Implant‐Driven Tibial Nerve Stimulation in the Treatment of Refractory Overactive Bladder Syndrome: 12‐Month Follow‐up

Objectives. To investigate feasibility and safety of implant‐driven tibial nerve stimulation. Materials and Methods. Eight patients with refractory overactive bladder were successfully treated with implanted percutaneous tibial nerve stimulation (PTNS). Patients were evaluated with bladder diaries, quality of life questionnaires, and physical examination before implantation, and at 3, 6, and 12 months of follow‐up. The primary objective was ≥ 50% reduction of the number of incontinence episodes and/or voids on bladder diary. The Wilcoxon signed ranks test was used. Results. At 3, 6 and 12 months, respectively five, six, and four patients met the primary objective. At 3‐ and 6‐month follow‐up, voiding and quality of life parameters had significantly (p < 0.05) improved. Urinary tract infection, temporarily walking difficulties, and spontaneous radiating sensations were reported as adverse events and no local infection, erosion, or dislocation. Conclusions. Implant‐driven tibial nerve stimulation seems to be feasible and safe.     

Does Sacral Neuromodulation Lead to Relevant Reduction in the Need for Intermittent Catheterization? A Single-Center Experience on Patients With Chronic Urinary Retention

Purpose: Sacral neuromodulation (SNM) is an approved method for second‐line treatment of different therapy refractory disorders of the urinary bladder. Alongside success in overactive bladder symptoms for detrusor overactivity, SNM also was shown to succeed in chronic urinary retention (UR) of various etiology. Methods: From October 2007 to December 2010, a cohort of 20 patients received two‐stage InterStim tined‐lead® (Medtronic Inc., Minneapolis, MN, USA) SNM therapy for UR. The number of electrodes implanted was decided by surgeons on the basis of patients' clinical presentation and extent of UR. Dependent on the treatment success, patients received either implantation of the implantable pulse generator (IPG) or the electrodes were removed. Median follow‐up time was 12 months (1–38 months). Results: All 20 patients, of whom 80% were female, suffered from idiopathic or neurogenic UR for a median 60 months (7–440 months) before SNM. Median patient age was 51 years (34–68 years). Eighteen (90%) of the stimulated patients showed significant success with implantation of IPG within a median of 43 days (15–93). In the follow‐up period, postvoid residual (PVR) urine of the permanent stimulated patients was reduced from a median of 350 mL to 135 mL. While this just did not reach statistical significance (p= 0.057), the median number of intermittent catheterizations (ICs) could be reduced relevantly from four to one per day (p= 0.021). The subgroup analysis of idiopathic and neurogenic UR showed relevant improvement of the vital parameters, but the number of patients was obviously too small to yield statistically significant results. Subgroup analysis according to the number of electrodes implanted revealed statistically significant reduction of IC only after unilateral SNM. PVR of ≤400 mL was a statistically significant predictor for success of SNM treatment. In the presented treatment period, only one mild adverse event occurred that could be handled conservatively. Conclusions: SNM can be a successful and secure second‐line therapy option for patients with chronic UR. Data suggest a more success‐promising situation for idiopathic cause of disease, but the number of patients was too small to reach statistical significance. Further prospective, randomized multicenter data concerning indications and number of electrodes are necessary and highly appreciated.     

Perampanel in patients with refractory and super‐refractory status epilepticus in a neurological intensive care unit: A single‐center audit of 30 patients

