VNAR development through antigen immunization of Japanese topeshark (Hemitriakis japanica).

The VNAR (Variable New Antigen Receptor) is the smallest single-domain antibody derived from the variable domain of IgNAR of cartilaginous fishes. Despite its biomedical and diagnostic potential, research on VNAR has been limited due to the difficulties in obtaining and maintaining immune animals and the lack of research tools. In this study, we investigated the Japanese topeshark as a promising immune animal for the development of VNAR. This shark is an underutilized fishery resource readily available in East Asia coastal waters and can be safely handled without sharp teeth or venomous stingers. The administration of Venus fluorescent protein to Japanese topesharks markedly increased antigen-specific IgM and IgNAR antibodies in the blood. Both the phage-display library and the yeast-display library were constructed using RNA from immunized shark splenocytes. Each library was enriched by biopanning, and multiple antigen-specific VNARs were acquired. The obtained antibodies had affinities of 1 × 10-8 M order and showed high plasticity, retaining their binding activity even after high-temperature or reducing-agent treatment. The dissociation rate of a low-affinity VNAR was significantly improved via dimerization. These results demonstrate the potential utility of the Japanese topeshark for the development of VNAR. Furthermore, we conducted deep sequencing analysis to reveal the quantitative changes in the CDR3-coding sequences, revealing distinct enrichment bias between libraries. VNARs that were primarily enriched in the phage display had CDR3 coding sequences with fewer E. coli rare codons, suggesting translation machinery on the selection and enrichment process during biopanning.

Subarachnoid Hemorrhage Related to a Ruptured Anterior Spinal Artery Aneurysm Associated with Bilateral Vertebral Artery Occlusion.

Objective: We report a rare case of a ruptured anterior spinal artery (ASA) aneurysm caused by bilateral vertebral artery (VA) occlusion. Case Presentations: A 78-year-old man suddenly developed severe headache and slight hemiparesis, and was admitted to our hospital. Computed tomography (CT) revealed subarachnoid hemorrhage, mainly in the posterior fossa. On emergency angiography, the right VA terminated at the origin of the posterior inferior cerebellar artery (PICA), and anastomoses between the PICA and the anterior inferior cerebellar artery (AICA) were observed, in addition to a saccular 3-mm aneurysm with bleb originating from the PICA-AICA anastomosis. Left vertebral arteriography demonstrated that the left VA was occluded segmentally at the V4 level and revealed a tortuous arterial network filling the distal VA. Based on the location of the bleeding, the right VA aneurysm was considered to have ruptured. After balloon test occlusion of the right VA, parent artery occlusion was performed without complications. The patient had no neurological changes immediately after surgery, but several hours later, he stopped breathing. Retrospective analysis revealed an ASA aneurysm, which was determined to be the bleeding source. Although conservative treatment was performed, he died the fourth day after onset without neurological improvement. Conclusion: In cases of subarachnoid hemorrhage associated with bilateral VA occlusion, an aneurysm formed by hemodynamic stress may be the source of hemorrhage. It is important to suspect aneurysms in the extracranial collaterals, such as the ASA, and intracranial collaterals such as the PICA-AICA anastomosis.

[A Case of Peripheral Middle Cerebral Artery Aneurysm Showing Repeated Morphological Changes].

We describe a case of a peripheral ruptured middle cerebral artery(MCA)aneurysm showing repeated morphological changes within a short period of 3 months. A 69-year-old woman was admitted to her primary care hospital with headache. Cranial computed tomography (CT) showed subarachnoid hemorrhage (SAH), but ruptured aneurysm was not confirmed on 4-vessel cerebral angiography. Conservative treatment was provided in the form of pain relief and blood pressure control. However, left internal carotid artery angiography (ICAG) conducted 12 days post-onset showed a peripheral MCA aneurysm, which was enlarged 1 week later. The patient did not tolerate balloon test occlusion, showing neurological deficit. Direct surgery was planned, but angiography on day 30 revealed a reduction in aneurysm size. Medical therapy was therefore continued for 1 month; however, the aneurysm showed repeated enlargements over 3 months. The patient therefore consulted our hospital for surgery, which was performed using a transsylvian approach. As we were unable to rule out pseudoaneurysm, we performed superficial temporal artery-MCA anastomosis as a form of trapping surgery. However, the lesion appeared to likely represent a congenital aneurysm when viewed macroscopically, so we performed neck clipping as a definitive treatment. Navigation and motor-evoked potential monitoring were useful to approach the aneurysm and predict the preservation of motor function. Histological examination revealed a congenital aneurysm with organized thrombus. The postoperative course was uneventful and the patient was discharged 2 weeks after surgery without any neurological deficit.

