Thomas Jochum

Increased pain sensitivity in alcohol withdrawal syndrome

Withdrawal from analgesic and addictive substances such as opioids or ethanol is associated with increased sensitivity to sensory stimulation in animal models.

Decreased sensitivity to thermal pain in rats bred for high anxiety-related behaviour is attenuated by citalopram or diazepam treatment

Complex interactions between pain perception, anxiety and depressive symptoms have repeatedly been described. However, pathophysiological or biochemical mechanisms underlying the alterations of pain perception in patients suffering from anxiety or depression still remain a matter of debate. Thus, we aimed to perform an investigation on pain perception in an animal model of extremes in anxiety-related behaviour, which might provide a tool for future studies. Here, thermal pain thresholds were obtained from rats with a genetic predisposition to high anxiety-related behaviour (HAB), including signs of comorbid depression-like behaviour and from controls (low-anxiety rats (LAB); cross-bred HAB and LAB rats; Wistar rats). Furthermore, the effect of eight-week antidepressive treatment using citalopram and of short-term anxiolytic treatment with diazepam on pain-related behaviour was assessed. Simultaneously, anxiety-related behaviour was monitored. At baseline, HAB animals showed 35% higher thresholds for thermal pain than controls. These were normalized to control levels after eight weeks of continuous citalopram treatment paralleled by a reduction of anxiety-related behaviour, but also acutely after diazepam administration. Overall, thermal pain thresholds in HAB animals are shifted in a similar fashion as seen in patients suffering from major depressive disorder. Antidepressive, as well as anxiolytic treatments, attenuated these differences. As the relative importance of the factors anxiety and depression cannot be derived from this study with certainty, extending these investigations to additional animal models might represent a valuable tool for future investigations concerning the interrelations between anxiety, depression, and pain at a molecular level.

Topiramate induced manic episode

Topiramate is a novel antiepileptic drug (AED) that has been in use for several years, mainly as add on treatment for partial and secondarily generalising seizures that are otherwise refractory to treatment.1 Despite the good efficacy of topiramate, dizziness, ataxia, double vision, and somnolence have been noted as the main side effects. While older AEDs such as carbamazepine and sodium valproate are now routinely used for the treatment of mood disorders, recent studies suggest that novel AEDs, such as lamotrigine, gabapentin, tiagabine, and topiramate, have mood stabilising efficacy as well.2 Exacerbation of psychotic symptoms has been reported but mostly in patients with pre-existing psychiatric disorders.3,4 However, more patients than previously assumed may be affected by a broader range of side effects. We present a case of a patient taking topiramate who presented with an acute manic episode, lacking any previous history of affective disorders or episodes. A 57 year old woman with a history of temporal lobe epilepsy was referred to our hospital by her local general practitioner due to suicidal ideation …

Is successful electroconvulsive therapy related to stimulation of the vagal system

BACKGROUND Electroconvulsive therapy (ECT) has been shown to exhibit strong beneficial effects in the treatment of major depressive disorder (MDD). While the exact underlying mechanisms are under debate, a role for the sympathetic response upon ECT has been suggested. When assessing patients with MDD for autonomic function, however, a loss of vagal function is prominent. OBJECTIVE Here, we aimed to assess the immediate effects of ECT on vagal activity and to test the hypothesis that surrogates of the latter correlate with therapeutic outcome. METHODS Twenty patients with MDD who underwent ECT treatment were assessed regarding their vagal function using electrophysiological measures and determination of pancreatic polypeptide (PP), which is known to be released upon vagal stimulation. Parameters were correlated to the improvement of disease severity upon ECT treatment. RESULTS Patients showed a significant increase of PP shortly after ECT which correlated with clinical improvement. Furthermore, the described association with the sympathetic phase after ECT could be verified. CONCLUSION ECT increases vagal activity which might be associated with the beneficial effect seen following this treatment. PP elevation after administration of ECT might be a useful parameter to estimate the degree of such vagal stimulation after treatment.

