Magnesium as an Effective Adjunct Therapy for Drug Resistant Seizures

Objective:To explore the use of magnesium (Mg), an endogenous ion and enzymatic co-factor used in a variety of medical applications, for the treatment of epileptic seizures resistant to traditional medical therapy.Background:For almost a century, Mg has been used as prophylaxis and treatment of seizures associated with eclampsia. Mg is a CNS depressant, with numerous functions intracellularly and extracellularly. However, because of the availability of well studied anticonvulsant drugs, Mg has not been tested widely in the treatment of epileptic seizures.Methods:A retrospective chart review of 22 cases of drug resistant epilepsy, where a trial of empiric oral Mg supplementation (mainly in the form of Mg-oxide) was conducted.Results:Oral Mg supplementation was associated with a significant decrease in the number of seizure days per month, from 15.3 ± 13.2 (mean ± SD) to 10.2 ± 12.6 at first follow up (3-6 months, p=0.021), and to 7.8 ± 10.0 seizure days/month at second follow up (6-12 months, p=0.004). Thirty-six percent had a response rate of 75% or greater at second follow-up. Two patients reported seizure freedom. Most patients were well maintained on MgO 420mg twice a day, or in 2 cases, Mg Lactate, without significant adverse effects, the most frequent being diarrhea (4/22).Discussion:These results suggest that oral Mg supplementation may prove to be a worthwhile adjunctive medication in treating drug intractable epilepsy.Conclusions:A prospective, double-blinded, placebo controlled study is warranted to evaluate the potential of Mg for the treatment of drug-resistant seizures.

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Drug Resistant Epilepsy Among Patients Attended The Neurosciences Hospital

AL-Kindy College Medical Journal ◽

10.47723/kcmj.v13i1.138 ◽

2019 ◽

Vol 13 (1) ◽

pp. 108-115

Author(s):

Nael Husain Zaer

Keyword(s):

Drug Resistance ◽

Medical History ◽

Refractory Epilepsy ◽

Seizure Freedom ◽

Drug Resistant ◽

Past Medical History ◽

Number Of Patients ◽

Drug Resistant Epilepsy ◽

Patients With Epilepsy

Background: Drug resistant epilepsy is defined as failure of adequate trials of two tolerated, appropriately chosen and used antiepileptic drug schedules to achieve sustained seizure freedom. Up to 30% of patients referred to clinics with a diagnosis of pharmaco-resistant epilepsy may have been misdiagnosed, and many can be helped by optimizing their treatment.Pseudoresistance, in which seizures persist because the underlying disorder has not been adequately or appropriately treated, must be ruled out or corrected before drug treatment can be considered to have failed. Objectives: The objectives of this study were to determine the causes of drug failure in patients with epilepsy and to differentiate between drug resistant epilepsy and pseudoresistant epilepsy. Type of the study: This is a retrospective study. Method: It is conducted in Baghdad governorate at the epilepsy clinic in the neurosciences hospital during the period from the 1st of February through July 2013. Two hundred patients with refractory epilepsy were involved. These patients attended the epilepsy clinic during 2011 and 2012. The data was collected from the files of the patients including age, gender, weight, history of presenting illness, type of seizure, drugs used, duration of disease, EEG and imaging findings, compliance and follow up. Results: Drug resistance epilepsy constituted a prevalence of 24% (128) as the total number of patients with epilepsy attending the hospital during the same period was 527.The mean age of patients with refractory epilepsy was 25 years. Male were 56.5% (113/200) and urban residents were 70.5% (141/200). The study revealed that 64% (128/200) of refractory epilepsy was attributed to drug resistance; while the remaining proportion was pseudoresistance 36% (72/200). The main cause of pseudoresistance was poor compliance 36.1% (26/72).The most common type of seizure in the sampled patients was generalized tonic clonic seizures in 51.5% (103/200).Compliance was found to be statistically associated with abnormal EEG finding, past medical history (hypertension, cardiac diseases, encephalitis, diabetes mellitus and any significant history) and quality of follow up. The follow-up was found to be statistically associated with the family history, past medical history( encephalitis and hypertension) and compliance of patient. Conclusion:A considerable number of patientsdiagnosed as cases of drug resistant epilepsy had another explanation causing drug failure.The study recommends the application of consensus definition for drug resistant epilepsy and periodic evaluation of patients with drug resistant epilepsy to exclude pseudoresistance.

