A questionnaire to collect unintended effects of transcranial magnetic stimulation: A consensus based approach.

Transcranial magnetic stimulation (TMS) has been widely used in both clinical and research practice. However, TMS might induce unintended sensations and undesired effects as well as serious adverse effects. To date, no shared forms are available to report such unintended effects. This study aimed at developing a questionnaire enabling reporting of TMS unintended effects. A Delphi procedure was applied which allowed consensus among TMS experts. A steering committee nominated a number of experts to be involved in the Delphi procedure. Three rounds were conducted before reaching a consensus. Afterwards, the questionnaire was publicized on the International Federation of Clinical Neurophysiology website to collect further suggestions by the wider scientific community. A last Delphi round was then conducted to obtain consensus on the suggestions collected during the publicization and integrate them in the questionnaire. The procedure resulted in a questionnaire, that is the TMSens_Q, applicable in clinical and research settings. Routine use of the structured TMS questionnaire and standard reporting of unintended TMS effects will help to monitor the safety of TMS, particularly when applying new protocols. It will also improve the quality of data collection as well as the interpretation of experimental findings.

Rufinamide for the treatment of epileptic spasms.

OBJECTIVE: The purpose of this study was to determine the safety and efficacy of rufinamide for treatment of epileptic spasms. METHODS: We retrospectively reviewed patients treated with rufinamide for epileptic spasms from January 2009 to March 2010. Age, presence of hypsarrhythmia, change in seizure frequency following rufinamide initiation, and side effects were assessed. Patients who had a ≥ 50% reduction in spasm frequency were considered responders. RESULTS: Of all 107 children treated with rufinamide during the study period, 38 (36%) had epileptic spasms. Median patient age was 7 years (range: 17 months to 23). One patient had hypsarrhythmia at the time of treatment with rufinamide, and 9 other patients had a history of hypsarrhythmia. Median starting dose of rufinamide was 9 mg/kg/day (range: 2-18) and median final treatment dose was 39 mg/kg/day (range: 8-92). All patients were receiving concurrent antiepileptic drug therapy, with the median number of antiepileptic drugs being 3 (range: 2-6). Median duration of follow-up since starting rufinamide was 171 days (range: 10-408). Responder rate was 53%. Median reduction in spasm frequency was 50% (interquartile range=-56 to 85%, P<0.05). Two patients (5%) achieved a >99% reduction in spasms. Rufinamide was discontinued in 7 of 38 patients (18%) because of lack of efficacy, worsening seizures, or other side effects. Minor side effects were reported in 14 of 38 patients (37%). CONCLUSIONS: Rufinamide appears to be a well-tolerated and efficacious adjunctive therapeutic option for children with epileptic spasms. A prospective study is warranted to validate our observations.

Neurophysiological evidence of preserved connectivity in tuber tissue.

We present a case of preserved corticospinal connectivity in a cortical tuber, in a 10 year-old boy with intractable epilepsy and tuberous sclerosis complex (TSC). The patient had multiple subcortical tubers, one of which was located in the right central sulcus. In preparation for epilepsy surgery, motor mapping, by neuronavigated transcranial magnetic stimulation (nTMS) coupled with surface electromyography (EMG) was performed to locate the primary motor cortical areas. The resulting functional motor map revealed expected corticospinal connectivity in the left precentral gyrus. Surprisingly, robust contralateral deltoid and tibialis anterior motor evoked potentials (MEPs) were also elicited with direct stimulation of the cortical tuber in the right central sulcus. MRI with diffusion tensor imaging (DTI) tractography confirmed corticospinal fibers originating in the tuber. As there are no current reports of preserved connectivity between a cortical tuber and the corticospinal tract, this case serves to highlight the functional interdigitation of tuber and eloquent cortex. Our case also illustrates the widening spectrum of neuropathological abnormality in TSC that is becoming apparent with modern MRI methodology. Finally, our finding underscores the need for further study of preserved function in tuber tissue during presurgical workup in patients with TSC.

