Posts Tagged seizure frequency

[Abstract + References] Efficacy and Safety of Cannabidiol in Epilepsy: A Systematic Review and Meta-Analysis



Approximately one-third of patients with epilepsy presents seizures despite adequate treatment. Hence, there is the need to search for new therapeutic options. Cannabidiol (CBD) is a major chemical component of the resin of Cannabis sativa plant, most commonly known as marijuana. The anti-seizure properties of CBD do not relate to the direct action on cannabinoid receptors, but are mediated by a multitude of mechanisms that include the agonist and antagonist effects on ionic channels, neurotransmitter transporters, and multiple 7-transmembrane receptors. In contrast to tetra-hydrocannabinol, CBD lacks psychoactive properties, does not produce euphoric or intrusive side effects, and is largely devoid of abuse liability.


The aim of the study was to estimate the efficacy and safety of CBD as adjunctive treatment in patients with epilepsy using meta-analytical techniques.


Randomized, placebo-controlled, single- or double-blinded add-on trials of oral CBD in patients with uncontrolled epilepsy were identified. Main outcomes included the percentage change and the proportion of patients with ≥ 50% reduction in monthly seizure frequency during the treatment period and the incidence of treatment withdrawal and adverse events (AEs).


Four trials involving 550 patients with Lennox–Gastaut syndrome (LGS) and Dravet syndrome (DS) were included. The pooled average difference in change in seizure frequency during the treatment period resulted 19.5 [95% confidence interval (CI) 8.1–31.0; p = 0.001] percentage points between the CBD 10 mg and placebo groups and 19.9 (95% CI 11.8–28.1; p < 0.001) percentage points between the CBD 20 mg and placebo arms, in favor of CBD. The reduction in all-types seizure frequency by at least 50% occurred in 37.2% of the patients in the CBD 20 mg group and 21.2% of the placebo-treated participants [risk ratio (RR) 1.76, 95% CI 1.07–2.88; p = 0.025]. Across the trials, drug withdrawal for any reason occurred in 11.1% and 2.6% of participants receiving CBD and placebo, respectively (RR 3.54, 95% CI 1.55–8.12; p = 0.003) [Chi squared = 2.53, degrees of freedom (df) = 3, p = 0.506; I2 = 0.0%]. The RRs to discontinue treatment were 1.45 (95% CI 0.28–7.41; p = 0.657) and 4.20 (95% CI 1.82–9.68; p = 0.001) for CBD at the doses of 10 and 20 mg/kg/day, respectively, in comparison to placebo. Treatment was discontinued due to AEs in 8.9% and 1.8% of patients in the active and control arms, respectively (RR 5.59, 95% CI 1.87–16.73; p = 0.002). The corresponding RRs for CBD at the doses of 10 and 20 mg/kg/day were 1.66 (95% CI 0.22–12.86; p = 0.626) and 6.89 (95% CI 2.28–20.80; p = 0.001). AEs occurred in 87.9% and 72.2% of patients treated with CBD and placebo (RR 1.22, 95% CI 1.11–1.33; p < 0.001). AEs significantly associated with CBD were somnolence, decreased appetite, diarrhea, and increased serum aminotransferases.


Adjunctive CBD in patients with LGS or DS experiencing seizures uncontrolled by concomitant anti-epileptic treatment regimens is associated with a greater reduction in seizure frequency and a higher rate of AEs than placebo.


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via Efficacy and Safety of Cannabidiol in Epilepsy: A Systematic Review and Meta-Analysis | SpringerLink

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[REVIEW] Epilepsy and Cannabis: A Literature Review – Full Text PDF


Epilepsy is considered to be one of the most common non-communicable neurological diseases especially in low to middle-income countries. Approximately one-third of patients with epilepsy have seizures that are resistant to antiepileptic medications. Clinical trials for the treatment of medically refractory epilepsy have mostly focused on new drug treatments, and result in a significant portion of subjects whose seizures remain refractory to medication. The off-label use of cannabis sativa plant in treating seizures is known since ancient times. The active ingredients of this plant are delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), the latter considered safer and more effective in treating seizures, and with less adverse psychotropic effects.

