Refractory Epilepsy-MRI, EEG and CT scan, a Correlative Clinical Study

Clinical Neurophysiology: EEG–Video Monitoring

Background Vagus nerve stimulation (VNS) is an effective treatment for patients with refractory epilepsy, yet with varied predictive factors and heterogeneous long-term outcomes. Adjustment of VNS parameters is critical for obtaining favorable efficacy. In this study, we aimed to investigate the long-term outcomes and the possible predictive factors of VNS in patients with refractory epilepsy. Methods Eighty-six patients (59 males and 27 females) who underwent VNS implantation for treatment of refractory epilepsy between May 2016 and May 2017 at five Epilepsy Centers were enrolled. The clinical data, including sex, age at epilepsy onset, VNS implantation, epilepsy duration, seizure type, MRI findings, history of neurosurgical operations, and responder rate (responders were those with ≥50% seizure reduction), were analyzed. Results Four-year follow-up data were available for 76 patients (53 males and 23 females). The mean current intensity at the last follow-up was 1.8 ± 0.3 mA (range: 0.75–2.5 mA). The mean seizure reduction was 36.2% at 6 months, 38.5% at 1 year, 69.4% at 3 years, and 56.7% at 4 years. A favorable outcome of ≥50% reduction in seizure frequency occurred in 40.0% of the patients at 6 months, 55.9% at 1 year with 4 patients being seizure-free, 63.2% at 3 years with 5 patients being seizure-free, and 68.4% at 4 years with 5 patients being seizure-free. Earlier onset age (P < 0.001) and shorter duration (P = 0.042) were associated with favorable prognosis. Compared with generalized tonic-clonic seizures, tonic seizures had a favorable outcome (P = 0.026). Twenty-three patients underwent neurosurgical operations before VNS implantation, and the responder rate was 60.9% at the last follow-up. Conclusions VNS is an adjunctive and effective treatment for patients with refractory epilepsy who are not good candidates for surgical resection or have failed to respond to surgical treatment. The stimulation efficacy increases over time after implantation, and earlier exposure to VNS improves the prognosis.

The use of zonisamide as add-on therapy in refractory partial epilepsy: experience from an epilepsy referral centre in a developing country

Both idiopathic generalized epilepsy and focal epilepsy may be associated with seizures in early childhood (Hamati‐Haddad and Abou‐Khalil, 1998). The majority of adults with refractory epilepsy have focal epilepsy, with a temporal lobe epileptic focus in ∼60–70% of which hippocampal (mesial temporal) sclerosis is the causative lesion in ∼80% (Van Paesschen et al ., 1995). In newly diagnosed focal epilepsy the prevalence of hippocampal sclerosis is ∼11% (Van Paesschen et al ., 1998). The aetiology of this common cause of focal epilepsy remains enigmatic. One of the few clues is its association with early childhood convulsion (ECC), particularly complicated ECC (usually defined as lasting >15 min, associated with focal neurological deficit or recurrent within 24 h). Approximately half of patients with hippocampal sclerosis report a history of complicated ECC (Kuks et al ., 1993), and 90% of patients with temporal lobe epilepsy and a history of complicated ECC have hippocampal sclerosis (Grunewald et al , 1994). ECCs affect between 2 and 4% of the population and are usually benign. However, after an ECC a small minority of children continue to have seizures or develop epilepsy later. The Child Health and Education Study, a birth cohort study, demonstrated that the risk of epilepsy depends on the type of seizure, being higher for complicated than simple ECCs, (4–6% versus 1–1.5% risk of epilepsy in the first 10 years of …

To study the outcome after hemispherectomy (HP) in a homogeneous adult patient population with refractory hemispheric epilepsy. Fourteen adult patients submitted to HP were studied. Patients had to be at least 18 years old, and have refractory epilepsy, clearly focal lateralized seizures and unilateral porencephalus consistent with early middle cerebral artery infarct on magnetic resonance imaging (MRI). All patients were submitted to functional hemispherectomy. We analyzed age of seizure onset, age by the time of surgery, gender, seizure type and frequency, interictal and ictal electroencephalography (EEG) findings, MRI and IQ scores preoperatively; seizure frequency, drug regimen, and IQ outcome were studied postoperatively. Mean follow-up was 64 months. All patients had frequent daily seizures preoperatively. All patients had unilateral simple partial motor seizures (SPS); 11 patients had secondarily generalized tonic-clonic (GTC) seizures and five patients had complex partial seizures (CPS), preoperatively. All patients had hemiplegia and hemianopsia. Twelve patients had unilateral EEG findings, and in two epileptic discharges were seen exclusively over the apparently normal hemisphere. Twelve patients were seizure-free after surgery and two patients had at least 90% improvement in seizure frequency. Pre- and postoperative mean general IQ was 84 and 88, respectively. Five of the twelve Engel I patients were receiving no drugs at last follow-up. There was no mortality or major morbidity. Our results suggest that well-selected adult patients might also get good results after HP. Although good results were obtained in our adult series, the same procedure yielded a much more striking result if performed earlier in life.

