Delayed exacerbation of third nerve palsy due to aneurysmal regrowth after endovascular coil embolization.

A 72-year-old woman with a painful left third cranial nerve palsy due to a basilar artery aneurysm situated between the superior cerebellar and posterior cerebral arteries was treated with Guglielmi detachable coils (GDCs). Despite a good initial angiographic result with a small residual neck and improvement in the ocular motility and pain, the patient experienced worsening of the third cranial nerve palsy 15 months later. Cerebral angiography confirmed coil compaction with aneurysmal regrowth. A second endovascular coil embolization resulted in complete obliteration of the aneurysm. The patient experienced complete resolution of the pain and partial resolution of the third cranial nerve palsy. In some patients, a small residual aneurysm neck after endovascular embolization therapy with GDCs can result in delayed aneurysmal regrowth due to coil compaction. Clinical manifestations may herald this dangerous regrowth.     

Transient oculomotor nerve palsy due to non-aneurysmal neurovascular compression

Acute oculomotor nerve palsy requires urgent exclusion of aneurysmal compression. We report a 62 year old man with a transient right third nerve palsy with pupillary involvement, who was found to have neurovascular compression of the cisternal oculomotor nerve as it curved over a duplicated superior cerebellar artery on high resolution MR imaging. Direct vascular compression should be considered in patients with isolated cranial neuropathies in whom other pathologies have been excluded.     

Isolated third nerve palsy associated with a ruptured anterior communicating artery aneurysm

Introduction  

An oculomotor palsy in the setting of aneurysmal subarachnoid hemorrhage is often due to compression by a posterior communicating artery aneurysm. Anterior communicating artery (ACOM) aneurysms may produce ophthalmologic symptoms of the anterior visual pathways, but rarely ever lead to a 3rd nerve palsy. This report describes a rare case of an isolated oculomotor palsy in a patient who experienced subarachnoid hemorrhage from an ACOM aneurysm. Clinical Presentation: A 46-year-old male presented to the emergency department with headache, emesis, and an isolated left third nerve palsy—the remainder of his exam was normal. A head CT showed diffuse subarachnoid hemorrhage that was later attributed to an ACOM aneurysm as determined by angiography.     

Evaluation of third ventriculostomy outcome by measuring optic nerve sheath diameter in adult hdyrocephalus

ObjectiveIt is difficult to demonstrate the success of the procedure in patients with third ventriculostomy. We evaluated that optic nerve sheath diameter (ONSD) measurement, which can reflect intracranial pressure, may be a criterion for decision of endoscopic third ventriculostomy (ETV) success.Methods28 adult patients suffering long overt standing ventriculomegaly (LOVA) who performed ETV were included in this retrospective study. The patients were divided into two groups as successful (group A) and failed ETV group (group B) according to their postoperative evaluation. ONSD was measured on pre- and post-operative computed tomography (CT) and Evan's index (EI), diameter of third ventricule (V3), the patency of ETV stoma and periventricular edema were evaluated by magnetic resonance imaging (MRI).ResultsThe mean ONSD was measured as 6.39 ± 0.92 mm for the right eye, 6.50 ± 0.91 mm for the left eye on preoperative CT. The mean ONSD by CT (after surgery) was 4.89 ± 0.87 mm for the right eye, 5.02 ± 0.1 mm for the left eye (p < 0.05). Postoperative group A and group B were compared according to ONSD measurement; mean ONSD in group A was 4.52 ± 0.69 mm for the right and 4.59 ± 0.9 mm for the left, mean ONSD in group B was 5.82 ± 0.51 mm for the right and 6.1 ± 0.32 mm for the left (p < 0.05). The best ONSD value for detecting failed ETV was 5.40 mm (sensitivity 90%, specifity 75%, AUROC 0.938) for right and 5.91 mm (sensitivity 90%, specifity 75%, AUROC 0.950) for left. EE was measured as 0.39 ± 0.12 mm on preoperative MRI and 0.39 ± 0.12 mm on postoperative MRI (p = 0.3). V3 was measured as 14.7 ± 2.47 mm on preoperative MRI and 10.47 ± 1.99 mm on postoperative MRI (p < 0.05).ConclusionThe statistical values obtained from study show that the ONSD measurement can help in the postoperative evaluation of patients, who had a ETV surgery.     