Clinical trials prior to two years ago have shown little to no significant effects of cannabis in reducing seizures. These trials seem to be underpowered, with a sample size less than 15. In contrast, more recent studies that have included over 100 participants showed that CBD use resulted in a significant reduction in seizure frequency. Adverse effects of CBD overall appear to be benign, while more concerning adverse effects (e.g., elevated liver enzymes) improve with continued CBD use or dose reduction.

In most of the trials, CBD is used in adjunct with epilepsy medication, therefore it remains to be determined whether CBD is itself antiepileptic or a potentiator of traditional antiepileptic medications. Future trials may evaluate the efficacy of CBD in treating seizures due to specific etiologies (e.g., post-traumatic, post-stroke, idiopathic).[…]

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[Abstract] Antiepileptic drug clearances during pregnancy and clinical implications for women with epilepsy


Objective To characterize the magnitude and time course of pregnancy-related clearance changes for different antiepileptic drugs (AEDs): levetiracetam, oxcarbazepine, topiramate, phenytoin, and valproate. A secondary aim was to determine if a decreased AED serum concentration was associated with increased seizure frequency.


Methods Women with epilepsy were enrolled preconception or early in pregnancy and prospectively followed throughout pregnancy and the first postpartum year with daily diaries of AED doses, adherence, and seizures. Study visits with AED concentration measurements occurred every 1–3 months. AED clearances in each trimester were compared to nonpregnant baseline using a mixed linear regression model, with adjustments for age, race, and hours postdose. In women on monotherapy, 2-sample t test was used to compare the ratio to target concentrations (RTC) between women with seizure worsening each trimester and those without.


Results AED clearances were calculated for levetiracetam (n = 18 pregnancies), oxcarbazepine (n = 4), topiramate (n = 10), valproate (n = 5), and phenytoin (n = 7). Mean maximal clearances were reached for (1) levetiracetam in first trimester (1.71-fold baseline clearance) (p = 0.0001), (2) oxcarbazepine in second trimester (1.63-fold) (p = 0.0001), and (3) topiramate in second trimester (1.39-fold) (p = 0.025). In 15 women on AED monotherapy, increased seizure frequency in the first, second, and all trimesters was associated with a lower RTC (p < 0.05).


Conclusion AED clearance significantly changes by the first trimester for levetiracetam and by the second trimester for oxcarbazepine and topiramate. Lower RTC was associated with seizure worsening. Early therapeutic drug monitoring and dose adjustment may be helpful to avoid increased seizure frequency.


via Antiepileptic drug clearances during pregnancy and clinical implications for women with epilepsy | Neurology

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[WEB SITE] The effects of vitamin D on epilepsy

Student NT editor Rebecca Hammond says we should be mindful of the importance of vitamin D.
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“Where has the sun gone?” and “Will we have a good summer?” are questions I and others living in Scotland have often asked ourselves.


Growing up, I always remembered vitamin D as being the ’sunshine vitamin’. However, since starting my nursing training, I have been interested in researching the importance and health benefits of vitamin D.

In the UK, we are encouraged to eat a healthy, balanced diet. This provides all needed nutrients excluding vitamin D. Oily fish has been identified as a significant source, whereas meat, egg yolks and other fortified foods, including margarine and some breakfast cereals, provide smaller amounts.

The prevalence of vitamin D deficiency in the UK is significant: during the winter, 30-40% of people in the general population and belonging to all age groups are vitamin D deficient. Near the end of the summer months, 13% of adolescents and 8% of adults are vitamin D deficient.

The intake of vitamin D and its status are imperative for overall health and wellbeing, as well as for bone and calcium-phosphate metabolism.

Without adequate vitamin D, bones may become brittle, thin or misshapenLiterature suggests that sufficient vitamin D status is protective against autoimmune diseases, cardiovascular disease, musculoskeletal disorders, neurocognitive dysfunction and respiratory infections.

