Responsive neurostimulation of thalamic nuclei for regional and multifocal drug-resistant epilepsy in children and young adults.

OBJECTIVE: Responsive neurostimulation (RNS) is a US FDA-approved form of neuromodulation to treat patients with focal-onset drug-resistant epilepsy (DRE) who are ineligible for or whose condition is refractory to resection. However, the FDA approval only extends to use in patients with one or two epileptogenic foci. Recent literature has shown possible efficacy of thalamic RNS in patients with Lennox-Gastaut syndrome and multifocal epilepsy. The authors hypothesized that RNS of thalamic nuclei may be effective in seizure reduction for patients with multifocal or regionalized-onset DRE. METHODS: The authors performed a retrospective chart review of all patients who had an RNS device managed at Texas Children's Hospital between July 2016 and September 2023, with at least one active electrode in the thalamic nuclei and ≥ 12 months of postimplantation follow-up. Information conveyed by the patient or their caregiver provided data on the change in the clinical seizure frequency, quality of life (QOL), and seizure severity between the preimplantation baseline visit and the last office visit (LOV). RESULTS: Thirteen patients (ages 8-24 years) were identified with active RNS leads in thalamic nuclei (11 centromedian and 2 anterior nucleus). At LOV, 46% of patients reported 50%-100% clinical seizure reduction (classified as responders), 15% reported 25%-49% reduction, and 38% reported < 25% reduction or no change. Additionally, 42% of patients reported subjective improvement in QOL and 58% reported improved seizure severity. Patients with focal cortical dysplasia (FCD) responded strongly: 3 of 5 (60%) reported ≥ 80% reduction in seizure burden and improvement in seizure severity and QOL. Patients with multifocal epilepsy and bilateral thalamocortical leads also did well, with all 3 reporting ≥ 50% reduction in seizures. CONCLUSIONS: RNS of thalamic nuclei shows promising results in reducing seizure burden for patients with multifocal or regional-onset DRE, particularly in a bilateral thalamocortical configuration or when addressing an underlying FCD.

Brain tumor-related epilepsy management: A Society for Neuro-oncology (SNO) consensus review on current management.

Tumor-related epilepsy (TRE) is a frequent and major consequence of brain tumors. Management of TRE is required throughout the course of disease and a deep understanding of diagnosis and treatment is key to improving quality of life. Gross total resection is favored from both an oncologic and epilepsy perspective. Shared mechanisms of tumor growth and epilepsy exist, and emerging data will provide better targeted therapy options. Initial treatment with antiseizure medications (ASM) in conjunction with surgery and/or chemoradiotherapy is typical. The first choice of ASM is critical to optimize seizure control and tolerability considering the effects of the tumor itself. These agents carry a potential for drug-drug interactions and therefore knowledge of mechanisms of action and interactions is needed. A review of adverse effects is necessary to guide ASM adjustments and decision-making. This review highlights the essential aspects of diagnosis and treatment of TRE with ASMs, surgery, chemotherapy, and radiotherapy while indicating areas of uncertainty. Future studies should consider the use of a standardized method of seizure tracking and incorporating seizure outcomes as a primary endpoint of tumor treatment trials.

Characteristics of non-sleep related apneas in children with alternating hemiplegia of childhood.

BACKGROUND: Non-sleep related apnea (NSA) has been observed in alternating hemiplegia of childhood (AHC) but has yet to be characterized. GOALS: Investigate the following hypotheses: 1) AHC patients manifest NSA that is often severe. 2) NSA is usually triggered by precipitating events. 3) NSA is more likely in patients with ATP1A3 mutations. METHODS: Retrospective review of 51 consecutive AHC patients (ages 2-45 years) enrolled in our AHC registry. NSAs were classified as mild (not needing intervention), moderate (needing intervention but not perceived as life threatening), or severe (needing intervention and perceived as life threatening). RESULTS: 19/51 patients (37 %) had 52 NSA events (6 mild, 11 moderate, 35 severe). Mean age of onset of NSA (± Standard Error of the Mean (SEM)): 3.8 ± 1.5 (range 0-24) years, frequency during follow up was higher at younger ages as compared to adulthood (year 1: 2.2/year, adulthood: 0.060/year). NSAs were associated with triggering factors, bradycardia and with younger age (p < 0.008 in all) but not with mutation status (p = 0.360). Triggers, observed in 17 patients, most commonly included epileptic seizures in 9 (47 %), anesthesia, AHC spells and intercurrent, stressful, conditions. Management included use of pulse oximeter at home in nine patients, home oxygen in seven, intubation/ventilatory support in seven, and basic CPR in six. An additional patient required tracheostomy. There were no deaths or permanent sequalae. CONCLUSIONS: AHC patients experience NSAs that are often severe. These events are usually triggered by seizures or other stressful events and can be successfully managed with interventions tailored to the severity of the NSA.