Predictors of recurrence after stent-assisted coil embolization of paraclinoid aneurysms

Stent-assisted coil embolization has been increasingly used to treat paraclinoid aneurysms. The study was aimed to evaluate safety and efficacy of stent-assisted coil embolization for paraclinoid aneurysms and explore the factors influencing the long-term outcomes. Under an institutional review board approved protocol, the clinical and angiographic data of 129 paraclinoid aneurysms in 120 patients (Male:Female = 36:84; median age, 52 years; range, 21–84) treated by stent-assisted coil embolization were reviewed retrospectively. Clinical status, aneurysmal morphology, treatment strategy and results were analyzed using Chi-squared tests in the univariate analysis and further analyzed using backward stepwise logistic regression. The univariate analysis indicated significance between the groups regarding hypertension, ruptured aneurysms, size, wide neck and immediate treatment results (P < 0.05). Multivariate logistic regression analysis found that ruptured aneurysms (odds ratio [OR] = 5.893, 95% confidence interval [CI], 1.512–23.054; p = 0.011), larger size (OR = 2.339; 95%CI, 1.148–4.781; p = 0.020) and hypertension (OR = 6.143; 95%CI, 1.560–24.183; p = 0.009) might be predictors of recurrence. Stent-assisted coil embolization of paraclinoid aneurysm has a risk of recurrence. Ruptured aneurysms, larger size and hypertension may be the risk factors for recurrence.     

Resolution of third nerve palsy despite persistent aneurysmal mass effect after flow diversion embolization of posterior communicating artery aneurysms

Posterior communicating artery (PCOM) aneurysms may cause third nerve palsies. The optimal treatment with clipping versus coiling remains controversial. Here we report on two cases of resolution of third nerve palsy after flow diversion embolization of large and giant PCOM aneurysms without adjuvant coil placement. The resolution of third nerve palsy was not preceded by significant shrinkage of the aneurysmal sac on MRI. However, one patient showed resolution of T2-weighted signal abnormalities in the midbrain and mesial temporal lobe despite a similar size of the aneurysm. Therefore, flow diversion embolization of a PCOM aneurysm may resolve oculomotor nerve palsies through decreasing arterial pulsations against the nerve or midbrain.     

Spontaneous resolution of aneurysmal third nerve palsy.

Palsy of the third cranial nerve developed in a 33-year-old woman in her third trimester of pregnancy as a result of compression by a posterior communicating artery aneurysm. Prepartum complications forced postponement of surgical treatment. The palsy spontaneously resolved over 3 weeks after delivery by cesarean section. Repeat angiography suggested that the aneurysmal sac had shrunk. Spontaneous complete resolution of a third nerve palsy does not exclude an aneurysmal cause.     

Long-term follow-up analysis of microsurgical clip ligation and endovascular coil embolization for dorsal wall blister aneurysms of the internal carotid artery

Blister aneurysms at non-branching sites of the dorsal internal carotid artery (dICA) are fragile, rare, and often difficult to treat. The purpose of this study is to address the demographics, treatment modalities, and long-term outcome of patients treated for dICA blister aneurysms. A retrospective review of medical records identified all consecutive patients who presented with a blister aneurysm from 2002 to 2011 at our institution. Eighteen patients (M = 7, F = 11; mean age: 48.4 ± 15.1 years; range: 15–65 years) harbored a total of 43 aneurysms, 25 of which were dorsal wall blister aneurysms of the ICA. Eleven (61.1%) patients presented with aneurysmal subarachnoid hemorrhage (aSAH), and 10 (55.6%) patients had multiple aneurysms at admission. Twelve patients had 18 aneurysms that were treated microsurgically. Five (41.7%) of these patients had a single recurrence that was retreated with subsequent repeat clip ligation. Six patients had 7 blister aneurysms that were treated with endovascularly. One (16.7%) of these patients had a single recurrence that was retreated with subsequent coil embolization. Postoperative vasospasm occurred in 8 (44.4%) patients, one of whom suffered from a stroke. This is one of the largest single-institution dICA blister aneurysm studies to date. There was no detected significant difference between microsurgical clip ligation and endovascular coil embolization in terms of surgical outcome. These blister aneurysms demonstrate a propensity to be associated with multiple cerebral aneurysms. Strict clinical and angiographic long-term follow-up may be warranted.Statement of SignificanceBlister aneurysms are focal wall defects covered by a thin layer of fibrous tissue and adventitia, lacking the usual collagenous layer. Due to their pathologically thin vessel wall, blister aneurysms are prone to rupture. The management of these rare and fragile aneurysms presents a number of challenges. Here, we address the long-term outcome of patients treated for blister aneurysms at non-branching sites of the dICA. The presented data and analysis is imperative to determine the necessary strict long-term clinical and angiographic follow-up.     

