Yoshua Esquenazi

Stereotactic laser ablation of epileptogenic periventricular nodular heterotopia

Periventricular nodular heterotopia (PVNH) is a neuronal migrational disorder often associated with pharmacoresistant epilepsy (PRE). Resective surgery for PVNH is limited by its deep location, and the overlying eloquent cortex or white matter. Stereotactic MR guided laser interstitial thermal therapy (MRgLITT) has recently become available for controlled focal ablation, enabling us to target these lesions. We here demonstrate the novel application and techniques for the use of MRgLITT in the management of PVNH epilepsy. Comprehensive presurgical evaluation, including intracranial EEG monitoring in two patients revealed the PVNH to be crucially involved in their PRE. We used MRgLITT to maximally ablate the PVNH in both cases. In the first case, seizure medication adjustment coupled with PVNH ablation, and in the second, PVNH ablation in addition to temporal lobectomy rendered the patient seizure free. A transient visual deficit occurred following ablation in the second patient. MRgLITT is a promising minimally invasive technique for ablation of epileptogenic PVNH, a disease not generally viewed as surgically treatable epilepsy. We also show here the feasibility of applying this technique through multiple trajectories and to create lesions of complex shapes. The broad applicability and long term efficacy of MRgLITT need to be elaborated further.

Clinical and Biochemical Impact of the d3 Growth Hormone Receptor Genotype in Acromegaly

CONTEXT Lack of exon 3 of the GH receptor (d3-GHR) has been associated with increased responsiveness to GH therapy. By analogy, we hypothesized that patients with acromegaly bearing the d3-GHR genotype may have a more morbid clinical and biochemical picture. OBJECTIVE Our objective was to determine whether the GHR genotype, by modifying tissue sensitivity to GH, influences the clinical/biochemical expression of acromegaly and its outcome after treatment. SETTING The study was conducted at a specialized clinic at a tertiary care hospital. DESIGN, PATIENTS, AND METHODS We conducted a prospective genotype investigation and retrospective analysis and correlation with clinical, biochemical, and outcome data from a group of 148 patients. Samples from 175 healthy blood donors were used as controls. GHR genotyping was performed by real-time PCR. MAIN OUTCOME MEASURES We assessed prevalence of the three GHR genotypes (fl/fl, d3/d3, and d3/fl), associations between the genotypes, and baseline as well as post-therapeutic characteristics. RESULTS Prevalence of the fl/fl, d3/d3, and d3/fl genotypes was 45, 22, and 32%, respectively, similar to what was found in the controls. Baseline characteristics were similar in carriers of the three genotypes. A positive correlation between IGF-I and log GH concentrations was significant only in homo- or heterozygous d3 carriers. Among d3-GHR carriers, diabetes, but no other comorbidities, was more prevalent (odds ratio = 2.02; 95% confidence interval = 0.96-4.2). d3-GHR carriers had significantly higher IGF-I concentrations after treatment. Multiple regression analysis revealed that the homo- or heterozygous lack of exon 3 was the strongest predictor of persistent biochemical activity (odds ratio = 1.29; 95% confidence interval = 0.65-2.58). CONCLUSIONS The absence of exon 3 of the GHR may be associated with a more morbid acromegalic clinical and biochemical picture and a lower chance of achieving IGF-I normalization after therapy.

Association Between Takotsubo Cardiomyopathy and Axitinib: Case Report and Review of the Literature

Introduction Axitinib, a small molecule tyrosine kinase inhibitor (TKI), has been approved as a second-line novel therapeutic agent in the treatment of advanced renal cell carcinoma (RCC). Axitinib blocks tumor angiogenesis by focusing specifically on the vascular endothelial growth factor receptor (VEGFR) pathway. Clinical trials have demonstrated improved progression-free and overall survival compared with other VEGF inhibitors and TKIs that are currently used as standard therapy. Commonly encountered cardiovascular adverse effects include hypertension, hypertensive crisis, and arterial-venous thrombotic events. Stress-induced cardiomyopathy, also known as takotsubo cardiomyopathy (TCM), has previously been reported in association with fluorouracil (FU), bevacizumab, and sunitinib, but to our knowledge, this relationship has never been described in patients undergoing chemotherapy with axitinib. TCM is a rare disorder that is characterized by acute transient left ventricular dysfunction without evidence of obstructive coronary artery disease. The clinical presentation of TCM cannot be distinguished from the symptoms of an acute myocardial infarction. We here describe a 71-year-old woman who developed TCM in the context of receiving adjuvant therapy with the recently US Food and Drug Administration–approved chemotherapeutic agent axitinib for RCC.

Resection strategies in tumoral epilepsy: Is a lesionectomy enough?

