Chronic high-frequency deep brain stimulation of the STN/SNr for progressive myoclonic epilepsy

Chronic high-frequency deep brain stimulation (DBS) may also be effective in patients with refractory epilepsy. A possible benefit has been postulated because of the connections that exist between the subthalamic nucleus (STN) and the superior colliculus. Individual case reports and pilot studies of successful DBS in different types of epilepsy have already been presented. Here, the case of a 39-year-old male with progressive myoclonic epilepsy is reported who remained severely impaired despite VNS and combined antiepileptic drug therapy. Bilateral DBS electrodes were implanted into the STN, followed by implantation of a neurostimulation system under general anesthesia. Adjustment and testing of the remaining contacts was done over several months postoperatively. Bilateral monopolar DBS reduced the intensity and frequency of seizures by 50%. The patient has so far been followed for 12 months. This is the first report of positive effects of DBS in progressive myoclonic epilepsy in an adult patient. A subsequent prospective study will have to investigate whether the STN or other target nuclei are most suitable for DBS in these types of epilepsy and which long-term results can be obtained.     

Familial Kufs' disease presenting as a progressive myoclonic epilepsy

Kufs' disease is the adult form of a group of disorders referred to as neuronal ceroid-lipofuscinosis or Batten's disease. We report here the clinical and anatomopathological features of two young brothers presenting with a progressive myoclonic epilepsy corresponding to type A of the disease according to Berkovic. The first clinical manifestations occurred before 20 years of age. Diagnosis was made in the older brother at autopsy and in the younger brother from a rectal biopsy. In addition to characteristic electron microscopic findings, enlarged neurons showed strong immunoreactivity against subunit c of mitochondrial ATP synthase which has been reported previously in only a few adult cases of neuronal ceroid-lipofuscinosis. An extensive review of the published cases underlines the rarity of this condition, particularly when onset is early. Received: 22 June 1999, Received in revised form: 29 December 1999, Accepted: 3 February 2000     

Chronic anterior thalamus stimulation for intractable epilepsy

PURPOSE: A significant number of patients with epilepsy remain poorly controlled despite antiepileptic medication (AED) treatment and are not eligible for resective surgery. Novel therapeutic methods are required to decrease seizure burden in this population. Several observations have indicated that the anterior thalamic region plays an important role in the maintenance and propagation of seizures. We investigated neuromodulation of the anterior thalamus by using deep-brain stimulation (DBS) in patients with intractable seizures. METHODS: Five patients with medically refractory epilepsy underwent stereotactic placement of and received stimulation through bilateral DBS electrodes in the anterior thalamus. RESULTS: Treatment showed a statistically significant decrease in seizure frequency, with a mean reduction of 54% (mean follow-up, 15 months). Two of the patients had a seizure reduction of > or =75%. No adverse effects were observed after DBS electrode insertion or stimulation. Unexpectedly, the observed benefits did not differ between stimulation-on and stimulation-off periods. CONCLUSIONS: DBS of the anterior thalamus is a safe procedure and possibly effective in patients with medically resistant seizures.     

Treatment of juvenile myoclonic epilepsy

Drug treatment of juvenile myoclonic epilepsy (JME) is mainly based on clinical experience and prospective and retrospective studies, with little evidence from randomized clinical trials. There are almost no head-to-head comparisons between old and new antiepileptic drugs (AEDs). Valproate is the drug of the first choice in men with JME. In women, lamotrigine (LTG) should be preferred regarding teratogenicity and side effects of valproate. Levetiracetam (LEV) is also effective. Recent data suggest that it may soon be used as first line treatment. Some AEDs can aggravate JME. In addition to AEDs, nonpharmacological treatments are important in JME. JME usually requires lifelong treatment because seizures nearly always return after withdrawal of therapy.     

Refractory epilepsy and deep brain stimulation

Up to one-third of all patients with epilepsy have epilepsy refractory to medical therapy. Surgical options include temporal lobectomy, focal neocortical resection, stereotactic lesioning and neurostimulation. Neurostimulatory options comprise vagal nerve stimulation, trigeminal nerve stimulation and deep brain stimulation (DBS). DBS enables structures in the brain to be stimulated electrically by an implanted pacemaker after a minimally invasive neurosurgical procedure and has become the therapy of choice for Parkinson’s disease refractory to or complicated by drug therapy. Here we review DBS for epilepsy, a powerful emerging treatment in the surgical armamentarium for drug refractory epilepsy, with a focus on extratemporal epilepsy.     

