The prognosis for patients with malignant glioma, which is the most common primary intracranial neoplasm, remains dismal despite significant progress in neurooncological therapies and technology. This is largely due to the inability of current treatment strategies to address the highly invasive nature of this disease. Malignant glial cells often disseminate throughout the brain, making it exceedingly difficult to target and treat all intracranial neoplastic foci, with the result that tumor recurrence is inevitable despite aggressive surgery and adjuvant radiotherapy and/or chemotherapy. The use of neural stem cells (NSCs) as delivery vehicles for tumor-toxic molecules represents the first experimental strategy aimed specifically at targeting disseminated tumor pockets. Investigators have demonstrated that NSCs possess robust tropism for infiltrating tumor cells, and that they can be used to deliver therapeutic agents directly to tumor satellites, with significant therapeutic benefit. With the aim of developing these findings into a clinically viable technology that would not be hindered by ethical and tissue rejection–related concerns, the use of adult tissue–derived stem cells has recently been explored. These technologies represent important progress in the development of a treatment strategy that can specifically target disseminated neoplastic pockets within the brain. Despite encouraging results in preclinical models, however, there are significant impediments that must be overcome prior to clinical implementation of this strategy. Key among these are an inadequate understanding of the specific tropic mechanisms that govern NSC migration toward invasive tumor, and the need to refine the processes used to generate tumor-tropic stem cells from adult tissues so that this can be accomplished in a clinically practicable fashion. Despite these limitations, the use of stem cell therapies for brain tumors holds significant promise and may emerge as an important therapeutic modality for patients with malignant glioma.
Moneeb Ehtesham, Charles B. Stevenson, and Reid C. Thompson
Charles B. Stevenson, Mahlon D. Johnson, and Reid C. Thompson
Dean A. Hertzler II, John J. DePowell, Charles B. Stevenson, and Francesco T. Mangano
Tethered cord syndrome (TCS) is a clinical condition of various origins that arises from tension on the spinal cord. Radiographic findings may include the conus medullaris in a lower than normal position, fatty infiltration of the filum terminale, lipomyelomeningocele, myelomeningocele, myelocystocele, meningocele, split cord malformations, dermal sinus, anorectal malformations, and intraspinal tumors. The clinical constellation of signs and symptoms associated with TCS may include dermatologic, urological, gastrointestinal, neurological, and orthopedic findings. The current review focuses on TCS by age group of the more common causes of the condition, including myelomeningocele, lipomyelomeningocele, as well as the adult presentation of occult TCS. Pertinent review of the neuroembryology and normal anatomical position of the conus medullaris is included.
Charles B. Stevenson, James L. Leach, Anita Gupta, and Kerry R. Crone
The operative indications and treatment algorithms for pediatric patients with Chiari Type I malformation (CM-I) vary widely. When an intradural approach and duraplasty are thought necessary at the time of surgery, neurosurgeons may elect to fulgurate or resect a portion of the cerebellar tonsils. Histological analyses of cerebellar tonsils resected during decompression in pediatric patients with CM-I have revealed multiple abnormal findings including extensive ischemic and degenerative changes. The authors describe an interesting phenomenon of cystic degeneration in the distal ends of the cerebellar tonsils in children undergoing operative treatment of CM-I.
The authors reviewed the clinical database of 440 pediatric patients who underwent surgical decompression for CM-I performed by a single surgeon. The clinical course, preoperative MR imaging and intraoperative ultrasound characteristics, and histological findings in 3 children found to have tonsillar cystic degeneration were analyzed and detailed.
Cystic changes were subtle but uniformly evident on preoperative MR imaging and were more readily apparent on intraoperative ultrasonography. In each patient, the tonsillar cyst was resected. Histological examination revealed areas of cystic degenerative change characterized by distortion of the normal cerebellar architecture with absent Purkinje and internal granular cell layers. All children experienced improvement in their symptoms, without complication, postoperatively.
Cystic degeneration of the tonsils in pediatric patients with CM-I is an uncommon pathological process most likely resulting from long-standing and excessive compression. Based on their experience, the authors advocate expeditious surgical treatment, including intradural exploration and capacious duraplasty, for patients in whom there is evidence of this phenomenon on preoperative imaging.
Weihong Yuan, Charles B. Stevenson, Mekibib Altaye, Blaise V. Jones, James Leach, Mykhailo Lovha, Noa Rennert, and Francesco T. Mangano
The aim of this study was to investigate diffusion tensor imaging (DTI), an objective and noninvasive neuroimaging technique, for its potential as an imaging biomarker to predict the need and timing of CSF diversion surgery in patients after prenatal myelomeningocele (MMC) repair.
This was a retrospective analysis of data based on 35 pediatric patients after prenatal MMC repair (gestational age at birth 32.68 ± 3.42 weeks, range 24–38 weeks; 15 females and 20 males). A logistic regression analysis was used to classify patients to determine the need for CSF diversion surgery. The model performance was compared between using the frontooccipital horn ratio (FOHR) alone and using the FOHR combined with DTI values (the genu of the corpus callosum [gCC] and the posterior limb of the internal capsule [PLIC]). For patients who needed to be treated surgically, timing of the procedure was used as the clinical outcome to test the predictive value of DTI acquired prior to surgery based on a linear regression analysis.
Significantly lower fractional anisotropy (FA) values in the gCC (p = 0.014) and PLIC (p = 0.037) and higher mean diffusivity (MD) values in the gCC (p = 0.013) were found in patients who required CSF diversion surgery compared with those who did not require surgery (all p values adjusted for age). Based on the logistic regression analysis, the FOHR alone showed an accuracy of performance of 0.69 and area under the receiver operating characteristic curve (AUC) of 0.60. The performance of the model was higher when DTI measures were used in the logistic regression model (accuracy = 0.77, AUC = 0.84 for using DTI values in gCC; accuracy = 0.75, AUC = 0.84 for using DTI values in PLIC). Combining the DTI values of the gCC or PLIC and FOHR did not improve the model performance when compared with using the DTI values alone. In patients who needed CSF diversion surgery, significant correlation was found between DTI values in the gCC and the time interval between imaging and surgery (FA: ρ = 0.625, p = 0.022; MD: ρ = −0.6830, p = 0.010; both adjusted for age and FOHR).
The authors’ data demonstrated that DTI could potentially serve as an objective biomarker differentiating patients after prenatal MMC repair regarding those who may require surgery for MMC-associated hydrocephalus. The predictive value for the need and timing of CSF diversion surgery is highly clinically relevant for improving and optimizing decision-making for the treatment of hydrocephalus in this patient population.