The Effect of Antiepileptic Drugs on Cognition: Patient Perceived Cognitive Problems of Topiramate versus Levetiracetam in Clinical Practice

Summary:  Introduction: Neurocognitive complaints may interfere with long-term antiepileptic drug (AED) treatment and are an important issue in clinical practice. Most data about drug-induced cognitive problems are derived from highly controlled short-term clinical trials. We analyzed such cognitive complaints for the two most commonly used AEDs in a clinical setting using patient perceived problems as primary outcome measure.
Method: All patients of the epilepsy center Kempenhaeghe that received topiramate (TPM) or levetiracetam (LEV) from the introduction to mid 2004 were analyzed using a medical information system, an automated medical file. Patients were analyzed after 6, 12, and 18 months of treatment.
Results: Four hundred and two patients used either TPM (n = 260) or LEV (n = 142); 18 months retention showed a statistically significant difference, revealing 15% more patients that continued LEV compared to TPM: 18 months retention 46% for TPM and 61% for LEV [F (1.400) = 3.313, p = 0.043]. Neurocognitive complaints accounted for a significant number of drug discontinuations and especially the high frequency of neurocognitive complaints in the first period of TPM treatment appeared to be significant different from LEV [F(2,547) = 3.192, p = 0.042]. In the remaining patients, the difference in neurocognitive complaints was not statistically significant.
Conclusion: cognitive complaints are common in TPM treatment and frequently lead to drug withdrawal. The impact of LEV on cognitive function is only mild. This leads to a much higher (15%) drug discontinuation rate for TPM compared to LEV.     

Residual Flow Signals Predict Complete Recanalization in Stroke Patients Treated With TPA

BACKGROUND: Residual blood flow around thrombus prior to treatment predicts success of coronary thrombolysis. The authors aimed to correlate the presence of residual flow signals in the middle cerebral artery (MCA) with completeness of recanalization after intravenous tissue plasminogen activator (TPA). METHODS: The authors studied consecutive patients treated with intravenous TPA therapy who had a proximal MCA occlusion on pretreatment transcranial Doppler (TCD). Patients were continuously monitored for 2 hours after TPA bolus. Absent residual flow signals correspond to the thrombolysis in brain ischemia (TIBI) 0 grade, and the presence of residual flow signals was determined as TIBI 1-3 flow grades. Complete recanalization was defined as flow improvement to TIBI grades 4-5. RESULTS: Seventy-five patients with a proximal MCA occlusion had median pre-bolus NIHSS 16 (85% with > or = 10 points). TPA bolus was given at 141 +/- 56 minutes (median 120 minutes). Complete recanalization was observed in 25 (33%), partial in 23 (31%), and no early recanalization was seen in 27 (36%) patients within 2 hours after TPA bolus. Only 19% with absent residual flow signals (TIBI grade 0, n = 26) on pretreatment TCD had complete early recanalization. If pretreatment TCD showed the presence of any residual flow (TIBI 1-3, n = 49), 41% had complete recanalization within 2 hours of TPA bolus (P = .03). CONCLUSIONS: Patients with detectable residual flow signals before IV TPA bolus are twice as likely to have early complete recanalization. Those with no detectable residual flow signals have less than 20% chance for complete early recanalization with intravenous TPA and may be candidates for intra-arterial therapies.     

Gastric ulceration caused by heater probe coagulation

A double-contrast upper gastrointestinal examination on a woman who had undergone endoscopic heater probe therapy one day earlier for multiple arteriovenous malformations revealed shallow, irregular, and linear ulcers at the sites of heater probe coagulation. Multiple shallow ulcers may therefore develop as a direct complication of heater probe therapy. Radiologists should be aware of this complication to avoid diagnostic confusion in these patients.     