In refractory status epilepticus (SE), γ‐aminobutyric acidergic drugs become less effective and glutamate plays a major role in seizure perpetuation. Data on the efficacy of perampanel (PER) in treatment of refractory SE in humans are limited. Here, we present a single‐center case series of patients with refractory SE who received PER orally in an intensive care unit. We retrospectively analyzed treatment response, outcome, and adverse effects of all patients with refractory SE in our Neurological Intensive Care Unit who received add‐on PER between September 2012 and February 2018. Thirty patients with refractory SE (median = 72 years, range = 18‐91, 77% women) were included. In 14 patients (47%), a high‐dose approach was used, with a median initial dose of 24 mg (range = 16‐32). In five patients (17%), SE could be terminated after PER administration (median dose = 6 mg, range = 6‐20 mg, 2/5 patients in high‐dose group). Clinical response was observed after a median of 24 hours (range = 8‐48 hours), whereas electroencephalogram resolved after a median of 60 hours (range = 12‐72 hours). Time to treatment response tended to be shorter in patients receiving high‐dose PER (median clinical response = 16 hours vs 18 hours; electroencephalographic response = 24 hours vs 72 hours), but groups were too small for statistical analysis. Continuous cardiorespiratory monitoring showed no changes in cardiorespiratory function after “standard” and “high‐dose” treatment. Elevated liver enzymes without clinical symptoms were observed after a median of 6 days in seven of 30 patients (23%; 57% high dose vs 43% standard dose), of whom six also received treatment with phenytoin (PHT). Outcome was unfavorable (death, persistent vegetative state) in 13 patients (43%; 39% high dose vs 61% standard dose), and good recovery (no significant disability, moderate disability) was achieved in nine patients (56% high dose vs 44% standard dose). Oral PER in loading doses up to 32 mg were well tolerated but could terminate SE only in a few patients (5/30; 17%). Long duration of SE, route of administration, and severe underlying brain dysfunction might be responsible for the modest result. An intravenous formulation is highly desired to explore the full clinical utility in the treatment of refractory SE.     

Efficacy and safety of perampanel oral loading in postanoxic super‐refractory status epilepticus: A pilot study

Refractory nonconvulsive status epilepticus (NCSE) occurs in 10%‐30% of patients following resuscitation after cardiac arrest. Both the optimal treatment and prognosis of postanoxic status epilepticus remain uncertain. We analyzed acute electroencephalographic changes, neurological outcome at 3 months, and adverse effects in consecutive postanoxic patients with super‐refractory NCSE treated with add‐on oral loading of perampanel. Eight postanoxic patients with super‐refractory NCSE were treated with perampanel (dose range = 6‐12 mg). All patients had continuous electroencephalographic monitoring showing definite generalized NCSE and favorable multimodal prognostic indicators (presence of brainstem reflexes, presence of bilateral N20 responses, absence of periodic discharges/generalized epileptic periodic discharges). In six patients (75%), status epilepticus resolved within 72 hours after administration of perampanel, without changing the comedication. Neurological outcomes at 3 months were return to normal or minimal disability in four patients (50%). A mild cholestatic liver injury, which required no specific treatment, was observed in five patients (62.5%). Perampanel 6‐12 mg oral loading appeared to be an effective option in selected patients with postanoxic super‐refractory NCSE with good prognostic indicators. In this patient population, our safety data indicate a risk of cholestasis.     

Urinary symptoms and urodynamic findings in patients with Machado–Joseph disease

The study evaluated the prevalence of clinical and urodynamic findings in the lower urinary tract of patients with Machado–Joseph (MJ) disease. One hundred twenty-two patients were retrospectively evaluated; 17 (13.9%) presented lower urinary tract dysfunction, 10 of them were women. The average age was 41.6 years. Urgency was found in 15 patients and incontinence in nine. The urodynamic study showed detrusor overactivity in eight patients, areflexia in one, and four with normal detrusor contractility. Bladder sensitivity was abnormal in six, bladder capacity was decreased in one, urine flow decreased in 13, post-voiding residue was greater than 100 ml in nine. We could not find sphincter dyssynergia. The average cytosine–adenine–guanine (CAG) repetition was higher in patients with abnormal detrusor contraction (89.9) than in patients with normal urodynamics (68.2) (p = 0.03). There was no statistical significance when comparing the averages of replicates for people with and without urgency urinary incontinence (p = 0.27 and p = 0.5, respectively). The rate of lower urinary tract dysfunction in patients with MJ disease was around 14%. The urodynamic study showed predominance of detrusor overactivity and urgency as the most common symptom. We found an association between the total number of CAG repetitions and changes in detrusor contractility.     

