Treatable fluctuating Parkinsonism and dementia in a patient with a dural arteriovenous fistula.
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Biomedical subjects
Toshisuke Sakaki
Publications and source records attributed to Toshisuke Sakaki.
Effect of carotid artery stenting on ocular circulation and chronic ocular ischemic syndrome.
BACKGROUND: The authors evaluated the effect of carotid artery stenting (CAS) on ocular circulation and chronic ocular ischemic syndrome. METHODS: We examined 38 patients with carotid artery stenosis (>80%) at its origin treated with CAS. Ocular circulation and symptoms were examined before, within 24 h, and 1 week, 1 month, and 3 months after CAS based on ophthalmic artery color Doppler flow imaging and ophthalmological examinations. RESULTS: Ocular circulation: Before CAS, 13 patients showed reversed ophthalmic artery flow, and 25 antegrade flow. Average peak systolic flow velocity was -0.038 m/s. Within 24 h after CAS, all patients showed antegrade ophthalmic artery flow; reversed flow before CAS was thus resolved. Average peak systolic flow velocity rose significantly to 0.36 m/s (p < 0.05). One week, 1 month and 3 months after CAS, there were no significant changes compared to the findings at 1 week after CAS. Ocular symptoms: Before CAS, 8 patients showed chronic ocular ischemic syndrome. During the follow-up period (mean: 2.8 years), the visual acuity improved in 7 cases. Average retinal artery pressure and arm-to-retina circulation time improved significantly to the normal level (p < 0.05). The other 30 patients complained of recurrent and worsened visual symptoms during the follow-up period. CONCLUSION: CAS was effective in improving ocular circulation, and also improved the chronic ocular ischemic syndrome caused by the severe carotid artery stenosis.
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Defective expression of HRK is associated with promoter methylation in primary central nervous system lymphomas.
OBJECTIVES: Recently, it has been reported that expression of the HRK gene was significantly reduced by hypermethylation in astrocytic tumors. Our aim is to verify the alterations in the HRK gene in primary central nervous system lymphomas (PCNSLs). METHODS: We analyzed the hypermethylation status and expression of the gene and 12q13.1 loss of heterozygosity in 31 PCNSLs. RESULTS: A total of 13 PCNSLs (31%) demonstrated hypermethylation in either the promoter or exon 1; loss of HRK expression was immunohistochemically observed in 9 tumors and was significantly associated with promoter methylation. In addition, higher apoptotic counts were associated with HRK positivity. PCNSLs with HRK methylation also showed methylation of multiple genes, such as p14ARF, p16INK4a, RB1, p27Kip1 and O6-MGMT. Patients with tumors demonstrating concurrent methylation of more than half of their genes demonstrated significantly poorer survival and earlier recurrence. Hypermethylation of the HRK promoter alone was not associated with overall outcome, but relapse-free survival was significantly shorter. CONCLUSIONS: Our findings suggest that transcriptional repression of HRK is caused by promoter hypermethylation in PCNSL, and that the loss of HRK associated with the methylation profile of other genes is a potential step in the modulation of cellular death by apoptosis during PCNSL tumorigenesis.
Apoptosis↗
Displacement of the facial nerve course by vestibular schwannoma: preoperative visualization using diffusion tensor tractography.
PURPOSE: To preoperatively visualize the course of the facial nerve, which is displaced by vestibular schwannoma, using diffusion tensor (DT) tractography, and to evaluate the agreement with surgical findings. MATERIALS AND METHODS: The subjects were eight patients with vestibular schwannoma who had undergone removal surgery. DT MR images were obtained and tracts that were considered to represent the facial nerve were constructed. We assessed the success rate for tract construction and evaluated the agreement between tractography findings and surgery. RESULTS: We obtained a tract that connected the internal auditory meatus and brainstem, and was considered to represent the facial nerve in seven of eight cases. The course of the constructed tract agreed with surgical findings in five of these seven cases. One exception was a case in which the tumor was too large to enable intraoperative observation of the facial nerve; however, the facial nerve appeared to be displaced anteriorly at intracapsular resection, in agreement with tractography. In the other case, the schwannoma was mostly cystic. CONCLUSION: Tractographs constructed using MR tensor images enabled us to identify tracts considered to represent facial nerves. We consider DT tractography to be a useful tool for preoperatively predicting facial nerve displacement in vestibular schwannoma.
