The Pioneering and Unknown Stereotactic Approach of Roeder and Orthner from Göttingen. Part II: Long-Term Outcome and Postmortem Analysis of Bilateral Pallidotomy in the Pre-Levodopa Era.

Before the advent of levodopa, pallidotomy was initially the most effective treatment for Parkinson disease, but it was soon superseded by thalamotomy. It is widely unknown that, similar to Leksell, 2 neurologists from Göttingen, Orthner and Roeder, perpetuated pallidotomy against the mainstream of their time. Postmortem studies demonstrated that true posterior and ventral pallidoansotomy sparing the overwhelming mass of the pallidum was accomplished. This was due to a unique and individually tailored stereotactic technique even allowing bilateral staged pallidotomies. In 1962, the long-term effects (3-year follow-up on average) of the first 18 out of 36 patients with staged bilateral pallidotomies were reported in great detail. Meticulous descriptions of each case indicate long-term improvements in parkinsonian rigidity and associated pain, as well as posture, gait, and akinesia (e.g., improved repetitive movements and arm swinging). Alleviation of tremor was found to require larger lesions than needed for suppression of rigidity. No improvement in speech, drooling, or seborrhea was observed. By 1962, the team had operated 13 patients with postencephalitic oculogyric crises with remarkable results (mean follow-up: 5 years). They also described alleviation of nonparkinsonian hyperkinetic disorders (e.g., hemiballism and chorea) with pallidotomy. The reported rates for surgical mortality and other complications had been remarkably low, even if compared to those reported after the revival of pallidotomy by Laitinen in the post-levodopa era. This applies also to bilateral pallidotomy performed with a positive risk-benefit ratio that has remained unparalleled to date. The intricate history of pallidotomy for movement disorders is incomplete without an appreciation of the achievements of the Göttingen group.

Adverse Effects of Plant Food Supplements and Plants Consumed as Food: Results from the Poisons Centres-Based PlantLIBRA Study.

Plant food supplements (PFS) are products of increasing popularity and wide-spread distribution. Nevertheless, information about their risks is limited. To fill this gap, a poisons centres-based study was performed as part of the EU project PlantLIBRA. Multicentre retrospective review of data from selected European and Brazilian poisons centres, involving human cases of adverse effects due to plants consumed as food or as ingredients of food supplements recorded between 2006 and 2010. Ten poisons centres provided a total of 75 cases. In 57 cases (76%) a PFS was involved; in 18 (24%) a plant was ingested as food. The 10 most frequently reported plants were Valeriana officinalis, Camellia sinensis, Paullinia cupana, Melissa officinalis, Passiflora incarnata, Mentha piperita, Glycyrrhiza glabra, Ilex paraguariensis, Panax ginseng, and Citrus aurantium. The most frequently observed clinical effects were neurotoxicity and gastro-intestinal symptoms. Most cases showed a benign clinical course; however, five cases were severe. PFS-related adverse effects seem to be relatively infrequent issues for poisons centres. Most cases showed mild symptoms. Nevertheless, the occurrence of some severe adverse effects and the increasing popularity of PFS require continuous active surveillance, and further research is warranted. Copyright © 2016 John Wiley & Sons, Ltd.

Acute selenium poisoning by paradise nuts (Lecythis ollaria).

Two previously healthy women developed nausea, vomiting, headache and dizziness for several days, a massive hair loss about 2 weeks later and a discoloration of the fingernails. Detailed diagnostic procedures did not reveal any pathological results. Therapeutic measures did not show any effect. Thallium and arsenic were within normal range in plasma. Delayed quantitative determination of selenium in blood, however revealed toxic values (in case I: 479 microg/L of serum, 8 weeks after ingestion, and in case II 300 microg/L of serum, 9 weeks after ingestion). In retrospect, a relation to the ingestion of paradise nuts could be established.

Chinese slimming capsules containing sibutramine sold over the Internet: a case series.

BACKGROUND: In recent years, the market for dietary supplements has grown. International products are readily available for purchase over the Internet. We report 17 cases of poisoning with a single product, said to be of purely herbal origin, that was bought over the Internet. A complete declaration of the ingredients was not available. METHODS: We performed a retrospective study of cases of poisoning documented by the Göttingen and Freiburg poison information centers from 2005 to 2008. In 4 cases, we were able to perform toxicological analyses of leftover capsules and urine samples. RESULTS: The manifestations of poisoning in the 17 documented cases included malaise, tachycardia, headache, agitation, arterial hypertension, nausea, vomiting, dyspnea, insomnia, left-sided chest pressure, elevated temperature, and, in two cases, psychosis after the substance was combined with atomoxetine and methylphenidate and with citalopram, olanzapine, and chlorprothixene. The frequency of cases rose markedly in the last year of the study. The toxicological analyses of all samples studied revealed sibutramine. The dose in each capsule was nearly twice the maximum daily dose sibutramine in the medication containing this substance that is licensed for use in Germany. CONCLUSIONS: Products available without a prescription whose contents are claimed to be purely herbal may nonetheless contain synthetic substances in concentrations far above the therapeutic range and may be a cause of poisoning. When taking the history of a patient possibly suffering from an intoxication, the physician should ask specifically about drugs, dietary supplements, and so-called lifestyle products that were obtained without a prescription. It would be desirable for the contents of all such products to be declared, as required by law, so that their suitability for the market can be checked.