Resection strategies in patients with tumor‐related epilepsy vary from lesionectomy to larger epilepsy operations with no consensus on optimal approaches. The objective of this study is to use our prior experience in the management of these patients, to derive optimal strategies for the surgical management of epilepsy related to brain tumors. A prospectively compiled database of epilepsy and tumor patients was used to identify patients who underwent surgical resection of a neoplasm but then developed epilepsy, or who presented with epilepsy and were found to harbor a brain tumor. Seizure frequency, histopathology, type of surgical resection, and outcomes were compiled. Of 235 epilepsy surgery patients and 75 low/intermediate grade glioma surgery patients, 13 (5.5%) and 21 (28%) patients, respectively, had tumoral epilepsy. Twenty‐two patients were male and 18 tumors were in the left hemisphere. Tumoral epilepsy occurred predominantly in temporal (50%) and perirolandic (26.5%) locations. The etiology was WHO grade I tumors in 29%, grade II in 35%, and grade III in 33%. In the epilepsy group, following lesionectomy in three and tailored resections in the majority, seizure outcomes were Engel class I in all except one case. In the tumor group, after the initial operation seven additional resections were performed due to seizure recurrence. Outcomes in this group were Engel class 1A in 18 patients and 1B, 1C and IIA in 1 patient each. Drawing upon these data, we propose a classification of the likely reasons of failure in seizure control in patients with tumoral epilepsy. This review reiterates the concept that a complete resection of the lesion is the best approach for dealing with tumors presenting with epilepsy. Overall excellent outcomes can be accomplished following aggressive initial tumor resection, re‐resection in the context of recurrence, and epilepsy style operations in selected patients with a longer history of seizures.

Traumatic rupture of an intracranial dermoid cyst: Case report and literature review

Background: Dermoid tumors are benign congenital cystic lesions that usually present with local mass effect. Very rarely, they present as spontaneous ruptures. Traumatic rupture of these dermoid cysts is an extremely rare event and only a handful of such cases have been ever reported. Case Description: A 47-year-old female presented to our hospital with a ruptured intracranial dermoid cyst following a mild head injury. The ruptured cyst contents were disseminated into the subarachnoid and intraventricular compartments, resulting in an obstructive hydrocephalus. After medical stabilization, she underwent gross total resection of the cyst using combined transsylvian, transcortical-transventricular, and sub-frontal approaches. A ventriculo-peritoneal shunt was eventually also needed. Conclusion: Traumatic rupture of an intracranial dermoid cyst is an extremely rare event and this is only the fourth such case reported in the literature. We presume that this rupture occurs due to sudden shifts in the cyst sac, which is adherent to some partially mobile intracranial contents. Although computed tomography (CT) is often adequate in making a diagnosis of this entity, magnetic resonance imaging (MRI) provides complete characterization of the extent of lipid dissemination, and is essential for operative planning. Intravenous steroids at presentation are helpful in managing the aseptic meningitis associated with rupture. Complete surgical resection is the goal, but must be weighed against the risk for injury to nearby vital structures. Hydrocephalus should be managed promptly, and patients should be monitored for it closely in the perioperative period. Even though the recurrence rate with subtotal resection is extremely rare, follow up should be done routinely.

Surgical management and outcome of iatrogenic radial nerve injection injuries

OBJECTIVE Iatrogenic injury to the radial nerve can occur following intramuscular or intravenous injections of the upper extremity. In this study, we review the injury mechanism, operative techniques, and outcomes of patients evaluated for radial nerve injection injuries. METHODS Data from 33 patients evaluated by the senior authors (DGK and DHK) from 1970-2011 with radial nerve injection injuries were reviewed retrospectively. All patients had injury of the nerve during injection. All corrective operations involved the use of direct intraoperative nerve action potential (NAP) recordings and either neurolysis, neurectomy, or suture/graft repair. The Louisiana State University Health Science (LSUHS) grading system was used for clinical assessment. RESULTS Of the 33 patients, 23 underwent surgical intervention for persistent neurological deficit and/or pain. Of the 24 patients evaluated for injuries at the arm level, 17 required surgical exploration and repair for persistent symptoms. Nine patients required external neurolysis because the lesions were in continuity and positive NAP recording was across the lesion. All of these patients achieved a Grade 4 or better in functional recovery. Eight patients with lesions in continuity but in which NAP could not be recorded underwent either end-to-end suture (7) or graft repair (1) following resection of a 3.0 cm non-recordable segment. All patients achieved Grade 3 or 4 functional recovery. Six patients with forearm injuries involving the superficial sensory branch of radial nerve underwent either neurolysis (3) or neurectomy (3). CONCLUSIONS Surgical exploration may be indicated when pain or disabling motor deficits persist. Early diagnosis and operative intervention can achieve favorable outcomes through exploration and radial nerve repair.