Long‐Term Effects of Electrical Neurostimulation in Patients With Unstable Angina: Refractory to Conventional Therapies

Background. Patients with unstable angina pectoris may become refractory to conventional therapies. Electrical neurostimulation with transcutaneous electrical stimulation and/or spinal cord stimulation has been shown to be effective for patients with refractory unstable angina pectoris in hospital settings. Our aim was to investigate the effects of electrical neurostimulation on outcomes of unstable angina after hospital discharge, in terms of hospital re‐admission rates and long‐term survival analysis. Method. Twenty‐seven consecutive patients with unstable angina pectoris, refractory to conventional therapies, received electrical neurostimulation in a tertiary referral hospital. We studied the number of hospital admissions in the year before when compared to the first year after electrical neurostimulation and performed survival analysis of the group. Results. Twenty‐six patients had beneficial effects of electrical neurostimulation during their admission to the hospital. During a mean follow‐up of 6.6 ± 4.1 years, electrical neurostimulation was still effective in 21 out of 26. In 11 patients with previous hospital admissions, the number of hospital admissions decreased significantly after electrical neurostimulation (p = 0.007). The combined mortality and (re)infarction rate after one‐year follow‐up was 14%. Conclusion. The results of this observational study show long‐term beneficial effects of electrical neurostimulation in a population of patients with unstable refractory angina. Therefore, electrical neurostimulation should be considered as a beneficial treatment for patients with unstable angina pectoris, refractory to conventional therapies.     

Pharmacokinetics of cannabidiol in children with refractory epileptic encephalopathy

Growing interest in the clinical use of cannabidiol (CBD) as adjuvant therapy for pediatric refractory epileptic encephalopathy emphasizes the need for drug treatment optimization. The aim of this study was to characterize the pharmacokinetics of CBD in pediatric patients with refractory epileptic encephalopathy receiving an oil‐based oral solution. To evaluate CBD concentrations, six serial blood samples per patient were collected after the morning dose of CBD, at least 21 days after the beginning of treatment. Twelve patients who received a median (range) dose of 12.2 (5.3‐19.4) mg/kg/d (twice daily) were included in the analysis. Median (range) CBD time to maximum plasma concentration, maximum plasma concentration, and area under the concentration versus time curve up to 6 hours after dosing were 3.2 hours (1.9‐6.2), 49.6 ng/mL (14.4‐302.0), and 226.3 ng ? h/mL (70.5‐861.3), respectively. CBD systemic exposure parameters were in the lower range of previous reports in pediatric patients receiving doses in a similar range. Most of our patients (83%) showed little CBD plasma level fluctuation during a dosing interval, comparable to that encountered after oral administration of an extended release drug delivery system. CDB administration was generally safe and well tolerated, and a novel levothyroxine‐CBD interaction was recorded. Similar to other studies, large interindividual variability in CBD exposure was observed, encouraging the use of CBD therapeutic drug monitoring.     

The Use of Implanted Programmable Infusion Pumps in the Management of Nonmalignant,Chronic Low‐Back Pain

Objectives. To assess the mode‐of‐use of implanted programmable infusion pumps in patients with nonmalignant, chronic low‐back pain. Materials and Methods. Charts from 101 consecutive eligible patients were analyzed retrospectively. Data were extracted relating to patient demographics, pump mode of infusion and flow rate, and medications used. Results. Morphine was the agent most frequently used and most patients received one medication at each visit. At the last visit, 94.1% of patients were receiving constant‐flow treatment; 90.1% had received such treatment for ≥ six months and 68.3% throughout the entire analysis period. For patients attaining constant‐flow treatment, mean time from implantation to start of such treatment was 2.7 months. Discussion. The results suggest that many patients with nonmalignant low‐back pain could be implanted with a constant‐flow pump when their programmable device needs replacing or, in some cases, at the start of intrathecal treatment. This would reduce costs and the requirement for surgery.     

