Pilot Safety and Feasibility Study of Non-invasive Limb Proprioceptive Cerebellar Stimulation for Epilepsy

Cerebellar stimulation reduces seizures in animals and in humans with drug-resistant epilepsy. In a pilot safety and feasibility study, we applied continuous cutaneous vibratory stimulation (limb proprioceptive cerebellar stimulation) to foot limb proprioceptive receptors to activate cerebellar, pontine, and thalamic structures in drug-resistant epilepsy patients for 8-h nocturnally up to 6-months after a 4-week pre-treatment control baseline. Seizure frequency was evaluated during the baseline control period, and at 6, 12, and 24 weeks after the control recordings. Five-subjects completed at least the first 6-week treatment. At 12-weeks, the median reduction in seizure frequency was −27.8% (mean reduction = −22.3%). Two subjects continued for 24 weeks, with a decline of −44.1 and −45.4%. This pilot study provides support for further clinical studies into the safety and efficacy of limb proprioceptive cerebellar stimulation for epilepsy.

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Vagus nerve stimulation for drug-resistant epilepsy

Practical Neurology ◽

10.1136/practneurol-2019-002210 ◽

2019 ◽

Vol 20 (3) ◽

pp. 189-198 ◽

Cited By ~ 1

Author(s):

Laura Pérez-Carbonell ◽

Howard Faulkner ◽

Sean Higgins ◽

Michalis Koutroumanidis ◽

Guy Leschziner

Keyword(s):

Vagus Nerve ◽

Seizure Frequency ◽

Nerve Stimulation ◽

Vagus Nerve Stimulation ◽

Therapeutic Option ◽

Drug Resistant ◽

Drug Resistant Epilepsy ◽

Randomised Controlled

Vagus nerve stimulation (VNS) is a neuromodulatory therapeutic option for drug-resistant epilepsy. In randomised controlled trials, VNS implantation has resulted in over 50% reduction in seizure frequency in 26%–40% of patients within 1 year. Long-term uncontrolled studies suggest better responses to VNS over time; however, the assessment of other potential predictive factors has led to contradictory results. Although initially designed for managing focal seizures, its use has been extended to other forms of drug-resistant epilepsy. In this review, we discuss the evidence supporting the use of VNS, its impact on seizure frequency and quality of life, and common adverse effects of this therapy. We also include practical guidance for the approach to and the management of patients with VNS in situ.

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Seizure frequency and social outcome in drug resistant epilepsy patients who do not undergo epilepsy surgery

Seizure ◽

10.1016/j.seizure.2011.04.010 ◽

2011 ◽

Vol 20 (7) ◽

pp. 580-582 ◽

Cited By ~ 8

Author(s):

Mar Carreño ◽

Juan Luis Becerra ◽

Joaquín Castillo ◽

Iratxe Maestro ◽

Antonio Donaire ◽

...

Keyword(s):

Seizure Frequency ◽

Epilepsy Surgery ◽

Drug Resistant ◽

Social Outcome ◽

Drug Resistant Epilepsy

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Topiramate Effectiveness as Add-on Therapy in Bulgarian Patients with Drug-resistant Epilepsy

Folia Medica ◽

10.3897/folmed.62.e50175 ◽

2020 ◽

Vol 62 (4) ◽

pp. 712-722

Author(s):

Ekaterina Viteva ◽

Zahari Zahariev

Keyword(s):