Huperzine A as a neuroprotective and antiepileptic drug: a review of preclinical research.

Huperzine A (HupA) is an acetylcholinesterase (AChE) inhibitor extracted from Huperzia Serrata, a firmoss, which has been used for various diseases in traditional Chinese medicine for fever and inflammation. More recently, it has been used in Alzheimer's disease and other forms of dementia with a presumed mechanism of action via central nicotinic and muscarinic receptors. HupA is marketed as a dietary supplement in the U.S. This article reviews newly proposed neuroprotective and anticonvulsant HupA properties based on animal studies. HupA exerts its effects mainly via α7nAChRs and α4ß2nAChRs, thereby producing a potent anti-inflammatory response by decreasing IL-1ß, TNF-α protein expression, and suppressing transcriptional activation of NF-κB signaling. Thus, it provides protection from excitotoxicity and neuronal death as well as increase in GABAergic transmission associated with anticonvulsant activity.

H-coil repetitive transcranial magnetic stimulation for treatment of temporal lobe epilepsy: A case report.

Low frequency repetitive TMS (rTMS) of a cortical seizure focus is emerging as an antiepileptic treatment. While conventional rTMS stimulators activate only superficial cortical areas, reaching deep epileptic foci, for example in temporal lobe epilepsy (TLE), is possible using specially designed H-coils. We report the results of rTMS in a young adult with pharmacoresistant bilateral TLE who underwent three courses (of 10, 15, and 30 daily sessions) of unilateral rTMS over the hemisphere from which seizures originated most often. Seizure frequency was assessed before and after each block of rTMS sessions, as was the tolerability of the procedure. Seizure frequency declined significantly, by 50 to 70% following each rTMS course. All sessions were well-tolerated.

Parallel instabilities of long-term potentiation, place cells, and learning caused by decreased protein kinase A activity.

To further elucidate the links among synaptic plasticity, hippocampal place cells, and spatial memory, place cells were recorded from wild-type mice and transgenic "R(AB)" mice with reduced forebrain protein kinase A (PKA) activity after introduction into a novel environment. Place cells in both strains were similar during the first exposure and were equally stable for recording sessions separated by 1 hr. Place cell stability in wild-type mice was unchanged for sessions separated by 24 hr but was reduced in R(AB) mice over the longer interval. This stability pattern parallels both the reduced late-phase long-term potentiation in hippocampal slices from R(AB) mice and the amnesia for context fear conditioning seen in R(AB) mice 24 but not 1 hr after training. The similar time courses of synaptic, network, and behavioral instability suggest that the genetic reduction of PKA activity is responsible for the defects at each level and support the idea that hippocampal synaptic plasticity is important in spatial memory.

Huperzine A prophylaxis against pentylenetetrazole-induced seizures in rats is associated with increased cortical inhibition.

Huperzine A (HupA) is a naturally occurring compound found in the firmoss Huperzia serrata. While HupA is a potent acetylcholinesterase inhibitor, its full pharmacologic profile is incompletely described. Since previous works suggested a capacity for HupA to prophylax against seizures, we tested the HupA antiepileptic potential in pentylenetetrazole (PTZ) rat epilepsy model and explored its mechanism of action by spectral EEG analysis and by paired-pulse transcranial magnetic stimulation (ppTMS), a measure of GABA-mediated intracortical inhibition. We tested whether HupA suppresses seizures in the rat PTZ acute seizure model, and quantified latency to first myoclonus and to generalized tonic-clonic seizure, and spike frequency on EEG. Additionally, we measured power in the EEG gamma frequency band which is associated with GABAergic cortical interneuron activation. Then, as a step toward further examining the HupA antiepileptic mechanism of action, we tested long-interval intracortical inhibition (LICI) using ppTMS coupled with electromyography to assess whether HupA augments GABA-mediated paired-pulse inhibition of the motor evoked potential. We also tested whether the HupA effect on paired-pulse inhibition was central or peripheral by comparison of outcomes following administration of HupA or the peripheral acetylcholinesterase inhibitor pyridostigmine. We also tested whether the HupA effect was dependent on central muscarinic or GABAA receptors by co-administration of HupA and atropine or PTZ, respectively. In tests of antiepileptic potential, HupA suppressed seizures and epileptic spikes on EEG. Spectral EEG analysis also revealed enhanced gamma frequency band power with HupA treatment. By ppTMS we found that HupA increases intracortical inhibition and blocks PTZ-induced cortical excitation. Atropine co-administration with HupA did not alter HupA-induced intracortical inhibition suggesting independent of muscarinic acetylcholine receptors mechanism in this model. Last, pyridostigmine did not affect the ppTMS-measured cortical inhibition suggesting that HupA-induced effect is centrally-mediated. Our data support antiepileptic HupA applications, and suggest that such activity may be via enhancement of GABAergic intracortical inhibition.