Micturitional disturbance in neuro-Behçet's syndrome

BACKGROUND: Micturitional disturbance is known to occur in neuro-Beh?et's syndrome (NBS). However, its pathophysiology is uncertain and few data are available concerning urodynamic findings. We describe our findings on micturitional histories and urodynamic studies in patients with NBS. METHODS: A history of urinary symptoms was obtained from nine patients with NBS [seven male, two female, aged 26 to 54 years; mean, 41 years]. Neurological and CT/MRI findings indicated that their lesions were located mainly in the cerebral cortex, basal ganglia, cerebellum, brainstem and the spinal cord. Symptomatic patients underwent urodynamic studies, including measurement of post-micturition residuals, urethral pressure profilometry and EMG cystometry. RESULTS: Six of the nine patients (67%) had urinary symptoms that included diurnal urinary frequency in five, sensation of urgency in five, urge urinary incontinence in five, voiding difficulty in five and nocturnal urinary frequency in four. None had urinary retention. Urodynamic studies performed in six patients showed post-micturition residuals in five (50-180 ml), increased maximum urethral closure pressure in two, decrease in four and increase in one of bladder capacities, detrusor hyperreflexia in five, decreased bladder sensation in one, brisk bulbocavernosus reflex in four, detrusor-sphincter dyssynergia in two and neurogenic sphincter EMG in one. CONCLUSION: Our results indicate that micturitional disturbance is not rare in patients with NBS. Supranuclear pelvic nerve dysfunction seems to be mainly responsible for the disturbance.     

Spinal Cord Stimulation for Axial Low Back Pain: A Prospective Controlled Trial Comparing 16‐Contact Insulated Electrodes with 4‐Contact Percutaneous Electrodes

Use of multicontact electrodes and programmable implanted pulse generators has increased the efficacy of spinal cord stimulation for pain. Some investigators find dual column electrodes advantageous for difficult‐to‐treat axial low back pain, but we have reported significantly improved measures with a single percutaneous midline electrode vs. dual percutaneous electrodes and even better results with an insulated, 1 × 4, midline electrode. In this study, 10 patients provided computerized, quantitative parameter measures for a temporary percutaneous 1 × 4 electrode and for a permanent insulated 2 × 8 electrode. Compared with the 2 × 8, the 1 × 4 resulted in marginally better patient‐rated (109%, p = 0.06) and computer‐calculated pain/paresthesia overlap (107%, p = 0.17); higher scaled amplitude to cover the low back (106%, NS); and significantly lower voltage (78%, p = 0.0004), increased extraneous coverage (141%, p = 0.0000), and improved symmetry (25%, p = 0.001). Thus, we observed no significant technical advantage for the insulated 2 × 8 in treating axial low back pain.     

A post hoc analysis of the long‐term safety and efficacy of perampanel in Asian patients with epilepsy

This post hoc analysis assessed the long‐term safety, tolerability, and efficacy of perampanel in Asian patients with refractory focal seizures; an additional analysis assessed the effect of perampanel on focal impaired awareness seizures (FIAS) with focal to bilateral tonic‐clonic (FBTC) seizures. In this subanalysis, data from Asian patients ≥12 years of age who had focal seizures with FBTC seizures despite taking one to 3 concomitant antiepileptic drugs at baseline, and who had entered either the long‐term extension phase of 3 phase‐3 perampanel trials (study 307) or the 10‐week extension phase of study 335, were analyzed for the effect of perampanel on duration of exposure, safety, and seizure outcomes. Of 874 Asian patients included in the analysis, 205 had previously received placebo during the double‐blind phase‐3 trials and 669 had previously received perampanel 2‐12 mg/day; 313 had FIAS with FBTC seizures at core study baseline. The median duration of exposure to perampanel was 385.0 days, and the retention rate at one year was 62.6%. Overall, during the first 52 weeks of perampanel treatment, 777 patients (88.9%) had treatment‐emergent adverse events (TEAEs), most of which were mild to moderate in severity. The most frequent TEAEs were dizziness (47.1%), somnolence (22.3%), and nasopharyngitis (17.4%). During the first 52 weeks of perampanel treatment, median percent change in seizure frequency per 28 days from pre‐perampanel baseline for all focal seizures was ?28.1%, and ?51.7% for FIAS with FBTC seizures. The 50% responder rate relative to pre‐perampanel baseline for all focal seizures was 33.8%, and 51.1% for FIAS with FBTC seizures. Long‐term treatment with perampanel in Asian patients had safety, tolerability, and efficacy similar to that of the global population in the phase‐3 trials and extension study 307. The safety profile and response rate suggest benefit for an Asian population of patients with refractory epilepsy.     

