Researchers usually conduct preclinical studies using animals to decide whether or not a potential therapy can be safely tested in a clinical study. For this purpose, appropriate animal models, treatment protocols, and endpoints should be determined. In addition, it is important to minimize bias and to perform adequate statistical analysis of the data collected from the animals in order to increase the reproducibility of any preclinical findings. This article summarizes the recent efforts made by stroke researchers to improve the predictive value of animal studies that test potential therapies against ischemic stroke.
ES/iPS cell technology has created a solution for the problems faced in fetal cell therapy for Parkinson's disease (PD), and especially, autografts can now be realized by using iPS cells. We have shown that human ES cell-derived dopaminergic neurons survived in Parkinson's disease model monkeys without tumors, and we have developed an efficient method for making a large quantity of dopaminergic progenitors using the Laminin-511 E8 fragment and cell sorting. Human iPS cell-derived dopaminergic progenitors survived and functioned in a PD rat model using this method. We have also confirmed that autografts of monkey-iPS cell-derived neurons elicited only a minimal immune response in the brain in contrast to allografts. We are planning a clinical study to observe the safety of PD patient-iPS cell-derived dopaminergic progenitors in autografting.
Optimal management of unruptured brain arteriovenous malformations (bAVMs) remains controversial. Unruptured bAVMs are believed to confer a life-long risk of hemorrhage at approximately 1-4% per year. Treatment modalities, such as neurosurgery, radiosurgery and embolization, are able to eliminate the risk of hemorrhage, but are associated with treatment risks. Thus the risk/benefit rationale of treating unruptured bAVMs is unclear. ARUBA (A Randomized Trial of Unruptured Brain Arteriovenous Malformation) was a multi-center randomized controlled trial conducted to compare conservative medical management and active intervention. It was terminated early due to a statistically significant superiority of medical management over interventional treatment, but has itself raised controversy because of its design, results and conclusions. Since its publication in 2014, the implications of ARUBA have already affected neurosurgical practice. However, due to ARUBA's limitations, the findings are not necessarily generalizable to all bAVMs. Treatment of bAVMs should be evaluated on an individual basis, accounting for the location of bAVMs, features of the angio-architecture, patient characteristics, and the individual institutions' experience with each modality of treatment.
It has been reported that metal artifacts make it difficult to use conventional computed tomography (CT) angiography to follow up the status of coil embolization of intracranial aneurysms. Recent advances in dual energy CT technology have made it possible to synthesize virtual monochromatic images and reduce beam-hardening artifacts. Energy subtraction image processing allowed density deletion of the coil within the aneurysm while keeping the contrast agent number high, thus eliminating artifacts from the coil and allowing evaluation of recurrence after coil embolization. Energy modulation allowed visualization of the intravascular stent and evaluation of the status of stent-assisted coil embolization. It is also possible to examine the status of an intravascular stent by optimizing the energy used to image the area after coil embolization. These advances in dual energy CT technology might influence the evaluation of risk in embolic events and guide the duration of anti-platelet therapy after coil embolization.
We studied the usefulness of the exoscope (VITOM Telescope, Karl Storz) assisted surgery combined use with the ViewSite (ViewSiteTM Brain Access System, Vycor Medical) for surgery of deep-seated tumors. Total removal of 6 deep-seated intraparenchymal tumors associated with severe brain edema was performed under visualization by an exoscope following insertion of a clear tube retractor between March and November 2014. Removal of the tumor was started from its surface at the point of contact with the tip of the ViewSite, and was continued in “inside to outside” fashion. Gross total resection was achieved in five patients with metastasis (n=4) or radiation necrosis (n=1), and biopsy was performed in one patient with malignant lymphoma. Microscopic examination found residual tumor in one case, and microscopic hemostasis was required in one case. The exoscope can provide a long working distance and a clear view from outside the operation field, so combined use with the ViewSite is very promising for surgery of deep-seated tumors.
We report an extremely rare case of epidermoid cysts that appeared as multiple intracranial lesions on imaging, leading to aseptic meningitis, hydrocephalus, and malignant transformation. A 67-year-old woman was hospitalized for investigation of headache, nausea, disorientation, and gait disturbance. Ventriculomegaly and the presence of two lesions were noted on CT : one was in the left cerebellopontine angle and the other in the left anterior horn of the lateral ventricle. Both were gadolinium-enhancing lesions on MRI. Cerebrospinal fluid examination revealed a mild increase of cells and protein, and the bacterial culture was negative. At first, a biopsy of the small intraventricular lesion was performed with neuroendoscopy, which was diagnosed pathologically as an epidermoid cyst. Placement of a ventricular peritoneal shunt improved the symptoms of aseptic meningitis and hydrocephalus. The main cerebellopontine angle lesion was monitored, but was resected 9 months later after growth had been noted. The diagnosis was squamous cell carcinoma. Despite radiation and chemotherapy, the disease progressed with intrathecal seeding and the prognosis was poor. It was inferred that the spontaneous rupture of an epidermoid cyst in the ventral brainstem caused aseptic meningitis and non-obstructive hydrocephalus, and the cyst became malignant after repeated, chronic stimulation or inflammation. An epidermoid cyst with unusual features such as contrast effect, aseptic meningitis, hydrocephalus, or multiple lesions may indicate malignant transformation.