Jens Lunkenheimer

CYP2D6 genotype: impact on adverse effects and nonresponse during treatment with antidepressants-a pilot study.

Treatment with antidepressants is frequently associated with adverse effects or insufficient clinical response. Several antidepressants are metabolized by cytochrome P450 (CYP) 2D6. The activity of this enzyme markedly varies among individuals from poor to ultrarapid metabolism on the basis of the polymorphism of the CYP2D6 gene. This association study investigated whether the CYP2D6 genotype distribution differs from that of the German white population either in patients with marked adverse effects or in nonresponders during treatment with antidepressants metabolized by CYP2D6.

The impact of the CYP2D6-polymorphism on dose recommendations for current antidepressants

Cytochrome P450 CYP2D6 represents an extensively characterized polymorphic drug-metabolizing enzyme. The CYP2D6-gene is highly polymorphic and more than 70 different alleles are known currently. The activity of the enzyme markedly varies among individuals from poor to intermediate and extensive up to ultrarapid metabolism on the basis of the polymorphism of the CYP2D6 gene. Association studies provide growing evidence for the clinical importance of the CYP2D6 polymorphism investigating whether the CYP2D6 genotype distribution differs from that of the normal population either in patients with marked adverse effects or in nonresponders during treatment with CYP2D6 substrates. However, these scientifically important studies present less information for dose adjustments necessary to individualize pharmacotherapy in a given clinical case. With respect to psychopharmacological drug metabolism several antidepressants were characterized as being CYP2D6 substrates. Thus, this review summarizes dose recommendations of current antidepressants.

Single versus bilateral external ventricular drainage for intraventricular fibrinolysis in severe ventricular haemorrhage

Background: Intraventricular fibrinolysis (IVF) through bilateral external ventricular drains (EVD) may provide better access of the thrombolytic agent to the intraventricular clot, potentially influencing clot clearance and outcome. Methods: Patients with spontaneous ganglionic intracerebral haemorrhage (ICH)<40 cm3 and intraventricular haemorrhage (IVH) with acute hydrocephalus have been treated with IVF. The decision for placement of one or two EVDs has been left to the discretion of the treating physician. CT volumetry, the effects on cerebrospinal fluid (CSF) circulation and outcome at 3 months have been analysed for patients with one (group I, n = 13) or two EVDs (group II, n = 14). Results: No difference was found in clot resolution between the two groups (clot half life 2.1 (SD 1.2) vs 2.4 (1.3) days). A separate analysis of the third and fourth ventricle clearance was similar (1.6 (0.6) versus 1.8 (0.8) days), indicating no difference in reconstitution of CSF circulation. A trend towards a longer EVD duration and higher infection rate was found in the bilateral EVD group. No difference was found in outcome at 3 months. Conclusions: Our results do not support the use of bilateral EVDs for IVF in patients with severe IVH.

The influence of mecamylamine on trigeminal and olfactory chemoreception of nicotine

Nicotine presented to the nasal cavity at low concentrations evokes ‘odorous’ sensations, and at higher concentrations ‘burning’ and ‘stinging’ sensations. A study in smokers and nonsmokers provided evidence of a relationship between the experience with the pharmacological action of S-(−)-nicotine and the perceived pleasantness/unpleasantness following nasal stimulation with S-(−)-nicotine. Mecamylamine, a nicotinic acetylcholine-receptor-(nAch-R) antagonist, was able to block painful responses following chemical stimulation of the human tongue and to block responses from the rats ethmoidal nerve. The aim of our study in humans was to investigate the effects of mecamylamine on the olfactory and the trigeminal chemoreception of nicotine enantiomers. In order to achieve this aim, we determined—before and after mecamylamine—(1) detection thresholds, trigeminal thresholds, and intensity estimates (stimulus intensity) and (2) recorded the negative mucosal potential (NMP) following nasal stimulation with nicotine in a placebo-controlled double blind study (n=15). CO2 was used as a trigeminal and H2S as an olfactory control stimulus. Mecamylamine significantly increased trigeminal thresholds of S-(−)-nicotine and reduced intensity estimates and NMPs following stimulation with nicotine enantiomers, whereas mecamylamine did not influence NMPs and trigeminal intensity estimates following stimulation with CO2. In contrast, mecamylamine did neither influence detection thresholds nor olfactory intensity estimates following stimulation with olfactory nicotine concentrations. These results demonstrate that the trigeminal nasal chemoreception of nicotine enantiomers, in contrast to CO2, is mediated by nAch-Receptors and give evidence that the olfactory chemoreception of nicotine is independent from peripheral nAch-Receptors.