Responsive Neurostimulation for the Treatment of Children With Drug-Resistant Epilepsy in Tuberous Sclerosis Complex.

BACKGROUND: To review seizure outcomes in children with tuberous sclerosis complex (TSC) and drug-resistant epilepsy (DRE) treated with the responsive neurostimulation (RNS) System. METHODS: We retrospectively reviewed children (<21 years old) with TSC implanted with the RNS System at Texas Children's Hospital between July 2016 and May 2022. RESULTS: Five patients meeting the search criteria were identified (all female). The median age of the RNS implantation was 13 years (range: 5 to 20 years). The median epilepsy duration before the RNS implantation was 13 years (range: 5 to 20 years). Surgeries before RNS implantation included vagus nerve stimulator placement (n = 2), left parietal resection (n = 1), and corpus callosotomy (n = 1). The median number of antiseizure medications tried before RNS was 8 (range: 5 to 12). The rationale for the RNS System implantation included seizure onset in eloquent cortex (n = 3) and multifocal seizures (n = 2). The maximum current density for each patient ranged between 1.8 and 3.5 µC/cm2, with an average daily stimulation of 2240 (range: 400 to 4200). There was an 86% median seizure reduction (range 0% to 99%) at a median follow-up duration of 25 months (range: 17 to 25 months). No patient experienced implantation or stimulation-related complications. CONCLUSIONS: We observed a favorable improvement in seizure frequency in pediatric patients with DRE secondary to TSC treated with the RNS System. The RNS System may be a safe and effective treatment for DRE in children with TSC.

An Initial Experience of Completion Hemispherotomy via Magnetic Resonance-Guided Laser Interstitial Therapy.

INTRODUCTION: In carefully selected patients with medically refractory epilepsy, disconnective hemispherotomy can result in significant seizure freedom; however, incomplete disconnection can result in ongoing seizures and poses a significant challenge. Completion hemispherotomy provides an opportunity to finish the disconnection. We describe the use of magnetic resonance-guided laser interstitial thermal ablation (MRgLITT) for completion hemispherotomy. METHODS: Patients treated with completion hemispherotomy using MRgLITT at our institution were identified. Procedural and seizure outcomes were evaluated retrospectively. RESULTS: Five patients (3 males) underwent six MRgLITT procedures (one child treated twice) for completion hemispherotomy at a median age of 6 years (range 1.8-12.9). Two children had hemimegalencephaly, two had Rasmussen encephalitis, and one had polymicrogyria. All five children had persistent seizures likely secondary to incomplete disconnection after their functional hemispherotomy. The mean time from open hemispherotomy to MRgLITT was 569.5 ± 272.4 days (median 424, range 342-1,095). One patient underwent stereoelectroencephalography before MRgLITT. The mean number of ablation targets was 2.3 ± 0.47 (median 2, range 2-3). The mean length of the procedure was 373 min ± 68.9 (median 374, range 246-475). Four of the five patients were afforded improvement in their neurocognitive functioning and speech performance after ablation, with mean daily seizure frequency at 1 year of 1.03 ± 1.98 (median 0, range 0-5). Two patients achieved Engel Class I outcomes at 1 year after ablation, one was Engel Class III, and two were Engel Class IV. The mean follow-up time was 646.8 ± 179.5 days (median 634, range 384-918). No MRgLITT-related complications occurred. Delayed retreatment (>1 year) occurred in three patients: one child underwent redo ablation and two underwent anatomic hemispherectomy. CONCLUSION: We have demonstrated the feasibility of a minimally invasive approach for completion hemispherotomy using MRgLITT. Delayed retreatment was needed in three patients; thus, further study of this technique with comparison to other surgical techniques is warranted.