Impaired cerebral autoregulation during acute alcohol withdrawal

Heavy alcohol consumption increases the risk for all major types of stroke and is associated with autonomic dysfunction during alcohol withdrawal syndrome (AWS). Cerebral autoregulation is the mechanism by which cerebral perfusion is maintained stable, representing an intrinsic protective system of the cerebral circulation. Here, we aimed to analyze the influence of acute AWS on cerebral hemodynamics in alcohol-dependent patients. We investigated 20 men in the unmedicated acute state of AWS and repeated the investigation 24h after initiation of clomethiazole treatment. Dynamic cerebral autoregulation (dCA) was assessed by the correlation coefficient index and transfer function analysis (phase and gain) from oscillations of arterial blood pressure and cerebral blood flow velocity (CBFV). The vasomotor reserve (VMR) was measured by the CO(2)-reactivity test. In addition, we assessed autonomic modulation by means of heart rate variability and baroreflex sensitivity. We observed impaired dynamic autoregulation as shown by a multivariate analysis of variance (p<0.038) including all parameters of dCA. Similar results were found for VMR at admission (p<0.05). Pair-wise comparison between baseline and treatment with clomethiazole revealed a significant improvement for the systolic correlation coefficient index (Sx; p<0.001). Furthermore, we found a strong association of autonomic dysfunction and impaired autoregulation indicated by a correlation between the LF/HF ratio and Sx (p<0.001). In conclusion, cerebral autoregulation and VMR are disturbed during acute AWS. Influences of autonomic dysbalance and mental state during withdrawal are suggested. The finding of an affected autoregulation during acute withdrawal might indicate an increased risk for cerebro-vascular disease.

Endothelial dysfunction during acute alcohol withdrawal syndrome

BACKGROUND Endothelial dysfunction (EF) is a central phenomenon in a variety of conditions associated with increased cardiovascular morbidity. Here, we investigated EF during acute alcohol withdrawal syndrome before and 24h after medication. We aimed to analyze microcirculation, applying the post-occlusive reactive hyperemia (PORH) test and spectral analysis of skin vasomotion as markers of EF. Additionally, we explored whether segmentation of spectral analysis data may disclose more detailed information on dynamic blood flow behavior. METHODS We investigated 30 unmedicated patients during acute alcohol withdrawal syndrome and matched controls. Patients were reinvestigated after 24h when half of them had been treated with clomethiazole. Capillary blood flow was assessed on the right forearm after compression of the brachial artery. Parameters of PORH such as time to peak (TP), slope and PORH indices were calculated. Spectral analysis was performed in order to study five different frequency bands. Withdrawal symptoms were quantified by means of the alcohol withdrawal scale (AW scale). RESULTS We observed a blunted hyperemic response in patients after occlusion of the brachial artery indicated by significantly increased TP and decreased PORH indices. In contrast, vasomotion as investigated by spectral analysis was not altered. Segmentation analysis revealed some alterations in the cardiac band at rest, and indicated differences between treated and untreated patients after 24h. CONCLUSION Our results suggest peripheral endothelial dysfunction in patients during acute alcohol withdrawal. No major influence of treatment was observed. Future studies need to address the relation of EF to cardiac morbidity during alcohol withdrawal.

Does parasympathetic modulation prior to ECT treatment influence therapeutic outcome