Endovascular treatment of recurrent intracranial aneurysms following previous microsurgical clipping with the Pipeline Embolization Device

The treatment of intracranial aneurysms with microsurgical clipping is associated with a very low rate of recurrence. However, in cases of aneurysm recurrence after previous clipping, microsurgical dissection due to adhesions and fibrosis may be challenging, and it may be difficult to safely occlude the recurrent lesion without the risk of significant morbidity. Flow-diverting stents have drastically changed the landscape of endovascular neurosurgery. We present two patients with large, recurrent supraclinoid internal carotid artery (ICA) aneurysms which were previously clipped 17 and 23 years ago at outside institutions. Both recurrent lesions were treated with the Pipeline Embolization Device (PED; ev3 Endovascular, Irvine, CA, USA) without radiographic or clinical complications. In the first patient, the 15 mm aneurysm significantly decreased in size at 6 month angiographic follow-up. The 21 mm aneurysm in the second patient was completely occluded 7 months following PED treatment. The moderate degree of in-stent stenosis present on initial follow-up imaging resolved on angiography 11 months post-treatment. The management of recurrent aneurysms after clipping is sparsely reported in the literature due to its infrequent occurrence. In carefully selected cases, flow-diverting stents may be used for complex aneurysms of the distal ICA, even for those which have recurred following microsurgical clipping.     

Vagus nerve stimulation: Longitudinal follow-up of patients treated for 5 years

We performed a retrospective, multicenter, open-label study to evaluate the efficacy of vagus nerve stimulation (VNS) in all patients in the Czech Republic who have received this treatment for at least 5 years (n = 90). The mean last follow-up was 6.6 ± 1.1 years (79 ± 13 months). The median number of seizures among all patients decreased from 41.2 seizures/month in the prestimulation period to 14.9 seizures/month at 5 years follow-up visit. The mean percentage of seizure reduction was 55.9%. The responder rate in these patients is in concordance with the decrease of overall seizure frequency. At 1 year after beginning the stimulation, 44.4% of patients were responders; this percentage increased to 58.7% after 2 years. At the 5 years last follow-up 64.4% of patients were responders, 15.5% experienced ≥90% seizure reduction, and 5.5% were seizure-free. A separate analysis of patients younger than 16 years of age showed lower efficacy rates of VNS in comparison to the whole group. Complications and chronic adverse effects occurred in 13.3% of patients. VNS is an effective and safe method to refractory epilepsy in common clinical practice.     

Comparing the effects of cortical resection and vagus nerve stimulation in patients with nonlesional extratemporal epilepsy

The main purpose of this retrospective study was to compare the effects of resective surgery (RESgr—26 patients) and vagus nerve stimulation (VNSgr—35 patients) on seizure frequency (2 and 5 years after surgery) in patients with nonlesional extratemporal epilepsy (NLexTLE). We analyzed hospital admission costs directly associated with epilepsy (HACE) in both groups at the same follow-up. The decrease in seizure frequency from the preoperative levels, in both VNSgr and RESgr, was statistically significant (p < 0.001). The seizure frequency reduction did not differ significantly between the follow-up visits for either group (p = 0.221 at 2 years and 0.218 at 5 years). A significantly higher number of Engel I and Engel I + II patients were found in RESgr than in VNSgr at both follow-up visits (p = 0.04 and 0.007, respectively). Using McHugh classification, we did not find statistically significant differences between both groups at both follow-up visits. Hospital admission costs directly associated with epilepsy/patient/year in both RESgr and VNSgr dropped significantly at 2- and 5-year follow-up visit and this reduction was not statistically different between RESgr and VNSgr (p = 0.232).Both VNS and resective surgery cause comparably significant seizure reduction in NLexTLE. Resective surgery leads to a greater number of patients with excellent postoperative outcome (Engel I + II). The HACE reduction is statistically comparable between both groups.     

