✓ The authors report their experience using a novel surgical approach for resecting tumors located in the posterior parahippocampal gyrus. Prior attempts to resect epileptogenic foci in this location have been limited by a significant risk of injury to lateral temporal lobe cortical and vascular structures. To avoid these potential complications, the authors have used a lateral occipitosubtemporal, computer-assisted stereotactic volumetric approach to resect radiographically defined tumors in seven patients with intraaxial neoplasms of the posteromedial temporal lobe. This series included one female and six male patients, ranging in age from 15 to 67 years, who presented with seizures, visual field loss, or headache. Gross-total resection of three high-grade gliomas, two gangliogliomas, and one mixed glioma was accomplished with no permanent morbidity or operative mortality. The authors conclude that this approach is advantageous for resecting tumors in this location because, by avoiding unnecessary brain resection or retraction, it significantly reduces the risk of injury to lateral temporal lobe structures, helps maintain precise spatial and anatomical orientation for the surgeon, and, like all computer-assisted volumetric approaches, delineates the margin between the tumor and surrounding neural tissue.
Howard L. Weiner and Patrick J. Kelly
Jafar J. Jafar and Howard L. Weiner
✓ In 15% of patients with spontaneous subarachnoid hemorrhage (SAH), the source of bleeding cannot be determined despite repeated cerebral angiography. However, some patients diagnosed as having “SAH of unknown cause” actually harbor undetected aneurysms. The authors report six patients with SAH who, despite multiple negative cerebral angiograms, underwent exploratory surgery due to a high clinical and radiographic suspicion for the presence of an aneurysm. Brain computerized tomography (CT) scans revealed blood located mainly in the basal frontal interhemispheric fissure in four patients, in the sylvian fissure in one patient, and in the interpeduncular cistern in one patient. The patients were evaluated as Hunt and Hess Grades I to III, and had undergone at least two high-quality cerebral angiograms that did not reveal an aneurysm. Vasospasm was visualized in two patients. Three patients rebled while in the hospital. Exploratory surgery was performed at an average of 12 days post-SAH. Five aneurysms were discovered at surgery and were successfully clipped. All four patients with interhemispheric blood were found to have an anterior communicating artery (ACoA) aneurysm. The patient with blood in the sylvian fissure was found to have a middle cerebral artery aneurysm. These aneurysms were partially thrombosed. No aneurysm was detected in the patient with interpeduncular SAH, despite extensive basilar artery exploration. Five patients had an excellent outcome and one patient developed diabetes insipidus. These results show that exploratory aneurysm surgery is warranted, despite repeated negative cerebral angiograms, if the patient manifests the classical signs of SAH with CT scans localizing blood to a specific cerebral blood vessel (particularly the ACoA) and if a second SAH is documented at the same site.
Leandro R. Piedimonte, Ian K. Wailes, and Howard L. Weiner
Mutations in one of two genes, TSC1 and TSC2, result in a similar disease phenotype by disrupting the normal interaction of their protein products, hamartin and tuberin, which form a functional signaling complex. Disruption of these genes in the brain results in abnormal cellular differentiation, migration, and proliferation, giving rise to the characteristic brain lesions of tuberous sclerosis complex (TSC) called cortical tubers. The most devastating complications of TSC affect the central nervous system and include epilepsy, mental retardation, autism, and glial tumors. Relevant animal models, including conventional and conditional knockout mice, are valuable tools for studying the normal functions of tuberin and hamartin and the way in which disruption of their expression gives rise to the variety of clinical features that characterize TSC. In the future, these animals will be invaluable preclinical models for the development of highly specific and efficacious treatments for children affected with TSC.
Leandro R. Piedimonte, Ian K. Wailes, and Howard L. Weiner
Understanding molecular pathways, signaling cascades, and genetic alterations activated during tumorigenesis is essential for the development of targeted cancer treatments. In children, tumors of the central nervous system are thought to arise from progenitor cells that show considerable temporal and spatial heterogeneity in a developmental environment that is different from that of the adult. Investigating the molecular basis of pediatric tumors is critical because it is likely to generate novel treatments. Animal models have brought many important advances in this field. In this review the authors discuss the mouse models based on the Sonic hedgehog pathway, which have provided a better knowledge of the genetic and molecular alterations of medulloblastoma.
Case report and discussion of current therapeutic management
Andrea F. Douglas, Howard L. Weiner, and David R. Schwartz
✓ The authors describe a patient who experienced a prolonged course of intrathecal baclofen withdrawal syndrome after removal of an implantable baclofen pump for treatment of pump infection and meningitis. The current literature outlines management options for the acute management of this syndrome. In this report the authors discuss the long-term presentation of this syndrome and suggest a treatment strategy for management of the syndrome.
A 37-year-old man who presented with a baclofen pump infection and meningitis experienced acute onset of intrathecal baclofen withdrawal syndrome 12 hours after the pump had been surgically removed. The patient's symptoms evolved into a severe, treatment-refractory withdrawal syndrome lasting longer than 1 month.
Oral baclofen replacement with adjunctive administration of parenteral γ-aminobutyric acid agonists only served to stabilize the patient's critical condition throughout his hospital course. Replacement of the baclofen pump and restoration of intrathecal delivery of the medication was necessary to trigger the patient's dramatic recovery and complete reversal of the withdrawal syndrome within approximately 48 hours.
These findings indicate that a more direct method of treating infected baclofen pumps than immediate surgical removal is necessary to prevent the onset of intrathecal baclofen withdrawal syndrome. Various options for preventing the onset of the syndrome while simultaneously treating the infection are discussed.
