Societal costs and quality of life analysis in patients undergoing resective epilepsy surgery: A one-year follow-up.

Although effectiveness of Resective Epilepsy Surgery (RES) for patients with drug-resistant epilepsy (DRE) is widely proven, research on the impact of societal costs (SC) is lacking. The aim of this study is to provide both clinical and economic outcomes of RES by offering an overview of treatment effectiveness as well as SC of RES in a cohort of 30 Dutch DRE patients. This project serves as a pilot project to offer an up-to-date model for larger cost-effectiveness studies. Medical consumption, productivity losses, disease-specific and generic health-related quality of life (QoL), and seizure frequency were assessed before and 3-, 6-, and 12-months post-surgery with validated questionnaires. Linear mixed models, ANOVAs, and logistic regressions were performed. SC for the first year after RES entailed €54,376 and decreased over time. Moreover, 50% of patients experienced a clinically important increase in disease-specific QoL and 53% of patients in generic health-related QoL. Lastly, 73% of patients reached seizure freedom 12 months postoperative. Seizure reduction was correlated with increase in disease-specific QoL. Within one year after surgery, RES leads to reduction in SC and improvements in QoL over time. Future research should encompass longer follow-up periods, larger sample size, and a cost-effectiveness analysis with a comparator.

Value of ultra-high field MRI in patients with suspected focal epilepsy and negative 3 T MRI (EpiUltraStudy): protocol for a prospective, longitudinal therapeutic study.

PURPOSE: Resective epilepsy surgery is a well-established, evidence-based treatment option in patients with drug-resistant focal epilepsy. A major predictive factor of good surgical outcome is visualization and delineation of a potential epileptogenic lesion by MRI. However, frequently, these lesions are subtle and may escape detection by conventional MRI (≤ 3 T). METHODS: We present the EpiUltraStudy protocol to address the hypothesis that application of ultra-high field (UHF) MRI increases the rate of detection of structural lesions and functional brain aberrances in patients with drug-resistant focal epilepsy who are candidates for resective epilepsy surgery. Additionally, therapeutic gain will be addressed, testing whether increased lesion detection and tailored resections result in higher rates of seizure freedom 1 year after epilepsy surgery. Sixty patients enroll the study according to the following inclusion criteria: aged ≥ 12 years, diagnosed with drug-resistant focal epilepsy with a suspected epileptogenic focus, negative conventional 3 T MRI during pre-surgical work-up. RESULTS: All patients will be evaluated by 7 T MRI; ten patients will undergo an additional 9.4 T MRI exam. Images will be evaluated independently by two neuroradiologists and a neurologist or neurosurgeon. Clinical and UHF MRI will be discussed in the multidisciplinary epilepsy surgery conference. Demographic and epilepsy characteristics, along with postoperative seizure outcome and histopathological evaluation, will be recorded. CONCLUSION: This protocol was reviewed and approved by the local Institutional Review Board and complies with the Declaration of Helsinki and principles of Good Clinical Practice. Results will be submitted to international peer-reviewed journals and presented at international conferences. TRIAL REGISTRATION NUMBER: www.trialregister.nl : NTR7536.

Changes in the frequency of benign focal spikes accompany changes in central information processing speed: a prospective 2-year follow-up study.

We prospectively examined whether changes in the frequency of benign focal spikes accompany changes in cognition. Twenty-six children with benign focal spikes (19 with Rolandic epilepsy) and learning difficulties were examined with repeated 24-hour EEG recordings, three cognitive tests on central information processing speed (CIPS), and questionnaires on cognition and behavior at baseline, 6months, and 2years. Antiepileptic drug changes were allowed when estimated necessary by the treating physician. At baseline, a lower CIPS was correlated with a higher frequency of diurnal interictal epileptiform discharges (IEDs) and with worse academic achievement. At follow-up, there was a significant correlation between changes in CIPS and EEG changes in wakefulness (in the same direction) when the EEG outcome was dichotomized in IED frequency "increased" or "not increased". Behavioral problems were more often observed in patients with higher frequency of IEDs in sleep at baseline and in those with ongoing IEDs compared with those with EEG remission (without or with sporadic IEDs in the recording) at the end of the study period. No changes were observed in the results of the questionnaires. A lower diurnal IED frequency at baseline, lack of serial IEDs, and occurrence of only unilateral IEDs were correlated with a higher chance of EEG remission at 2-year follow-up. Electroencephalography remission could not be predicted from other epilepsy variables except from seizure freedom in the last six months. Our results confirm the nonbenign character of 'benign' focal spikes. Whether an early and stable EEG remission can be achieved through antiepileptic treatment and whether this is of benefit for cognitive development should be examined in prospective placebo-controlled randomized trials.