Adverse Events ◽

Seizure Frequency ◽

Dynamic Assessment ◽

University Hospital ◽

Drug Resistant ◽

Seizure Severity ◽

Impaired Awareness ◽

Eeg Recordings ◽

Drug Resistant Epilepsy ◽

Stable Improvement

Introduction: There are no reliable prospective studies on the effectiveness of topiramate in Bulgarian adult patients with drug-resistant epilepsy. Aim: The aim of the study was to conduct an open, prospective study on various aspects of topiramate (TPM) effectiveness in Bulgarian patients with drug-resistant epilepsy.  Patients and methods: The study included patients with epilepsy who attended the Clinic of Neurology at the University Hospital in Plovdiv, Bulgaria. Patients completed diaries for seizure frequency, seizure severity, and adverse events. There were regular documented visits at 3 or 6 months during the first year of TPM treatment and at 6 months afterwards, with a dynamic assessment of seizure fre-quency, severity, adverse events, and EEG recordings.  Results: TPM was used as an add-on treatment in 120 patients (69 males, mean age 37 years). There was a relatively mild and stable dynamic improvement of seizure severity, a satisfactory seizure frequency reduction in 37% of participants, a stable mean seizure fre-quency reduction (47%) from month 6 to month 24 of treatment and a stable responder rate (48-51%) during the same period. New seizure types (focal with impaired awareness with/without evolution to bilateral tonic-clonic seizures) occurred in 5 patients. There were adverse events (dizziness/vertigo, irritability, speech disturbances, memory impairment, concentration problems, tremor, loss of appe-tite and weight, weakness, numbness, bradypsychia, confusion, visual hallucinations, sleepiness, insomnia, headache, itching, unstable gait, nausea, and vomiting) in 20% of patients.  Conclusions: TPM treatment is associated with low and stable improvement of seizure severity, good and stable improvement of sei-zure frequency, possible worsening of seizure control and appearance of new seizure types, good safety and tolerability.

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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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Serum level of C-reactive protein and interleukin-6 in children with drug-resistant epilepsy

European Journal of Inflammation ◽

10.1177/2058739218808165 ◽

2018 ◽

Vol 16 ◽

pp. 205873921880816 ◽

Cited By ~ 1

Author(s):

Mohamed M Elwan ◽

Nirmeen A Kishk ◽

Rasha A El-Kapany ◽

Ibrahim E Al-Ahmer ◽

Ahmed Elkady

Keyword(s):

Seizure Frequency ◽

Interleukin 6 ◽

Age Of Onset ◽

Serum Levels ◽

Control Group ◽

Drug Resistant ◽

C Reactive Protein ◽

Mri Findings ◽

Reactive Protein ◽

Drug Resistant Epilepsy

There is increasing evidence that chronic inflammation affects the pathophysiology of epilepsy, especially the drug-resistant type. Drug-resistant epilepsy is a challenging condition, because of the difficulties in its management, and its unclear epileptogenesis. This study is looking at C-reactive protein (CRP) and interleukin-6 (IL-6) levels in those with drug-resistant epilepsy and the correlation of these levels with seizure frequency. Hence, 40 children with drug-resistant epilepsy were included in this study and compared with 20 healthy volunteers (as a control group). Participants were aged between 5 and 15 years. Patients were divided into two subgroups, those with daily seizures (Group A1) and those with monthly seizures (Group A2). Serum levels of CRP and IL-6 were measured in all participants. The clinical characteristics, electroencephalography, and magnetic resonance imaging (MRI) findings were then compared. CRP levels were significantly higher in Group A1, at 21.88–93.29 mg/L than both Group A2 and the control group, at 3.02–40.37 mg/L and 2.23–13.18 mg/L, P < 0.01 and P < 0.001, respectively. The IL-6 levels were also significantly higher in Group A1, at 153.60–597.80 ng/L than in both Group A2 and the control group, at 97.40–232.50 ng/L and 12.00–96.30 ng/L, P < 0.01 and P < 0.001, respectively. Significantly higher levels of CRP and IL-6 were associated with earlier age of onset ( P < 0.01), seizure frequency ( P < 0.05), and the frequency of status epilepticus ( P < 0.01). Moreover, frequent-generalized motor seizures are correlated with elevated CRP and IL-6 levels. As a result, this systemic inflammatory reaction in children may contribute to drug-resistant seizure and potentially could be used as biomarkers to be correlated with disease severity and prognosis.

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Seizure frequency reduction after posteromedial hypothalamus deep brain stimulation in drug-resistant epilepsy associated with intractable aggressive behavior

Epilepsia ◽

10.1111/epi.13025 ◽

2015 ◽

Vol 56 (7) ◽

pp. 1152-1161 ◽

Cited By ~ 16

Author(s):

Juan C. Benedetti-Isaac ◽

Martin Torres-Zambrano ◽

Andres Vargas-Toscano ◽

Esther Perea-Castro ◽

Gabriel Alcalá-Cerra ◽

...