Adult↗
Effects of increasing concentrations of propofol on jugular venous bulb oxygen saturation in neurosurgical patients under normothermic and mildly hypothermic conditions.
BACKGROUND: Recent evidence suggested that propofol can deteriorate the cerebral oxygen balance compared with inhalational anesthetics. However, dose-related influences of propofol on cerebral oxygen balances were not clearly investigated. In the current study, the authors investigated the effects of increasing concentrations of propofol on jugular venous bulb oxygen saturation (Sj(O2)) in neurosurgical patients under normothermic and mildly hypothermic conditions. METHODS: After institutional approval and informed consent were obtained, 30 adult patients undergoing elective craniotomy were studied. Patients were randomly allocated to either normothermic or hypothermic group (n = 15 in each group). In the normothermic and hypothermic groups, tympanic membrane temperature was maintained at 36.5 degrees and 34.5 degrees C, respectively. Sj(O2) was measured at predicted propofol concentrations of 3, 5, and 7 microg/ml using a target-controlled infusion system in both groups. RESULTS: At a predicted propofol concentration of 3 microg/ml, there were no significant differences in Sj(O2) values between the normothermic and hypothermic groups, although the incidence of desaturation (Sj(O2) < 50%) was significantly higher in the normothermic group than in the hypothermic group (30% vs. 13%; P < 0.05). Sj(O2) values and the incidence of desaturation remained unchanged during the changes in predicted propofol concentration from 3 to 7 microg/ml both in the normothermic and hypothermic groups. CONCLUSION: The results indicated that the increasing concentrations of propofol did not affect Sj(O2) values in neurosurgical patients under normothermic and mildly hypothermic conditions.
Adult↗
Delayed reconstruction by titanium mesh-bone graft composite in pyogenic spinal infection: a long-term follow-up study.
OBJECTIVE: Use of instrumentation in spinal osteomyelitis remains controversial because of the perceived risk of persistent infection related to a devitalized graft and spinal hardware. Particularly, limited information is available regarding the long-term follow-up of patients. We retrospectively reviewed the use of titanium mesh-bone graft composite after corpectomy in pyogenic spinal infection with a minimum 3-year follow-up outcome. METHODS: Four patients, two men and two women, with cervical and thoracic myelopathy caused by cervical (two cases) and thoracic (two cases) osteomyelitis and epidural abscess, were treated. Their age ranged from 49 to 74 years (mean age 58 years). In one case, the coexisting medical condition was diabetes. Neurologic deficits caused by direct spinal cord compression due to epidural abscess, segmental deformity, and instability were observed in all cases. After infection was clinically controlled by intravenous antibiotics, anterior debridement and fusion using titanium mesh cage along with anterior plate were performed. Two-stage treatment was performed in two cases. RESULTS: The postoperative course was uneventful; all patients experienced relief of symptoms. No evidence of recurrence or residual infection was observed in any patient during the average follow-up period of 42-56 months (average 49.0 months). CONCLUSIONS: Once infection is clinically controlled, a titanium mesh-bone graft composite and plate in combination with aggressive debridement might provide an effective therapy for spinal osteomyelitis requiring surgery. Despite studying a small number of patients, we can conclude that titanium mesh reconstruction can be useful as a surgical method in selected low-risk patients with vertebral osteomyelitis.
Bone Transplantation↗
Complications and long-term follow-up results in titanium mesh cage reconstruction after cervical corpectomy.