The effects of vagus nerve stimulation on tryptophan metabolites in children with intractable epilepsy.

BACKGROUND: The mechanism of action of vagus nerve stimulation (VNS) in intractable epilepsy is not entirely clarified. It is believed that VNS causes alterations in cytokines, which can lead to rebalancing the release of neurotoxic and neuroprotective tryptophan metabolites. We aimed to evaluate VNS effects on tryptophan metabolites and on epileptic seizures and investigated whether the antiepileptic effectiveness correlated with changes in tryptophan metabolism. METHODS: Forty-one children with intractable epilepsy were included in a randomized, active-controlled, double-blind study. After a baseline period of 12 weeks, all children underwent implantation of a vagus nerve stimulator and entered a blinded active-controlled phase of 20 weeks. Half of the children received high-output (therapeutic) stimulation (n=21), while the other half received low-output (active control) stimulation (n=20). Subsequently, all children received high-output stimulation for another 19 weeks (add-on phase). Tryptophan metabolites were assessed in plasma and cerebrospinal fluid (CSF) by use of liquid chromatography-tandem mass spectrometry (LC-MS/MS) and compared between high- and low-output groups and between the end of both study phases and baseline. Seizure frequency was recorded using seizure diaries. Mood was assessed using Profile of Mood States (POMS) questionnaires. RESULTS: Regarding tryptophan metabolites, anthranilic acid (AA) levels were significantly higher at the end of the add-on phase compared with baseline (p=0.002) and correlated significantly with improvement of mood (τ=-0.39, p=0.037) and seizure frequency reduction (τ=-0.33, p<0.01). No significant changes were found between high- and low-output groups regarding seizure frequency. CONCLUSION: Vagus nerve stimulation induces a consistent increase in AA, a neuroprotective and anticonvulsant tryptophan metabolite. Moreover, increased AA levels are associated with improvement in mood and reduction of seizure frequency.

[Anti-NMDA-receptor encephalitis: a new axis-III disorder in the differential diagnosis of childhood disintegrative disorder, early onset schizophrenia and late onset autism]. / Anti-NMDA-receptorencefalitis: een nieuwe as III-stoornis in de differentiaaldiagnose van desintegratiestoornis van de kinderleeftijd, vroeg optredende schizofrenie en laat optredend autisme.

Childhood disintegrative disorder (CDD), early onset schizophrenia (EOS), and late onset autism (LOA) often follow a similar course: initially, development is normal, then there is a sudden neuropsychiatric deterioration of social interaction and communication skills, which is combined with a decline in intelligence and reduction in daily activities. A 9-year-old boy was admitted to the paediatric ward with acute onset of secondary epileptic seizures. It was not long until the boy's symptoms resembled that of patients with cdd, eos and loa. Intensive tests led to the diagnosis of anti-NMDA-receptor encephalitis. Anti-NMDA-receptor encephalitis should be regarded as a possible organic cause underlying the syndromal presentation of CDD, EOS and LOA.

Vagus nerve stimulation has a positive effect on mood in patients with refractory epilepsy.

BACKGROUND: Preliminary research on the efficacy of vagus nerve stimulation (VNS) indicated additional effects on neuropsychological variables like mood and quality of life (QOL). OBJECTIVES: The objectives of this prospective longitudinal observational cohort study were to assess the effects of VNS on mood, QOL and cognition in patients with refractory epilepsy and to determine whether these effects occur dependent of seizure control. METHODS: We included 41 patients with refractory epilepsy; treated with VNS as part of usual patient care. A neuropsychological battery was performed during baseline and repeated after 6 months of VNS in order to compare neuropsychological variables before and after VNS. All patients completed seizure diaries. RESULTS: Significant improvements were observed for both mood and QOL after 6 months of VNS; based on the results in the POMS and QOLIE-89 questionnaires (p<0.05). There was no significant change in cognition. Mean percentage change in seizure frequency was -9.0%, while 20% of the patients achieved a seizure frequency reduction of 50% or more. No significant correlation was found between changes in seizure frequency and improvements in mood or QOL. CONCLUSIONS: VNS is associated with improvements in both mood and QOL in patients with refractory epilepsy. Since these improvements appeared to be independent of seizure control, the results of this study indicate an additional antidepressant effect of VNS, which can be of extra value in view of the high co-morbidity of mood disturbances in patients with epilepsy.