Benign myoclonic epilepsy in infancy followed by childhood absence epilepsy

Benign myoclonic epilepsy in infancy (BMEI) is a rare syndrome included among idiopathic generalized epilepsies (IGE) and syndromes with age-related onset. Recently, it has been shown that a few patients with BMEI later had other epilepsy types mainly IGE but never childhood absence epilepsy (CAE).We report a patient who at 11 months of age showed isolated myoclonic jerks occurring several times a day. The ictal video-EEG and polygraphic recording revealed generalized discharge of spike-wave (SW) lasting 1–2 s associated with isolated bilateral synchronous jerk involving mainly the upper limbs controlled by valproic acid (VPA).At 6 years and 8 months the child developed a new electroclinical feature recognized as CAE. The ictal EEG disclosed a burst of rhythmic 3 Hz generalized SW.Our case is the first patient with BMEI reported in the literature who later developed a CAE.This finding suggests a common neurobiological and genetic link between different age-related epileptic phenotypes.     

Deep brain stimulation in patients with refractory temporal lobe epilepsy

PURPOSE: This pilot study prospectively evaluated the efficacy of long-term deep brain stimulation (DBS) in medial temporal lobe (MTL) structures in patients with MTL epilepsy. METHODS: Twelve consecutive patients with refractory MTL epilepsy were included in this study. The protocol included invasive video-EEG monitoring for ictal-onset localization and evaluation for subsequent stimulation of the ictal-onset zone. Side effects and changes in seizure frequency were carefully monitored. RESULTS: Ten of 12 patients underwent long-term MTL DBS. Two of 12 patients underwent selective amygdalohippocampectomy. After mean follow-up of 31 months (range, 12-52 months), one of 10 stimulated patients are seizure free (>1 year), one of 10 patients had a >90% reduction in seizure frequency; five of 10 patients had a seizure-frequency reduction of > or =50%; two of 10 patients had a seizure-frequency reduction of 30-49%; and one of 10 patients was a nonresponder. None of the patients reported side effects. In one patient, MRI showed asymptomatic intracranial hemorrhages along the trajectory of the DBS electrodes. None of the patients showed changes in clinical neurological testing. Patients who underwent selective amygdalohippocampectomy are seizure-free (>1 year), AEDs are unchanged, and no side effects have occurred. CONCLUSIONS: This open pilot study demonstrates the potential efficacy of long-term DBS in MTL structures that should now be further confirmed by multicenter randomized controlled trials.     

Treatment of myoclonic dystonia with transcutaneous electrical nerve stimulation

The use of a transcutaneous nerve stimulator yielded positive results in a condition marked by involuntary movements (tremors and myoclonias) and dystonia. In the absence of clues to the pathophysiology of the myoclonus and dystonia, it is argued that transcutaneous stimulation induces an action on the neurotransmitters that inhibits neuromuscular function.

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Sommario L'uso dello stimolatore nervoso transcutaneo ha dato positivi risultati in una forma caratterizzata da movimenti involontari (tremori e mioclonie) e da distonia. Data la nostra mancanza di elementi interpretativi sulla patofisiologia del mioclono e della distonia gli AA. ritengono che la stimolazione transcutanea determina una azione sui neurotrasmettitori tale da inibire la disfunzione neuromuscolare.

     

Benign myoclonic epilepsy in infants: electroclinical features and long-term follow-up of 34 patients

PURPOSE: Benign myoclonic epilepsy in infants (BMEI) is a rare epileptic syndrome characterized only by generalized myoclonic seizures (MSs) in normal children during the first 2 years. Our aim was to assess the electroclinical features and the follow-up of this syndrome. METHODS: BMEI was confirmed by electroencephalogram (EEG) in four neuropediatric units in France between 1981 and 2002. Clinical and electroencephalographic findings at diagnosis and during the follow-up were collected. The Vineland scale or Wechsler scale or both were used to perform neuropsychological evaluations. RESULTS: We report 34 patients with BMEI characterized by MSs occurring many times a day. The ictal EEG showed a generalized discharge of polyspikes, polyspikes-and-waves, or spikes-and-waves. The interictal EEG was usually normal. A family history of febrile seizures (FSs) or epilepsy was noted in six patients. A history of FSs was noted in 11 patients. Eleven patients had reflex MSs. Monotherapy with valproic acid was effective in 23 of 30 treated patients. The onset of epilepsy was known in all patients. Four patients had seizures after the initial symptoms. Juvenile myoclonic epilepsy developed in two patients, and cryptogenic partial epilepsy in another. Neuropsychological outcome was evaluated in 20 patients (10 with Wechsler scales and 17 with the Vineland scale). Cognitive functions were normal in 17 patients, whereas developmental delay was observed in three others. CONCLUSIONS: BMEI is clinically characterized by myoclonic seizures involving the upper part of the body, occurring many times a day. The ictal EEG showed a generalized discharge of polyspikes, polyspikes-and-waves, or spikes-and-waves. The interictal EEG was usually normal. Reflex MSs were frequently observed, suggesting that two distinctive syndromes are not necessary. BMEI may be followed by juvenile myoclonic epilepsy. Despite a generally favorable neuropsychological outcome, mental retardation can be observed more frequently than in the general population.     