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Efficacy and tolerability of clobazam in adults with drug-refractory epilepsy

Neurology Clinical Practice ◽

10.1212/cpj.0000000000000992 ◽

2020 ◽

pp. 10.1212/CPJ.0000000000000992

Author(s):

Alisha Jamil ◽

Noah Levinson ◽

Michael Gelfand ◽

Chloe E. Hill ◽

Pouya Khankhanian ◽

...

Keyword(s):

Adverse Effects ◽

Seizure Frequency ◽

Retrospective Chart Review ◽

Adjunctive Treatment ◽

Drug Resistant ◽

Before And After ◽

Initial Cohort ◽

Epilepsy Classification ◽

Drug Resistant Epilepsy

ObjectivesTo evaluate the effectiveness and tolerability of clobazam as an adjunctive treatment for adults with drug-resistant epilepsy.MethodsWe performed a single-center, retrospective chart review of patients ≥18 years of age with drug-resistant epilepsy who started clobazam between 2010 and 2018. Included patients had outpatient visits both before and ≥1 month after clobazam initiation. Epilepsy classification, seizure frequency before and after clobazam, duration of clobazam treatment, and adverse effects were analyzed.ResultsA total of 417 patients met inclusion criteria. Mean age was 37.5 years, and 54% of patients were female. Patients were on a mean of 2.4 antiepileptic drugs at time of initiation of clobazam. Epilepsy types were focal (56.8%), Lennox-Gastaut syndrome (LGS) (21.1%), generalized (15.1%), and unclassified (7.0%). At the first follow-up visit ≥1 month after clobazam initiation, 50.3% of patients had >50% reduction in seizure frequency, and 20.5% were seizure-free. Of the initial cohort, 17.1% were followed >1 year and were seizure-free at last follow-up. Response rates did not differ between different epilepsy classifications. Fifty-one percent of patients experienced ≥1 side effect, most commonly lethargy/fatigue (30.7%) or mood changes (10.8%). A total of 178 (42.6%) patients discontinued clobazam, most commonly due to adverse effects (55%).ConclusionsClobazam is effective and safe as a long-term adjunctive therapy for adults with drug-resistant epilepsy; efficacy in off-label use is similar to that in LGS.Classification of evidenceThis study provides Class IV evidence that clobazam is an effective treatment for adults with drug-resistant epilepsy, independent of epilepsy classification.

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Tailored multilobar disconnective epilepsy surgery in the posterior quadrant

Journal of Neurosurgery ◽

10.3171/2019.1.jns183103 ◽

2020 ◽

Vol 132 (5) ◽

pp. 1345-1357 ◽

Cited By ~ 3

Author(s):

Michele Rizzi ◽

Martina Revay ◽

Piergiorgio d’Orio ◽

Pina Scarpa ◽

Valeria Mariani ◽

...

Keyword(s):

Safety Profile ◽

Class I ◽

Seizure Outcome ◽

Seizure Freedom ◽

Type I ◽

Drug Resistant ◽

Presurgical Evaluation ◽

Posterior Quadrant ◽

Drug Resistant Epilepsy

OBJECTIVESurgical treatment of drug-resistant epilepsy originating from the posterior quadrant (PQ) of the brain often requires large multilobar resections, and disconnective techniques have been advocated to limit the risks associated with extensive tissue removal. Few previous studies have described a tailored temporoparietooccipital (TPO) disconnective approach; only small series with short postoperative follow-ups have been reported. The aim of the present study was to present a tailored approach to multilobar PQ disconnections (MPQDs) for epilepsy and to provide details about selection of patients, presurgical investigations, surgical technique, treatment safety profile, and seizure and cognitive outcome in a large, single-center series of patients with a long-term follow-up.METHODSIn this retrospective longitudinal study, the authors searched their prospectively collected database for patients who underwent MPQD for drug-resistant epilepsy in the period of 2005–2017. Tailored MPQDs were a posteriori grouped as follows: type I (classic full TPO disconnection), type II (partial TPO disconnection), type III (full temporooccipital [TO] disconnection), and type IV (partial TO disconnection), according to the disconnection plane in the occipitoparietal area. A bivariate statistical analysis was carried out to identify possible predictors of seizure outcome (Engel class I vs classes II–IV) among several presurgical, surgical, and postsurgical variables. Preoperative and postoperative cognitive profiles were also collected and evaluated.RESULTSForty-two consecutive patients (29 males, 24 children) met the inclusion criteria. According to the presurgical evaluation (including stereo-electroencephalography in 13 cases), 12 (28.6%), 24 (57.1%), 2 (4.8%), and 4 (9.5%) patients received a type I, II, III, or IV MPQD, respectively. After a mean follow-up of 80.6 months, 76.2% patients were in Engel class I at last contact; at 6 months and 2 and 5 years postoperatively, Engel class I was recorded in 80.9%, 74.5%, and 73.5% of cases, respectively. Factors significantly associated with seizure freedom were the occipital pattern of seizure semiology and the absence of bilateral interictal epileptiform abnormalities at the EEG (p = 0.02). Severe complications occurred in 4.8% of the patients. The available neuropsychological data revealed postsurgical improvement in verbal domains, whereas nonunivocal outcomes were recorded in the other functions.CONCLUSIONSThe presented data indicate that the use of careful anatomo-electro-clinical criteria in the presurgical evaluation allows for customizing the extent of surgical disconnections in PQ epilepsies, with excellent results on seizures and an acceptable safety profile.