A comprehensive clinico‐pathological and genetic evaluation of bottom‐of‐sulcus focal cortical dysplasia in patients with difficult‐to‐localize focal epilepsy

Aims. We comprehensively studied the clinical presentation, stereo‐EEG and MRI findings, histopathological diagnosis, and brain somatic mutations in a retrospective series of drug‐resistant patients with difficult‐to‐localize epilepsy due to focal cortical dysplasia at the bottom of a sulcus (BOS‐FCD). Methods. We identified 10 patients with BOS‐FCD from the Cleveland Clinic epilepsy surgery database submitted for intracranial video‐EEG monitoring. Brain MRI, including voxel‐based morphometric analysis and surgical tissue submitted for histopathology, was reviewed. Paraffin tissue samples from five patients were made available for targeted next‐generation sequencing. Postsurgical follow‐up was available in nine patients. Results. BOS‐FCD was identified in the superior frontal sulcus in six patients, inferior frontal sulcus in one patient, central sulcus in one patient, and intraparietal sulcus in two patients. All patients had stereotyped seizures. Intracranial EEG recordings identified ictal onset at the BOS‐FCD in all 10 patients, whereas ictal scalp EEG had a localizing value in only six patients. Complete resection was achieved by lesionectomy or focal corticectomy in nine patients. Histopathologically, six patients had FCD type IIb and three had FCD type IIa. Next‐generation sequencing analysis of DNA extracted from lesion‐enriched (micro‐dissected) tissue from five patients with FCD type II led to the identification of a germline frameshift insertion in DEPDC5, introducing a premature stop in one patient. Eight out of nine patients with available follow‐up were completely seizure‐free (Engel Class IA) after a mean follow‐up period of six years. Conclusion. Our results confirm previous studies classifying difficult‐to‐localize BOS‐FCD into the emerging spectrum of FCD ILAE type II mTORopathies. Further studies with large patient numbers and ultra‐deep genetic testing may help to bridge the current knowledge gap in genetic aetiologies of FCD.     

Distal Baclofen Pump Catheter Migration Associated with Far‐Lateral Paraspinal Surgical Placement

Objectives. The increased rigidity and spasms implicit to patients being treated with baclofen provide a potential source of drug delivery system–related complications. Placement of the intrathecal catheter from the far‐lateral paraspinal approach has been advocated to avoid catheter fracture as previously reported with a midline approach. A thin fascial layer and increased muscle bulk laterally could increase motion of catheters placed in this position. The authors report on a series of patients found to have spinal catheter migration out from the thecal sac following a far‐lateral paraspinal surgical approach. Materials and Methods. The medical records of six consecutive patients who required revision of an intrathecal baclofen infusion system secondary to spinal catheter migration were included in this retrospective review. Each patient failed to respond to oral antispasmodic therapy and showed a positive response to a trial of intrathecal baclofen before initial pump implantation. Clinical notes and operative reports were reviewed. Results. All patients had a baclofen pump inserted with the intrathecal catheter placed through the far‐lateral portion of the paraspinal musculature entering above the lumbar vertebral pedicle. In all cases, the spinal catheter migrated and was found coiled outside of the thecal sac. In two patients, this occurred on two separate occasions. Mean time to catheter revision following implantation was 7 ± 2 months. Conclusions. Spinal catheter migration from the subarachnoid space can occur with intrathecal baclofen infusion systems. Alternative methods for spinal catheter placement warrant further study.     

