida (ACZ) o Topiramato (TPM) en el tratamiento de la hipertensión endocraneana idiopática. Objetivos Secundarios: Uso de Presión de apertura como parámetro indicador para uso de ACZ o TPM. MATERIALES Y MÉTODOS: Tipo de estudio: Descriptivo Retrospectivo Observacional. RESULTADOS: La media de seguimiento fue de 11 meses, con un rango entre 6-12 meses Se estudiaron 5 pacientes con diagnóstico de Hipertensión Endocraneana Idiopática. Del total de los pacientes 5 (100%) tenían F.O patológico y como síntoma cardinal cefalea, 2 (40%) además vómitos. 3 (60%) fue tratado con Topiramato (TPM) mientras que 2 (40%) recibió acetazolamida (ACZ), ambos sin complicaciones (p= 0,07) Del total de los pacientes 3(60%) presento presión de apertura menor de 40 mmHg mientras que en los restantes 2 (40%) fue mayor a 40 mmHg. De estos últimos el 1 paciente recibió TPM y 1 paciente ACZ. Dos pacientes (40%) presentaron en el seguimiento una recaída sintomática, al intentar descender la medicación. No se pudo definir como parámetro de decisión la presión de apertura en del uso de uno u otro medicamento ya que al evaluar el uso de TPM y ACZ en pacientes con presión de apertura mayor a 41 mmHg solo se detallaron 2 pacientes cada uno tratado con un medicamento de los anteriormente descriptos. (Chi cuadrado p= 0.44). Ninguno de los pacientes tratados requirió otro tratamiento complementario como PL seriadas o válvula de derivación ventrículo peritoneal. CONCLUSION: No se logró determinar beneficio en el uso de un medicamento sobre otro en el tratamiento de la hipertensión endocraneana idiopática (p=0,07), pese al tamaño muestral, el cual podría ser un limitante. Coincidentemente con la literatura sigue sin haber evidencia suficiente. No existe un algoritmo de consenso en cuanto al correcto manejo terapéutico y farmacológico de esta entidad. El uso de TPM o ACZ no condiciona la posterior aparición de complicaciones (p= 0.45) El estudio oftalmológico es esencial para diagnóstico y seguimiento. No se pudo establecer correlación entre el valor obtenido en la medición de la presión de apertura y el tratamiento instaurado. (AU)

INTRODUCTION: The term Pseudotumor cerebri is reserved for those endocranial hypertensio (EH) that resemble clinically the existence of a brain tumor, due to alteration of the circulation of the cerebrospinal fluid (CSF). Classically, the Dandy-Smith criteria for diagnosis are described. TYPE OF STUDY: Descriptive observational. OBJECTIVE: Primary Objective: To determine the benefit of the use of Azetazolamide (ACZ) or Topiramate (TPM) in the treatment of idiopathic endocranial hypertension Secondary Objectives: Use of Opening Pressure as indicator parameter for use of ACZ or TPM. MATERIALS AND METHODS: Observed patients(N:5) per clinic with diagnosis of EIH by criteria of Dandy-Smith in the period 2013-2017. I was performed in all patients: RMNC s/contrast Fundus oculi Lumbar puncture + opening pressure. RESULTS: Of the total of patients (5) 100% had F.O pathological and as cardinal symptom headache, and 40% also vomiting. The mean follow-up was 11 months 60% of the patients was treated with topiramate (TPM) while 40% received acetazolamide (ACZ), both without complications. Of the total of patients 60% presented less than 40 opening pressure mmHg, while that in the remaining 40% was greater than 40 mmHg, of which 50% received TPM and 50% ACZ. 40% presented in tracking a symptomatic relapse, trying to get off the medication. None of the treated patients required other adjunctive therapy such as serial PL or ventricleperitoneal shunt. CONCLUSIONS: It was not possible to determine benefit in the use of one drug over another in the treatment of idiopathic intracranial hypertension (p = 0.07), despite the sample size, which could be a limitation. Coincidentally with the literature there is still not enough evidence. There is no consensus algorithm regarding the correct therapeutic and pharmacological management of this entity. The use of TPM or ACZ does not condition the subsequent appearance of complications (p = 0.45) The ophthalmological study is essential for diagnosis and follow-up. No correlation could be established between the value obtained in the measurement of the opening ression and the treatment established. (AU)

Using Ecological Momentary Assessment to Identify Mechanisms of Change: An Application From a Pharmacotherapy Trial With Adolescent Cannabis Users.

OBJECTIVE: The present study used youth's in vivo reports of subjective responses to cannabis while smoking in their natural environments to identify real-world mechanisms of topiramate treatment for cannabis misuse. METHOD: Participants were 40 cannabis users (≥ twice weekly in past 30 days), ages 15-24 years (47.5% female), with at least one cannabis use episode during the final 3 weeks of a 6-week, randomized clinical trial. Youth reported subjective "high" while smoking, stimulation, sedation, stress, craving, and grams of marijuana used in the natural environment via wireless electronic devices. Bayesian multilevel structural equation modeling (MSEM) evaluated mediation via indirect effect tests. RESULTS: Significant within (daily) and between (person) variability and distinctive within and between effects supported the MSEM approach. Subjective high while smoking was significantly reduced for youth in the topiramate condition, relative to placebo, and the indirect effect of reduced subjective high on total grams of cannabis smoked that day was significant. Indirect effects through other subjective responses were not significant. CONCLUSIONS: The results of this initial study suggest that altering subjective responses to smoking, specifically subjective high, may be a key target for developing adjunctive pharmacotherapies for cannabis misuse. More generally, this work provides an example for applying ecological momentary assessment and analytic techniques to evaluate mechanisms of behavior change in longitudinal data.