Compared to the general population, individuals with learning disabilities have an increased risk of developing low bone mineral density, osteopenia, osteoporosis and fractures. This is mainly attributed to the higher prevalence of obesity or undernutrition, inactive lifestyles and polypharmacy.

Epilepsy is the most common neurological condition within the learning disability population. One in four people with a learning disability experience epilepsy, compared to one in five in the general population.

”The identified prevalence of vitamin D deficiencies among epilepsy patients is high”

Approximately, 30% of individuals with learning disabilities are prescribed anti-epileptic drugs (AEDs), an identified risk factor for fractures and low bone-mass density. Reasons for this have not been definitively known, but it could potentially be due to AEDs breaking down the body’s vitamin D stores at a higher degree than normal.

Consequently, this could result in AEDs causing a vitamin D deficiency, which could potentially lead to osteoporosis and osteomalaica and an increased risk of fractures.

The identified prevalence of vitamin D deficiencies among epilepsy patients is high, however, the number of research studies assessing the effect of vitamin D on seizure control is limited.

One of these research studies, conducted in 2012, measured vitamin D levels and through the administration of vitamin D3, normalised levels in 13 patients with pharmacoresistant epilepsy.

To identify whether vitamin D3 was impactful on seizure frequency, the study compared numbers of seizures during a 90-day period, prior and following treatment commencement. The study found the median seizure reduction to be 40% and concluded that normalisation of vitamin D levels can have an anticonvulsant effect.

Due to very little evidence on the effect of vitamin D on epilepsy, it is acknowledged that this area needs researched further. However, as nurses this is something we could be mindful of.


via The effects of vitamin D on epilepsy | Opinion | Nursing Times

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[WEB SITE] Health Beat: Slowing down seizures

MIAMI – Mark Weinberg has trouble remembering the car accident that changed his life at 16.

“My parents say I was in a coma for four days,” he shared.

Weinberg survived but suffered a severe brain injury and started having seizures every week.

“I’ll go up to someone and say, ‘Can you hold my hand? I think I’m having a seizure,'” he said.

Dr. Andres Kanner, the chief of the epilepsy division at the University of Miami’s Miller School of Medicine, said a seizure is like a short circuit in the brain.

“They can lose awareness of their surroundings and be unresponsive and they don’t know what’s happening around them,” Kanner explained.

Kanner said medication can control seizures in 70 percent of patients, but for Weinberg, that wasn’t the case.

“I think I’ve been on almost every medicine,” Weinberg said.

Now, new technology is helping patients like Weinberg. It’s called responsive neuro stimulation, or the RNS system.

“Imagine a pacemaker, which has a computer chip in it,” Kanner said.

The device made by Neuropace is implanted under the scalp and connected to the areas in the brain causing seizure activity.

“As it detects that abnormal pattern, it sends an electrical stimulation,” Kanner continued.

That stimulation prevents the seizure from happening. Since having the device implanted, Weinberg’s seizures have been cut in half.

“Even if I do have them, they’re shorter, so I’m not as scared as I used to be,” Weinberg said.

Now, he’s going to college, living a life with fewer seizures.

Kanner said studies show the device is safe and does not affect cognitive function. Kanner said in the first year, 30 to 40 percent of patients notice their seizure frequency may be cut in half.

via Health Beat: Slowing down seizures – WFMZ

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[WEB SITE] Slowing down seizures

MIAMI, Fla. (Ivanhoe Newswire) — According to the Epilepsy Foundation, one in 26 Americans will develop the seizure disorder at some point in their lives. Now, new technology is decreasing the frequency of seizures, helping patients live healthier lives.

Mark Weinberg has trouble remembering the car accident that changed his life at 16.

“My parents say I was in a coma for four days,” Weinberg shared.

Weinberg survived but suffered a severe brain injury and started having seizures every week.

“I’ll go up to someone and say can you hold my hand, I think I’m having a seizure,” he said.

Andres Kanner, MD, Chief of the Epilepsy Division at the University of Miami Miller says a seizure is like a short circuit in the brain.

Dr. Kanner explained, “They can lose awareness of their surroundings and be unresponsive and they don’t know what’s happening around them.”