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Outcomes after hemispherectomy in adult patients with intractable epilepsy: institutional experience and systematic review of the literature

Journal of Neurosurgery ◽

10.3171/2016.9.jns151778 ◽

2018 ◽

Vol 128 (3) ◽

pp. 853-861 ◽

Cited By ~ 4

Author(s):

Courtney M. Schusse ◽

Kris Smith ◽

Cornelia Drees

Keyword(s):

Neuropsychological Testing ◽

Case Series ◽

Intractable Epilepsy ◽

Adult Patients ◽

Morbidity Rate ◽

Seizure Outcome ◽

Seizure Freedom ◽

Surgical Tool ◽

Drug Resistant Epilepsy

OBJECTIVEHemispherectomy is a surgical technique that is established as a standard treatment in appropriately selected patients with drug-resistant epilepsy. It has proven to be successful in pediatric patients with unilateral hemispheric lesions but is underutilized in adults. This study retrospectively evaluated the clinical outcomes after hemispherectomy in adult patients with refractory epilepsy.METHODSThis study examined 6 cases of hemispherectomy in adult patients at Barrow Neurological Institute. In addition, all case series of hemispherectomy in adult patients were identified through a literature review using MEDLINE and PubMed. Case series of patients older than 18 years were included; reports of patients without clear follow-up duration or method of validated seizure outcome quantification were excluded. Seizure outcome was based on the Engel classification.RESULTSA total of 90 cases of adult hemispherectomy were identified, including 6 newly added by Barrow Neurological Institute. Sixty-five patients underwent functional hemispherectomy; 25 patients had anatomical hemispherectomy. Length of follow-up ranged from 9 to 456 months. Seizure freedom was achieved in 80% of patients. The overall morbidity rate was low, with 9 patients (10%) having new or additional postoperative speech or language dysfunction, and 19 patients (21%) reporting some worsening of hemiparesis. No patients lost ambulatory or significant functional ability, and 2 patients had objective ambulatory improvement. Among the 41 patients who underwent additional formal neuropsychological testing postoperatively, overall stability or improvement was seen.CONCLUSIONSHemispherectomy is a valuable surgical tool for properly selected adult patients with pre-existing hemiparesis and intractable epilepsy. In published cases, as well as in this series, the procedure has overall been well tolerated without significant morbidity, and the majority of patients have been rendered free of seizures.

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Safety of responsive neurostimulation in pediatric patients with medically refractory epilepsy

Journal of Neurosurgery Pediatrics ◽

10.3171/2020.5.peds20118 ◽

2020 ◽

Vol 26 (5) ◽

pp. 525-532 ◽

Cited By ~ 1

Author(s):

Fedor Panov ◽

Sara Ganaha ◽

Jennifer Haskell ◽

Madeline Fields ◽

Maite La Vega-Talbott ◽

...