Ruptured large basilar artery aneurysm associated with an arteriovenous malformation in hereditary hemorrhagic telangiectasia.

A 53-year-old woman presented with intracranial hemorrhage caused by a ruptured cerebral aneurysm. Digital subtraction angiography revealed a large aneurysm arising from the top of the basilar artery and a Spetzler-Martin grade 3 arteriovenous malformation. Endovascular embolization of the aneurysm was completed with a slight neck remnant. Medical examination confirmed that she suffered from hereditary hemorrhagic telangiectasia (HHT). HHT is a rare autosomal dominant disorder characterized by multiple mucocutaneous telangiectasia and associated vascular malformations. This case suggests that the prognosis for HHT patients with treatable aneurysms should be as good as that of healthy individuals. Consequently, neurosurgeons should suspect underlying HHT in all patients with cerebral vascular malformations.

[Two cases of cervical carotid artery stenosis with high risk post-operative hyperperfusion treated with dexmedetomidine after carotid endarterectomy].

Dexmedetomidine is a central alpha2 adrenoceptor agonist recently shown to be a safe and acceptable sedative agent for patients requiring sedation after brain surgery. We report two patients successfully treated by carotid endarterectomy (CEA) with postoperative management under dexmedetomidine anesthesia for transient ischemic attack (TIA) resulting from severe stenosis of the internal carotid artery (ICA). Case 1: A 75-year-old man was admitted to our hospital with aphasia and weakness of the right side of his body. Although no evidence of acute cerebral infarction was obtained on magnetic resonance imaging (MRI)/diffusion-weighted image (DWI), MR angiography (MRA) revealed severe stenosis of the left cervical ICA. (123)I-IMP-single photon emission tomography (SPECT) and transcranial Doppler (TCD) revealed marked reduction of cerebral blood flow in the left cerebral hemisphere. Although CEA induced hyperperfusion, aggressive control of blood pressure under dexmedetomidine anesthesia enabled effective management of the resulting hyperperfusion syndrome. The patient was discharged without neurological deficits. Case 2: A 68-year-old man was admitted to our hospital with amaurosis fugax and numbness of the right side of his body. Although no evidence of acute cerebral infarction was obtained on MRI/DWI, MRA disclosed severe stenosis of the left cervical ICA. (123)I-IMP-SPECT revealed extremely low perfusion and disturbance of vascular reactivity in the territory of the left ICA. Although conservative therapy was performed, crescendo TIA was noted. Revascularization using CEA was therefore performed. After surgery, hyperperfusion was observed in the same fashion as in case 1, and again aggressive control of blood pressure under dexmedetomidine anesthesia enabled effective management of the resulting hyperperfusion syndrome. The patient was discharged 1 month postoperatively without neurological deficits. Dexmedetomidine is a safe and acceptable sedative drugs preventing hyperperfusion syndrome after CEA.

Endovascular treatment for ruptured distal anterior inferior cerebellar artery aneurysm -case report-.

A 73-year-old woman presented with subarachnoid hemorrhage caused by a ruptured left distal anterior inferior cerebellar artery (AICA) aneurysm. Computed tomography showed a thin subarachnoid hemorrhage in the ambient cistern, and digital subtraction angiography revealed an aneurysm arising from the lateral branch of the left AICA, which was separate from the meatal loop. Endovascular treatment was performed to achieve parent artery occlusion using two Guglielmi detachable coils. Postoperatively, the patient had no complications except for left hearing disturbance, and she was independent in daily life. Endovascular parent artery occlusion for distal AICA aneurysm, especially distal from the meatal loop, can avoid sacrificing the internal auditory artery if the lateral branch of the AICA could be occluded more distally from the meatal loop. Sufficient collateral circulation prevents major infarction, and this strategy may be the first-line treatment choice.

Bilateral vertebral artery dissecting aneurysm with subarachnoid hemorrhage treated with staged bilateral vertebral artery coil occlusion: a case report.