Direct motor evoked potentials and cortical mapping using the NIM® nerve monitoring system: A technical note

Motor evoked potentials (MEPs) are commonly used to prevent neurological injury when operating in close proximity to the motor cortex or corticospinal pathway. We report a novel application of the NIM® nerve monitoring system (Medtronic@ NIM response 3.0) for intraoperative direct cortical (dc)-MEPs monitoring. A 69-year-old female patient presented with a 4 month history of progressive left hemiparesis resulting from a large right sided posterior frontal meningioma that abutted and compressed the motor cortex. Motor cortical mapping and MEPs were indicated. The patient was anesthetized and maintained on total intravenous anesthetics. Compound muscle action potentials (CMAP) of the right upper limb were monitored using the NIM system. After a craniotomy was performed, we first used the Ojemann stimulator (monopolar) for dc-stimulation and then switched to use the monopolar nerve stimulator probe of the NIM system. The CMAP response was successfully elicited using the NIM stimulating probe (pulse width = 250 s, train frequency = 7 pulses/s, current = 20 mA). A gross total resection of the tumor was achieved with intermittent cortical mapping of MEPs. There were no intraoperative complications and the patient’s motor function was preserved after the surgery. In this case, we reported the successful use of the NIM nerve monitoring system to elicit dc-MEPs under general anesthesia. The advantages of using this system include a simple set up and application, neurosurgeon familiarity, wide availability and lower cost. dc-MEPs can be achieved using the NIM system. We conclude that the NIM nerve monitoring system is a feasible alternative to standard neurophysiological monitoring systems.     

Diffuse scalp malignant peripheral nerve sheath tumor with intracranial extension in a patient with neurofibromatosis type 1

We describe a rare scalp malignant peripheral nerve sheath tumor (MPNST) with cranial destruction and intracranial extension in a 52-year-old male with neurofibromatosis type 1 (NF1). The scalp tumor measured 22 cm × 18 cm, with local surface ulceration. Skin examination revealed many café-au-lait spots and small, hard dermal nodules on the trunk. CT scans revealed the scalp tumor to have heterogeneous density with partial destruction of the right parietal cranium; on T1-weighted MRI the scalp tumor displayed heterogeneous hypointensity, whereas on T2-weighted and fluid-attenuated inversion recovery MRI it was hyperintense. The tumor was excised totally and the scalp reconstructed using a skin flap isolated from the lateral aspect of the left thigh. Histological examination confirmed that the tumor was an MPNST. The patient recovered uneventfully and was well at the 6-month follow-up, with no local or other tumor recurrence noted.     

Outcomes of endoscopic third ventriculostomy in adults

Endoscopic third ventriculostomy (ETV) is an alternative to ventriculoperitoneal shunting for treatment of hydrocephalus. Studies have reported favorable outcomes for up to three-quarters of adult patients. We performed the first ETV outcomes study using an administrative claims database, examining current practice for adult patients in the United States. We interrogated the Truven Health MarketScan® database for Current Procedural Terminology codes corresponding to ETV and ventriculoperitoneal shunt from 2003- to 2011, including patients over 18 years and data from initial and subsequent hospitalizations. ETV failure was defined as any subsequent ETV or shunt procedure. Five hundred twenty-five patients underwent ETV with 6 months minimum follow-up. Mean age was 45.9 years (range: 18–86 years). Mean follow-up was 2.2 years (SD: 1.6 years, range: 0.5–8.4 years). Etiology of hydrocephalus was 21.3% tumor, 9.0% congenital/aqueductal stenosis, 15.8% hemorrhage, and 53.9% others. ETV was successful in 74.7% of patients. Of 133 who failed, 25 had repeat ETV; 108 had shunt placement. Longer length of stay for index surgery was associated with higher risk of failure (hazard ratio (HR): 1.03, p < 0.001), as was history of previous shunt (HR: 2.45, p < 0.001). Among patients with repeat surgeries, median time to failure was 25 days. This study represents a longitudinal analysis of nationwide ETV practice over 9 years. Success rate in this large cohort is similar to that published by other single-center retrospective studies. Age and geographic variation may be associated with surgeon choice of ETV or shunt placement after failure of the initial ETV.     

Meta-analysis of stent-assisted coiling versus coiling-only for the treatment of intracranial aneurysms