Dyspepsie und Helicobacter-pylori-Infektion bei Besch?ftigten eines gro?en Industrieunternehmens Ergebnisse der prospektiven BASF-Helicobacter-pylori-Vorsorgeaktion

Zusammenfassung Hintergrund: Die Assoziation zwischen Helicobacter-pylori-(H.-pylori-)Infektion und Dyspepsie wird kontrovers diskutiert. Im Rahmen der BASF-H.-pylori-Vorsorgeaktion wurde u. a. die Prävalenz von Dyspepsie bei arbeitsfähigen Personen ermittelt sowie der Zusammenhang mit der H.-pylori-Infektion und der Erfolg einer Eradikationstherapie untersucht. Probanden und Methodik: 6 132 Beschäftigte der BASF wurden untersucht und im Rahmen einer standardisierten Anamnese u. a. zu dyspeptischen Beschwerden befragt. Diese wurden entsprechend der führenden Symptomatik den Dyspepsiesubtypen vom Ulkustyp, Dysmotilitätstyp, Refluxtyp und unspezifischen Typ zugeordnet. Bei allen Beschäftigten wurde die Seroprävalenz (IgG-ELISA) der H.-pylori-Infektion bestimmt. Allen H.-pylori-positiven Personen mit Dyspepsie wurde weitere Diagnostik in Form einer Ösophagogastroduodenoskopie und einer Sonographie des Abdomens bei Fachärzten empfohlen und eine H.-pylori-Eradikationstherapie (Italian-Triple-Therapie) angeboten. In einer Untergruppe endoskopisch untersuchter Beschäftigter mit peptischer Ulkuskrankheit (PUD, n = 37) bzw. Non-Ulcer-Dyspepsie (NUD; n = 39) wurde der prognostische Wert der im Western Blot ermittelten Antikörper gegen CagA und VacA untersucht. Ergebnisse: 1 255 der 6 143 Beschäftigten (20,4%) berichteten über Dyspepsie. 492 Personen mit Dyspepsie (39,2%) waren gleichzeitig H.-pylori-positiv. Bei Personen ohne dyspeptische Symptome betrug die H.-pylori-Prävalenz 35,8%. Personen mit unterschiedlichen Dyspepsiesubtypen unterschieden sich nicht hinsichtlich der H.-pylori-Prävalenz. Personen, die häufige und intensive dyspeptische Beschwerden angaben, waren allerdings signifikant häufiger H.-pylori-positiv (OR 2,09, CI 1,43-3,05). Die Seroprävalenz von CagA und VacA bei Personen mit PUD unterschied sich nicht signifikant von derjenigen bei Personen mit NUD. 458 H.-pylori-positiven Personen wurde die Eradikation empfohlen. 330 Personen (72,1%) folgten der Empfehlung. 128 (27,9%) ließen sich nicht behandeln. An der Nachkontrolle nach 12 Monaten nahmen 402 Personen (87,8%) teil, davon waren 300 behandelt, 102 nicht. Der serologisch analysierte Eradikationserfolg lag bei 81,5%. 42,8% der erfolgreich behandelten Personen berichteten über Besserung ihrer Beschwerden, 33,2% über Beschwerdefreiheit. Bei den nicht behandelten Personen war dies nur in 16,7% bzw. in 37,3% der Fall. Vermehrte Refluxbeschwerden traten nach erfolgreicher Eradikation nicht auf. Schlussfolgerung: Wir konnten keinen generellen Zusammenhang zwischen Dyspepsie und H.-pylori-Infektion in einem großen Kollektiv arbeitsfähiger Personen erkennen. Häufige und intensive dyspeptische Symptome scheinen allerdings ein prädikativer Faktor für die H.