The study is to investigate the expression and significance of microRNA-3686 in peripheral blood of refractory epilepsy patients (RE). 83 patients with untreated epilepsy were selected as the experimental group. During the treatment, According to diagnostic criteria for refractory epilepsy, 15 patients were diagnosed with refractory epilepsy (RE group) and 68 cases in no refractory epilepsy group (NRE group). 50 patients in the normal group were selected as the control group. The results showed that the expression of microRNA-3686 in the peripheral blood of the experimental group was lower than that of the control group (P < 0.05). The levels of P-gp and MRP1 in peripheral blood of patients in RE group were higher than those in NRE group (P < 0.05). microRNA-3686 was negatively correlated with P-gp (r= – 0.799, P < 0.05), and had no correlation with MRP1 (r= 0.279, P= 0.314); ROC curve showed microRNA-3686 prediction RE of the area under the curve of epilepsy AUC was 0.733, 95% CI (0.603–0.863), (P < 0 05). In Conclusion the microRNA-3686 is low in peripheral blood of patients with refractory epilepsy and may be involved in the resistance of epilepsy by regulating P-gp, but not MRP1.

Evaluating the efficacy of transcranial direct current stimulation for refractory epilepsy: A meta-analysis of RCTs and non-RCTs

We explored factors that may predispose patients to adverse mood effects during treatment with vigabatrin (gamma-vinyl GABA; VGB): mood disorders before VGB treatment, type of epilepsy, seizure type and seizure frequency, type and number of comedication, and VGB dose. The clinical relevance of such a study is that it may help identify circumstances in which VGB should be administered with caution. Seventy-three patients (40 males, 33 females), all with refractory epilepsies, who received VGB as add-on therapy, were assessed by the Amsterdamse Stemmingslyst (ASL), a mood-rating scale, before the start of treatment, and demographic and clinical data were recorded. The patients were followed for 6 months after the start of VGB treatment. Treatment with VGB had to be discontinued in 38 patients (52% of the total sample). Mood problems were the main reason for discontinuation in 9 (12.3% of the total sample). In 6 other patients, mood problems were mentioned as the reason for discontinuing treatment, in combination with lack of drug efficacy. Development of adverse mood effects could not be predicted by a specific mood profile on the ASL. Before treatment, the "mood problems discontinuation group" did not show extreme scores for any assessed areas of mood and no significant differences from other patients were noted on the mood scales. Neither did clinical or demographic data show statistically confirmed specific characteristics for the mood problems discontinuation group, though the patients tended to use more antiepileptic drugs (AEDs) as cotherapy, to have a slightly lower daily dose of VGB, to be slightly older, and were mostly female.(ABSTRACT TRUNCATED AT 250 WORDS)

Quality of life predictors in patients with epilepsy and cognitive disabilities

Comparison of CT scan and MRI findings in the diagnosis of Japanese encephalitis.

Background Nearly 30% of patients with epilepsy are refractory to currently available antiseizure drugs (ASDs). Although the U.S. Food and Drug Administration approved perampanel (PER) for patients as young as 4 years, there are limited data on using PER in children. Objective The aim of this study was to determine the efficacy and tolerability of adjunctive PER treatment in children with refractory epilepsy (RE). Methodology This prospective intervention study was conducted in the tertiary care center, in Bengaluru, India from December 2020 to May 2022. PER was added after the failure of a minimum of two ASDs and patients with 6 months follow-up. Treatment response was classified as complete, partial, or none with ≥90, ≥50, and <50% reduction in seizure frequency, respectively. Adverse events and discontinuation data were used to assess tolerability. Results Our cohort consisted of 100 cases, a mean age of 9.3 ± 3.8 years and male:female ratio of 3:1. The predominant seizure type was generalized seizures (74%), and concomitant enzyme-inducing ASD use was noted in 27%. Structural etiology was noted in 57%. A total of 76% of participants responded to PER therapy (46% complete response and 30% partial response), while 23% showed no response and 1% discontinued the treatment. Adverse events were observed in 25% of participants (11/25 [44%] drowsiness/sedation, 10/25 [40%] behavioral problems, and 4 [16%] other side effects). Early PER add-on provided a statistically significant benefit over late PER add-on (p = 0.01). Response to PER did not differ significantly with the type of seizure and ASD used (p > 0.05). Conclusion Adjunctive PER therapy is safe and effective for treating children with RE. An early add-on of PER is more beneficial in controlling seizures than a late add-on.