Helicobacter pylori infection in patients with Barrett's oesophagus: a prospective immunohistochemical study.

The prevalence of Helicobacter pylori infection in patients with Barrett's oesophagus was studied prospectively. A sensitive immunohistochemical staining of H pylori was performed in oesophageal and gastric biopsies of 73 patients from a surveillance group with this condition. H pylori was detected in 11 cases of Barrett's mucosa (15%) and in 26 gastric mucosa specimens (35.6%). All cases positive in Barrett's mucosa were also positive in the stomach. In Barrett's oesophagus, H pylori was never found on specialised epithelium. The percentage of Barrett's mucosa showing inflammatory changes was similar in specimens with and without H pylori, both for chronic (81% v 79%) and acute (9% v 10%) infiltrates. These results indicate that H pylori infection does not play an aetiological role in Barrett's oesophagus and that colonisation of the metaplastic mucosa by this bacteria is related with the presence of gastric type mucosa in the oesophagus and of H pylori infection in the stomach.

Adaptation of Jena 5000 photocoagulator to continuous wave laser power source.

We describe the modifications made in adapting a Jena 5,000 photocoagulator to a tunable dye laser power source and discuss the principles of the tunable dye laser.

[Human chronic gastritis associated with non-Helicobacter pylori spiral organisms (Gastrospirillum hominis). Four cases and review of the literature]. / Gastrite chronique associée chez l'homme à la présence de germes spiralés non-Helicobacter pylori (Gastrospirillum hominis). Présentation de 4 cas avec revue de la littérature.

Four cases of human active chronic gastritis associated with Gastrospirillum hominis, a recently described spiral shaped organism are presented. These 4 cases originated from a series of 1976 consecutive gastric biopsies, i.e. a prevalence of 0.25 percent in our material, are compared with Helicobacter pylori prevalence of 45 percent. Histopathological findings were chronic active gastritis with mild or no atrophy. Electron microscopy showed spiral bacteria with terminal flagellae, identical to those previously described in the literature. These bacteria have not yet been cultured; similar organisms are found in many animal species, and it seems that they do not provoke gastric inflammation. Gastrospirillum hominis could be responsible for cases of Helicobacter pylori negative chronic gastritis in man, but its pathogenicity remains to be demonstrated.

[Treatment of duodenal ulcer outbreak with omeprazole. Results of a multicenter non-controlled study]. / Traitement de l'ulcère duodénal en poussée par l'oméprazole. Résultats d'une étude non contrôlée multicentrique.

Sixty-one patients with symptomatic endoscopically confirmed duodenal ulcer, 5 mm or more in diameter, were treated with omeprazole 30 mg once daily in the morning for 4 weeks. Complete ulcer healing was assessed by endoscopy performed after 15 and, if necessary, 29 days of treatment. The healing rate as 83 p. 100 (49/59 patients) after 2 weeks, and 98 p. 100 (58/59 patients) after 4 weeks. Only 5 patients remained symptomatic on day 15. Fifty-six patients did not take any antacid during the course of treatment. There were few adverse effects. No clinically significant changes in laboratory parameters were observed. These results confirm: the remarkable efficiency of omeprazole in short-term treatment of duodenal ulcer, the good tolerance to this drug, at least in short duration treatment.