Intrathecal Morphine Infusion for Chronic Non‐Malignant Pain: A Multiple Center Retrospective Survey

Intrathecal morphine (ITM) is commonly used for the treatment of cancer pain. There is reluctance for its use in France to treat chronic noncancer pain. In order to appreciate its popularity, efficacy, dose escalation with time, and long‐term tolerance, we carried out a retrospective study in the neurosurgery departments of university teaching hospitals in France involved in intrathecal drug therapy. Only 44 patients with chronic noncancer pain used implanted pumps for ITM treatment. Nineteen patients were available for detailed analysis. This survey concerns these 19 patients. There were 13 women and six men. Their average age was 48.8 years (range: 30–69 y). The mean duration of pain before pump implantation was 100 months (range: 12–240 m). The mean follow‐up since implantation was 54 m (range: 4–144 m). Thirteen patients were suffering from postsurgery lumbar and radicular pain. The average initial and final dose per day of morphine was 1.3 mg (range: 1–2 mg) and 2.5 mg (range: 1–6.7 mg) for patients with nociceptive pain and 1.2 mg (range: 0.7–2 mg) and 3 mg (range: 1–10 mg) for patients with mixed pain, respectively. Five (26.3%) of 19 patients returned to their initial jobs. Increase in activity level was reported as good in seven patients (36.8%). Patient satisfaction rate was 90%. The VAS rate was reduced to 49.2% of the initial values while the subjective pain relief was estimated at 67.8%. Two cases (10.5%) of late pump site infection and two patients (10.5%) with catheter displacements were recorded. Side effects imputable to morphine included; constipation, somnolence, decreased libido, weight gain, amenorrhoea, vomiting, nightmares, and itching. No development of tolerance or addiction were recorded. We conclude that in well selected cases ITM should be considered as a possible therapeutic option in the treatment of intractable chronic benign pain.     

Efficacy and tolerability of zonisamide as add‐on in brain tumor‐related epilepsy: preliminary report

Background –  Zonisamide (ZNS) is an antiepileptic drug (AED) with broad spectrum action that demonstrated a good efficacy in controlling seizures as add‐on in adult and pediatric epilepsy. To date there have been no studies on ZNS in patients with brain tumor‐related epilepsy (BTRE). Aim of the study –  To evaluate efficacy and tolerability of ZNS as add‐on in BTRE. Methods– We followed six patients suffering from BTRE who had already been treated with other AEDs and who had had not experienced adequate seizure control. Three patients underwent chemotherapy while being treated with ZNS. Mean duration of follow‐up was 8 months. Results –  Mean seizure number in the last month prior to the introduction of ZNS had been 27.7/month. ZNS mean dosage was of 283.3 mg/day. At last follow‐up, the mean seizure number was reduced to 8.8/month. Responder rate was 83.3%.Two patients discontinued the drug because of side effects. There were no other reported side effects. Conclusions –  Preliminary data on the use of ZNS in add‐on in patients with BTRE indicate that this drug may represent a valid alternative as add‐on in this particular patient population. However, larger samples are necessary to draw definitive conclusions.     

Mechanisms of status epilepticus: α‐Amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid receptor hypothesis