Dr. Kanner says medication can control seizures in 70 percent of patients. But for Mark that wasn’t the case.

Weinberg said, “I think I’ve been on almost every medicine.”

Now new technology is helping patients like Mark. It’s called responsive neuro stimulation or the RNS system.

“Imagine a pacemaker, which has a computer chip in it,” said Dr. Kanner.

The device made by Neuropace is implanted under the scalp and connected to the areas in the brain causing seizure activity.

Dr. Kanner continued, “As it detects that abnormal pattern it sends an electrical stimulation.”

That stimulation prevents the seizure from happening. Since having the device implanted, Weinberg’s seizures have been cut in half.

“Even if I do have them they’re shorter so I’m not as scared as I used to be,” Weinberg told Ivanhoe.

Now he’s going to college, living a life with fewer seizures.

Dr. Kanner says studies show the device is safe and does not affect cognitive function. Dr. Kanner says in the first year 30 to 40 percent of patients notice their seizure frequency may be cut in half.


via Slowing down seizures – KTVA 11 – The Voice of Alaska

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[REVIEW] Evidence for cannabis and cannabinoids for epilepsy: a systematic review of controlled and observational evidence – Full Text


Review evidence for cannabinoids as adjunctive treatments for treatment-resistant epilepsy. Systematic search of Medline, Embase and PsycINFO was conducted in October 2017. Outcomes were: 50%+ seizure reduction, complete seizure freedom; improved quality of life (QoL). Tolerability/safety were assessed by study withdrawals, adverse events (AEs) and serious adverse events (SAEs). Analyses were conducted in Stata V.15.0. 36 studies were identified: 6 randomised controlled trials (RCTs), 30 observational studies. Mean age of participants was 16.1 years (range 0.5–55 years). Cannabidiol (CBD) 20 mg/kg/day was more effective than placebo at reducing seizure frequency by 50%+(relative risk (RR) 1.74, 95% CI 1.24 to 2.43, 2 RCTs, 291 patients, low Grades of Recommendation, Assessment, Development and Evaluation (GRADE) rating). The number needed to treat for one person using CBD to experience 50%+ seizure reduction was 8 (95% CI 6 to 17). CBD was more effective than placebo at achieving complete seizure freedom (RR 6.17, 95% CI 1.50 to 25.32, 3 RCTs, 306 patients, low GRADE rating), and improving QoL (RR 1.73, 95% CI 1.33 to 2.26), however increased risk of AEs (RR 1.24, 95% CI 1.13 to 1.36) and SAEs (RR 2.55, 95% CI 1.48 to 4.38). Pooled across 17 observational studies, 48.5% (95% CI 39.0% to 58.1%) of patients reported 50%+ reductions in seizures; in 14 observational studies 8.5% (95% CI 3.8% to 14.5%) were seizure-free. Twelve observational studies reported improved QoL (55.8%, 95% CI 40.5 to 70.6); 50.6% (95% CI 31.7 to 69.4) AEs and 2.2% (95% CI 0 to 7.9) SAEs. Pharmaceutical-grade CBD as adjuvant treatment in paediatric-onset drug-resistant epilepsy may reduce seizure frequency. Existing RCT evidence is mostly in paediatric samples with rare and severe epilepsy syndromes; RCTs examining other syndromes and cannabinoids are needed.


The International League Against Epilepsy (ILAE) defines epilepsy as a disease of the brain,  diagnosis of which requires: (a) at least two unprovoked seizures occurring >24 hours apart; (b) one unprovoked seizure and a probability for further seizures of at least 60%, occurring over the next 10 years or (c) the diagnosis of an epilepsy syndrome.1 Between 70% and 80% of patients with new-onset epilepsy achieve complete seizure control using antiepileptic drugs such as valproate or carbamazepine.2 In 20%–30% who are drug-resistant,3 4 there is great interest in investigating novel agents to reduce seizure frequency and severity. For the purposes of this review, the ILAE’s definition of drug-resistant epilepsy—the failure of adequate trials of two tolerated and appropriately chosen and used antiepileptic drugs (AEDs) schedules (as either monotherapies or in combination) to achieve seizure freedom5—is used. For the 30% of patients who experience drug-resistant epilepsy, the efficacy of alternative and adjunctive therapies is likely to be of great interest.