-pylori-Seropositivität zu sein. Die serologisch bestimmbaren Virulenzfaktoren tragen nicht zur Unterscheidung PUD oder NUD bei. Die Eradikationstherapie führte nach 1 Jahr zwar häufiger zur Besserung, aber nicht häufiger zu Beschwerdefreiheit bei Beschäftigten mit dyspeptischen Beschwerden im Vergleich zu unbehandelten Personen. Abstract Background: The role of Helicobacter pylori (H. pylori) infection in dyspepsia is controversial. In the course of a health initiative within a large industrial corporation, we investigated the prevalence of both dyspepsia and positive H. pylori serology and the outcome of eradication therapy in symptomatic H. pylori positive employees. Test Persons and Methods: H. pylori serology (IgG ELISA) was determined in 6,143 employees of BASF AG Ludwigshafen/Germany who were also asked to complete a standardized health history administered by a physician. Peptic ulcer disease (PUD) and dyspepsia subgroups were defined based on past medical history and symptom profiles using the criteria of Heading. Upper GI endoscopy, abdominal ultrasound and eradication therapy (Italian Triple Therapy) was recommended for symptomatic H. pylori positive individuals. The prognostic value of antibodies against CagA and VacA was evaluated in 37 and 39 employees with PUD and non-ulcer dyspepsia (NUD) confirmed by endoscopy, respectively. Results: Of 6,143 employees, 1,255 (20.4%) were classified as dyspeptic, 492 (39.2%) of whom were H. pylori positive. The seroprevalence of H. pylori in asymptomatic employees was 35.8%. There were no significant differences in H. pylori seroprevalence among dyspepsia subgroups (reflux only, dysmotility only, reflux/dysmotility, ulcer-like and non-specific). However, individuals reporting severe dyspeptic symptoms were significantly more likely to be H. pylori positive (OR 2.09, CI 1.43-3.05). The seroprevalence of CagA and VacA was not significantly different among employees with NUD compared to referents or among employees with NUD compared to those with PUD. 330 (72%) of 458 employees with dyspepsia received eradication therapy, 128 persons refused therapy. Based on a 12-month follow-up of 402 individuals (300 of whom had received therapy), eradication success was 81.5% as judged by serology. Of the successfully treated employees, 33.2% reported a total absence and 42.8% reported a decrease in symptoms. Among the employees who refused therapy, the corresponding percentages were 37.3% and 16.7%, respectively. An increase in reflux complaints was not observed among treated employees. Conclusion: In a large active employee population, at most a very weak association was observed between the prevalence of H. pylori seropositivity and dyspepsia. Frequent and severe dyspeptic symptoms were associated with an increased rate of H. pylori seropositivity. The analysis of the virulence factors is not particularly helpful in discriminating PUD or NUD. Eradication of H. pylori infection leads to a decrease in dyspeptic symptoms after 12 months, but not more often to their complete absence compared to untreated individuals.     