BACKGROUND: Vertebral artery dissecting aneurysm is now increasingly recognized as a cause of posterior circulation stroke in young adults. Here, we report a case of bilateral VADA with SAH, treated by bilateral coil occlusion using GDCs. CASE DESCRIPTION: A 64-year-old woman was admitted to our hospital with consciousness disturbance (Hunt and Kosnik: grade 4). Computed tomography showed diffuse SAH with a thick hematoma in the left C-P angle. Magnetic resonance angiography, 3D-CTA, and cerebral angiography revealed bilateral VADAs. First, the ruptured left VADA involving the PICA and a perforating branch was treated by occluding the lower half of the VADA and the proximal VA with GDCs in the acute stage. Thereafter, the residual VADA and contralateral VADA exhibited enlargement on cerebral angiography and MRA for 2 months after the initial surgery; thus, the right VADA was occluded by GDCs just proximal to the right PICA after confirming BTO tolerance. CONCLUSION: Staged bilateral VA coil occlusions combined with BTO may be one of the treatment strategies for bilateral VADA with SAH in cases presenting surgical difficulty due to anatomical factors or severe grade of SAH.

[Two cases of main trunk artery occlusion associated with multiple cerebral aneurysms].

We report 2 cases of multiple aneurysms (AN) associated with main trunk artery occlusion. CASE 1: A 52-year-old male was admitted to our hospital with dysarthria and weakness of the right side of the body. Computed tomography (CT) showed cerebral infarction in the left corona radiata. MR angiography and conventional angiography showed occlusion of the left middle cerebral artery (MCA) and saccular aneurysms (ANs) at the origin of the anterior communicating artery (A-com) and bifurcation of the right MCA. Subsequent 123I-IMP-single photon emission tomography (SPECT) revealed marked reduction of cerebral blood flow and disturbed reactivity to acetazolamide in the left cerebral hemisphere. Superficial temporal artery (STA)-MCA anastomosis was performed to improve cerebral blood flow and reduce hemodynamic stress for AN of the A-com and right MCA. At 5 months after the first operation, neck clipping was performed successfully for the non-ruptured A-com AN and right MCA AN. CASE 2: A 65-year-old male was admitted to our hospital. CT revealed subarachnoid hemorrhage (SAH), and 3D-computed tomographic angiography (CTA) and cerebral angiography showed basilar top AN, A-com AN and right MCA AN associated with right internal carotid artery occlusion. Right ACA and MCA territories were visualized from the A-com artery and posterior cerebral artery. STA-MCA anastomosis was performed to improve cerebral blood flow and reduce hemodynamic stress for ANs. In the same operation, successful neck clipping was performed for BA top AN and right MCA AN. In such cases as these, particularly in ischemic cases associated with main trunk artery occlusion, it was important to consider surgery for AN after STA-MCA anastomosis in anticipation of improved cerebral blood flow and reduce hemodynamic stress for AN.

[A case of rheumatoid factor-positive hypertrophic spinal pachymeningitis].

A 54-year-old female was admitted to our hospital with the complaint of progressive gait disturbance, starting with left abdominal pain 1 month previously. She developed acute paraparesis and stocking-anesthesia type sensory disturbance within a few days. MR imagings on admission, revealed an encircled subdural mass at the Th1-9 vertebral level, and her spinal cord was compressed at several places at the Th5-6. The subdural mass showed low intensity on T1 and T2 weighted image, and was homogenously enhanced after Gd-DTPA administration. Laboratory data revealed elevation of rheumatoid factor, CH50, C3, C4, and C-reactive protein. An emergency operation was performed by left hemilaminectomy from Th4 to Th6. The subdural mass was resected as far as possible, followed by dural plasty and initiation of steroid intraoperatively. Histopathologic examination of the resected lesion documented a hypertrophic pathymeningitis. Postoperatively, her neurological findings were improved immediately, followed by adjuvant therapy. Recurrence was not present on radiographic images 3 years after surgery. Laboratory data normalized within 4 months. Hypertrophic pachymeningitis is a rare case, and it is difficult to diagnose preoperatively. If there are subdural mass lesions at the multiple vertebral levels, we should suspect this disease. Treatment by immediate decompressive surgery and continuous adjuvant therapy was effective in our case.