Preclinical studies suggest that naturally occurring cannabinoids (phytocannabinoids) have anticonvulsant effects which are mediated by the endocannabinoid system.6 Cannabidiol (CBD) and cannabidivarin have shown antiseizure effects in both in vivo and in vitro models. In contrast to tetrahydrocannabinol (THC), CBD does not produce euphoric or intrusive psychoactive side effects when used to treat seizures.7 Cannabinoids have been proposed as an adjunctive treatment for epilepsy7 and parents of children with epilepsy report using CBD products.8–10 There are a number of phase III human trials underway of CBD as an adjunctive therapy for treatment resistant paediatric and adult epilepsies.11 12

Recently Israel, the Netherlands, Germany and Canada have legislated to allow the use of cannabinoids for medicinal purposes. In Australia, Federal and state legislation that allows doctors to prescribe cannabinoids is being implemented. Systematic reviews are required to synthesise the evidence for individual conditions for which cannabinoids may be used to inform clinical practice and patient guidance.

This review considers evidence on the safety and efficacy of cannabinoids as adjunctive treatments for drug-resistant epilepsy. As previous reviews noted a lack of controlled studies,13 14 we synthesised evidence from randomised controlled trials (RCTs) and observational studies.[…]

Continue —> Evidence for cannabis and cannabinoids for epilepsy: a systematic review of controlled and observational evidence | Journal of Neurology, Neurosurgery & Psychiatry

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[ARTICLE] Atmospheric Pressure and Seizure Frequency in the Epilepsy Unit: Preliminary Observations – Full Text


Summary: Objective: To demonstrate that seizure frequency in patients undergoing video EEG telemetry does not correlate with atmospheric pressure (AP) changes.

Method: Historical automated AP data from weather stations in the Seattle Metropolitan area were correlated to seizure frequency and type in consecutive patients undergoing video EEG telemetry at our institution from April 2005–April 2006. Daily maximum, minimum and range of atmospheric pressures were correlated to daily number of events (seizures, pseudoseizures, unknown) per patient. Alternatively, whether or not events occurred during a change of greater or less than 5.5 mBar per day were used to evaluate odds ratios of events occurring.

Results: Of 191 patients, 96 were diagnosed with epilepsy, 60 with pseudoseizures, and 40 had different diagnoses. A total of 159 seizures, 59 pseudoseizures, and 40 unknown events occurred. No correlation between daily mean, maximum or minimum pressure change with seizure or other event frequency was seen. With increased daily AP range an increase in daily seizure per known seizure patient occurred (P = 0.03). Patients with known epilepsy showed an OR of a seizure occurring of 2.80 (95% CI 1.22–6.42 P = 0.02) if pressure changed more than 5.5 mBar that day.

Conclusions: Surprisingly, in patients with known epilepsy, increased seizure frequency occurred with changes in barometric pressure, particularly over 5.5 mBar range per day. Speculative mechanisms of AP change on seizure susceptibility are discussed.


One of the great riddles in epilepsy is why some patients develop seizures after hyperventilation (HV). Innate HV responses occur in various settings including high altitudes, diminished partial pressures of O2, elevations in CO2, and increased metabolic demand (West, 2004). Atmospheric pressures (AP) directly influence partial pressures of O2 and furthermore, pressure alterations are associated with human seizures, though mainly triggered within artificial environments of high-pressure hyperbaric chambers (Boldrey and Millichap, 1966; Hampson and Atik, 2003; Yildiz, 2004). Despite this observation, few objective studies specifically address if differing atmospheric pressures alter seizure frequencies. The studies that have, utilized self-reported diaries or ER presentations (Asensi et al., 1977).

We hypothesized daily atmospheric pressures would not alter seizure frequency in patients undergoing video EEG telemetry (VEEG) at our institution. We set out to test this hypothesis using public access Seattle-specific atmospheric data and our VEEG telemetry event frequency data.