Prolonged seizures of status epilepticus (SE) result from failure of mechanisms of seizure termination or activation of mechanisms that sustain seizures. Reduced γ‐aminobutyric acid type A receptor–mediated synaptic transmission contributes to impairment of seizure termination. However, mechanisms that sustain prolonged seizures are not known. We propose that insertion of GluA1 subunits at the glutamatergic synapses causes potentiation of α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic receptor (AMPAR)‐mediated neurotransmission, which helps to spread and sustain seizures. The AMPAR‐mediated neurotransmission of CA1 pyramidal neurons was increased in animals in SE induced by pilocarpine. The surface membrane expression of GluA1 subunit–containing AMPARs on CA1 pyramidal neurons was also increased. Blockade of N‐methyl‐d ‐aspartate receptors 10 minutes after the onset of continuous electrographic seizure activity prevented the increase in the surface expression of GluA1 subunits. N‐methyl‐d ‐aspartate receptor antagonist MK‐801 in conjunction with diazepam also terminated seizures that were refractory to MK‐801 or diazepam alone. Future studies using mice lacking the GluA1 subunit expression will provide further insights into the role of GluA1 subunit–containing AMPAR plasticity in sustaining seizures of SE.     

Seizures in patients with Alzheimer’s disease or vascular dementia: A population‐based nested case–control analysis

Purpose: Patients with Alzheimer’s disease (AD) have an increased risk of developing seizures or epilepsy. Little is known about the role of risk factors and about the risk of developing seizures/epilepsy in patients with vascular dementia (VD). The aim of this study was to assess incidence rates (IRs) of seizures/epilepsy in patients with AD, VD, or without dementia, and to identify potential risk factors of seizures or epilepsy. Methods: We conducted a follow‐up study with a nested case–control analysis using the United Kingdom–based General Practice Research Database (GPRD). We identified patients aged ≥65 years with an incident diagnosis of AD or VD between 1998 and 2008 and a matched comparison group of dementia‐free patients. Conditional logistic regression was used to estimate the odds ratio (OR) with a 95% confidence interval (CI) of developing seizures/epilepsy in patients with AD or VD, stratified by age at onset and duration of dementia as well as by use of antidementia drugs. Key Findings: Among 7,086 cases with AD, 4,438 with VD, and 11,524 matched dementia‐free patients, we identified 180 cases with an incident diagnosis of seizures/epilepsy. The IRs of epilepsy/seizures for patients with AD or VD were 5.6/1,000 person‐years (py) (95% CI 4.6–6.9) and 7.5/1,000 py (95% CI 5.7–9.7), respectively, and 0.8/1,000 py (95% CI 0.6–1.1) in the dementia‐free group. In the nested case–control analysis, patients with longer standing (≥3 years) AD had a slightly higher risk of developing seizures or epilepsy than those with a shorter disease duration, whereas in patients with VD the contrary was observed. Significance: Seizures or epilepsy were substantially more common in patients with AD and VD than in dementia‐free patients. The role of disease duration as a risk factor for seizures/epilepsy seems to differ between AD and VD.     

Digital Subtraction Angiography‐Dynavision in Pretreatment Planning for Embolization of Dural Arterio‐Venous Fistulas

BACKGROUND AND PURPOSE

We have found DSA‐Dynavision with multiplanar reconstruction very helpful in understanding the complex anatomy and planning of treatment of carotico‐cavernous fistulas. The purpose of our study was to examine whether using DSA‐Dynavision in pretreatment planning results in better outcome after endovascular treatment of dural arterio‐venous fistulas (dAVFs).

METHODS

Patients with dAVF treated with endovascular embolization were retrospectively identified from our interventional neuroradiology database. Patients were assessed and divided into those with DSA‐Dynavision and those without. They were compared for procedural time, angiographic evidence of cure, rates of resolution of cortical venous reflux (CVR), complications, and need for postembolization surgery.

RESULTS

Eighty‐six percent of 28 patients (mean age 57 years, range 1.67‐84 years) had Borden type 3 DAVF; 7% had Borden type 2; and 7% had Borden type 1. DSA‐Dynavision was used in 14 of 28 (50%) patients. Fewer patients with DSA‐Dynavision required postendovascular embolization surgery (7% vs. 50%, P = .01) and fewer DSA‐Dynavision patients had CVR postprocedure (29% vs. 71%, P = .023). Mean procedural time (207 vs. 249 minutes; P = .40); permanent neurological complication rates (7% vs. 7%, P = 1.0); rate of immediate angiographic occlusion (64% vs. 29%, P = .061), and reported resolution of symptoms (79% vs. 53%, P = .18) were not significantly different. There was no significant difference in follow‐up (mean: 75 vs 120 weeks, P = .47).