[A case of high-aged idiopathic spinal cord herniation from dural defect].

Idiopathic spinal cord herniation was assumed to be a rare disease. However, the incidence of discovering this condition appears to have been increasing recently with advances in neuroradiological diagnosis using magnetic resonance imaging (MRI) and computed tomographic myelogram (CTM). We present herein an operated case of high-aged idiopathic spinal cord herniation. A 71-year-old female presented with spastic paresis of the right lower limb and sensory disturbance of pain and temperature below the level of the left Th4 dermatome, consistent with Brown-Séquard syndrome. MRI and CTM revealed right ventral displacement of the spinal cord and dilatation of the dorsal subarachnoid space at Th2/3. Laminectomy of Th1-3 was performed, herniated spinal cord was untethered and repositioned, and the dural defect was sealed with GORE-TEX dura substitute. Postoperative MRI revealed normal location of the spinal cord and neurological state improved slightly. The patient was discharged 1 month after the operation. Among many cases of spinal cord herniations, this is considered to be a rare case of idiopathic spinal cord herniation in an elderly patient.

[Case of clipping of a ruptured aneurysm of the posterior cerebral artery (P2) via the transchoroidal-fissure approach].

A 59-year-old female was found to be drawn in a swimming pool and transferred to our hospital. The patient was comatose on admission (Hunt & Kosnk: Grade IV). Computed tomography (CT) showed diffuse subarachnoid hemorrhage (SAH) with thick hematoma in the left ambient cistern. Conventional cerebral angiography and 3D-digital subtraction angiography revealed aneurysms (ANs) of the left posterior cerebral artery (P2), and bifurcation of the left internal carotid and posterior communicating arteries (IC-PC). Successful neck clipping was performed the same day through the temporal horn via the insula for ruptured P2 AN, and the non-ruptured IC-PC AN was also obliterated using a pterional approach. Postoperative course was uneventful except for initial disturbance of consciousness and aphasia. The patient was discharged with no neurological deficit 1 month after surgery. This approach may be preferable in cases involving high positioned PCA AN in the ambient cistern, particularly in the acute phase of severe SAH, as the brain is protected from the detrimental effects of strong temporal retraction and a wider working space is provided.

Delayed hemorrhage from completely obliterated arteriovenous malformation after gamma knife radiosurgery.

A 43-year-old female was treated with gamma knife radiosurgery (GKS) for right frontal arteriovenous malformation (AVM) manifesting as absence seizures. Complete nidus obliteration was confirmed on angiography 4 years after GKS. However, she experienced recurrence of her previous seizures and delayed hemorrhage occurred within the treated nidus, despite absence of abnormalities by repeated angiography 81 months after GKS. She was treated conservatively and discharged home without neurological deficits. The risk of hemorrhage from obliterated AVM is significantly reduced but not eliminated after radiosurgery. Recanalization of thrombus that is too small to detect by neuroimaging may result in delayed hemorrhage.

"Kissing aneurysms" of the anterior communicating artery treated with coil embolization.

PURPOSE: To present a case of kissing aneurysms of the anterior communicating artery treated with endovascular coil embolization and discuss the advantages and disadvantages of this technique compared with neck clipping. CASE REPORT: A 48-year-old man became drowsy and was admitted to the hospital; he had right hemiparesis and aphasia. Computed tomography revealed diffuse subarachnoid hemorrhage; diagnostic angiography identified an aneurysm at the left A1-A2 junction of the anterior communicating artery and another in the distal anterior cerebral artery (ACA). Endovascular coil embolization was performed on the same day. During the procedure, the 3-mm-diameter junctional aneurysm was successfully packed with coils, but an additional aneurysm was suspected; right carotid angiography following embolization of the left aneurysm clearly showed a mirror image aneurysm of the right A1-A2 junction. The right aneurysm was treated using the same technique. The broad-necked ACA aneurysm was unsuitable for embolization, so neck clipping was performed 5 weeks later. The patient was discharged to his home following complete recovery 7 weeks after the coil embolization. CONCLUSIONS: Kissing aneurysms are a rare and specific type of multiple aneurysms that require caution in diagnosis and surgical management. Endovascular treatment may be suitable because it does not involve dissection around the aneurysms.

[Currarino triad: a case report].