Peroneal muscular atrophy with ataxia and partial myoclonic epilepsy

Summary Two brothers, 17 and 11 years old, presented with pes cavus, absence of deep tendon reflexes, peripheral vibratory sensory loss, ataxia, tremor, nystagmus, dysarthria and partial myoclonic epilepsy. Electromyography showed severe slowing of motor conduction velocity in the lower extremities and increased distal latencies. A peroneal nerve biopsy showed absence of myelin sheath in most fibres resulting in numerous demyelinated nerve fibres. The father and seven uncles on the paternal side had pes cavus, hammer toes and moderate vibratory peripheral sensory loss. Three of seven siblings had slow motor conduction velocities on EMG. None had EEG abnormalities. Epilepsy started at an early age in both patients with myoclonic jerks of the right arm especially during sleep. EEG recordings were characterized by focal or diffuse epileptiform discharges. In the elder brother a partial motor epileptic status occurred with adversive seizures involving the right side of the body. He died of a broncopneumonia after 3 days of this epileptic status. Histopathological examination showed a severe demyelination of dentato-rubral pathways in the cerebellum and a partial degeneration of Goll and Burdach's tracts in the cervical spinal cord. The nosological classification of this syndrome is discussed and an autosomal dominant inheritance with incomplete penetrance or variable expressivity is suggested.

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Zusammenfassung Bei zwei Brüdern im Alter von 17 und 11 Jahren fanden sich Pes cavus, fehlende Muskeleigenreflexe, hochgradig gestörte Tiefensensibilität, eine Ataxie, ein Nystagmus, eine Dysarthrie und eine partielle Epilepsie mit myoklonischen Anfällen. Elektromyographisch ließ sich eine hochgradige Verlangsamung der motorischen Erregungsleitung an den unteren Extremitäten mit verlängerter distaler Latenz nachweisen. Eine Biopsie des Nervus peronaeus ergab einen vollständigen Myelinverlust zahlreicher Fasern. Sowohl der Vater wie 7 Onkel väterlicherseits hat einen Pes cavus, Hammerzehen und leichte periphere Sensibilitätsstörungen. Bei 3 von 7 Untersuchten fanden sich eine Verlangsamung der motorischen Erregungsleitung peripherer Nerven. EEG im Bereiche der Norm.Die epileptischen Anfälle manifestierten sich zunächst als Myoklonie der oberen rechten Extremitäten besonders während des Schlafes. Im EEG der beiden Exploranden zeigten sich fokale oder generalisierte epileptische Entladungen. Beim älteren der Brüder trat ein Status partialer motorischer Anfälle mit rechtsseitigen Adversiv-Attacken auf. Er starb plötzlich an einer Bronchopneumonie am 3. Tag des Status epilepticus. Die neuropathologische Untersuchung ergab eine nahezu vollständige Demyelinisierung des Tractus dentatorubralis und eine partielle Degeneration des Gollschen und Burdachschen Tractus im Halsmark. Die Zuordnung dieses Syndromes wird diskutiert und es wird eine autosomal dominante Vererbung mit unvollständiger Penetranz beziehungsweise unterschiedlicher Expressivität angenommen.