CONCLUSION

The use of DSA‐Dynavision in planning of endovascular treatment of dAVF is associated with higher rates of elimination of CVR and less need for postembolization surgery.     

Parametric subtracted post‐ictal diffusion tensor imaging for guiding direct neurostimulation therapy

Parametric subtracted post‐ictal diffusion tensor imaging (pspiDTI) is a novel imaging technique developed at our center to visualize transient, patient‐specific, ictal‐associated water diffusion abnormalities in hippocampal‐associated axonal tissue. PspiDTI can elucidate putative connectivity patterns, tracing ictal propagation following a partial‐onset seizure without generalization secondarily. PspiDTI compares two DTI volumes acquired during the early post‐ictal period (<4 hr), and baseline inter‐ictal interval (>24 hr post‐seizure). This technique performs a voxel‐wise parametric test to identify statistically significant transient ictal‐associated changes in water diffusivity involving white matter (WM). Our technique was applied to six patients with refractory partial‐onset epilepsy who were candidates for direct cortical responsive neurostimulation (RNS) therapy. Global and region‐specific fractional anisotropy decreases, relative to baseline, were detected in all patients with a 17.01% (p < .01) relative mean decrement, while trace increases were found in 6/6 (100%) patients with a 13.30% (p < .01) relative global mean increment. Changes in diffusivity were anatomically compared with transient hyper‐perfusion as detected by subtracted ictal SPECT co‐registered to MRI (SISCOM). In 5/6 (83.33%) patients, alterations in WM diffusivity were detected adjacent to the SISCOM signal localized predominantly in gray matter. In 4/6 patients, post‐implant RNS electrocorticography revealed early ictal propagation between implanted RNS depth leads guided by pspiDTI, hence validating concordant abnormal diffusivity regions detected by our technique. PspiDTI can complement the conventional pre‐surgical evaluation to provide additional crucial information regarding WM ictal‐propagation pathways between predominantly gray matter ictal‐onset zones. When incorporated into a multi‐modality pre‐surgical workflow, pspiDTI can aid in defining critical nodes between ictogenic regions. This information can be used to strategically implant a limited set of two RNS depth leads for maximizing the extent to which direct cortical RNS can modulate a potentially extensive epileptogenic network.     

De novo KCNT1 mutations in early‐onset epileptic encephalopathy

KCNT1 mutations have been found in epilepsy of infancy with migrating focal seizures (EIMFS; also known as migrating partial seizures in infancy), autosomal dominant nocturnal frontal lobe epilepsy, and other types of early onset epileptic encephalopathies (EOEEs). We performed KCNT1‐targeted next‐generation sequencing (207 samples) and/or whole‐exome sequencing (229 samples) in a total of 362 patients with Ohtahara syndrome, West syndrome, EIMFS, or unclassified EOEEs. We identified nine heterozygous KCNT1 mutations in 11 patients: nine of 18 EIMFS cases (50%) in whom migrating foci were observed, one of 180 West syndrome cases (0.56%), and one of 66 unclassified EOEE cases (1.52%). KCNT1 mutations occurred de novo in 10 patients, and one was transmitted from the patient's mother who carried a somatic mosaic mutation. The mutations accumulated in transmembrane segment 5 (2/9, 22.2%) and regulators of K⁺ conductance domains (7/9, 77.8%). Five of nine mutations were recurrent. Onset ages ranged from the neonatal period (<1 month) in five patients (5/11, 45.5%) to 1–4 months in six patients (6/11, 54.5%). A generalized attenuation of background activity on electroencephalography was seen in six patients (6/11, 54.5%). Our study demonstrates that the phenotypic spectrum of de novo KCNT1 mutations is largely restricted to EIMFS.