Keyword(s):

Pediatric Patients ◽

Pediatric Population ◽

Complete Removal ◽

Seizure Freedom ◽

Drug Resistant ◽

Invasive Treatment ◽

Single Center Study ◽

Drug Resistant Epilepsy ◽

Main Complication

OBJECTIVEApproximately 75% of pediatric patients who suffer from epilepsy are successfully treated with antiepileptic drugs, while the disease is drug resistant in the remaining patients, who continue to have seizures. Patients with drug-resistant epilepsy (DRE) may have options to undergo invasive treatment such as resection, laser ablation of the epileptogenic focus, or vagus nerve stimulation. To date, treatment with responsive neurostimulation (RNS) has not been sufficiently studied in the pediatric population because the FDA has not approved the RNS device for patients younger than 18 years of age. Here, the authors sought to investigate the safety of RNS in pediatric patients.METHODSThe authors performed a retrospective single-center study of consecutive patients with DRE who had undergone RNS system implantation from September 2015 to December 2019. Patients were followed up postoperatively to evaluate seizure freedom and complications.RESULTSOf the 27 patients studied, 3 developed infections and were treated with antibiotics. Of these 3 patients, one required partial removal and salvaging of a functioning system, and one required complete removal of the RNS device. No other complications, such as intracranial hemorrhage, stroke, or device malfunction, were seen. The average follow-up period was 22 months. All patients showed improvement in seizure frequency.CONCLUSIONSThe authors demonstrated the safety and efficacy of RNS in pediatric patients, with infections being the main complication.

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Efficacy of VNS for Drug-Resistant Epilepsy in Structural Brain Lesions

The Open Neurology Journal ◽

10.2174/1874205x02014010085 ◽

2020 ◽

Vol 14 (1) ◽

pp. 85-92

Author(s):

Hanin Al-Gethami ◽

Ashwaq AlShahrani ◽

Mubarak Aldosari ◽

Majed AlHameed

Keyword(s):

Surgical Intervention ◽

Intractable Epilepsy ◽

Brain Lesions ◽

Drug Resistant ◽

Significant Difference ◽

The Mean ◽

Drug Resistant Epilepsy ◽

Over Time ◽

Structural Brain

Background: Vagus nerve stimulation (VNS) has been used for the treatment of drug-resistant epilepsy, especially in patients who are not candidates for surgical intervention. In fact, it was approved by the US FDA in 1997 as an adjunctive treatment for medically intractable epilepsy. Objective: In this study, we investigated the efficacy of VNS in drug-resistant epilepsy associated with structural brain lesions (SBLs). Methods: We retrospectively analyzed the effect of VNS on 25 patients diagnosed with intractable epilepsy-associated SBL, and compared the results to 19 patients with intractable epilepsy and normal neuroimaging. All patients underwent VNS insertion at the National Neurosciences Institute, King Fahad Medical City (Riyadh, Saudi Arabia) between 2008 and 2018. Results: The response rate (RR) for patients with drug-resistant epilepsy-associated SBL was 24% after 3 months, 36% after 6 months, and 48% after 1 year, reaching 76% over time. The mean follow-up period was 63.3 months. For non-SBL patients, the RR was 10.5% after 3 months, 36.8% after 6 months, and 47.4% after 1 year, reaching 73.7% over time. The mean follow-up period was 59.2 months. There was no statistically significant difference between the two groups regarding RR, VNS settings, and other parameters, including anti-epileptic drug use and demographics data. Conclusion: VNS is strongly considered for intractable epilepsy in SBL patients, especially if they are not candidates for surgical intervention. Over time, those patients will receive increased benefits from VNS therapy.

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Heart rate variability analysis for the identification of the preictal interval in patients with drug-resistant epilepsy

Scientific Reports ◽

10.1038/s41598-021-85350-y ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Adriana Leal ◽

Mauro F. Pinto ◽

Fábio Lopes ◽

Anna M. Bianchi ◽

Jorge Henriques ◽

...

Keyword(s):