Electroconvulsive therapy (ECT) is an established treatment option for major depressive disorder when other treatments have failed. However, the underlying mechanisms responsible for these therapeutical effects are insufficiently understood to date. Furthermore, treatment outcome is difficult to predict. Recent research suggested an important role of autonomic modulation for successful treatment. We aimed to examine putative associations between autonomic modulation and response to ECT treatment and hypothesized a role for vagal modulation prior to therapy. Twenty-four patients with MDD who received ECT were assessed by means of heart rate and blood pressure variability analysis as well as baroreflex sensitivity measurements before, during and after a course of ECT. Autonomic parameters from the complete study population revealed that ECT did not significantly alter basic autonomic modulation after six sessions. Analyses showed a significant association of the reduction of HAMD scores during therapy when compared with baseline autonomic function as reflected in SDNN(RR) (p<0.004), Forbword(RR) (p<0.025) and compression entropy Hc(RR) (p<0.0003). A significant correlation was observed when overall HAMD reduction and changes of LFnu(RR) (p<0.026) or HFnu(RR) (p<0.026) during the course of therapy were analyzed. Our findings suggest that high levels of parasympathetic modulation at baseline might be associated with a beneficial effect upon ECT treatment. Adding to this, levels of parasympathetic activity seemed to increase in patients who respond to ECT treatment. Given these findings can be confirmed in future studies, autonomic modulation might be used as a predictor for therapeutic efficacy of ECT.

Neurobrucellosis with thalamic infarction: a case report

Brucellosis is prevalent in North and East Africa, the Middle East, South and Central Asia, South and Central America and the Mediterranean countries of Europe. In 5% of cases it may lead to central nervous system manifestation presenting most often as a meningitis or meningoencephalitis. Here we report and discuss a case of neurobrucellosis with meningitis with cranial nerves neuritis. A 56-year-old German male was admitted with bilateral abducens nerve palsy, amblyacousia and intractable headaches. An enzyme-linked immunosorbent assay (ELISA) revealed antibodies against Brucella in serum and cerebrospinal fluid (CSF). Additionally, our patient suffered from an infarction of the left thalamus. In conclusion, in cases of unresponsive meningitis or meningoencephalitis and history of travel in endemic regions, neurobrucellosis should be considered. If initial microbiological tests fail, complementary investigations such as ELISA are indicated to detect Brucella species in serum and/or CSF.

Heart rate turbulence during acute alcohol withdrawal syndrome

BACKGROUND Alcohol withdrawal syndrome is associated with an increased incidence of cardiac arrhythmias and sudden cardiac death. Heart rate turbulence (HRT) parameters were applied during withdrawal to estimate cardiac regulation during treatment with clomethiazole. METHODS Twenty-two patients suffering from alcohol withdrawal syndrome were included in the study. Heart rate regulation was obtained by means of Holter ECG analyzing time intervals before medication, and 2 and 6h after medication. Slope and onset of HRT were calculated in addition to heart rate variability (HRV) parameters. Furthermore, we calculated the slope and the onset of ectopic beat-like events. RESULTS Heart rate variability parameters indicated a minor reduction of vagal modulation during withdrawal syndrome. Especially, the fractal scaling exponent BBI alpha1 (4-16) indicated the autonomic shift. In contrast to HRV parameters, no significant changes were observed in the HRT parameters. Significant correlations were observed between severity of withdrawal, as assessed by the AWS scale, and the fractal scaling exponent BBI alpha2 (16-64), and the onset and the slope of HRT of ectopic beat-like activity. CONCLUSION Increased sympathetic modulation during withdrawal and clomethiazole treatment is not associated with changes of heart rate turbulence parameters predictive of cardiac death after myocardial infarction.

Application of an Electronic Nose to Diagnose Liver Cirrhosis from the Skin Surface

The human body odor contains of different volatile organic compounds. In patients with liver cirrhosis and patients who are addicted to alcohol the compound of sweat and volatile gases are changed because of the liver dysfunction and remaining alcoholics and alcoholic decomposition products within the blood. This leads to changes of the metabolic balance. Therefore, the purpose of this study was to apply an electronic nose for detecting such metabolic changes at the skin surface. A special applicator was developed to collect and analyze the transpired dermal gases directly on the skin surface. The measured values were analyzed by principal component analysis and quadratic discriminant function analysis. We could show in a pilot study on 25 patients that an electronic nose is able to detect changes in the human body odor and to discriminate between healthy subjects (controls), patients with liver cirrhosis and primed alcoholic addicted patients.