Keyword(s):

Deep Brain Stimulation ◽

Aggressive Behavior ◽

Seizure Frequency ◽

Brain Stimulation ◽

Drug Resistant ◽

Drug Resistant Epilepsy ◽

Deep Brain

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Seizure frequency can be reduced by changing intracranial pressure: A case report in drug-resistant epilepsy

Epilepsy & Behavior Case Reports ◽

10.1016/j.ebcr.2017.12.005 ◽

2018 ◽

Vol 10 ◽

pp. 14-17 ◽

Cited By ~ 4

Author(s):

Daiki Uchida ◽

Ayataka Fujimoto ◽

Tomohiro Yamazoe ◽

Takamichi Yamamoto ◽

Hideo Enoki

Keyword(s):

Case Report ◽

Intracranial Pressure ◽

Seizure Frequency ◽

Drug Resistant ◽

Drug Resistant Epilepsy

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Interleukin-1β in peripheral monocytes is associated with seizure frequency in pediatric drug-resistant epilepsy

Journal of Neuroimmunology ◽

10.1016/j.jneuroim.2021.577475 ◽

2021 ◽

pp. 577475

Author(s):

Gaku Yamanaka ◽

Tomoko Takamatsu ◽

Shinichiro Morichi ◽

Takashi Yamazaki ◽

Izuru Mizoguchi ◽

...

Keyword(s):

Seizure Frequency ◽

Interleukin 1Β ◽

Drug Resistant ◽

Pediatric Drug ◽

Drug Resistant Epilepsy

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Imaging the Extent and Location of Spatiotemporally Distributed Epileptiform Sources from MEG Measurements

10.1101/2021.11.09.467915 ◽

2021 ◽

Author(s):

Xiyuan Jiang ◽

Shuai Ye ◽

Abbas Sohrabpour ◽

Anto Bagic ◽

Bin He

Keyword(s):

Focal Epilepsy ◽

Real Data ◽

Drug Resistant ◽

Interictal Spikes ◽

Source Imaging ◽

Non Invasive ◽

Eeg Source Imaging ◽

Surgical Evaluation ◽

Extended Sources ◽

Drug Resistant Epilepsy

Non-invasive MEG/EEG source imaging provides valuable information about the epileptogenic brain areas which can be used to aid presurgical planning in focal epilepsy patients suffering from drug-resistant seizures. However, the source extent estimation for electrophysiological source imaging remains to be a challenge and is usually largely dependent on subjective choice. Our recently developed algorithm, fast spatiotemporal iteratively reweighted edge sparsity minimization (FAST-IRES) strategy, has been shown to objectively estimate extended sources from EEG recording, while it has not been applied to MEG recordings. In this work, through extensive numerical experiments and real data analysis in a group of focal drug-resistant epilepsy patients interictal spikes, we demonstrated the ability of FAST-IRES algorithm to image the location and extent of underlying epilepsy sources from MEG measurements. Our results indicate the merits of FAST-IRES in imaging the location and extent of epilepsy sources for pre-surgical evaluation from MEG measurements.

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Transcutaneous Vagus Nerve Stimulation

European Neurological Review ◽

10.17925/enr.2011.06.04.254 ◽

2011 ◽

Vol 6 (4) ◽

pp. 254 ◽

Cited By ~ 43

Author(s):

Jens Ellrich ◽

Keyword(s):

Vagus Nerve ◽

Nerve Stimulation ◽

Vagus Nerve Stimulation ◽

Drug Resistant ◽

Non Invasive ◽

Transcutaneous Vagus Nerve Stimulation ◽

The Common ◽

Myelinated Fibres ◽

Drug Resistant Epilepsy ◽

Intended Use

Invasive vagus nerve stimulation (VNS) is an approved treatment for drug-resistant epilepsy. Besides its recognised clinical efficacy, there are major drawbacks, such as invasiveness and a great many side effects. Therefore there is a medical demand for transcutaneous VNS (t-VNS®), which combines selective, non-invasive access to vagus nerve afferents with a low risk profile. Both treatments excite thick myelinated fibres of vagus nerve branches that project to the nucleus of the solitary tract in the brainstem. Preclinical data emphasise the equivalent anticonvulsive effects of both methods. Based upon the common mode of action and the first clinical data, the t-VNS device received Conformité Européenne (CE) approval. Besides the approved intended use for drug-resistant epilepsy and depression, a future clinical trial will address the efficacy of t-VNS in chronic pain.

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