Reducing Ataxic Side Effects from Ventral Intermediate Nucleus of the Thalamus Deep Brain Stimulation Implantation in Essential Tremor: Potential Advantages of Directional Stimulation.

OBJECTIVE: The aim of the study was to retrospectively evaluate the effect of directional deep brain stimulation (DBS) on ataxia in an essential tremor patient population. MATERIALS AND METHODS: A retrospective chart review of documented Scale for Assessment and Rating of Ataxia (SARA) scores were analyzed using a case-control design. All subjects we evaluated were treated at a single, tertiary care academic center. We reviewed 14 patients who underwent bilateral ventral intermediate nucleus of the thalamus (VIM) implantation with microelectrode recording, with electrodeposition and segmented contact orientation confirmed via postoperative computed tomography. The main outcome was to determine change in ataxia scores between directional versus monopolar circumferential stimulation. RESULTS: Fourteen patients (9 males, median age at implantation 69 [range 63-82]) underwent surgery between October 2017 and July 2020 at the UNC Movement Disorders Center. SARA scores between directional stimulation and monopolar circumferential stimulation demonstrated a significant reduction in total scores with best possible segmented stimulation (n = 13, p < 0.0001, 95% confidence interval [CI] -3.496 to -6.789). This difference remained statistically significant even after removing the SARA tremor subscore (n = 13, p < 0.0001, 95% CI -3.155 to -6.274). In line with prior reports, SARA score changes from the preoperative state were generally worsened when applying monopolar circumferential stimulation bilaterally (n = 13, p = 0.655; 95% CI -2.836 to 4.359), but improved with directional stimulation (n = 13, p = 0.010; 95% CI -1.216 to -7.547). CONCLUSION: This retrospective analysis appears to show evidence for improved outcomes through directional stimulation in bilateral VIM DBS implantation with reduction of ataxic side effects that have traditionally plagued postoperative results, all while providing optimized tremor reduction via stimulation.

Feasibility of stereo electroencephalogram (SEEG) with little to no scalp bone; a case report.

Stereo electroencephalogram (SEEG) electrode placement with cranially fixed guide bolts is recognized as one of the most accurate and safest implantation strategies to sample deep and buried cortex during certain clinical scenarios involving epilepsy surgery. Bone thickness of less than 2 mm is a relative contraindication to SEEG. Here, we describe a case drug-resistant focal epilepsy where prior craniotomies, infections and radiation therapy yielded limited skull bone requiring invasive EEG monitoring. Due to the inability to use bolts over areas with limited skull bone, we successfully utilized a combination of the standard and a modified SEEG techniques for implantation and stabilization of intracranial electrodes without complications. This strategy enabled optimal intracranial EEG monitoring and surgical management of the patient's drug-resistant focal seizures.

Mesial temporal resection following long-term ambulatory intracranial EEG monitoring with a direct brain-responsive neurostimulation system.

OBJECTIVE: To describe seizure outcomes in patients with medically refractory epilepsy who had evidence of bilateral mesial temporal lobe (MTL) seizure onsets and underwent MTL resection based on chronic ambulatory intracranial EEG (ICEEG) data from a direct brain-responsive neurostimulator (RNS) system. METHODS: We retrospectively identified all patients at 17 epilepsy centers with MTL epilepsy who were treated with the RNS System using bilateral MTL leads, and in whom an MTL resection was subsequently performed. Presumed lateralization based on routine presurgical approaches was compared to lateralization determined by RNS System chronic ambulatory ICEEG recordings. The primary outcome was frequency of disabling seizures at last 3-month follow-up after MTL resection compared to seizure frequency 3 months before MTL resection. RESULTS: We identified 157 patients treated with the RNS System with bilateral MTL leads due to presumed bitemporal epilepsy. Twenty-five patients (16%) subsequently had an MTL resection informed by chronic ambulatory ICEEG (mean = 42 months ICEEG); follow-up was available for 24 patients. After MTL resection, the median reduction in disabling seizures at last follow-up was 100% (mean: 94%; range: 50%-100%). Nine patients (38%) had exclusively unilateral electrographic seizures recorded by chronic ambulatory ICEEG and all were seizure-free at last follow-up after MTL resection; eight of nine continued RNS System treatment. Fifteen patients (62%) had bilateral MTL electrographic seizures, had an MTL resection on the more active side, continued RNS System treatment, and achieved a median clinical seizure reduction of 100% (mean: 90%; range: 50%-100%) at last follow-up, with eight of fifteen seizure-free. For those with more than 1 year of follow-up (N = 21), 15 patients (71%) were seizure-free during the most recent year, including all eight patients with unilateral onsets and 7 of 13 patients (54%) with bilateral onsets. SIGNIFICANCE: Chronic ambulatory ICEEG data provide information about lateralization of MTL seizures and can identify additional patients who may benefit from MTL resection.