Endovascular coil embolization is a widely accepted and useful treatment modality for intracranial aneurysms. However, the principal limitation of this technique is the high aneurysm recurrence. The adjunct use of stents for coil embolization procedures has revolutionized the field of endovascular aneurysm management, however its safety and efficacy remains unclear. Two independent reviewers searched six databases from inception to July 2015 for trials that reported outcomes according to those who received stent-assisted coiling versus coiling-only (no stent-assistance). There were 14 observational studies involving 2698 stent-assisted coiling and 29,388 coiling-only patients. The pooled immediate occlusion rate for stent-assisted coiling was 57.7% (range: 20.2%–89.2%) and 48.7% (range: 31.7%–89.2%) for coiling-only, with no significant difference between the two (odds ratio [OR} = 1.01; 95% confidence intervals [CI}: 0.68–1.49). However, progressive thrombosis was significantly more likely in stent-assisted coiling (29.9%) compared to coiling-only (17.5%) (OR = 2.71; 95% CI: 1.95–3.75). Aneurysm recurrence was significantly lower in stent-assisted coiling (12.7%) compared to coiling-only (27.9%) (OR = 0.43; 95% CI: 0.28–0.66). In terms of complications, there was no significant difference between the two techniques for all-complications, permanent complications or thrombotic complications. Mortality was significantly higher in the stent-assisted group 1.4% (range: 0%–27.5%) compared to the coiling-only group 0.2% (range: 0%–19.7%) (OR = 2.16; 95% CI: 1.33–3.52). Based on limited evidence, stent-assisted coiling shows similar immediate occlusion rates, improved progressive thrombosis and decreased aneurysm recurrence compared to coiling-only, but is associated with a higher mortality rate. Future randomized controlled trials are warranted to clarify the safety of stent-associated coiling.     

Intraprocedural retrieval of migrated coils during endovascular aneurysm treatment with the Trevo Stentriever device

Coil migration during endovascular treatment of intracranial aneurysms occurs in 2–6% of cases. As endovascular coiling of aneurysms has become increasingly popular and as endovascular technology continues to rapidly evolve, the prevalence of intraprocedural coil migration will invariably rise. Since coil masses are highly thrombogenic, migration out of the aneurysm sac into the parent artery may result in large territory infarcts which subsequently manifest as significant neurological morbidity. Therefore safe and timely retrieval of migrated coils is essential to avoiding poor angiographic and clinical outcomes. A 66-year-old woman with an unruptured 5 × 3 mm, wide-necked posterior communicating artery aneurysm was referred for endovascular treatment. During coiling with the dual catheter technique, both initially deployed coils dislodged from the aneurysm sac and migrated distally into the middle cerebral artery. After failed retrieval with an Alligator device (Chestnut Medical Technologies, Menlo Park, CA, USA), we used two Trevo devices (Concentric Medical, Mountain View, CA, USA) in succession to successfully retrieve the migrated coils. The aneurysm was then occluded with stent-assisted coil embolization. There were no post-procedural angiographic or clinical complications. The patient was subsequently discharged home without neurological deficit. This case illustrates the first use of the Trevo device for retrieval of migrated coils during endovascular treatment of an intracranial aneurysm to our knowledge. Due to the lack of guidelines defining the standard management of intraprocedural coil migration, current strategies are based on retrospective review of published reports and expert opinion. We present a unique and effective method for endovascular retrieval of displaced coils using a Trevo Stentriever device.     

Aneurysmal acute subdural hemorrhage: Prognostic factors associated with treatment

Acute subdural hematoma is an uncommon presentation of aneurysmal hemorrhage that has been identified as a poor prognostic sign. Current series are small, have short follow-up, or were collected over a long period during which treatment evolved. To evaluate prognostic factors, we analyzed a large modern series of aneurysmal subdural hematoma (aSDH) with long-term follow-up. A prospectively maintained database was queried for patients presenting with aSDH from 2001–2013. Thirty patients met the study criteria. Statistical analysis was performed with unpaired t-test or Fisher’s exact test. Aneurysm treatment involved open clipping (n = 18), endosaccular coiling (n = 8), both (n = 1), or no treatment (n = 3). Good Glasgow Outcome Scale score at discharge was present in 20% and increased to 40% at 6–12 months postoperatively. Good clinical presentation was associated with good final outcome in 75%, whereas poor clinical presentation correlated with good outcome in 30%. Good outcome correlated with younger age (p = 0.04), smaller aneurysm (p = 0.04), and lower Hunt-Hess score (HH) at intervention (p = 0.04). Favorable outcome did not correlate with sex, race, presence of subarachnoid or intraparenchymal hemorrhage, size or laterality of hemorrhage, midline shift, aneurysm treatment modality, or HH at admission (p > 0.15). There was no difference between good and poor outcomes in terms of time to treatment or hematoma evacuation. Poor clinical presentation may be exaggerated by mass effect of hematoma; aggressive treatment is not futile. Presenting neurological status, age, and aneurysm size are predictors of outcome, while laterality and size of hematoma and extent of midline shift are not, suggesting that clinical status is more important than radiographic findings.     

