Long term effect of vagus nerve stimulation in pediatric intractable epilepsy: an extended follow-up

Purpose

Over the past two decades, vagus nerve stimulation (VNS) has become an accepted and viable treatment modality for intractable epilepsy both in children and adults. Earlier studies have demonstrated short-term seizure outcomes, usually for up to 5 years; so far, none have reported an extended outcome in children. We aimed to assess long term seizure outcome in children with intractable epilepsy for more than 5 years.

Methods

We identified patients who had VNS implantation for treatment of intractable epilepsy from March 2000 to March 2015 at our Epilepsy Center and collected data including demographic, age at epilepsy onset and VNS implantation, duration of epilepsy, seizure type, number of antiepilepsy drugs (AEDs), and monthly seizure frequency before VNS implantation and at the last clinic visit. Phone surveys were conducted with patients without recent clinic follow-up.

Results

Fifty-six patients (aged 4–17 at the time of implant) are the subjects of the study. Seizure reduction of >50 % was achieved in 9.8 % (6th month), 24 % (2nd year), 46.4 % (3rd year), and 54 %(5th year), and overall 35 (62.5 %) of the 56 subjects had a greater than 50 % reduction in seizure frequency at the last follow-up. Eleven patients became seizure free. The results, once obtained, were maintained steadily or even improved over time without any loss of efficacy during the follow-up. The only parameter, significantly related with clinical response, was age at seizure onset. The most frequent adverse events were hoarseness, cough, sore throat, and anorexia, experienced by 13 patients. Two patients had local wound infections and lead to the removal of the stimulator. An improvement in alertness, attention, and psychomotor activity, independent of the efficacy of vagal nerve stimulation, was observed in 8 patients.

Conclusion

To our knowledge, this is the first pediatric study evaluating seizure outcome over more than 5 years of follow-up, and demonstrates a favorable seizure outcome of >50 % seizure frequency in 62.5 % of patients and seizure freedom in 11 patients. It is well tolerated over an extended period of time.

     

Transcranial direct current stimulation improves seizure control in patients with Rasmussen encephalitis

Aim. Rasmussen encephalitis is associated with severe seizures that are unresponsive to antiepileptic drugs, as well as immunosuppressants. Transcranial direct current stimulation (t‐DCS) is a non‐invasive and safe method tried mostly for focal epilepsies with different aetiologies. To date, there is only one published study with two case reports describing the effect of t‐DCS in Rasmussen encephalitis. Our aim was to investigate the effect of t‐DCS on seizures in Rasmussen encephalitis and to clarify its safety. Methods. Five patients (mean age: 19; three females), diagnosed with Rasmussen encephalitis were included in this study. Patients received first cathodal, then anodal (2 mA for 30 minutes on three consecutive days for non‐sham stimulations), and finally sham stimulation with two‐month intervals, respectively. Three patients received classic (DC) cathodal t‐DCS whereas two patients received cathodal stimulation with amplitude modulation at 12 Hz. Afterwards, all patients received anodal stimulation with amplitude modulation at 12 Hz. In the last part of the trial, sham stimulation (a 60‐second stimulation with gradually decreasing amplitude to zero in the last 15 seconds) was applied to three patients. Maximum current density was 571 mA/m2 using 70 mm × 50 mm wet sponge electrodes with 2‐mA maximum, current controlled stimulator, and maximum charge density was 1028 C/m2 for a 30‐minute stimulation period. Results. After cathodal stimulation, all but one patient had a greater than 50% decrease in seizure frequency. Two patients who received modulated cathodal t‐DCS had better results. The longest positive effect lasted for one month. A second trial with modulated anodal stimulation and a third with sham stimulation were not effective. No adverse effect was reported with all types of stimulations. Conclusion. Both classic and modulated cathodal t‐DCS may be suitable alternative methods for improving seizure outcome in Rasmussen encephalitis patients.     

Physical training for intermittent claudication: a comparison of structured rehabilitation versus home-based training

In a non-randomized, open-label study results after a structured institution-based peripheral arterial occlusive disease (PAD) rehabilitation program were compared with the results of training at home. Three groups were compared: group 1 (n = 19) PAD rehabilitation; group 2 (n = 19) PAD rehabilitation + clopidogrel 75 mg once daily; group 3 (n = 21) home-based training. The training period was 3 months for all groups, which was followed by a 3-month observation phase (without prescribed training). The rehabilitation program consisted of 3 training hours per week. Background variables, demographics, and baseline claudication distances were comparable between groups. After 3 months of training the absolute claudication distances (ACD) improved by 82.7%, 131.4%, and 5.4% for groups 1, 2 and 3. The initial claudication distances (ICD) changed by 163.8%, 200.6%, and 44.4%, respectively. All changes, except the ACD result for group 3, were statistically significant (p < or = 0.05). Structured training groups (1 and 2) performed significantly better than group 3 (p < or = 0.05). When results from groups 1 and 2 were pooled, ACDs changed from 493.3 +/- 218.1 to 1026.0 +/- 468.9 m, delta 546.0 +/- 378.8 m [95% CI 417.8-674.2 ml; p < or = 0.05. ICDs improved from 175.3 +/- 110.8 m to 493.1 +/- 326.7 m, delta 320.8 +/- 315.9 m [95% CI 213.9-427.7 m]; p < or = 0.05. The difference between the pooled mean results of the structured training groups and the results of group 3 amounted to 474.3 m [95% CI 270.2-678.4 m] and 242.4 m [95% CI 99.0-385.7 m], for ACD and ICD, respectively. Structured, supervised PAD rehabilitation is a highly efficacious treatment for intermittent claudication and may be regarded as the present gold standard among conservative treatment options.     