Epilepsy Surgery in Young Children With Tuberous Sclerosis Complex: A Novel Hybrid Multimodal Surgical Approach.

BACKGROUND: Surgery has become integral in treating children with tuberous sclerosis complex (TSC)-related drug-resistant epilepsy (DRE). OBJECTIVE: To describe outcomes of a multimodal diagnostic and therapeutic approach comprising invasive intracranial monitoring and surgical treatment and compare the complementary techniques of open resection and magnetic resonance-guided laser interstitial thermal therapy. METHODS: Clinical and radiographic data were prospectively collected for pediatric patients undergoing surgical evaluation for TSC-related DRE at our tertiary academic hospital. Seizure freedom, developmental improvement, and Engel class were compared. RESULTS: Thirty-eight patients (20 females) underwent treatment in January 2016 to April 2019. Thirty-five underwent phase II invasive monitoring with intracranial electrodes: 24 stereoencephalography, 9 craniotomy for grid/electrode placement, and 2 grids + stereoencephalography. With the multimodal approach, 33/38 patients (87%) achieved >50% seizure freedom of the targeted seizure type after initial treatment; 6/9 requiring secondary treatment and 2/2 requiring a third treatment achieved >50% freedom. The median Engel class was II at last follow-up (1.65 years), and 55% of patients were Engel class I/II. The mean age was lower for children undergoing open resection (2.4 vs 4.9 years, P = .04). Rates of >50% reduction in seizures (86% open resection vs 88% laser interstitial thermal therapy) and developmental improvement (86% open resection vs 83% magnetic resonance-guided laser interstitial thermal therapy) were similar. CONCLUSION: This hybrid approach of using both open surgical and minimally invasive techniques is safe and effective in treating DRE secondary to TSC. Clinical trials focused on treatment method with longer follow-up are needed to determine the optimal candidates for each approach and compare the treatment modalities more effectively.

Comparison of Surgical Outcomes in Individuals With Hypothalamic Hamartoma Alone or With Other Potentially Epileptogenic Focal Lesions.

BACKGROUND: Hypothalamic hamartoma is a rare condition associated with refractory seizures. It can occur in isolation or with additional epileptogenic lesions. The aim of this study was to investigate the effects of additional potentially epileptogenic lesions on surgical outcomes in individuals with hypothalamic hamartoma. METHODS: We conducted a chart review of 112 patients with hypothalamic hamartoma who underwent magnetic resonance imaging (MRI)-guided laser interstitial thermal therapy targeted to the hypothalamic hamartoma. We compared surgical outcomes after at least six months of postoperative follow-up (N = 65) between patients with hypothalamic hamartoma alone and those with hypothalamic hamartoma plus additional potentially epileptogenic lesions. RESULTS: Sixteen out of 112 (14%) patients had additional epileptogenic lesions, including focal cortical dysplasia, gray matter heterotopia, and polymicrogyria. Ten out of 16 patients with additional lesions and 55 out of 96 patients with hypothalamic hamartoma alone had more than six months of follow-up and are included in the outcome analysis. Mean follow-up in these patients is 21.5 ± 17.3 months (standard deviation, range: 7.3-76.8 months) for patients with hypothalamic hamartoma alone and 16.1 ± 15.0 months (standard deviation, range: 6.6-58.2 months) for those with hypothalamic hamartoma plus additional epileptogenic lesions. Fewer patients with hypothalamic hamartoma plus other lesions had Engel class I/II outcomes than patients with hypothalamic hamartoma alone (5/10 [50%] vs 46/55 [83.6%]; P = 0.031). CONCLUSIONS: MRI-guided laser interstitial thermal therapy remains an effective treatment option for patients with hypothalamic hamartoma. However, the outcome of surgical procedures targeted to the hypothalamic hamartoma may be less favorable in patients who have hypothalamic hamartoma coexisting with other potentially epileptogenic focal lesions. Thus, an additional surgical workup is warranted for these patients who have failed surgical treatment of hypothalamic hamartoma.