Heart Rate ◽

Heart Rate Variability ◽

Linear Time ◽

Epileptic Seizures ◽

Heart Rate Variability Analysis ◽

Drug Resistant ◽

Clustering Methods ◽

Temporal Lobe Seizures ◽

New Perspective ◽

Drug Resistant Epilepsy

AbstractElectrocardiogram (ECG) recordings, lasting hours before epileptic seizures, have been studied in the search for evidence of the existence of a preictal interval that follows a normal ECG trace and precedes the seizure’s clinical manifestation. The preictal interval has not yet been clinically parametrized. Furthermore, the duration of this interval varies for seizures both among patients and from the same patient. In this study, we performed a heart rate variability (HRV) analysis to investigate the discriminative power of the features of HRV in the identification of the preictal interval. HRV information extracted from the linear time and frequency domains as well as from nonlinear dynamics were analysed. We inspected data from 238 temporal lobe seizures recorded from 41 patients with drug-resistant epilepsy from the EPILEPSIAE database. Unsupervised methods were applied to the HRV feature dataset, thus leading to a new perspective in preictal interval characterization. Distinguishable preictal behaviour was exhibited by 41% of the seizures and 90% of the patients. Half of the preictal intervals were identified in the 40 min before seizure onset. The results demonstrate the potential of applying clustering methods to HRV features to deepen the current understanding of the preictal state.

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A prospective controlled study about sleep disorders in drug resistant epilepsy

Sleep Medicine ◽

10.1016/j.sleep.2020.09.001 ◽

2020 ◽

Vol 75 ◽

pp. 434-440

Author(s):

Melanie Bergmann ◽

Manuela Prieschl ◽

Ambra Stefani ◽

Anna Heidbreder ◽

Gerald Walser ◽

...

Keyword(s):

Sleep Disorders ◽

Controlled Study ◽

Drug Resistant ◽

Drug Resistant Epilepsy ◽

Prospective Controlled Study

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Utility of diffusion tensor imaging studies linked to neuronavigation and other modalities in repeat hemispherotomy for intractable epilepsy

Journal of Neurosurgery Pediatrics ◽

10.3171/2015.7.peds15101 ◽

2016 ◽

Vol 17 (4) ◽

pp. 483-490 ◽

Cited By ~ 10

Author(s):

Erin N. Kiehna ◽

Elysa Widjaja ◽

Stephanie Holowka ◽

O. Carter Snead ◽

James Drake ◽

...

Keyword(s):

Diffusion Tensor Imaging ◽

Diffusion Tensor ◽

Intractable Epilepsy ◽

Seizure Freedom ◽

Rasmussen’S Encephalitis ◽

Initial Procedure ◽

Surgical Options ◽

Failed Surgery ◽

Association Fibers

OBJECT Hemispherectomy for unilateral, medically refractory epilepsy is associated with excellent long-term seizure control. However, for patients with recurrent seizures following disconnection, workup and investigation can be challenging, and surgical options may be limited. Few studies have examined the role of repeat hemispherotomy in these patients. The authors hypothesized that residual fiber connections between the hemispheres could be the underlying cause of recurrent epilepsy in these patients. Diffusion tensor imaging (DTI) was used to test this hypothesis, and to target residual connections at reoperation using neuronavigation. METHODS The authors identified 8 patients with recurrent seizures following hemispherectomy who underwent surgery between 1995 and 2012. Prolonged video electroencephalography recordings documented persistent seizures arising from the affected hemisphere. In all patients, DTI demonstrated residual white matter association fibers connecting the hemispheres. A repeat craniotomy and neuronavigation-guided targeted disconnection of these residual fibers was performed. Engel class was used to determine outcome after surgery at a minimum of 2 years of follow-up. RESULTS Two patients underwent initial hemidecortication and 6 had periinsular hemispherotomy as their first procedures at a median age of 9.7 months. Initial pathologies included hemimegalencephaly (n = 4), multilobar cortical dysplasia (n = 3), and Rasmussen's encephalitis (n = 1). The mean duration of seizure freedom for the group after the initial procedure was 32.5 months (range 6–77 months). In all patients, DTI showed limited but definite residual connections between the 2 hemispheres, primarily across the rostrum/genu of the corpus callosum. The median age at reoperation was 6.8 years (range 1.3–14 years). The average time taken for reoperation was 3 hours (range 1.8–4.3 hours), with a mean blood loss of 150 ml (range 50–250 ml). One patient required a blood transfusion. Five patients are seizure free, and the remaining 3 patients are Engel Class II, with a minimum follow-up of 24 months for the group. CONCLUSIONS Repeat hemispherotomy is an option for consideration in patients with recurrent intractable epilepsy following failed surgery for catastrophic epilepsy. In conjunction with other modalities to establish seizure onset zones, advanced MRI and DTI sequences may be of value in identifying patients with residual connectivity between the affected and unaffected hemispheres. Targeted disconnection of these residual areas of connectivity using neuronavigation may result in improved seizure outcomes, with minimal and acceptable morbidity.

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