     

The cognitive effects of amygdalohippocampal deep brain stimulation in patients with temporal lobe epilepsy

The aim of this study was to examine the effects of amygdalohippocampal deep brain stimulation (AH-DBS) on cognitive functioning in patients with refractory temporal lobe epilepsy. The population consisted of 10 patients (7 men) who underwent ipsilateral (n = 8) or bilateral (n = 2) AH-DBS. Intellectual and neuropsychological evaluation was performed before and 6 months after initiation of AH-DBS. Group analyses revealed no overall pattern of change in cognitive measures, but improvement was seen in emotional well-being. Individual results varied over a broad spectrum ranging from no cognitive effects to negative effects on intelligence capacities, divided attention, and concept formation, to positive effects on speed of information processing and speed of finger movements. AH-DBS is a valuable treatment alternative for patients with refractory epilepsy that appears to have no major adverse neuropsychological consequences and enhances emotional well-being on the group level. Individual results are too diverse at this moment to allow viable interpretation. Additional studies are needed to confirm these preliminary results.     

Electrical stimulation of the anterior nucleus of the thalamus for the treatment of intractable epilepsy

PURPOSE: Animal studies and sporadic case reports in human subjects have suggested that intermittent electrical stimulation of the anterior nucleus of the thalamus reduces seizure activity. We embarked on an open-label pilot study to determine initial safety and tolerability of bilateral stimulation of the anterior nucleus of the thalamus (ANT), to determine a range of appropriate stimulation parameters, and to begin to gather pilot efficacy data. METHODS: We report an open-label pilot study of intermittent electrical stimulation of the anterior nucleus of the thalamus in five patients (three men, two women; age range, 24-47 years), with follow-up between 6 and 36 months. All patients had intractable partial epilepsy. Four of the five patients also had secondarily generalized seizures. Stimulation was delivered by bilateral implantable, programmable devices by using an intermittent, relatively high-frequency protocol. Stimulation parameters were 100 cycles per second with charge-balanced alternating current; pulse width, 90 ms; and voltages ranging between 1.0 and 10.0 V. Seizure counts were monitored and compared with preimplantation baseline. RESULTS: Four of the five patients showed clinically and statistically significant improvement with respect to the severity of their seizures, specifically with respect to the frequency of secondarily generalized tonic-clonic seizures and complex partial seizures associated with falls. One patient showed a statistically significant reduction in total seizure frequency. No adverse events could clearly be attributed to stimulation. None of the patients could determine whether the stimulator was on or off at these parameters. CONCLUSIONS: Electrical stimulation of the ANT appears to be well tolerated. Preliminary evidence suggests clinical improvement in seizure control in this small group of intractable patients. Further controlled study of deep brain stimulation of the anterior nucleus is warranted.     

High and low frequency electrical stimulation in non-lesional temporal lobe epilepsy

In patients with pharmacologically intractable epilepsy who are not eligible for surgery, deep brain stimulation is currently under evaluation as an alternative treatment. Optimal stimulation parameters, including high (HFS) versus low frequency (LFS) stimulation, are not well defined. Here, we report the effects of HFS (130 pulses per second, pps) and LFS (5pps) of the principal epileptogenic focus, in three patients with non-lesional temporal lobe epilepsy. HFS, but not LFS, was associated with a reduction of the interictal discharges and absence of seizures. HFS may be beneficial in patients with non-lesional temporal lobe epilepsy who are not surgical candidates.     

Electrical stimulation of the anterior nucleus of the thalamus for intractable epilepsy: a long-term follow-up study

PURPOSE: The anterior nucleus of the thalamus (ANT) modulates temporal lobe and hypothalamic activities, and relays information to the cingulate gyrus and entorhinal cortex. Deep brain stimulation (DBS) of the ANT has been reported to decrease seizure activity in a limited number of human subjects. However, long-term effect of chronic ANT stimulation on such patients remains unknown. We report long-term follow-up results in four patients receiving ANT stimulation for intractable epilepsy. METHODS: Four patients underwent stereotactic implantation of quadripolar stimulating electrodes in the bilateral ANT, guided by single-unit microelectrode recording. Electrode location was confirmed by postoperative magnetic resonance imaging (MRI). The stimulator was activated 2-4 weeks following electrode insertion; initial stimulation parameters were 4-5 V, 90-110 Hz, and 60-90 micros. Seizure frequency was monitored and compared with preimplantation baseline frequency. Intelligence quotient (IQ) test and auditory P300 response were performed before and after implantation of electrodes. RESULTS: Four patients (one man with generalized seizures, and three women with partial seizures and secondary generalization) aged 18-45 years old were studied with mean follow-up period of 43.8 months. The four patients demonstrated a sustained effect of 49% (range, 35-76%) seizure reduction to ANT stimulation. Simple insertion of DBS electrodes (Sham period, no stimulation) produced a mean reduction in seizures of 67% (range, 44-94%). One patient was seizure-free for 15 months with anticonvulsant medications. One patient had a small frontal hemorrhage and a second patient had extension erosion over scalp; no resultant major or permanent neurological deficit was observed. Preoperative IQ index and auditory P300 were not significantly different with those after electrodes implantation. CONCLUSIONS: Implantation of electrodes in the ANT and subsequent stimulation is associated with a significant reduction in seizure frequency. However, our study could not differentiate whether the implantation itself, the subsequent stimulation or postimplantation drug manipulation had the greatest impact. These experimental results prompt further controlled study in a large patient population.     