Antiepileptic drug management in pediatric patients with brain tumor-related epilepsy.

BACKGROUND: Patients with brain tumor-related epilepsy (BTRE) are at a higher risk of significant morbidity, lower quality of life, and increased risk of mortality. We surveyed providers regarding anti-seizure medication (ASM) management in pediatric BTRE to determine if practices are standard or markedly variable. METHODS: An anonymous voluntary online survey was sent to members of the Child Neurology Society. Providers were asked specific questions regarding initiation and wean of ASMs and if this was dependent on multiple factors. Demographic information was collected. RESULTS: Fifty-one providers responded to the survey. Ninety-four percent of providers would start an ASM after a second seizure. Eighty-four percent chose levetiracetam as the preferred ASM. Management was variable when based on tumor location, extent of surgical resection, pathology, and tumor prognosis. Statistically significant differences in responses regarding management were identified when comparing neurologists and epileptologists, providers with formal neuro-oncology or epilepsy training, providers at large institutions, and years of experience. For patients who underwent a gross total resection of the tumor, neuro-oncology and epilepsy-trained providers were more likely to wean off ASMs (p < 0.049). Providers without formal training in neuro-oncology or epilepsy were more likely to get an EEG prior to making a decision about weaning off ASMs (p < 0.016). CONCLUSION: These results suggest that ASM management in BTRE varies greatly according to sub-specialty and experience. Further studies and potential development of guidelines are needed to identify the most appropriate management of ASMs for BTRE.

Epileptic Spasms in a Large Hypothalamic Hamartoma Cohort.

INTRODUCTION: Hypothalamic hamartoma is rarely associated with epileptic spasms. We describe epileptic spasms in a large cohort of hypothalamic hamartoma patients. METHODS: We performed a retrospective chart review between March 2011 and March 2020 to identify patients with hypothalamic hamartoma and epilepsy. RESULTS: We identified 114 patients with hypothalamic hamartoma and epilepsy, only 3 male patients (2.6%) also had epileptic spasms. The epileptic spasms developed between 6 and 18 months of age. Epileptic spasms resolved with oral prednisolone in 1 and with vigabatrin in the second patient. The third patient continued epileptic spasms despite multiple antiepileptic drugs and partial resection of hypothalamic hamartoma. All 3 patients underwent laser-ablation of hypothalamic hamartoma at the age of 14, 29, and 63 months. The seizure burden decreased by 100%, 84%, and 93% at follow-up (3-47 months). CONCLUSIONS: Epileptic spasms are rare in hypothalamic hamartoma patients and early laser-ablation could potentially treat epileptic spasms and all other seizure types associated with hypothalamic hamartoma.

Safety and efficacy of stereoelectroencephalography in pediatric focal epilepsy: a single-center experience.

OBJECTIVE: Patients with medically refractory localization-related epilepsy (LRE) may be candidates for surgical intervention if the seizure onset zone (SOZ) can be well localized. Stereoelectroencephalography (SEEG) offers an attractive alternative to subdural grid and strip electrode implantation for seizure lateralization and localization; yet there are few series reporting the safety and efficacy of SEEG in pediatric patients. METHODS: The authors review their initial 3-year consecutive experience with SEEG in pediatric patients with LRE. SEEG coverage, SOZ localization, complications, and preliminary seizure outcomes following subsequent surgical treatments are assessed. RESULTS: Twenty-five pediatric patients underwent 30 SEEG implantations, with a total of 342 electrodes placed. Ten had prior resections or ablations. Seven had no MRI abnormalities, and 8 had multiple lesions on MRI. Based on preimplantation hypotheses, 7 investigations were extratemporal (ET), 1 was only temporal-limbic (TL), and 22 were combined ET/TL investigations. Fourteen patients underwent bilateral investigations. On average, patients were monitored for 8 days postimplant (range 3-19 days). Nearly all patients were discharged home on the day following electrode explantation. There were no major complications. Minor complications included 1 electrode deflection into the subdural space, resulting in a minor asymptomatic extraaxial hemorrhage; and 1 in-house and 1 delayed electrode superficial scalp infection, both treated with local wound care and oral antibiotics. SEEG localized the hypothetical SOZ in 23 of 25 patients (92%). To date, 18 patients have undergone definitive surgical intervention. In 2 patients, SEEG localized the SOZ near eloquent cortex and subdural grids were used to further delineate the seizure focus relative to mapped motor function just prior to resection. At last follow-up (average 21 months), 8 of 15 patients with at least 6 months of follow-up (53%) were Engel class I, and an additional 6 patients (40%) were Engel class II or III. Only 1 patient was Engel class IV. CONCLUSIONS: SEEG is a safe and effective technique for invasive SOZ localization in medically refractory LRE in the pediatric population. SEEG permits bilateral and multilobar investigations while avoiding large craniotomies. It is conducive to deep, 3D, and perilesional investigations, particularly in cases of prior resections. Patients who are not found to have focally localizable seizures are spared craniotomies.