The authors report a case of Currarino triad with a combination of anterior sacral meningocele and mature teratoma, sacral body deformity, anorectal stenosis, and tethered cord. A newborn girl suffered from vomiting, abdominal distension and constipation. Initially, a diverting colostomy was performed at the age of one month. 7 months later, at the age of 8 months, we performed posterior sagittal anorectoplasty (PSARP): As a result, extirpation of teratoma, excision of meningocele, untethering of the spinal cord, and anorectoplasty were achieved simultaneously without complication. We suggest the use of an MRI to specify the presence of anosacral and spinal cord anomalies in patients with intractable constipation and we recommend combined pediatric and neurosurgical assessment and management for all cases of Currarino triad.

Primary intracerebral hemorrhage in Izumo City, Japan: incidence rates and outcome in relation to the site of hemorrhage.

OBJECTIVE: The aim of this community-based study was to investigate the incidence rates and outcome of primary intracerebral hemorrhage (ICH) in relation to the site of hemorrhage. METHODS: The subjects were 350 patients with primary first-ever ICH who were treated during the 8-year period 1991 to 1998 in Izumo City, Japan. RESULTS: The crude and age- and sex-adjusted incidence rates for all types of ICH were 52 and 47 per 100,000 population, respectively, for all ages. The most common site of ICH was the putamen (120 patients, 34%), followed by the thalamus (115, 33%), lobar areas (53, 15%), brainstem (30, 9%), cerebellum (25, 7%), and caudate nucleus (7, 2%). The crude and age- and sex-adjusted annual incidence rates per 100,000 population were 18 and 16 for putaminal, 17 and 15 for thalamic, 8 and 7 for lobar, 4 and 3 for cerebellar, 4 and 4 for brainstem, and 1 and 1 for caudate hemorrhages, respectively. The Glasgow Coma Scale scores on admission were best in patients with cerebellar hemorrhage and worst in those with brainstem hemorrhage. Surgery was performed for 34% of putaminal, 9% of thalamic, 14% of caudate, 21% of lobar, and 32% of cerebellar hemorrhages but not for brainstem hemorrhages. The 30-day case fatality rate was 11% for putaminal, 9% for thalamic, 14% for caudate, 11% for lobar, 0% for cerebellar, and 53% for brainstem hemorrhages. When patients with ICH were analyzed as a whole, the overall survival rates at 30 days, 3 months, and 3 years were 87, 83, and 73%, respectively. Both the short-term and long-term outcomes after ICH were directly related to the site of hemorrhage and the severity of bleeding, which was assessed by the hematoma volume and Glasgow Coma Scale score. Overall, 190 (54%) of 350 patients had a favorable outcome, and 55 (16%) had died at discharge. CONCLUSION: Marked differences were observed in the incidence rates and outcome of primary ICH in relation to the site of hemorrhage. The differences in outcome were primarily a result of differences in the severity of bleeding for each ICH subtype.

[A surgical case of tectal cavernous malformation presented by hydrocephalus].

We report a surgical case of tectal cavernous malformation presented by hydrocephalus. This 30-year-old man suffered from headache and nausea due to an obstructive hydrocephalus caused by a cavernous malformation in the tectum. Magnetic resonance (MR) images on admission showed a small lesion depicted as isointensity on the T1-weighted image, hyperintensity on the T2-weighted image, and accompanied with peripheral low-signal intensity rim, suggesting a tectal cavernous malformation. After admission, ventricular drainage was performed and the patient's symptoms improved immediately. He underwent a ventriculoperitoneal shunt ten days after the ventricular drainage. Postoperative CT scan showed an enlargement of the tectal mass with hemorrhagic change, but there was no deterioration in his neurological status. Cerebral angiography demonstrated no vascular stain or venous malformation. Microsurgical removal of the tectal mass was then performed via an occipital transtentorial approach. Histopathology proved a cavernous malformation and MR images at follow-up demonstrated total excision. Postoperatively, an upward gaze palsy appeared, but gradually improved within a month. Management strategy of brain stem cavernous malformation is controversial. Occasionally, brain stem hemorrhage may become critical. Therefore, we recommend aggressive surgical extirpation of symptomatic brain stem cavernous malformation, if it is accessible, if hemorrhage is present, and if the patient's condition permits it.