Motor responses to afferent stimulation in juvenile myoclonic epilepsy

PURPOSE: To document whether the mechanisms responsible for myoclonic jerks in juvenile myoclonic epilepsy (JME) are similar to those causing other forms of myoclonus. METHODS: We studied somatosensory evoked potentials, the conditioning effect of cutaneous afferents on motor potentials evoked by transcranial magnetic stimulation (TMS), and intracortical inhibition and facilitation in response to paired TMS in a group of nine patients with JME and 20 normal controls. RESULTS: Intracortical inhibition was abnormal, whereas cortical somatosensory evoked potentials and TMS conditioned by cutaneous afferents were unaltered in JME patients. CONCLUSIONS: Abnormal processing of cutaneous afferents would not appear to contribute to myoclonus in JME.     

Thalamic and cortical hyperexcitability in juvenile myoclonic epilepsy

ObjectivesJuvenile myoclonic epilepsy (JME) is a genetic generalized epilepsy marked by cortical hyperexcitability. Recent neuroimaging data suggested also a thalamic role in sustaining epileptic propensity in JME. However, thalamic hyperexcitability was not demonstrated so far. Low-frequency (LF-SEPs) and high-frequency somatosensory evoked potentials (HF-SEPs) are very sensitive to thalamic (early HF-SEPs burst, eHFO) and cortical (late HF-SEPs burst, lHFO) excitability. The aim of our experiment was to explore and discern the role of thalamic and cortical excitability in epileptic susceptibility of JME through a LF-SEPs and HF-SEPs study.MethodsTwenty-three subjects with JME (11 females, 30.2 ± 9.8-year-old) and 23 healthy control subjects (12 females, age: 34.7 ± 7.7-year-old) underwent right median LF-SEPs scalp recordings. Cp3′-Fz traces were filtered (400–800 Hz) to reveal HF-SEPs. All JME patients were on drug treatment and seizure free, except for sporadic myoclonus.ResultsN20 LF-SEPs amplitude (p < 0.009), areas of totHFO, eHFO and lHFO (all p < 0.005) and totHFO duration (p = 0.013) were increased in JME respect to healthy subjects. totHFO area was negatively correlated with the number of antiepileptic drugs (rho = -0.505, sig.: 0.027), while eHFO area was positively correlated with the myoclonus frequency (rho = 0.555, sig = 0.014).ConclusionsWe demonstrated that in JME the thalamic hyperexcitability assists the cortical one in sustaining epileptic susceptibility.SignificanceOur results support the concept of JME as a network and genetic disorder.     

Some clinical and EEG aspects of benign juvenile myoclonic epilepsy

Twelve patients with benign juvenile myoclonic epilepsy (BJME) representing 4% of our population of epileptics (n = 275) are presented. Only two patients (17%) had myoclonic jerks as the only seizure type. Seven (58%) had generalized tonic-clonic seizures (GTCS) and myoclonus. Three patients (25%) had absence seizures (AS), GTCS, and myoclonic jerks. Electroencephalographic evidence of photosensitivity was found in four (33%). Auditory precipitation of seizures was found in one patient. As is the case with other primary generalized epilepsies, the onset of BJME seems to be age specific. In our series the mean age of onset in years was 4.3 for AS, 14.75 for myoclonic jerks, and 16.4 for GTCS. It took an average of 8.5 years from the onset of BJME (range, 2-20 years) and 6.5 years from the onset of GTCS (range, 2 months-6 years) until the condition was properly recognized. Five patients experienced at least one episode of myoclonic status epilepticus. Generalized, paroxysmal, symmetric polyspike and slow wave discharges are the typical EEG finding. These complexes, however, showed considerable interpatient variability. Sleep deprivation proved to be the most valuable activating procedure. Valproic acid monotherapy effectively controlled myoclonic jerks as well as associated GTCS in most patients.     