Pregnancy-associated plasma protein-A and asthma

Pregnancy-associated plasma protein-A (PAPP-A) is potentially a proatherosclerotic metalloproteinase and a new inflammatory marker. Investigators sought to evaluate the significance of PAPP-A in patients with asthma. Blood samples were collected from 35 patients and 20 control subjects. Serum PAPP-A was determined by enzyme-linked immunosorbent assay. PAPP-A levels of patients with asthma (8.1±5.0 mU/L) were higher than those of the control group (4.9±2.1 mU/L) (P < .01). A significant correlation was noted between serum PAPP-A concentration and asthma severity (r=.581;P < .01). Investigators concluded that PAPP-A may contribute to airway smooth muscle hyperplasia as an insulin-like growth factor-dependent insulin-like growth factor-binding protein-4 protease in patients with asthma.     

IFCC primary reference procedures for the measurement of catalytic activity concentrations of enzymes at 37 degrees C. International Federation of Clinical Chemistry and Laboratory Medicine. Part 6. Reference procedure for the measurement of catalytic concentration of gamma-glutamyltransferase.

This paper is the sixth in a series dealing with reference procedures for the measurement of catalytic activity concentrations of enzymes at 37 degrees C and the certification of reference preparations. Other parts deal with: Part 1. The Concept of Reference Procedures for the Measurement of Catalytic Activity Concentrations of Enzymes; Part 2. Reference Procedure for the Measurement of Catalytic Concentration of Creatine Kinase; Part 3. Reference Procedure for the Measurement of Catalytic Concentration of Lactate Dehydrogenase; Part 4. Reference Procedure for the Measurement of Catalytic Concentration of Alanine Aminotransferase; Part 5. Reference Procedure for the Measurement of Catalytic Concentration of Aspartate Aminotransferase; Part 7. Certification of Four Reference Materials for the Determination of Enzymatic Activity of Gamma-Glutamyltransferase, Lactate Dehydrogenase, Alanine Aminotransferase and Creatine Kinase at 37 degrees C A document describing the determination of preliminary upper reference limits is also in preparation. The procedure described here is deduced from the previously described 30 degrees C IFCC reference method. Differences are tabulated and commented on in Appendix 1.     

Effects of LDL-immunoapheresis on plasma concentrations of vitamin E and carotenoids in patients with familial hypercholesterolemia

Recently very potent extracorporeal cholesterol-lowering treatment options have become available for patients with hypercholesterolemia. LDL immunoapheresis treatment selectively removes LDL and lipoprotein(a) from the circulation. Since LDL is the major carrier of lipophilic antioxidants in plasma, the purpose of the present study was to assess the effects of a single LDL apheresis treatment on plasma concentrations of tocopherols (alpha- and gamma-tocopherol) and carotenoids (alpha- and beta-carotene, zeaxanthin, cryptoxanthin, canthaxanthin, lycopene, and retinol). Plasma antioxidant concentrations were determined by HPLC in 7 patients with familial hypercholesterolemia before and after LDL immunoapheresis treatment. Plasma concentrations of both alpha- and gamma-tocopherol and the different carotenoids were significantly reduced by LDL apheresis. However, when standardized for cholesterol to adjust for cholesterol removal, alpha- and gamma-tocopherol, retinol, and the more polar carotenoids lutein and zeaxanthin increased in response to apheresis treatment, while the more unpolar carotenoids such as beta-carotene and lycopene did not change. These data demonstrate that a single LDL immunoapheresis treatment affects tocopherols and individual carotenoids differently. This may be explained by differences in chemical structure and preferential association with different lipoproteins. These results further imply that tocopherols, lutein, zeaxanthin, and retinol, are associated in part with lipoproteins and other carriers such as retinol-binding protein that are not removed during apheresis treatment.     

Narratives of a man with severe chronic heart failure and his wife in palliative advanced home care over a 4.5-year period

The aim of this paper is to illuminate meanings of living the 'ups and downs', through the narratives of one man with severe, chronic heart failure (CHF) and his wife in palliative advanced home care (PAHC). Narrative interviews were conducted over a 4.5-year period and a phenomenological-hermeneutic method was used to interpret the text.The analysis resulted in one theme and four sub-themes. Meanings of living the 'ups and downs' is symbolically understood as being captive in a roller-coaster ride, side by side. In togetherness one helps one another to integrate the illness into everyday life.When, the inevitable 'downs' come one alleviates them as much as possible and/or just endures them waiting to see if one outlives them. During the 'ups' one seizes every opportunity to live, doing the things one likes and discovering new possibilities in life. Sharing the safety belt on the 'roller coaster', offered by the PAHC team, evokes feelings of security.However, the safety belt is adjusted to the man with severe CHF leaving the wife without comfort and at times uncertain, especially in the deepest 'downs'. Our results indicate that the importance of medical treatment may increase over time.The ability to recognize symptoms and signs of deterioration may be facilitated by a trusted PAHC team's repeated questions about the condition. Furthermore it is important to offer support directly to the close relatives.