Consecutive hourly atmospheric pressure data spanning April 2005–April 2006 from automated National Oceanographic and Atmospheric Administration stations (NOAA) were downloaded into a statistical package (SPSS V 11.0.1, Chicago, IL). Data from two stations were used: the first, a sea-level buoy in Seattle’s Elliot Bay approximately a half-mile west and three-hundred feet below our telemetry unit (47°36′18′ N 122°20′18′ W) and the second a land- based station three miles nor-nor-west and 290 feet below our telemetry unit (47°39′44″ N 122°26′09″ W) (National data buoy center, 2006). Data were parsed to include daily high, low, mean, and range of atmospheric pressure recordings for the corresponding day two of VEEG. The data were not corrected for altitude as we assumed the correction would be a constant and of no meaning in correlative analysis.

Seizure frequency and other data from day two, by our definition Tuesday, of consecutive patients undergoing VEEG were collected over a year. Day two of telemetry was chosen so as to maximize patient numbers and minimize effects of residual antiepileptic drugs (AED). AED taper regimens are patient-dependent in our unit, historically 95% of our patients, including those with suspected pseudoseizures, have their anticonvulsant medications stopped at admission day one. The average length of stay in our VEEG unit is four days. By choosing day two various potential confounders can be essentially randomized: these include alternative drug taper regimens, and minimization of patients preparing for hospital discharge and as such only undergoing a half day of VEEG. The latter consideration becomes particularly important when including our control pseudoseizure group, who do not stay as long as our epilepsy patients. Collected values included the number of patients monitored, the number of seizures each patient had, and the classification of seizure (epileptic, psychogenic, or unknown). Events were classified by multidisciplinary conference review; if there was any uncertainty as to an event it was classified as an unknown event.

Pearson’s rank sum correlations of mean, maximum, minimum, and atmospheric pressure ranges with event frequency were performed (Table 1) as were correlations with event frequency per group (i.e., number of seizures per patient with epilepsy on that day) (Figure 1). In order to minimize effects of multiple sampling errors or outlying effects from patients with extremely frequent seizure, odds ratios (OR) were also calculated. Either the median pressure range (5.5 mBar) or one standard deviation above median (9.3 mBar) served as dichotomization points i.e., daily range ≤5.5 mBar, or >5.6 mBar. This was used to then classify if patient with known epilepsy, pseudoseizures, or unknown spells had an event that day. The p-values were conservatively calculated using two-tailed Fisher’s exact. Additional study of daily atmospheric pressure trend (rising greater than 4 mBar per day, declining by more than 4 mBar per day or no obvious trend in rising or falling pressure) were similarly evaluated. Significance was determined if p < 0.05. Our institutional review board approved this study. […]

Figure 1.

Figure 1. Scatterplot of daily seizures per epilepsy patient plotted against range of barometric pressure in 24 period.

Continue —>  Atmospheric Pressure and Seizure Frequency in the Epilepsy Unit: Preliminary Observations – Doherty – 2007 – Epilepsia – Wiley Online Library


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[ARTICLE] Cathodal transcranial direct-current stimulation for treatment of drug-resistant temporal lobe epilepsy: A pilot randomized controlled trial – Full Text HTML



To investigate the effect of cathodal transcranial direct-current stimulation (c-tDCS) on seizure frequency in patients with drug-resistant temporal lobe epilepsy (TLE).


Twenty-nine patients with drug-resistant TLE participated in this study. They were randomized to experimental or sham group. Twenty participants (experimental group) received within-session repeated c-tDCS intervention over the affected temporal lobe, and nine (sham group) received sham tDCS. Paired-pulse transcranial magnetic stimulation was used to assess short interval intracortical inhibition (SICI) in primary motor cortex ipsilateral to the affected temporal lobe. SICI was measured from motor evoked potentials recorded from the contralateral first dorsal interosseous muscle. Adverse effects were monitored during and after each intervention in both groups. A seizure diary was given to each participant to complete for 4 weeks following the tDCS intervention. The mean response ratio was calculated from their seizure rates before and after the tDCS intervention.


