Vagus Nerve Stimulation Amplifies Task-Induced Cerebral Blood Flow Increase.

BACKGROUND: Vagus nerve stimulation (VNS) is an established palliative surgical treatment for refractory epilepsy. Recently, pairing VNS with rehabilitation received growing attention for their joint effect on neural plasticity. However, objective biological measurements proving the interaction between VNS effects and cortical recruitment are lacking. Studies reported that VNS induced little blood flow increase in the cerebral cortex. OBJECTIVE: This study tested the hypothesis that pairing VNS with a cognitive task amplifies task-induced cerebral blood flow (CBF). METHODS: This study included 21 patients implanted with vagus nerve stimulator to treat refractory epilepsy. Near-infrared spectroscopy (NIRS) with sensors on the forehead measured CBF changes in the frontal cortices in response to VNS. Cerebral blood flow was measured when VNS was delivered during a resting state or a verbal fluency task. We analyzed the VNS effect on CBF in relation to stimulation intensity and clinical responsiveness. RESULTS: We observed no CBF change when VNS was delivered during rest, irrespective of stimulation intensity or responsiveness. Cerebral blood flow changed significantly when a verbal fluency task was paired with VNS in a stimulation intensity-dependent manner. Cerebral blood flow changes in the non-responders showed no intensity-dependency. CONCLUSION: Our results could be an important biological proof of the interaction between VNS effects and cortical recruitment, supporting the validity of pairing VNS with rehabilitation.

Spontaneous Temporal Pole Encephalocele Presenting with Epilepsy: Report of Two Cases.

BACKGROUND: Refractory temporal lobe epilepsy due to spontaneous temporal pole encephalocele is a rare but increasingly recognized condition. Optimal surgical management is complicated by the lack of knowledge regarding both the extent of the epileptogenic area and the need for repair of the encephalocele. CASE DESCRIPTION: We report two cases that add significant information to these issues. In Case 1, with a 5-year history of refractory seizures, implantation of diagnostic subdural electrodes into the anterior temporal base happened to abolish the seizures completely. No structural changes were evident on postoperative magnetic resonance imaging. In Case 2, with a large encephalocele and a 5-year history of refractory seizures, surgical disconnection of the temporal pole successfully abolished seizures without any need for encephalocele repair. CONCLUSIONS: These two cases support the view that the epileptogenic area is confined to within the temporal pole for spontaneous temporal pole encephalocele. Temporopolar disconnection represents one surgical option for this entity that achieves seizure cessation without requiring extra repair procedures.

Construction and expression of anti-Tn-antigen-specific single-chain antibody genes from hybridoma producing MLS128 monoclonal antibody.

Anti-Tn-antigen monoclonal antibody MLS128 has affinity for three consecutive Tn-antigens (Tn3) more than Tn2. The major aim of this study was to isolate genes encoding MLS128 variable domains to produce a large quantity of recombinant MLS128 antibodies, in turn, allowing the conduct of studies on precise interactions between Tn3- or Tn2-epitopes and MLS128. This study describes cloning of the variable region genes of MLS128, construction of the variable region genes in single-chain variable fragments (scFv) and two scFvs conjugated with human IgG(1) hinge and Fc regions (scFv-Fc) types, and their respective expression in bacterial and mammalian cell. MLS128 scFv protein with the expected specificity and affinity was successfully prepared from inclusion bodies accumulating in Escherichia coli. Construction, expression and purification of two types of MLS128-scFv-Fc proteins with differing linker lengths in Chinese hamster ovary cells demonstrated that the purified scFv-Fc proteins had binding activity specific to the glycoprotein-expressing Tn-antigen clusters. These results revealed that VL and VH genes cloned from the hybridoma represent those of MLS128 and that recombinant antibodies produced from these genes should provide sufficient amounts of binding domains for use in 3D structural studies such as NMR and X-ray analysis.

Right temporal lobe plays a role in verbal memory.

OBJECTIVES: Comparison of preoperative and postoperative neurological functions in patients undergoing resection of brain tumors, in combination with data from diffusion tensor imaging (DTI) studies, can provide direct evidence of anatomical localization of brain function. The goal of the present study was to use these techniques to characterize memory function of the right temporal lobe in five patients with right temporal lobe brain tumors. METHODS: Memory function was tested using the Wechsler Memory Scale-Revised (WMS-R) before and after surgery in five patients with right temporal lobe brain tumors. Preoperative DTI was performed in four of five cases. RESULTS: In all cases, general and verbal memory, including verbal paired association, significantly improved after surgery (P<0.05). The right inferior longitudinal fasciculus (ILF) was compressed by the tumor in all cases. CONCLUSION: These results suggest that the right temporal lobe plays a role in verbal memory and that this function may be associated with the right ILF.

Damage to the upper portion of area 19 and the deep white matter in the left inferior parietal lobe, including the superior longitudinal fasciculus, results in alexia with agraphia.

Analysis of lesions and symptoms in patients with brain tumors combined with information from diffusion tensor imaging provides direct evidence of the anatomical localization of brain function. Using these methods, we evaluated 8 patients who underwent surgery for metastatic brain tumors located in the left occipital lobes between 2007 and 2009. Preoperatively, 4 patients (cases 1-4) had alexia with agraphia while the other 4 patients (cases 5-8) did not. Tractography for the superior longitudinal fasciculus (SLF) was performed before surgery in case 1. The common brain tumors in cases 1-4 were located in the upper portion of area 19, and peritumor edema in that area resulted in compromise of the deep white matter of the inferior parietal lobe (IPL). The SLF was compressed and disrupted in the white matter of the IPL near the upper portion of area 19 in case 1. In cases 5-8, the brain tumors were not located in the upper portion of area 19. These results suggest that damage to the upper portion of area 19 and to the white matter in the left IPL, including the SLF, resulted in alexia with agraphia.

