Faculty Bibliography

Subependymal giant cell tumors (SGCTs) are observed in 5-20% of patients with tuberous sclerosis complex (TSC) but account for approximately 25% of neurological morbidity. The authors report the case of a 7-year-old girl with TSC and multiple cortical tubers who presented with worsening seizures in the context of the rapid growth of a cystic, calcified, extraventricular SGCT in the right frontal lobe, initially thought to represent a cortical tuber. The tumor and surrounding tubers were excised, and clinical seizures resolved. This is the first report of an extraventricular SGCT in a child with TSC outside the neonatal period

Large acquired intracranial defects can result from trauma or surgery. When reoperation is required because of infection or tumor recurrence, management of the intracranial dead space can be challenging. By providing well-vascularized bulky tissue, intracranial microvascular free flaps offer potential solutions to these life-threatening complications. A multi-institutional retrospective chart and radiographic review was performed of all patients who underwent microvascular free-flap surgery for salvage treatment of postoperative intracranial infections between 1998 and 2006. A total of six patients were identified with large intracranial defects and postoperative intracranial infections. Four patients had parenchymal resections for tumor or seizure and two patients had posttraumatic encephalomalacia. All patients underwent operative debridement and intracranial free-flap reconstruction using the latissimus dorsi muscle ( N = 2), rectus abdominis muscle ( N = 2), or omentum ( N = 2). All patients had titanium ( N = 4) or Medpor ( N = 2) cranioplasties. We concluded that surgery or trauma can result in significant intracranial dead space. Treatment of postoperative intracranial infection can be challenging. Vascularized free tissue transfer not only fills the void, but also provides a delivery system for immune cells, antibodies, and systemically administered antibiotics. The early use of this technique when intracranial dead space and infection coexist is beneficial

We present our technique for extraoperative functional mapping in awake children with supratentorial tumors near eloquent cortex. This technique may help optimize tumor resection and/or the functional outcome, especially when an awake craniotomy is not possible or in the setting of coincident seizures. After subdural electrode implantation, extraoperative functional mapping and seizure focus mapping were performed, followed by staged tumor resection. Gross total resection was achieved in 6 patients and subtotal resection in 2. No complications due to electrode placement or invasive monitoring were observed. Staged resection of pediatric brain tumors near the eloquent cortex appears safe, allows functional mapping in awake patients, and may assist in decisions between maximal tumor resection and optimal functional outcome

AIM: The aim of the study was to evaluate the surgical treatment of epilepsy and detection of possible early surgery predictive elements in patients with tuberous sclerosis complex (TSC). MATERIALS AND METHODS: Forty-two TSC patients with epilepsy were selected and divided into two main groups: definite and fruste forms. Definite forms were divided into different groups: patients with pharmacologically controlled epilepsy, patients with pharmacoresistant epilepsy excluded from surgery after an extensive presurgical assessment, and patients with a pharmacoresistant epilepsy who underwent surgery. We compared the definite TSC groups to identify elements that predict surgical candidacy. Second, we compared all operated patients to assess surgical outcome. CONCLUSION: We found several factors that could predict a surgical intervention even if identification of patients with refractory epilepsy who can benefit from surgery is an evolving process. Also, several positive factors for good surgical outcome were identified. Patients with the fruste form had excellent surgical outcome

BACKGROUND:Individual magnetic resonance imaging (MRI) disease severity measures, such as atrophy or lesions, show weak relationships to clinical status in patients with multiple sclerosis (MS). OBJECTIVE:To combine MS-MRI measures of disease severity into a composite score. DESIGN/METHODS:Retrospective analysis of prospectively collected data. SETTING/METHODS:Community-based and referral subspecialty clinic in an academic hospital. PATIENTS/METHODS:A total of 103 patients with MS, with a mean (SD) Expanded Disability Status Scale (EDSS) score of 3.3 (2.2), of whom 62 (60.2%) had the relapsing-remitting, 33 (32.0%) the secondary progressive, and 8 (7.8%) the primary progressive form. MAIN OUTCOME MEASURES/METHODS:Brain MRI measures included baseline T2 hyperintense (T2LV) and T1 hypointense (T1LV) lesion volume and brain parenchymal fraction (BPF), a marker of global atrophy. The ratio of T1LV to T2LV (T1:T2) assessed lesion severity. A Magnetic Resonance Disease Severity Scale (MRDSS) score, on a continuous scale from 0 to 10, was derived for each patient using T2LV, BPF, and T1:T2. RESULTS:The MRDSS score averaged 5.1 (SD, 2.6). Baseline MRI and EDSS correlations were moderate for BPF, T1:T2, and MRDSS and weak for T2LV. The MRDSS showed a larger effect size than the individual MRI components in distinguishing patients with the relapsing-remitting form from those with the secondary progressive form. Models containing either T2LV or MRDSS were significantly associated with disability progression during the mean (SD) 3.2 (0.3)-year observation period, when adjusting for baseline EDSS score. CONCLUSION/CONCLUSIONS:Combining brain MRI lesion and atrophy measures can predict MS clinical progression and provides the basis for developing an MRI-based continuous scale as a marker of MS disease severity.

Epilepsy surgery for medically refractory seizures among patients with tuberous sclerosis complex (TSC) is a well-accepted treatment option. Many epilepsy centers around the world have published their experience over the past several years, supporting the idea that the best seizure control is obtained when a single tuber and associated epileptogenic zone is documented and targeted surgically. Recent advances in imaging and physiological techniques that reveal the epileptogenic zone have been used successfully in children with TSC who are being evaluated for surgery. As a result, a number of different surgical strategies have emerged, each reflecting the experience, strengths, and referral biases of the individual treating teams. Experience suggests that some patients with TSC who present with seizures that are difficult to localize and do not meet the classic selection criteria for epilepsy surgery may, nevertheless, benefit from surgery. Tuberectomy alone is often not sufficient for obtaining seizure control. Intracranial electrode recordings performed in a large number of children with TSC undergoing epilepsy surgery have raised new questions about the relationship of the cortical tuber to the epileptogenic zone in TSC. A careful assessment of the risks and benefits of any surgical strategy, compared with those associated with continued refractory epilepsy, should be considered by the treating team in conjunction with the patient's family. Epilepsy surgery has not only benefited many children with TSC, but it also facilitates the understanding of epileptogenesis in TSC

We describe diffuse glioma-like infiltrates in excised tubers in five out of forty Tuberous sclerosis complex (TSC) patients undergoing excision of a tuber at our institution within the last 10 years. All patients presented with refractory seizures. Resection specimens from four patients had the pathognomonic histologic features of neuroglial hamartomas (tubers) and in one case there was cortical microdysgenesis lacking cells typical of TSC. All lesions were associated with an infiltrate of atypical, mostly elongate, glioma-like small cells, which were immunoreactive for GFAP in three, and pS6 (a marker for activity of the mTOR pathway), in two cases. MAP-2 and CD34, were negative and MIB-1 (Ki67) immunostains ranged from <1-21%. Array-based comparative genomic hybridization revealed that these proliferative phenomena were associated with 21 different copy number aberrations in comparison with a tuber without atypical infiltrates. Postoperatively (follow-up period ranging from 8 to 34 months) none of the patients have any evidence of a glioma. We report that tubers resected for treatment of seizures are sometimes associated with glioma-like lesions, which are indistinguishable from infiltrating gliomas by morphology and immunohistochemistry. Genomic analysis with SNP arrays revealed copy number changes which may be associated with the pathogenesis of such infiltrates