Young people considering nursing as a career: starters vs. non-starters.

This study focused on applicants who were accepted to a nursing education program but did not begin their studies, thus wasting time, effort and money. Of 953 accepted applicants, 27% did not enter the program. Significant variables differentiating starters from non-starters were higher psychometric score, higher paternal education, lower priority for nursing studies, older age, non-Israeli country of birth and not completed army service. The study relating to starters vs. non-starters is one aspect of a large study (Ehrenfeld, Rotenberg, Sharon, & Bergman, 1995). In most nursing education programs the number of applicants exceed the faculty's capacity, and suitable candidates must be rejected. It is therefore both wasteful and disappointing when accepted applicants change their mind and do not actually begin in the program. In light of the costs and complexities involved in the student screening process and the continuous efforts extended today all over the world to raise the standards of nursing education and care, the factors differentiating starters from non-starters may have important implications. The aim of the present study was to evaluate the screening process at the Tel Aviv University baccalaureate nursing program and determine which variables were predictive of starters and non-starters among accepted applicants.

[Are lymphocytic and collagenous colitis two forms of a single disease? Arguments taken from a biopsy quantitative study]. / La colite lymphocytaire et la colite collagène sont-elles une seule et même maladie? Arguments tirés d'une étude quantitative sur biopsie.

Collagenous colitis and lymphocytic colitis are defined by a clinicopathologic syndrome with chronic watery diarrhea, microscopic lesions of colonic biopsies, and normal barium enema and colonoscopy. A histopathological study was performed on multiple colorectal biopsies to compare 12 cases of collagenous colitis (defined by a subepithelial collagen thicker than 10 microns) and 7 cases of lymphocytic colitis (defined by a number of intraepithelial lymphocytes more than 20 per 100 epithelial cells at least in one biopsied site). The study included a semiquantitative analysis of inflammatory infiltrate in the lamina propria, crypts distortion and epithelial detachment. The number of intraepithelial lymphocytes per 100 epithelial cells was determined in surface epithelium and crypts. The subepithelial collagen thickening was studied by computerised morphometry. The intraepithelial lymphocytes, villous atrophy and thickness of the subepithelial collagen were also determined in gastric and duodenal biopsies. In collagenous colitis, the subepithelial collagenous thickness ranged from 10 to 40 microns in the colon (median 20.99 microns). In 4 cases of collagenous colitis, no thickening of the collagen plate was seen in the rectum. We found constant epithelial detachment and mucosal distortion. In lymphocytic colitis, the thickness of the subepithelial collagen ranged from 6 to 10 microns in 4 cases and was less than 6 microns in 3 cases (median 6.24 microns). The median number of intraepithelial lymphocytes in surface epithelium was 22.35 (range 18.2 to 40) in lymphocytic colitis versus 12.22 (range 4.6 to 24.4) in collagenous colitis. In conclusion, we observed an overlap of both the collagenous plate thickness and the number of intraepithelial lymphocytes in collagenous colitis and lymphocytic colitis. This result favours a unified histogenesis for these two entities.

[Association of stomach ulcer and Helicobacter pylori. Prognostic implications]. / Association ulcère gastrique-Helicobacter pylori. Implication pronostique.

