Panagiota Kyriakou

Multiple sclerosis and seizures: possible role of Helicobacter pylori

We have read with interest the proposition by Anderson and Rodriguez [1] that an increase in interleukin (IL)-18, and its associated induction of indoleamine 2, 3-dioxygenase (IDO) and quinolinic acid, mediates seizure activity in multiple sclerosis (MS) at least partly via an increase in interferon-gamma (IFN-c), accompanied by blood–brain barrier (BBB) permeability. Recent studies showed an association between Helicobacter pylori infection (Hp-I) and epilepsy, especially with poor prognosis [2]. Moreover, using histology, the practical gold standard for current Hp-I diagnosis, we showed a strong association between Hp-I and MS in a Greek cohort [3]. In this respect, we proposed that Hp-I, by inducing pro-inflammatory cytokine production and BBB disruption [4], may lead to neuroinflammation and neuronal damage in epilepsy, thereby triggering seizures induction and epilepsy progression [5]. Specifically, a series of factors have been implicated in inducing BBB disruption, including inflammatory mediators (e.g. cytokines and chemokines induced by Hp-I) and oxidative stress [5,6]. Hp could indirectly affect the brain through the release of numerous pro-inflammatory cytokines, such as IL-1b, IL-18, IFN-c [7] mentioned by the authors, or tumor necrosis factor (TNF)-a acting at a distance. TNF-a may contribute to BBB disruption and pathogenesis of neuronal inflammatory damage in neurodegenerative diseases and epilepsy; IL-1b, IL-6, and TNF-a influence the pathogenesis of seizures and course of epilepsy, and the primary BBB lesion is involved in seizures induction/epileptogenesis [8]. Likewise, an influx of Hp-infected monocytes, owing to defective autophagy resulting in Hp replication in autophagic vesicles, through the disrupted BBB might lead to brain degeneration and epilepsy development partially by potential activation of natural killer cells and IFN-c production, detrimental for MS; Hp VacA cytotoxin promotes intracellular survival of the bacterium and modulates host immune responses. Of note, Hp is known to be associated with the increase in IDOdependent mechanisms. Viewing the aforementioned data and because half of the world s population is infected withHp, it would be interesting to know whether the authors have considered Hp-I as a potential confounder involved in the pathophysiology of MS-associated increased seizure activity and therefore its management.

Association between Helicobacter pylori infection and Alzheimer’s disease in Japan

We read with interest the paper by Shiota et al. [1], who reported that older age and male sex were significantly associated with Alzheimer’s disease. Moreover, the authors reported a lack of association between Helicobacter pylori infection (Hp-I) status and Alzheimer’s disease in their Japanese cohort, suggesting that their findings might be explained by the much higher prevalence of Hp-I in the general Japanese than in the European population. We herein wish to emphasize two essential concerns regarding the methodological limitations which may render the results of this study highly debatable. The first is that both age and sex, found to be associated with Alzheimer’s disease, were not matched in the two study groups (p \ 0.001 and p = 0.01, respectively), and thus comparisons between the two study groups (i.e., Alzheimer’s disease patients and controls) cannot be expected to establish any firm conclusions. The second concern is that the very high Hp-I prevalence in the general Japanese population around 70 years old, reported by the authors, and, deductively, in the control group of the study, renders the study underpowered, meaning it requires probably thousands of participants in order to prove whether an association between Alzheimer’s disease and Hp-I can be established or excluded; it requires a very large population to be screened to prove or not a statistical difference in Hp-I among patients with Alzheimer’s disease and the general Japanese population. In view of the aforementioned methodological limitations, we deduce that this study can neither confirm the lack of association between the Hp-I status and Alzheimer’s disease in the Japanese population, nor is it comparable with the European studies indicating such an association [2–4].

Sinus nodal response to adenosine relates to the severity of sinus node dysfunction.

AIMS It is unknown as to whether the result of adenosine testing for the diagnosis of sinus node dysfunction (SND) depends on the clinical presentation. We investigated whether syncope or presyncope are associated with a more pronounced sinus nodal inhibition by adenosine in SND. METHODS AND RESULTS We studied 46 patients with SND, 33 with syncope or presyncope and 13 without such history. Controls were 30 subjects undergoing electrophysiological studies for supraventricular tachycardia or unexplained syncope. We calculated the corrected sinus node recovery time after intravenous adenosine 0.15 mg/kg (ADSNRT) as well as after atrial pacing (CSNRT). Corrected sinus node recovery time values >525 ms were considered abnormal. Corrected sinus node recovery time after adenosine injection was more prolonged in SND patients with syncope or presyncope as compared with those without such history [median: 4900 inter-quartile range (IQR): 920-8560 ms vs. median: 280 IQR: 5-908 ms; P< 0.005]. In SND patients with syncope or presyncope ADSNRT was more prolonged than CSNRT (median: 4900 IQR: 920-8560 ms vs. median: 680 IQR: 359-1650 ms, P< 0.01). In SND patients without syncope or presyncope no statistical difference was noted between ADSNRT and CSNRT (median: 280 IQR: 5-908 ms vs. median: 396 IQR: 270-600 ms, P = 0.80). The sensitivity of CSNRT for SND diagnosis was 57% and the specificity was 100%. A cut-off of 1029 ms for ADSRNT yields the same sensitivity with a specificity of 96.6%. CONCLUSION In patients with SND syncope or presyncope relate to an exaggerated sinus nodal suppression by adenosine. Prolonged ADSNRT can diagnose cases with severe underlying SND where a more aggressive management strategy is probably warranted.

Electrophysiological markers predicting impeding AV-block during ablation of atrioventricular nodal reentry tachycardia

Radiofrequency (RF) ablation of the slow pathway (SP) in atrioventricular nodal reentry tachycardia (AVNRT) is occasionally complicated with atrioventricular block (AVB) often predicted by junctional beats (JB) with loss of ventriculo‐atrial (VA) conduction.