Vagoglossopharyngeal-Associated Syncope Due to a Retained Bullet in the Jugular Foramen

Gunshot wounds (GSWs) to the head are frequently fatal. Rarely, the bullet may lodge in the skull base and not cause significant brain injury. Typically, the bullet fragments are felt to be inert and do not require operative extirpation if they are within the bony confines of the skull base. We report the case of a bullet in the jugular foramen causing recurrent syncope that resolved after surgical removal of the bullet. The medical records from a patient who suffered a GSW to the head were retrospectively reviewed and the treatment and outcome documented. In 2000, a 20-year-old man suffered a GSW to the head. Immediate evaluation revealed the bullet in the right skull base at the jugular foramen, but no parenchymal brain injury. One year after the GSW, he began to experience stereotypical spells resulting in loss of consciousness. Extensive cardiovascular workup was normal. In 2002, the patient underwent removal of the bullet. He has been syncope-free since the operation and returned to his career in the military. We believe the retained bullet in this patient was irritating the IX-X cranial nerves, resulting in syncope, similar to the mechanism in vagoglossopharyngeal neuralgia. Removing the bullet relieved the irritation and stopped the syncopal spells.

Neurosurgical Residency Training in Latin America: Current status, Challenges, and Future opportunities

BACKGROUND This analysis provides an overview of neurosurgery residency programs in Latin America; it evaluates strengths, weaknesses, and limitations within the Latin American Federation for Societies in Neurosurgery countries. Considering the shared cultural background between these neighboring countries and globalization of neurosurgical education, similarities in training characteristics and equal opportunities are expected. However, program differences are inevitable and should be investigated to promote collaboration and homogenization of training. METHODS A 39-item survey was distributed to 970 neurosurgeons and residents in Latin America to assess aspects including working conditions, teaching, research, training, educational opportunities, and socioeconomics. RESULTS In total, 276 neurosurgeons (28%) from 16 countries completed the survey. The average participants age was 37 ± 7 years, and the average duration of residency programs was 5 ± 1 years. Trainees participated in around 5-10 cases during the typical 80-100 work hour week. Only 5% of survey respondents had a day off after a night shift, and 60% worked at least 3 night shifts per week. Only 34% had a mentorship program, Morbidity and mortality conferences were reported by 57% and research activities were compulsory in 45%. Satisfaction with evaluation methods was reported in 29%, although 96% reported satisfaction with their training programs overall. CONCLUSIONS This study is the first of its kind to review neurosurgical training in Latin Americas. Suggested areas of improvement include regulation of working hours, implementation of mentorship programs and standardized examinations, protected research time, increased support for conferences, and more opportunities for exchange rotations that will potentially bolster collaboration between programs.

Fluciclovine, Anti-1-Amino-3-[18F]-Fluorocyclobutane-1-Carboxylic Acid: A Novel Radiotracer for Meningioma

BACKGROUND Meningiomas are the most common primary intracranial tumors. The current diagnosis and treatment of meningioma is dependent on computed tomography and magnetic resonance imaging, with follow-up management relying mainly on magnetic resonance imaging. The limitations of these structural imaging modalities include delineation of the tumor extent, tumor grade, and differentiation from other meningioma mimickers, especially in or around the skull base. Because studies with positron emission tomography (PET) have shown that PET is able to fulfill some of these gaps, the use of PET for meningiomas has been steadily increasing. Fluciclovine, also known as anti-1-amino-3-[18F]-fluorocyclobutane-1-carboxylic acid (Axumin), is a new PET radiotracer approved by the Food and Drug Administration in 2016 for the detection of suspected recurrent prostate cancer with elevated prostate-specific antigen levels. Because the radiotracer is new, very little is known about the utility of this tracer in brain tumors. CASE DESCRIPTION We present 3 cases of meningioma with avid uptake of fluciclovine. In each of these cases, the meningioma was incidentally found during surveillance using PET imaging in patients with prostate cancer. CONCLUSIONS These cases illustrate that this new radiotracer has the potential to be a complementary tool in the meningioma workup, treatment, and follow-up, especially for skull base lesions.

Familial Syndromes Involving Meningiomas Provide Mechanistic Insight Into Sporadic Disease

Abstract Currently, there is an incomplete understanding of the molecular pathogenesis of meningiomas, the most common primary brain tumor. Several familial syndromes are characterized by increased meningioma risk, and the genetics of these syndromes provides mechanistic insight into sporadic disease. The best defined of these syndromes is neurofibromatosis type 2, which is caused by a mutation in the NF2 gene and has a meningioma incidence of approximately 50%. This finding led to the subsequent discovery that NF2 loss-of-function occurs in up to 60% of sporadic tumors. Other important familial diseases with increased meningioma risk include nevoid basal cell carcinoma syndrome, multiple endocrine neoplasia 1 (MEN1), Cowden syndrome, Werner syndrome, BAP1 tumor predisposition syndrome, Rubinstein-Taybi syndrome, and familial meningiomatosis caused by germline mutations in the SMARCB1 and SMARCE1 genes. For each of these syndromes, the diagnostic criteria, incidence in the population, and frequency of meningioma are presented to review the relevant clinical information for these conditions. The genetic mutations, molecular pathway derangements, and relationship to sporadic disease for each syndrome are described in detail to identify targets for further investigation. Familial syndromes characterized by meningiomas often affect genes and pathways that are also implicated in a subset of sporadic cases, suggesting key molecular targets for therapeutic intervention. Further studies are needed to resolve the functional relevance of specific genes whose significance in sporadic disease remains to be elucidated.