Ultrasound assessment of sural nerve in Charcot–Marie-Tooth 1A neuropathy

ObjectiveNerve ultrasound (US) has been used to study peripheral nerve disease, and increase of the cross-sectional area (CSA) has been described in demyelinating polyneuropathy. The objective of the current study is to characterise the US features of the sural nerve in a sample of Charcot–Marie-Tooth (CMT) 1A patients.MethodsA total of 20 CMT1A patients were enrolled. As control group we studied 37 age- and sex-matched subjects. All patients underwent clinical examination, neurophysiology and US evaluation of the bilateral sural nerve and right ulnar nerve. US results were correlated with neurophysiology and clinical data.ResultsSural nerve CSA was not increased in the majority of patients (70%), whereas an increased ulnar nerve CSA was present in the whole sample. Inverse relations were found between CSA of the ulnar nerve and body mass index (BMI) (p < 0.0002, R = ?0.8) and CSA of the sural nerve and age (right 0.006, R = ?0.6, left 0.002, R = ?0.6 and left and right p = 0.00003, R = ?0.4).ConclusionsUS showed ulnar CSA enlargement and normal sural nerve CSA.SignificanceThe significance of normal sural nerve CSA in CMT1A patients need to be further investigated, possibly through longitudinal studies.     

Endovascular treatment of ruptured tiny,wide-necked posterior communicating artery aneurysms using a modified stent-assisted coiling technique

The endovascular treatment of patients with tiny, wide-necked aneurysms is technically challenging, due to the small volume for microcatheterization and coil stabilization inside the aneurysm sac. We performed a retrospective study to evaluate the feasibility, effectiveness, and safety of stent-assisted embolization for patients with ruptured, tiny, wide-necked posterior communicating artery (PcomA) aneurysms. Between January 2007 and August 2011, 17 tiny, wide-necked PcomA aneurysms that had ruptured were treated at our institution using a modified stent-assisted technique, with delivery of the first coil inside the aneurysm followed by placement of a self-expanding stent via a second microcatheter. All patients were treated successfully using this modified stent-assisted coiling technique. Initial results showed aneurysm occlusion of Raymond Class 1 in 10 patients, Class 2 in four patients, and Class 3 in three patients. The angiographic follow-up results for 13 patients (mean, 12.5 months) showed that all aneurysms remained stable or improved, without any in-stent stenosis or recurrence. Of the other four patients, three refused angiography for economic or personal reasons, and one was lost in follow-up. Clinical follow-up of 16 patients for a mean of 23.8 months showed no death or rebleeding. These results imply that endovascular treatment of ruptured tiny, wide-necked PcomA aneurysms using our modified stent-assisted coiling technique is safe and feasible. This technique improves the long-term outcomes of these aneurysms by increasing the packing density and diverting the intra-aneurysmal blood flow.     

A prospective long-term study of external trigeminal nerve stimulation for drug-resistant epilepsy

BackgroundExternal trigeminal nerve stimulation (eTNS) is an emerging noninvasive therapy for drug-resistant epilepsy (DRE). We report the long-term safety and efficacy of eTNS after completion of a phase II randomized controlled clinical trial for drug-resistant epilepsy.MethodsThis was a prospective open-label long-term study. Subjects who completed the phase II randomized controlled trial of eTNS for DRE were offered long-term follow-up for 1 year. Subjects who were originally randomized to control settings were crossed over to effective device parameters (30 s on, 30 s off, pulse duration of 250 s, frequency of 120 Hz). Efficacy was assessed using last observation carried forward or parametric imputation methods for missing data points. Outcomes included change in median seizure frequency, RRATIO, and 50% responder rate.ResultsThirty-five of 50 subjects from the acute double-blind randomized controlled study continued in the long-term study. External trigeminal nerve stimulation was well tolerated. No serious device-related adverse events occurred through 12 months of long-term treatment. At six and twelve months, the median seizure frequency for the original treatment group decreased by -2.39 seizures per month at 6 months (-27.4%) and -3.03 seizures per month at 12 months (-34.8%), respectively, from the initial baseline (p < 0.05, signed-rank test). The 50% responder rates at three, six, and twelve months were 36.8% for the treatment group and 30.6% for all subjects.ConclusionThe results provide long-term evidence that external trigeminal nerve stimulation is a safe and promising long-term treatment for drug-resistant epilepsy.