The efficacy and side effects of topiramate on refractory epilepsy in infants and young children: A multi-center clinical trial

Background:Previous studies have associated coeliac disease (CD) and gluten sensitivity (defined as the presence of anti-gliadin antibodies and positive immunogenetics) with cerebellar degeneration and epilepsy with occipital calcifications. Hippocampal sclerosis...

Objective To observe the effectiveness of low⁃frequency and subthreshold repetitive transcranial magnetic stimulation (rTMS) on patients with refractory epilepsy. Methods Twelve subjects with refractory and focal epilepsy were involved. rTMS as a treatment with 600 pulses, intensity of 90% motor resting threshold and 0.50 Hz frequency was administrated once per day, 5 days as one course. Five of twelve patients accepted the second course treatment. The number of seizure frequency, seizure days, and seizure latency at pre ⁃ and pro ⁃ treatment were measured and compared. Meanwhile, the data of electroencephalography (EEG) was collected for calculation. Compared epileptic spike discharges in the EEG and relative power of each frequency distribution (%) by using the software running on MATLAB 7.0. Results rTMS significantly decreased the frequency and days of seizures after 5 days of the first treatment in all 12 patients (t = 2.450, P = 0.032; t = 2.797, P = 0.017), and prolonged seizure latency in 8 patients. Furthermore, high⁃frequency β band relative power distribution showed significant increase (t = ⁃ 2.703, P = 0.021), especially in α band (t = ⁃ 3.680, P = 0.004); while low⁃frequency δ band decreased (t = 3.047, P = 0.011). The amount of EEG sharp waves was reduced significantly (t = 2.411, P = 0.035). Compared with the first course, these indexes were improved in the second treatment. The changes of δ and α bands were great, especially δ band decreased by 2.08 times which suggested that EEG background waves were improved evidently. Conclusion Low ⁃ frequency and subthreshold rTMS can decrease the events of epileptic seizures, prolong seizure latency, and improve epileptic EEG discharges. As a new method in the area of non ⁃ drug ⁃ induced neuro ⁃ modulation, low ⁃ frequency rTMS is a safe and effective treatment for refractory epilepsy. It shows good prospects for clinical application of low ⁃frequency rTMS in refractory epilepsy. DOI：10.3969/j.issn.1672-6731.2010.02.018

The assessment of patients with refractory epilepsy presents both a challenge and an opportunity. The use of appropriate instruments to carefully and consistently measure a patient's seizure type and frequency, hormonal function, and medication side effects and the impact of those variables on quality of life ensures consistent, standardized assessment. A patient's epilepsy then can be classified as refractory based on any combination of factors that preclude a reasonably normal life-style by current practice standards, given the person's capabilities. Diagnostic studies and treatment strategies should address all significant adverse findings resulting from the assessment process. Accurate diagnosis of seizure type usually requires electroencephalographic (EEG) monitoring. Postictal hormonal assays and periodic measurements of estrogen and progesterone may be useful diagnostically in a selected group of patients. Awareness of a patient's compliance history, environmental stressors, and seizure triggers may reduce seizure frequency without a change in medication. For patients with medication intolerance, the usual strategy is to modify the medication regimen or treatment schedule to minimize side effects while maximizing seizure control and compliance. For most patients, monotherapy provides a greater therapeutic window than combination therapy. Devising an effective and safe therapeutic regimen is an ongoing process and can be lengthy depending on seizure type(s), frequency, and temporal pattern; anticonvulsant pharmacokinetics; drug interactions and side effects; patient's life-style; and other factors. Serial measurements of quality-of-life variables may assist in the process. Rapid strides have been recently made, and as the pace of new antiepileptic drug development quickens and surgical centers become more widely available, clinicians will need to redefine refractoriness as the expectations improve for patients with epilepsy.