Helicobacter pylori is known to be responsible for most cases of chronic gastritis, but its role in the outcome of gastric ulcer is unknown. The purpose of this study was to determine the prevalence of H. pylori infection before and after treatment of gastric ulcer, the micro-organism being untreated. The trial involved 26 patients with an acute episode of gastric ulcer, who had undergone endoscopy with biopsy of the antrum, the fundus and the ulcer rim at the initial examination and then 6 weeks and 1 year after the diagnosis. At day 0, 25 acute ulcers were associated with chronic H. pylori gastritis; one patient had neither gastritis nor H. pylori infection. The H. pylori count correlated with the activity of chronic gastritis and with the extension of intestinal metaplasia; it was not modified by the healing of gastric ulcer observed in 24/26 patients on day 360. These results confirm the existence of a close association between H. pylori, chronic gastritis and gastric ulcer. It also suggests that H. pylori is not directly involved in the healing or recurrence of gastric ulcer.

Reasons for student attrition on nursing courses: a study.

Student attrition (dropping out) wastes time and resources which schools of nursing can ill afford. This study from Israel sets out to identify the reasons for student attrition and finds that academic failure is only one factor. The authors suggest some ways in which high risk students can be identified and helped.

Treatment of duodenal ulcer with rioprostil: a randomized multicentre double-blind study.

The effectiveness of rioprostil, 300 micrograms b.d. is evaluated in evolutive duodenal ulcer in a double-blind study in five French and North African centres. A total of 115 patients are included in the study (57 in the rioprostil group and 58 in the placebo group). After a 4-week treatment period, a significantly higher endoscopic healing rate is observed in the rioprostil group (57%) compared with the placebo group (33%) (p less than 0.01). The mean time with abdominal pain is significantly lower in the rioprostil group (5.6 +/- 4.4 days) compared to the placebo group (12.7 +/- 5 days) (p less than 0.001). Clinical and biological tolerance is excellent. The only side effect is diarrhoea (3.5% in the rioprostil group). In only one case does diarrhoea necessitate cessation of treatment. Rioprostil, 300 micrograms b.d., is thus effective in the treatment of developing duodenal ulcer.

Rasmussen's encephalitis presenting as focal cortical dysplasia.

Rasmussen's encephalitis is a rare syndrome characterized by intractable seizures, often associated with epilepsia partialis continua and symptoms of progressive hemispheric dysfunction. Seizures are usually the hallmark of presentation, but antiepileptic drug treatment fails in most patients and is ineffective against epilepsia partialis continua, which often requires surgical intervention. Co-occurrence of focal cortical dysplasia has only rarely been described and may have implications regarding pathophysiology and management. We describe a rare case of dual pathology of Rasmussen's encephalitis presenting as a focal cortical dysplasia (FCD) and discuss the literature on this topic.

Early thalamic lesions in patients with sleep-potentiated epileptiform activity.

OBJECTIVE: To compare the prevalence and type of early developmental lesions in patients with a clinical presentation consistent with electrical status epilepticus in sleep either with or without prominent sleep-potentiated epileptiform activity (PSPEA). METHODS: We performed a case-control study and enrolled patients with 1) clinical features consistent with electrical status epilepticus in sleep, 2) ≥1 brain MRI scan, and 3) ≥1 overnight EEG recording. We quantified epileptiform activity using spike percentage, the percentage of 1-second bins in the EEG tracing containing at least 1 spike. PSPEA was present when spike percentage during non-REM sleep was ≥50% than spike percentage during wakefulness. RESULTS: One hundred patients with PSPEA (cases) and 47 patients without PSPEA (controls) met the inclusion criteria during a 14-year period. Both groups were comparable in terms of clinical and epidemiologic features. Early developmental lesions were more frequent in cases (48% vs 19.2%, p = 0.002). Thalamic lesions were more frequent in cases (14% vs 2.1%, p = 0.037). The main types of early developmental lesions found in cases were vascular lesions (14%), periventricular leukomalacia (9%), and malformation of cortical development (5%). Vascular lesions were the only type of early developmental lesions that were more frequent in cases (14% vs 0%, p = 0.005). CONCLUSIONS: Patients with PSPEA have a higher frequency of early developmental lesions and thalamic lesions than a comparable population of patients without PSPEA. Vascular lesions were the type of early developmental lesions most related to PSPEA.