Stimulation of tumor growthin vitro andin vivo by suramin on the VX2 model

Suramin is an antitrypanosomal compound with confirmed efficacy against several human malignancies. It is generally assumed that its mechanism of action includes the interaction with different growth factors, unlike most of the anticancer drugs. Its anticancer activity has not been testedin vivo against squamous cell carcinoma. The purpose of this study was to assess the efficacy and toxicity of suraminin vivo andin vitro on the VX2 tumor model at therapeutic monitored plasma concentrations. We determined the pharmacokinetics of suramin in rabbits, and modelized its administration in order to obtain plasma concentrations between 150 and 300 μg/ml throughout the treatment course of 3 weeks. Under these conditions, antitumor effects of suramin were evaluatedin vivo by comparing liver tumor involvement in suramin-treated and control rabbits. Liver involvement was quantified by image analysis andin vitro effects were also determined at the same concentrations.In vivo, suramin promoted liver tumor growth significantly (p<0.05), compared to untreated controls.In vitro, suramin significantly stimulated tumor cell growth at concentrations above 200 μg/ml (p<0.01). Suramin may have stimulatory effects on tumor growth in squamous cell carcinoma at relevant plasma drug concentrations. Caution should be taken in further trials in patients with squamous cell carcinomas.     

Femoroacetabular impingement in 45 professional athletes: associated pathologies and return to sport following arthroscopic decompression

Femoroacetabular impingement (FAI) occurs when an osseous abnormality of the proximal femur (cam) or acetabulum (pincer) triggers damage to the acetabular labrum and articular cartilage in the hip. Although the precise etiology of FAI is not well understood, both types of FAI are common in athletes presenting with hip pain, loss of range-of-motion, and disability in athletics. An open surgical approach to decompressing FAI has shown good clinical outcomes; however, this highly invasive approach inherently may delay or preclude a high level athlete’s return to play. The purpose of this study was to define associated pathologies and determine if an arthroscopic approach to treating FAI can allow professional athletes to return to high-level sport. Hip arthroscopy for the treatment of FAI allows professional athletes to return to professional sport. Between October 2000 and September 2005, 45 professional athletes underwent hip arthroscopy for the decompression of FAI. Operative and return-to-play data were obtained from patient records. Average time to follow-up was 1.6 years (range: 6 months to 5.5 years). Forty two (93%) athletes returned to professional competition following arthroscopic decompression of FAI. Three athletes did not return to play; however, all had diffuse osteoarthritis at the time of arthroscopy. Thirty-five athletes (78%) remain active in professional sport at an average follow-up of 1.6 years. Arthroscopic treatment of FAI allows professional athletes to return to professional sport.     

Assessment of the reliability and validity of panoramic imaging for assessment of mandibular condyle morphology using both MRI and clinical examination as the gold standard.

OBJECTIVES: The purpose of this study was to evaluate both reliability and validity of the assessment of the shape of the mandibular condyle in panoramic images of the TMJ. STUDY DESIGN: Forty subjects were included and were examined according to the Research Diagnostic Criteria for Temporomandibular Disorders. Panoramic radiographs (PRs) and magnetic resonance images (MRIs) were completed for all subjects. Both MRIs and PRs were rated by raters blinded to the clinical diagnosis. Kappa statistics were used to compare the results of the raters of the PRs. Additionally, the specificity and the sensitivity of the PRs were calculated for 2 scenarios: one with MRI and the other with clinical findings as the gold standard. RESULTS: The sensitivity was 0.94 (specificity = 0.45) for the assumption that MRI is the gold standard and 0.86 (specificity = 0.49) for the assumption that the clinical examination is the gold standard. For reliability, the results for kappa ranged from 0.06 to 0.327. CONCLUSION: It can be concluded that PRs are not a reliable method of accurately judging the shape of the mandibular condyle.     

Palliative Tumortherapie im Verdauungstrakt

Ohne Zusammenfassung     

Use of stereotactic PET images in dosimetry planning of radiosurgery for brain tumors: clinical experience and proposed classification.

We developed a technique that allows the routine integration of PET in stereotactic neurosurgery, including radiosurgery. We report our clinical experience with the combined use of metabolic (i.e., PET) and anatomic (i.e., MRI and CT) images for the radiosurgical treatment of brain tumors. We propose a classification describing the relative role of the information provided by PET in this multimodality image-guided approach. METHODS: Between December 1999 and March 2003, 57 patients had stereotactic PET as part of their image acquisition for the planning of gamma knife radiosurgery. Together with stereotactic MRI and CT, stereotactic PET images were acquired on the same day using either (18)F-FDG or (11)C-methionine. PET images were imported in the planning software for the radiosurgery dosimetry, and the target volume was defined using the combined information of PET and MRI or CT. To analyze the specific contribution of the PET findings, we propose a classification that reflects the strategy used to define the target volume. RESULTS: The patients were offered radiosurgery with PET guidance when their tumor was ill-defined and we anticipated some limitation of target definition on MRI alone. This represents 10% of the radiosurgery procedures performed in our center during the same period of time. There were 40 primary brain lesions, 7 metastases, and 10 pituitary adenomas. Abnormal PET uptake was found in 62 of 72 targets (86%), and this information altered significantly the MRI-defined tumor in 43 targets (69%). CONCLUSION: The integration of PET in radiosurgery provides additional information that opens new perspectives for the optimization of the treatment of brain tumors.