Use of Anesthesia for Imaging Studies and Interventional Procedures in Children.

Ongoing investigation from the Pediatric Anesthesia NeuroDevelopment Assessment (PANDA) study hopes to examine the long-term effect on cognitive and language development of a single anesthetic exposure in children undergoing inguinal hernia repair. The fifth PANDA Symposium, held in April 2016, continued the mission of previous symposia to examine evidence from basic science and clinical studies on potential neurotoxic effects of anesthetics on developing brain. At the 2016 Symposium, a panel of specialists from nonsurgical pediatric disciplines including anesthesiology, radiology, neurology, gastroenterology, oncology, cardiology, and critical care reviewed use of anesthesia in their practices, including how concern over possible neurodevelopmental effects of early childhood anesthetic exposure has changed discussion with patients and families regarding risks and benefits of imaging studies and interventional procedures involving sedation or anesthesia. This paper summarizes presentations from nonsurgical pediatric specialists at the 2016 PANDA Symposium.

Germline De Novo Mutations in GNB1 Cause Severe Neurodevelopmental Disability, Hypotonia, and Seizures.

Whole-exome sequencing of 13 individuals with developmental delay commonly accompanied by abnormal muscle tone and seizures identified de novo missense mutations enriched within a sub-region of GNB1, a gene encoding the guanine nucleotide-binding protein subunit beta-1, Gß. These 13 individuals were identified among a base of 5,855 individuals recruited for various undiagnosed genetic disorders. The probability of observing 13 or more de novo mutations by chance among 5,855 individuals is very low (p = 7.1 × 10(-21)), implicating GNB1 as a genome-wide-significant disease-associated gene. The majority of these 13 mutations affect known Gß binding sites, which suggests that a likely disease mechanism is through the disruption of the protein interface required for Gα-Gßγ interaction (resulting in a constitutively active Gßγ) or through the disruption of residues relevant for interaction between Gßγ and certain downstream effectors (resulting in reduced interaction with the effectors). Strikingly, 8 of the 13 individuals recruited here for a neurodevelopmental disorder have a germline de novo GNB1 mutation that overlaps a set of five recurrent somatic tumor mutations for which recent functional studies demonstrated a gain-of-function effect due to constitutive activation of G protein downstream signaling cascades for some of the affected residues.

Focal resection of leptomeningeal angioma in a rare case of Sturge-Weber syndrome without facial nevus.

Sturge-Weber syndrome (SWS) is a neurocutaneous disorder comprised typically of a facial nevus, leptomeningeal angioma with calcifications, and seizures. SWS without a port-wine stain is a rare variant with only 30 cases reported in the literature. Here, a case of an 8-year-old girl with no cutaneous abnormalities presenting with medically intractable epilepsy and MRI and CT findings consistent with SWS is described. The patient underwent multistage surgery with subdural electrode monitoring before and after resection of the epileptogenic focus, with complete excision of the lesion and postoperative resolution of her seizures. This is the first reported case of three-stage surgery for localized resection of the seizure focus for SWS.

Novel 9q34.11 gene deletions encompassing combinations of four Mendelian disease genes: STXBP1, SPTAN1, ENG, and TOR1A.