The experimental group showed a significant increase in SICI compared to the sham group (F = 10.3, p = 0.005). None of the participants reported side effects of moderate or severe degree. The mean response ratio in seizure frequency was −42.14% (standard deviation [SD] 35.93) for the experimental group and −16.98% (SD 52.41) for the sham group.


Results from this pilot study suggest that tDCS may be a safe and efficacious nonpharmacologic intervention for patients with drug-resistant TLE. Further evaluation in larger double-blind randomized controlled trials is warranted.

Key Points

  • Within-session repeated (9-20-9 protocol) c-tDCS has shown no or minimal side effects in patients with drug-resistant temporal lobe epilepsy
  • Cortical excitability was reduced, as measured by SICI, after one application of c-tDCS using the 9-20-9 protocol in patients with drug-resistant temporal lobe epilepsy
  • Seizure rates reduced by 42% after one application of c-tDCS using the 9-20-9 protocol in patients with drug-resistant temporal lobe epilepsy
Epilepsy impacts 50 million people (1% of the population) worldwide.[1] Management for patients with epilepsy includes antiepileptic drugs (AEDs), and for some patients with drug-resistant seizures, surgery. Temporal lobe epilepsy (TLE) is often resistant to AEDs,[2] and >40% of patients with epilepsy have adverse reactions to AEDs. Removing the epileptogenic regions surgically is not always feasible for patients, and the outcome is not ideal in 30–50% of cases.[3] Consequently, alternative methods of seizure control warrant more investigation.

The excitability of the γ-aminobutyric acid (GABA)ergic intracortical inhibitory circuits in primary motor cortex (M1) can be assessed noninvasively in humans by paired-pulse transcranial magnetic stimulation (TMS). In this technique, two stimuli are delivered 1–5 msec apart through the same coil. The first stimulus is subthreshold for a motor response; however, it activates intracortical inhibition (ICI) circuits and reduces the size of the motor evoked potentials (MEPs) elicited by the second stimulus, which is supra-threshold for a motor response.[4] It has been shown that ICI measured using this method reflects the cortical activity of GABAergic interneurons in the M1 area.[5] This inhibition is termed short-interval intracortical inhibition or SICI.

ICI circuits have been assessed extensively with a paired-pulse paradigm in patients with epilepsy.[6-8] Several studies on drug-naive patients with focal epilepsy showed a decrease in SICI in the ipsilateral hemisphere.[9-15] Badawy et al. showed increased M1 excitability and decreased SICI in 35 patients with focal epilepsy 24 h before and after a seizure.

Transcranial direct current stimulation (tDCS) is a well-established cortical stimulation method that can be used noninvasively to modulate neuronal excitability in humans.[16] In this technique, a low intensity current (1–2 mA) is used that can affect the membrane potentials in two ways. Cathodal tDCS (c-tDCS) hyperpolarizes the resting membrane potentials, whereas anodal tDCS acts toward depolarization.[16] Modification of seizure network excitability by tDCS is a potentially valuable noninvasive alternative for reducing the excitability of this abnormal network in patients with epilepsy and thereby reducing the seizure rates in this population.

The aim of this study was to examine the effects of this noninvasive therapeutic approach on seizure frequency in this group of patients. We hypothesized that compared to sham tDCS, application of c-tDCS over the temporal lobe in patients with drug-resistant TLE, decreases seizure frequency and increases intracortical inhibition in the ipsilateral M1 area.

Continue —> Cathodal transcranial direct-current stimulation for treatment of drug-resistant temporal lobe epilepsy: A pilot randomized controlled trial – Zoghi – 2016 – Epilepsia Open – Wiley Online Library

Figure 1.

Experimental set-up. All participants received one session of c-tDCS or sham tDCS paradigm (9-20-9 protocol). The active surface electrode (cathode) was placed over the temporal lobe in the affected hemisphere. The return (anode) electrode was placed over the supraorbital area contralateral to the stimulated hemisphere. SICI was assessed before and after tDCS intervention. Seizure rates were recorded for 4 weeks after tDCS intervention.

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