Impaired language performance as a precursor or consequence of Rolandic epilepsy?

OBJECTIVES: A correlation between language impairment and Rolandic epilepsy is frequently reported. It is unknown whether this language impairment develops gradually as a consequence of Rolandic epilepsy or precedes the onset of seizures. In the latter case both language impairment and Rolandic epilepsy may be symptoms of an underlying syndrome or both develop during the process of epileptogenesis. METHODS: Non-comparative clinical cohort study of 48 children with Rolandic epilepsy (children's mean age is 9 years, and 7 months; SD is 1 year, and 8 months). They were screened for previous and current language impairment and their reading skills were examined. RESULTS: 23% of children with Rolandic epilepsy had speech therapy in the past and 35% repeated a year on primary school, which is more often compared to the Dutch population of children. Their results on a reading task revealed lower scores. CONCLUSIONS: Language is impaired in children with Rolandic epilepsy. In some children this impairment of language may even be a precursor, for the Rolandic epilepsy. It is undecided however, whether the language impairment develops gradually after the onset of epilepsy, whether Rolandic epilepsy and language impairment are both symptoms of an underlying syndrome or both develop during the process of epileptogenesis as we observed in some children the onset of language impairment before the onset of epilepsy.

Nocturnal epileptiform EEG discharges, nocturnal epileptic seizures, and language impairments in children: review of the literature.

This review addresses the effect on language function of nocturnal epileptiform EEG discharges and nocturnal epileptic seizures in children. In clinical practice, language impairment is frequently reported in association with nocturnal epileptiform activity. Vice versa, nocturnal epileptiform EEG abnormalities are a common finding in children with specific language impairment. We suggest a spectrum that is characterized by nocturnal epileptiform activity and language impairment ranging from specific language impairment to rolandic epilepsy, nocturnal frontal lobe epilepsy, electrical status epilepticus of sleep, and Landau-Kleffner syndrome. In this spectrum, children with specific language impairment have the best outcome, and children with electrical status epilepticus of sleep or Landau-Kleffner syndrome, the worst. The exact nature of this relationship and the factors causing this spectrum are unknown. We suggest that nocturnal epileptiform EEG discharges and nocturnal epileptic seizures during development will cause or contribute to diseased neuronal networks involving language. The diseased neuronal networks are less efficient compared with normal neuronal networks. This disorganization may cause language impairments.

Shoulder function after latissimus dorsi transfer in breast reconstruction.

BACKGROUND/AIMS: Latissimus dorsi (LD) transfer in the case of breast reconstruction remains frequently used because this muscle provides a good size source of tissue in reconstructive surgery. Given that, the consequences of the LD removal on shoulder function and the actual loss of maximal strength developed must be investigated. METHODS: Twenty women (50 ± 7.5 years old) were evaluated before surgery, 3 and 6 months after an unilateral transfer of a pedicle flap of LD muscle used for breast reconstruction. Women performed a bilateral shoulder isokinetic assessment [for the internal rotators (IRs) and external rotators and for the abductor and adductor (ADD) muscles] allowing the establishment of bilateral muscular deficit status and the study of agonist/antagonist muscle ratios. The algofunctional and clinical status of the shoulders was analysed by the means of Constant score and specific shoulder clinical tests. The women did not perform any specific strengthening of muscle shoulder after surgery. RESULTS: The isokinetic assessment showed a muscle weakness 3 and 6 months after LD transfer, mainly on the ADDs (33 ± 9% at 6 months) and on the IRs (16 ± 11% at 6 months). The Constant score significantly decreased after surgery on the operated shoulder. Women with a Constant score impairment showed pain during specific shoulder clinical tests. We also found a correlation between Constant score impairment and internal rotators weakness or rotator muscle imbalance. CONCLUSION: Given those results, we could advocate a specific shoulder strengthening after LD transfer, focused mainly on the IRs and ADDs.