Bartosz T. Grobelny, Howard L. Weiner, and David H. Harter
A 4-year-old girl with a history of thoracic meningocele repair at the age of 3 months presented with progressive myelopathy. An intramedullary thoracic epidermoid was identified on MRI. The patient underwent excision of the epidermoid and subsequently returned to neurological baseline. This case illustrates the potential for delayed development of intraspinal epidermoid after initial repair of a simple meningocele.
Shaun D. Rodgers, Luigi Bassani, Howard L. Weiner, and David H. Harter
Subependymal giant cell astrocytomas (SEGAs) are benign tumors, most commonly associated with tuberous sclerosis complex (TSC). Arising from the lateral ependymal surface, these tumors may obstruct one or both foramina of Monro, resulting in hydrocephalus and often requiring treatment. Although interhemispheric-transcallosal and transcortical-transventricular approaches have been the standard methods for resecting these tumors, advances in neuroendoscopic techniques have expanded SEGAs as a potential target for endoscopic resection.
The authors present a case of an endoscopically resected SEGA with stereotactic guidance in a 4-year-old girl with TSC. A gross-total resection of an enlarging SEGA was achieved. This represents one of the early case reports of endoscopically resected SEGAs. Although recent advances in medical treatment for SEGAs with mammalian target of rapamycin (mTOR) pathway inhibitors have shown promising initial results, the long-term safety and efficacy of mTOR inhibitors has yet to be determined. The propensity of these tumors to cause obstructive hydrocephalus requires that a surgical option remain. Neuroendoscopic approaches may allow a safe and effective technique.
Proceedings from the Second International Symposium on Central Nervous System Germ Cell Tumors
Mark M. Souweidane, Mark D. Krieger, Howard L. Weiner, and Jonathan L. Finlay
The successful treatment of children with a primary CNS germ cell tumor can be greatly influenced by the neurosurgeon involved in the diagnostic and therapeutic care of these children. Variability in surgical philosophies no doubt exists due to the relatively infrequent incidence of these tumors, a lack of consensus regarding diagnostic and therapeutic approaches, and the advent of recent surgical innovations. Many of these issues were discussed at the Second International Symposium on Central Nervous System Germ Cell Tumors through presented abstracts and invited presentations. The neurosurgical aspects of these proceedings are summarized here in an effort to present the agreed-upon and debated issues that may confront the pediatric neurosurgeon.
Donato Pacione, Francine Blei, Orrin Devinsky, Howard L. Weiner, and Jonathan Roth
Surgery is increasingly used to treat children with refractory epilepsy. Before surgery, the authors routinely evaluated the coagulation profile to identify coagulation abnormalities not established by personal and family history, physical examination, and routine screening tests.
Thirty-nine consecutive children undergoing testing prior to epilepsy surgery were prospectively evaluated. The authors evaluated a detailed hematological history and an elaborative hematological panel including complete blood count, hepatic panel, anticoagulant levels, coagulation profile (prothrombin time, partial thromboplastin time, international normalized ratio, fibrinogen, thrombin time, von Willebrand antigen, ristocetin cofactor, factor VIII, and individual factor assays when indicated) and platelet aggregation studies (in the presence of adenosine diphosphate, epinephrine, collagen, and ristocetin). Patient variables included tuberous sclerosis complex (TSC), age at epilepsy onset, age at surgery, seizure frequency, number and type of antiepileptic drugs, recent or present ketogenic diet, and use of selective serotonin reuptake inhibitors.
Ten children (25.6%) had either coagulation or platelet function abnormalities. Abnormal coagulation was identified in 5 children, and abnormal platelet function was discovered in 6. A diagnosis of TSC was associated with a platelet function abnormality (p = 0.012), whereas children without TSC had a higher rate of coagulopathy (p = 0.041). None of the other characteristics reached statistical significance. In 2 patients (5.1%) with TSC and platelet aggregation abnormalities, the authors noted normal standard screening laboratory studies and an uneventful detailed personal and family history. One of these 2 patients developed a significant intraoperative bleeding complication.
A preoperative screening with standard laboratory studies and detailed history may not be adequate to fully examine underlying coagulation abnormalities in children with refractory epilepsy. Platelet aggregation studies should be considered in patients with TSC.
Joel S. Katz, Sarah S. Milla, Graham C. Wiggins, Orrin Devinsky, Howard L. Weiner, and Jonathan Roth
Tuberous sclerosis complex (TSC) can manifest with 3 principal intracranial pathological entities: cortical tubers, subependymal nodules (SENs), and subependymal giant cell astrocytomas (SEGAs). The authors analyzed the location and growth of intraventricular lesions in a large cohort of patients with TSC.
After institutional review board protocol approval, the authors retrospectively reviewed brain MRI scans of TSC patients for whom at least 1 electronically stored cranial MRI study was available. Collected data included location, size, and growth over time of all intraventricular lesions.
The authors reviewed 560 scans in 103 patients, who harbored 496 intraventricular lesions. Of the 496 lesions, 157 lesions were located along the caudate-thalamic groove (CTG) in 88 patients. Twenty SEGAs were operated on. The remaining 339 lesions were distributed along the lateral ventricle, always in contact with the course of the caudate nucleus, and were presumed to be SENs. Twenty-two patients with more than 4 years of follow-up had 34 lesions along the CTG, of which 23 were stable in size and 11 grew. All other intraventricular lesions were stable. Seven-Tesla MRI showed the intimate association of SENs and the caudate nucleus in 1 patient.
Intraventricular lesions in TSC patients are located throughout the lateral ventricular wall. Their location exclusively follows the course of the caudate nucleus. Only lesions along the CTG showed the potential to grow, and these were then identified as SEGAs. The remaining lesions were SENs. Understanding why these lesions develop in relation to the caudate nucleus may offer insights into therapy.