PURPOSE: A number of genes in the 9q34.11 region may be haploinsufficient. However, studies analyzing genotype-phenotype correlations of deletions encompassing multiple dosage-sensitive genes in the region are lacking. METHODS: We mapped breakpoints of 10 patients with 9q34.11 deletions using high-resolution 9q34-specific array comparative genomic hybridization (CGH) to determine deletion size and gene content. RESULTS: The 9q34.11 deletions range in size from 67 kb to 2.8 Mb. Six patients exhibit intellectual disability and share a common deleted region including STXBP1; four manifest variable epilepsy. In five subjects, deletions include SPTAN1, previously associated with early infantile epileptic encephalopathy, infantile spasms, intellectual disability, and hypomyelination. In four patients, the deletion includes endoglin (ENG), causative of hereditary hemorrhagic telangiectasia. Finally, in four patients, deletions involve TOR1A, of which molecular defects lead to early-onset primary dystonia. Ninety-four other RefSeq genes also map to the genomic intervals investigated. CONCLUSION: STXBP1 haploinsufficiency results in progressive encephalopathy characterized by intellectual disability and may be accompanied by epilepsy, movement disorders, and autism. We propose that 9q34.11 genomic deletions involving ENG, TOR1A, STXBP1, and SPTAN1 are responsible for multisystemic vascular dysplasia, early-onset primary dystonia, epilepsy, and intellectual disability, therefore revealing cis-genetic effects leading to complex phenotypes.

Somatic activation of AKT3 causes hemispheric developmental brain malformations.

Hemimegalencephaly (HMG) is a developmental brain disorder characterized by an enlarged, malformed cerebral hemisphere, typically causing epilepsy that requires surgical resection. We studied resected HMG tissue to test whether the condition might reflect somatic mutations affecting genes critical to brain development. We found that two out of eight HMG samples showed trisomy of chromosome 1q, which encompasses many genes, including AKT3, a gene known to regulate brain size. A third case showed a known activating mutation in AKT3 (c.49G→A, creating p.E17K) that was not present in the patient's blood cells. Remarkably, the E17K mutation in AKT3 is exactly paralogous to E17K mutations in AKT1 and AKT2 recently discovered in somatic overgrowth syndromes. We show that AKT3 is the most abundant AKT paralog in the brain during neurogenesis and that phosphorylated AKT is abundant in cortical progenitor cells. Our data suggest that somatic mutations limited to the brain could represent an important cause of complex neurogenetic disease.

Gelastic epilepsy and hypothalamic hamartomas: neuroanatomical analysis of brain lesions in 100 patients.

Hypothalamic hamartomas present with isolated fits of ictal laughter (gelastic epilepsy) or a combination of gelastic and other types of seizures. Many of these patients also suffer from cognitive decline, neuropsychiatric comorbidities and precocious puberty. Although there is a large body of anecdotal evidence about hypothalamic hamartomas and gelastic seizures, many questions still remain to be answered. For instance, which specific hypothalamic regions are most affected by the location of hamartomas causing laughing versus other types of seizures? Does the neuroanatomical localization of the lesions differ in cases with only gelastic seizures or a combination of gelastic and other types of seizures? Does the location of the lesions correlate with the presence of precocious puberty, and does the type of lesion influence the severity or the type of seizures? In a retrospective review of clinical and structural neuroimaging data from 100 cases of gelastic epilepsy and hypothalamic hamartoma, we aimed to address these questions by analysing the clinical presentation and the neuroanatomical features of the hypothalamic lesions in these patients. Our findings suggest that in all 100 cases, lesions were centred at the level of the mammillary bodies in the posterior hypothalamus. Compared with the patients with pure gelastic seizures (n = 32), those with gelastic and other types of seizures (n = 68) had significantly longer duration of epilepsy (P < 0.001), whereas age of seizure onset, the volume of lesions and the proximity to the mammillary bodies were not different between the two groups. In contrast, patients with cognitive or developmental impairment and those with precocious puberty had significantly larger lesions involving the anterior and posterior hypothalamus.

Intraoperative monitoring of motor evoked potentials in very young children.