Brain death in low-income countries: a report from Malawi.

Most low-income nations have no practice guidelines for brain death; data describing brain death in these regions is absent. Our retrospective study describes the prevalence of brain death among patients treated in an intensive care unit (ICU) at a referral hospital in Malawi. The primary outcome was designation of brain death in the medical chart. Of 449 ICU patients included for analysis between September 2016 and May 2018, 43 (9.6%) were diagnosed with brain death during the ICU admission. The most common diagnostic reasons for admission among these patients were trauma (49%), malaria (16%) and postoperative monitoring after general abdominal surgery (19%). All patients diagnosed with brain death were declared dead in the hospital, after cardiac death. In conclusion, the incidence of brain death in a Malawi ICU is substantially higher than that seen in high-income ICU settings. Brain death is not treated as clinical death in Malawi.

Using Lean Quality Improvement Tools to Increase Delivery of Evidence-Based Tobacco Use Treatment in Hospitalized Neurosurgical Patients.

BACKGROUND: Health care providers routinely undertreat tobacco dependence, indicating a need for innovative ways to increase delivery of evidence-based care. Lean, a set of quality improvement (QI) tools used increasingly in health care, can help streamline processes, create buy-in for use of evidence-based practices, and lead to the identification of solutions on the basis of a problem's root causes. To date, no published research has examined the use of Lean tools in tobacco dependence. A 12-month QI project using Lean tools was conducted to increase delivery of evidence-based tobacco use treatment (TUT) to hospitalized neurosurgical patients. METHODS: The study team developed a nicotine replacement therapy (NRT) and counseling protocol for neurosurgery inpatients who indicated current tobacco use and used Lean tools to increase protocol adherence. Rates of NRT prescription, referrals to counseling, and follow-up phone calls were compared pre- and postintervention. Secondary measures included patient satisfaction with intervention, quit rates, and reduction rates at 4 weeks postdischarge. RESULTS: Referrals to counseling doubled from 31.7% at baseline to 62.0% after implementation of the intervention, and rates of nicotine replacement therapy (NRT) prescriptions during hospitalization and at discharge increased from 15.3% to 28.5% and 9.0% to 19.3%, respectively. Follow-up phone call rates also dramatically increased. The majority of satisfaction survey respondents indicated that counseling had a positive or neutral impact on stress level and overall satisfaction. CONCLUSION: Lean tools can dramatically increase use of evidence-based TUT in hospitalized patients. This project is easily replicable by professionals seeking to improve delivery of tobacco treatment. These findings may be particularly helpful to inpatient surgical departments that have traditionally been reticent to prescribe NRT.

Initial experience in hybrid PET-MRI for evaluation of refractory focal onset epilepsy.

PURPOSE: We aim to evaluate the utility/improved accuracy of hybrid PET/MR compared to current practice separate 3T MRI and PET-CT imaging for localization of seizure foci. METHOD: In a pilot study, twenty-nine patients undergoing epilepsy surgery evaluation were imaged using PET/MR. This subject group had 29 previous clinical 3T MRI as well as 12 PET-CT studies. Prior clinical PET and MR images were read sequentially while the hybrid PET/MR was concurrently read. RESULTS: The median interval between hybrid PET/MR and prior imaging studies was 5 months (range 1-77 months). In 24 patients, there was no change in the read between the clinical exams and hybrid PET/MR while new anatomical or functional lesions were identified by hybrid PET/MR in 5 patients without significant clinical change. Four new anatomical MR lesions were seen with concordant PET findings. The remaining patient revealed a new abnormal PET lesion without an MR abnormality. All new PET/MR lesions were clinically significant with concordant EEG and/or SPECT results as potential epileptic foci. CONCLUSION: Our initial hybrid PET-MRI experience increased diagnostic yields for detection of potential epileptic lesions. This may be due to the unique advantage of improved co-registration and simultaneous review of both structural and functional data.