Memantine fails to facilitate partial cigarette deprivation in smokers – no role of Memantine in the treatment of nicotine dependency?

Summary.The efficacy of Memantine in the treatment of nicotine dependency in humans remained to be evaluated. The aims of our pilot study were to investigate (1) the effectiveness of Memantine in facilitating smoking reduction and (2) the influence of Memantine on the perception of nicotine. In order to achieve these aims we conducted a placebo controlled double-blind parallel group study in smokers (n = 20 per group). Before the beginning of the treatment-phase (10/20 mg Memantine per day) all participants were instructed to reduce smoking (partial deprivation). Before and during partial deprivation we registered the daily cigarette consumption and craving estimates. Following nasal stimulation with nicotine enantiomers hedonic and intensity estimates and the discrimination ability were assessed. Memantine failed to facilitate smoking reduction and did not influence the perception of nicotine with the exception of a weak reduction of olfactory intensity estimates reaching statistical significance for one nicotine enantiomer only.

Isolated meningomyeloradiculitis following infection with tick borne encephalitis virus

Tick borne encephalitis viruses (TBEV) constitute an increasing ealth-care problem in Europe due to possible debilitating neuological complications. These viruses are spread by tick-bite, or n special instances by consumption of animal milk products [1]. BEV-infections are generally characterized by an initial flu-like rodromal stadium and in some cases a second phase with diverse eurological manifestations ranging from meningitis and meninoencephalitis to meningoencephalomyelitis [2,3]. Patients with pinal cord involvement due to TBEV-infection generally have a orse prognosis and a relatively low tendency to clinical improveent. Cases with isolated myelitic syndromes are very rare [4,5]. ere we report a case of TBEV-infection with a neuroradiologically roven isolated meningomyeloradiculitis.

Bilateral enhancement of the cranial nerves III-XII in severe Miller-Fisher syndrome.

Dr. Ines Christine Kiphuth Department of Neurology, University of Erlangen-Nuremberg Schwabachanlage 6 DE–91054 Erlangen-Nuremberg (Germany) Tel. +49 9131 853 3001, Fax +49 9131 853 6597 E-Mail ines-christine.kiphuth@uk-erlangen.de A 23-year-old female developed palsy of the cranial nerves, tetraplegia, severe ataxia and required ventilation. Electrophysiological and CSF findings supported the clinical diagnosis of an acute polyradiculoneuritis. MRI revealed pathologic gadolinium enhancement of the cranial nerves and the cauda equina ( fig. 1 , 2 ). The patient improved after immunosuppressive treatment. Received: April 6, 2009 Accepted: April 16, 2009 Published online: August 7, 2009

Morbus Parkinson — Therapie im fortgeschrittenen Stadium

ZusammenfassungMit dem Alter wird die Therapie des Morbus Parkinson zunehmend komplexer. Neben motorischen und nicht-motorischen Symptomen bestehen im fortgeschrittenen Stadium häufig Wirkfluktuationen der medikamentösen Therapie sowie neuropsychiatrische und autonome Störungen, die der Arzt mitbehandeln muss. Die Kombination aus medikamentösen und funktionellen Therapien kann die Situation verbessern.