Production of anti-carbohydrate antibodies by phage display technologies: potential impairment of cell growth as a result of endogenous expression.

Anti-mannotriose (Man3) antibodies were previously isolated from a Keio phage library displaying human single chain variable fragments (scFvs) using a neoglycolipid, Man3- dipalmitoylphosphatidylethanolamine. Of three genes constructed, the 5A3 clone was expressed in mouse myeloma NS0 cells as a conjugate with human IgG(1) Fc (scFv-Fc) and characterized (Sakai, K., Shimizu, Y., Chiba, T., Matsumoto-Takasaki, A., Kusada, Y., Zhang, W., Nakata, M., Kojima, N., Toma, K., Takayanagi, A., Shimizu, N., and Fujita-Yamaguchi, Y. (2007) Biochemistry 46, 253-262; Zhang, W., Matsumoto-Takasaki, A., Kusada, Y., Sakaue, H., Sakai, K., Nakata, M., and Fujita-Yamaguchi, Y. (2007) Biochemistry 46, 263-270). Similarly, anti-Le(x) phages were screened from the same library with lacto-N-fucopentaose III (LNFPIII; Le(x))-dipalmitoylphosphatidylethanolamine. Of five phage clones isolated, two scFv genes were constructed to express scFv-Fc proteins in NS0 cells. As was experienced with anti-Man3 scFv-Fc clones, only one anti-LNFPIII clone, 1F12, was successfully produced and purified as an scFv-Fc protein. Although anti-LNFPIII 1F12 and anti-Man3 5A3 scFv-Fc proteins were secreted into media, a decline in scFv-Fc production was observed with both stable clones during early passages. Transient expression of anti-LNFPIII and anti-Man3 scFv-Fc genes in COS-7 cells and subsequent analyses of scFv-Fc protein expression revealed accumulation of translated proteins in the endoplasmic reticulum for scFv-Fc proteins derived from clones that did not survive as stable clones. This report describes the following: (i) isolation of anti-LNFPIII scFv genes; (ii) purification of anti-LNFPIII scFv-Fc proteins from stably and transiently expressed cells; and (iii) extracellular or intracellular localization of two anti-LNFPIII and three anti-Man3 scFv-Fc proteins. The results suggest that expression of anti-Man3 and other anti-carbohydrate antibodies in mammalian cells is disadvantageous for cell growth.

Damage of left temporal lobe resulting in conversion of speech to Sutra, a Buddhist prayer stored in the right hemisphere.

The present study describes a case of a right-handed 74-year-old woman with a brain tumor who showed conversion of speech to Sutra, a Buddhist prayer, which was stored in the right hemisphere according to the Wada test. After surgery, relative improvement in the speech disorder was observed, and frequency of speech production of simple normal words with normal phonology increased. These observations indicate that damage to left temporal lobe resulted in conversion of speech to Sutra, and that Sutra was stored in this patient's right hemisphere.

Deficits in the left inferior longitudinal fasciculus results in impairments in object naming.

The functional characteristics of the left inferior longitudinal fasciculus (ILF) remain unclear. The present study describes a case of a right-handed 74-year-old woman with a brain tumor who showed marked deterioration in object naming ability after invasion of the tumor into the medial region of the left posterior (middle and inferior) temporal lobe just beside the atrium of the lateral ventricle. Diffusion tensor imaging showed possible interruption of the left ILF after invasion of tumor at this site. By contrast, the left superior longitudinal fasciculus (SLF) remained intact after invasion of tumor, and the inferior fronto-occipital fasciculus (IFOF) was already disrupted prior to tumor invasion. These observations indicate that intact ILF function may be required for object naming ability.

Preparation of asialo-agalacto-glycophorin A for screening of anti-Tn antibodies.

Oncogenic antigens such as Tn-antigen (GalNAcα-Ser/Thr) are involved in metastatic processes and are associated with a poor prognosis, thus representing excellent targets for cancer intervention. Available anti-Tn antibodies which can be applied for therapeutics or diagnostics are severely limited mostly because the Tn-antigen epitope by itself is too small to be antigenic in addition to the fact that many carbohydrates are self-antigens. To characterize anti-Tn monoclonal antibodies as well as to perform panning and screening for isolation of anti-Tn single chain variable fragments from phage-display libraries, a large quantity of inexpensive Tn-antigens are needed. In this study, thus, glycophorin A which is a highly glycosylated sialoglycoprotein with approximately 12 O-glycans was sequentially treated with sialidase and ß-galactosidase to remove sialic acid and galactose residues. The resulted product was shown to be an asialo-agalacto-glycophorin A which is reactive to an anti-Tn-antigen antibody. The simple preparation procedures described here would greatly help production and characterization of potentially valuable anti-Tn-antigen antibodies, which can be readily developed for cancer therapeutics and diagnostics.

Surgical treatment of a dural arteriovenous fistula in the superior petrosal sinus of an elderly patient with minimal suboccipital craniotomy: case report.

An 85-year-old woman presented with a dural arteriovenous fistula of the superior petrosal sinus manifesting as venous infarction of the cerebellum. Magnetic resonance imaging and angiography revealed right cerebellar swelling, venous engorgement, and an arteriovenous fistula in the superior petrosal sinus. Our initial attempt to obliterate the lesion through a transvenous endovascular approach failed, so we successfully treated the fistula via surgical interruption of the superior petrosal vein through a small suboccipital craniotomy. Careful examination of the pattern of venous drainage is important to determine surgical indications. This case indicates that minimally invasive open surgery can be effective even in an elderly patient.