Triple pathological findings in a surgically amenable patient with mesial temporal lobe epilepsy.

Mesial temporal sclerosis (MTS) is a well-recognized cause of intractable epilepsy; however, coexistence with focal cortical dysplasia (FCD) is less common. Middle fossa epidermoid cysts are rare and may involve the temporal lobe. Most epidermoids are clinically silent, slow-growing, and seldom associated with overt symptomatology, including seizures. We describe a patient with multiple comorbidities including left MTS and a large epidermoid cyst involving the left quadrigeminal plate cistern compressing upon the cerebellar vermis and tail of the left hippocampus, resulting in refractory left temporal lobe epilepsy. The patient underwent left anterior temporal lobectomy. The surgical pathology demonstrated a third pathological finding of left temporal FCD type Ia. The patient has been seizure-free since the surgery. This case provides additional information with regard to the understanding of epileptogenicity and surgical planning in patients with MTS and epidermoid cysts.

Posterior fossa neoplasm and PHACES syndrome: a case report.

A 4-year-old girl with PHACES syndrome (posterior fossa brain malformations, hemangiomas, arterial anomalies, cardiac anomalies/coarctation of the aorta, eye abnormalities, and sternal clefting/supraumbilical raphe) developed a cerebellar pilocytic astrocytoma 18 months after resolution of her neck, ear, and thoracic hemangiomas. Because cutaneous hemangiomas may have involuted by the time a patient is diagnosed with a central nervous system neoplasm, it seems possible that in other such patients the association may have gone unrecognized. Cerebellar pilocytic astrocytoma may be a rare manifestation of the posterior fossa malformations of PHACES.

Determinants of ictal epileptiform patterns in the hippocampal slice.

PURPOSE: The transition from an interictal to an ictal pattern of epileptiform activity is a strategic target for antiepileptic drug (AED) action. Both the muscarinic agonist pilocarpine and the selective group I metabotropic glutamate receptor (mGluR) agonist (RS)-3,5-dihydroxyphenylglycine (DHPG) produce prolonged synchronous activity in the hippocampal slice that resembles ictal discharges. We evaluated the role of synaptic mechanisms and release of calcium from intracellular stores in the generation of prolonged ictal oscillations. METHODS: Pilocarpine (10 microM) in 7.5 mM[K+]o or DHPG (100 microM) in 5 mM[K+]o artificial cerebrospinal fluid (ACSF) were bath applied to hippocampal slices, and extracellular recordings were made from the CA3 region. The pattern of activity was characterized as ictal if prolonged oscillations of discharges occurred at >2 Hz lasting for >3 s. The pattern of epileptiform activity was characterized and compared with the pattern observed after bath application of pharmacologic agents. RESULTS: The AMPA/kainic acid (KA) glutamate receptor blocker DNQX (20 microM) dampened and stopped ictal oscillations; however, antagonism of N-methyl-d-aspartate (NMDA) or gamma-aminobutyric acid (GABAA) receptors had minimal effects on ictal patterns. Ictal discharges were suppressed by dantrolene (30-100 microM), which blocks release of calcium from intracellular stores, or thapsigargin (1-5 microM), which inhibits the adenosine triphosphatase (ATPase) that maintains intracellular calcium stores. The L-type calcium channel antagonist nifedipine (1 microM) blocked ictal activity produced by pilocarpine or DHPG. CONCLUSIONS: Ictal discharges produced by pilocarpine or DHPG depended on intact synaptic transmission mediated by AMPA/KA receptors, release of calcium from intracellular stores, and L-type calcium channel activation. The results suggest that muscarinic and group I mGluRs activate a positive-feedback system that creates calcium oscillations and prolonged neuronal synchronization mediated by recurrent excitatory synaptic connections in the CA3 region of the hippocampus.