The garlic ingredient diallyl sulfide inhibits cytochrome P450 2E1 dependent bioactivation of acrylamide to glycidamide.

Genotoxic effects of acrylamide are supposed to result from oxidative biotransformation to glycidamide. After incubation of rat liver slices with acrylamide we detected free glycidamide using a liquid chromatography tandem mass spectrometric method. Glycidamide formation was diminished in the presence of the cytochrome P450 2E1 inhibitor diallyl sulfide (DAS), which is a specific ingredient of garlic. This may be relevant to human health since the suggested carcinogenic risk of dietary acrylamide may be reduced by concomitant intake of garlic.

Most effective stimulation site in subthalamic deep brain stimulation for Parkinson's disease.

The optimal stimulation site in subthalamic deep brain stimulation (STN-DBS) was evaluated by correlation of the stereotactic position of the stimulation electrode with the electrophysiologically specified dorsal STN border. In a series of 25 electrodes, best clinical results with least energy consumption were found in contacts located in the dorsolateral border zone, whereas contacts within the subthalamic white matter, e.g., zona incerta, were significantly less effective. We suggest that the dorsolateral STN border should be covered by STN-DBS.

In vitro investigation of a standardized dried extract of Citrullus colocynthis on liver toxicity in adult rats.

A standardized extract of Citrullus colocynthis used as an oral natural laxative in folk medicine was tested for its influence on liver function parameters in vitro. Cytochrome P450 (CYP) dependent production of reactive oxygen species (ROS) under the influence of Citrullus colocynthis extract was investigated by means of stimulated lipid peroxidation (LPO), H2O2 formation and amplified chemiluminescence in rat liver microsomes. In rat liver 9000 x g supernatants 4 monooxygenase reactions mediated by different CYP forms were measured. Putative hepatotoxic effects of Citrullus colocynthis extract were measured by means of potassium and GSH concentrations in and LDH leakage from precision-cut rat liver slices. For possible hepatoprotective effects the influence of the extract on carbon tetrachloride-induced changes of these parameters was investigated. Citrullus colocynthis extract in concentrations higher than 10 microg/ml incubation mixture proved to inhibit lipid peroxidation and ROS-production as well as CYP1A-, 2B- and 3A-dependent reactions with typical substrates. In contrast, H2O2 production was not reduced under the influence of the extract, a slight but significant increase was seen. Citrullus colocynthis extract was found to be free of hepatotoxic effects in concentrations up to 100 microg/ml incubation mixture when liver slices were incubated in William's medium E for 22 hours. All viability parameters used were not influenced by the extract of Citrullus colocynthis. Carbon tetrachloride induced hepatotoxicity could not be prevented or alleviated. Moreover, the damage was sometimes enhanced by higher extract concentrations.

Dyskinesias and grip control in Parkinson's disease are normalized by chronic stimulation of the subthalamic nucleus.

Deep-brain stimulation of the subthalamic nucleus appears to reduce levodopa-induced dyskinesias, but whether this effect is caused by the reduction of the total levodopa ingestion or represents a direct effect on the motor system is unknown. Precision grip force of grasping movements and levodopa-induced dyskinesias was analyzed in 10 parkinsonian patients before and after 3 months of deep-brain stimulation of the subthalamic nucleus. Peak grip force was abnormally increased before surgery in the off-drug state and, particularly, in the on-drug state (sensitization). This grip force upregulation normalized with chronic deep-brain stimulation in both conditions (desensitization). Peak-dose dyskinesias also improved, and off-dystonia was completely abolished. Mean dosage of dopaminergic drugs was reduced, but force overflow and dyskinesias were equally improved in 2 patients without a reduction. Despite the same single levodopa test dose, force excess and levodopa-induced dyskinesias were drastically reduced after 3 months of deep-brain stimulation of the subthalamic nucleus. This indicates that direct effects of deep-brain stimulation of the subthalamic nucleus on levodopa-induced dyskinesias are likely to occur. Grip force overflow is a promising parameter to study the desensitizing effect of chronic deep-brain stimulation on levodopa-induced dyskinesias.