OBJECT: Neurophysiological monitoring of motor evoked potentials (MEPs) during complex spine procedures may reduce the risk of injury by providing feedback to the operating surgeon. While this tool is a well-established surgical adjunct in adults, clinical data in children are sparse. The purpose of this study was to determine the reliability and safety of MEP monitoring in a group of children younger than 3 years of age undergoing neurosurgical spine procedures. METHODS: A total of 10 consecutive spinal procedures in 10 children younger than 3 years of age (range 5-31 months, mean 16.8 months) were analyzed between January 1, 2008, and May 1, 2010. Motor evoked potentials were elicited by transcranial electric stimulation. A standardized anesthesia protocol for monitoring consisted of a titrated propofol drip combined with bolus dosing of fentanyl or sufentanil. RESULTS: Motor evoked potentials were documented at the beginning and end of the procedure in all 10 patients. A mean baseline stimulation threshold of 533 ± 124 V (range 321-746 V) was used. Six patients maintained MEP signals ≥ 50% of baseline amplitude throughout the surgery. There was a greater than 50% decrease in intraoperative MEP amplitude in at least 1 extremity in 4 patients. Two of these patients returned to baseline status by the end of the case. Two patients had a persistent decrement or variability in MEP signals at the end of the procedure; this correlated with postoperative weakness. There were no complications related to the technique of monitoring MEPs. CONCLUSIONS: A transcranial electric stimulation protocol monitoring corticospinal motor pathways during neurosurgical procedures in children younger than 3 years of age was reliably and safely implemented. A persistent intraoperative decrease of greater than 50% in this small series of 10 pediatric patients younger than 3 years of age predicted a postoperative neurological deficit. The authors advocate routine monitoring of MEPs in this pediatric age group undergoing neurosurgical spine procedures.

Hyperperfusion on magnetic resonance imaging in acute chemotherapy-related leukoencephalopathy.

Acute chemotherapy-related leukoencephalopathy can present similar to acute stroke with symptoms including aphasia, dysarthria, and hemiplegia. Differentiation based on clinical appearance is challenging, and physicians must distinguish between the 2 conditions rapidly to institute appropriate therapies. An 8-year-old male with acute lymphoblastic leukemia receiving chemotherapy, including intrathecal methotrexate, presented to our emergency center with 2 hours of expressive aphasia and flaccid right hemiplegia. Emergent magnetic resonance imaging (MRI) was obtained, demonstrating diffusion restriction within bilateral corona radiata and centrum semiovale. Magnetic resonance perfusion revealed mildly increased perfusion, a finding inconsistent with ischemic stroke and previously unreported in acute chemotherapy-related leukoencephalopathy without necrosis. This increased perfusion conclusively eliminated stroke from the clinical differential. Magnetic resonance perfusion imaging proved valuable to rapidly distinguish acute chemotherapy-related leukoencephalopathy from ischemia, and the evaluation of perfusion alterations in this disorder may provide further insight into the pathophysiology of this entity.

Neuropathology of a fatal case of posterior reversible encephalopathy syndrome.

The pathology of posterior reversible encephalopathy syndrome (PRES) is undefined, since it is rarely fatal and is biopsied in only exceptional circumstances. We describe rapidly progressive PRES following stem cell transplant for acute lymphoblastic leukemia. After development of altered mental status, this 8-year-old girl had T2 prolongation of the white matter in a posterior-dominant distribution, eventually developing cerebellar edema, hemorrhage, hydrocephalus, and herniation. Despite surgical and medical management, she died 36 hours later. At autopsy, the occipital and cerebellar white matter and focal occipital cortical gray matter showed a spectrum of microvascular changes, including dilated perivascular spaces containing proteinaceous exudates and macrophages, as well as fibrinoid necrosis and acute hemorrhage, in a distribution corresponding to the neuroimaging abnormalities and reminiscent of those seen in patients with acute hypertensive encephalopathy. Of note, similar microvascular changes were not seen in the kidney or other systemic sites. Thus, the findings indicate a brain-specific microvascular compromise as the substrate of PRES, at least in the rare instance of cases progressing to fatal outcome.