Familial infantile myoclonic epilepsy: clinical features in a large kindred with autosomal recessive inheritance

PURPOSE: To describe the clinical features of a large kindred with familial infantile myoclonic epilepsy (FIME) with autosomal recessive inheritance, and to discuss the nosology of the early infantile myoclonic epilepsies (IMEs). METHODS: The family descends from the intermarriage of two couples of siblings. In a previous study, we mapped the genetic locus to chromosome 16p13.We analyzed results of family records and personal history, psychomotor development, neurologic examination, epilepsy features, and EEG recordings for each subject. RESULTS: FIME has a strong penetrance (eight affected of 14 subjects) and a homogeneous clinical picture. Like the benign form of infantile myoclonic epilepsy (BIME), FIME is a true idiopathic IME with unremarkable history, no neurologic or mental impairment, good response to treatment, and normal interictal EEG pattern. Conversely, onset with generalized epileptic seizures without fever (four patients) or with fever (one patient), frequency and duration of the myoclonic seizures, occurrence of generalized tonic--clonic seizures (GTCSs) in all patients and persistence of seizures into adulthood are characteristics of the severe infantile myoclonic epilepsy (SIME). CONCLUSIONS: Clinical overlap probably exists among the myoclonic epilepsies of infancy. FIME differs from other forms of IME in its phenotypic features. The peculiar mode of inheritance is explained by the genetic background of the family. Genetic studies suggest linkage to chromosome 16 in familial cases of true IME.     

Mutation in the mitochondrial tRNAIle gene causes progressive myoclonus epilepsy

PurposeThe group of the rare progressive myoclonic epilepsies (PME) include a wide spectrum of mitochondrial and metabolic diseases. In juvenile and adult ages, MERRF (myoclonic epilepsy with ragged red fibres) is the most common form. The underlying genetic defect in most patients with the syndrome of MERRF is a mutation in the tRNALys gene, but mutations were also detected in the tRNAPhe gene.MethodHere, we describe a 40 year old patient with prominent myoclonic seizures since 39 years of age without a mutation in the known genes who underwent intensive clinical, genetic and functional workup.ResultsThe patient had a slight mental retardation and a severe progressive hearing loss based on a defect of the inner ear on both sides. Ictal electroencephalography (EEG) showed bilateral occipital and generalized spikes and polyspikes induced and aggravated by photostimulation. A cranial magnetic resonance imaging (cMRI) detected a global cortical atrophy of the brain and mild periventricular white matter lesions. The electromyography (EMG) was normal but the muscle biopsy showed abundant ragged red fibres. Sequencing of the mitochondrial DNA from the skeletal muscle biopsy revealed a novel heteroplasmic mutation (m.4279A>G) in the tRNAIle gene which was functionally relevant as tested in single skeletal muscle fibre investigations.ConclusionMutations in tRNAIle were described in patients with chronic progressive external ophthalmoplegia (CPEO), prominent deafness or cardiomyopathy but, up to now, not in patients with myoclonic epilepsy. The degree of heteroplasmy of this novel mitochondrial DNA mutation was 70% in skeletal muscle but only 15% in blood, pointing to the diagnostic importance of a skeletal muscle biopsy also in patients with myoclonic epilepsy.     

Chronic subthreshold subdural cortical stimulation for the treatment of focal epilepsy originating from eloquent cortex

Medically refractory epilepsy remains a major medical problem worldwide. Although some patients are eligible for surgical resection of seizure foci, a proportion of patients are ineligible for a variety of reasons. One such reason is that the foci reside in eloquent cortex of the brain and therefore resection would result in significant morbidity. This retrospective study reports our experience with a novel neurostimulation technique for the treatment of these patients. We identified three patients who were ineligible for surgical resection of the intracranially identified seizure focus because it resided in eloquent cortex, who underwent therapeutic trial of focal cortical stimulation delivered through the subdural monitoring grid. All three patients had a significant reduction in seizures, and two went on to permanent implantation, which resulted in long‐term reduction in seizure frequency. In conclusion, this small case report provides some evidence of proof of concept of the role of targeted continuous neocortical neurostimulation in the treatment of medically refractory focal epilepsy, and provides support for ongoing investigations into this treatment modality. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here .