Suppression of pilocarpine-induced ictal oscillations in the hippocampal slice.

Activation of muscarinic cholinergic receptors produces oscillations in the hippocampal slice that resemble the theta rhythm, but also may produce abnormal synchronous activity that is more characteristic of epileptiform activity. We used pilocarpine, a muscarinic agonist and convulsant, and an elevation in extracellular potassium (5-7.5 mM) to produce synchronous neuronal activity that was prolonged (>2 s) and mimicked synchronization noted during seizures in vivo (ictal activity). In the CA3 region of adult rat hippocampal slices, prolonged ictal oscillations consisted of rhythmic field potentials occurring at 4-10 Hz for up to 30 s (ictal duration) that occurred in a regular periodic pattern every 12-166 s (ictal interval). The duration and interval between ictal oscillations were measured before and after application of drugs to define determinants of ictal occurrence. High threshold calcium channel antagonists (nifedipine and verapamil) blocked ictal activity. Release of calcium from intracellular stores also appeared to be important for ictal synchronization because ictal activity was blocked by dantrolene, an inhibitor of calcium release from intracellular stores, and by thapsigargin which blocks the ATPase that maintains intracellular calcium stores. These suppressive effects appeared to be postsynaptic because nifedipine, dantrolene, and thapsigargin had no effect on evoked fEPSPs. Enhancement of presynaptic inhibition by activation of GABA(B) or adenosine A(1) receptors suppressed ictal activity and depressed the amplitude of evoked population synaptic potentials. The results point to an important role for high threshold calcium channels and release of calcium from intracellular stores in addition to strength of synaptic connections in generation of prolonged oscillations that underlie seizure activity.

Focal cortical dysplasias in eloquent cortex: functional characteristics and correlation with MRI and histopathologic changes.

PURPOSE: Focal cortical dysplasia (CD) is increasingly recognized as a common pathologic substrate of medically intractable epilepsy. As these lesions are often localized in the frontal lobe (therefore in potentially eloquent cortex), an understanding of the functional status of the involved region(s) and of its anatomic and pathologic correlates is of prime importance. The purpose of this study is to assess the function of focal CD in relation to magnetic resonance imaging (MRI) and histopathologic features. METHODS: Eight patients operated on for medically intractable epilepsy with histologically proven focal CD involving putative eloquent cortex in the frontal lobe (perirolandic and Broca's areas) were included in the study. Functional regions (motor and language) and epileptogenic areas were assessed by extraoperative electrocorticographic recording and electrical cortical mapping. Cortical functions were correlated with the extent of epileptogenicity on electrocorticographic recordings, MRI features, and histologic characteristics. RESULTS: Language or motor areas were colocalized with epileptogenic regions (n=6 of 8, 75%), but were not mapped in regions of increased signal on fluid-attenuated inversion recovery (FLAIR) MRI (when they were identified) on preoperative MRI (n=5 of 5, 100%). Histologically, balloon cells were almost exclusively found in nonfunctional regions with FLAIR MRI abnormalities. When resected, regions of motor cortex were characterized by cortical dyslamination, columnar disorganization, and dysmorphic neurons, but were devoid of balloon cells. CONCLUSIONS: We found an absence of language or motor functions in perirolandic and Broca's areas that showed decreased epileptogenicity, histopathological evidence of CD with balloon cells and FLAIR MRI signal increase. Language and motor functions were present in epileptogenic and dysplastic areas with no balloon cells and no FLAIR signal abnormalities. These findings have implications on options for epilepsy surgery in patients with CD.

Surgery for hemispheric malformations of cortical development.

The treatment of patients with hemispheric malformations of cortical development presents a challenging clinical problem that often requires surgical intervention. The development of a safe and effective treatment strategy for these patients requires an extensive work-up with a great deal of attention to a variety of multidisciplinary testing methods. In this article, the authors describe the presurgical evaluation of patients with hemispheric malformations of cortical development and epilepsy and review the surgical techniques currently available. They also detail some of the controversial issues regarding surgical treatment of these patients.