OBJECTIVE: The incidence of the complications and long-term outcome with a minimum 2-year follow-up of anterior cervical reconstruction using titanium mesh cage is evaluated. Relevant literature was also reviewed to discuss the potential risk factors of the complications of this procedure. METHODS: From 1999 to 2003, 26 patients with cervical spine disorders, (12 patients with OPLL, 7 with cervical spondylosis, 3 with vertebral tumors, 2 with osteomyelitis, and 2 with traumatic lesions) were operated on by this procedure. The series included 14 males and 12 females with a mean age of 60.9 years. Corpectomy was performed on 1 (14 cases), 2 (12 cases). Autologous bone fragments were taken from the excised vertebra. RESULTS: The average improvement rate as scored on the neurosurgical cervical spine scale was 67.4%. The average follow-up period was 54.3 months (range, 24 to 72 months) in 21 who were followed up, and bone union was observed in all cases (22/22 cases) that could be followed up for more than 6 months postoperatively. The average time required for fusion was 6.7 months. Postoperative complications included dyspnea (1 case) and cerebrospinal fluid leakage (2 cases), which was treated by lumbar drainage, without any additional repair operation. No hardware-related complications or adjacent segment degenerative changes were encountered during the follow-up periods. CONCLUSIONS: This reconstruction technique yielded good clinical results and helped to avoid complications associated with harvesting bone from the iliac crest donor site. However, risk factors related to the method should be carefully considered.
Adult↗
Two-stage management for vertebral osteomyelitis and epidural abscess: technical note.
OBJECTIVE: The incidence of spinal infections has increased in recent years, and vertebral osteomyelitis and epidural abscess are issues of great concern for spine surgeons. We retrospectively reviewed our cases treated by two-stage management for vertebral osteomyelitis and epidural abscess. METHODS: The series consisted of nine patients (five men and four women); their ages ranged from 49 to 77 years (mean age, 60.6 yr). Coexisting medical conditions were diabetes mellitus in one case and long-term steroid intake in another. Myelopathy or radicular pain was caused by osteomyelitis and an epidural abscess in all patients. Cervical, thoracic, and lumbar osteomyelitis was detected in three, four, and two patients, respectively; epidural abscess was pyogenic in four patients, tuberculous in three, and unknown in two patients. Our surgical strategy involved anterior debridement or drainage and application of an external orthosis postoperatively during the first stage. After clinical control of the infection by using organism-specific intravenous antibiotics as far as possible, as confirmed by normal erythrocyte sedimentation rate and/or C-reactive protein, second stage surgery was performed. This included complete debridement of all necrotic bone and soft tissues, and stable reconstruction with or without instrumentation (six and three patients, respectively). RESULTS: The postoperative course was uneventful with relief of the symptoms after the second surgery. No evidence of recurrence or residual infection was observed in any patient, as shown by erythrocyte sedimentation rate and/or C-reactive protein levels during a follow-up period averaging 26.6 months (range, 2-56 mo). CONCLUSION: Without denying the efficacy of the single-stage surgery, two-stage management can be a reasonable alternative for carefully selected patients who have spinal infection.
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Use of differentiating embryonic stem cells in the Parkinsonian mouse model.
Progressive loss of dopaminergic neurons in the substantia nigra pars compacta and the following reduction in striatal dopamine cause Parkinson's disease (PD). Transplantation of dopamine-producing cells into the striatum is a proposed treatment modality. In this report, we describe a model experiment assessing the effectiveness of mouse embryonic stem (ES) cell-derived dopaminergic neurons using a mouse model of PD. ES cells were shown to be an attractive and promising source for the generation of dopaminergic neurons, and the mouse PD model was useful to assess the efficacy of transplantation therapy with dopamine-producing cells, including ES cell-derived dopaminergic neurons.
Animals↗
Surgical removal of a live worm by stereotactic targeting in cerebral sparganosis. Case report.
A 64-year-old man presented with generalized tonic clonic convulsion followed by weakness of the right lower extremity. He had a medical history of hypertension, hyperlipidemia, and right cerebellar infarction. Computed tomography (CT) showed a small high density nodule with an enhanced perifocal low density area in the left occipital lobe. T1-weighted magnetic resonance (MR) imaging showed a ring-shaped and partial string-like nodule with enhancement by gadolinium. T2-weighted MR imaging showed the white matter of the left occipital lobe as high intensity. CT and MR imaging seemed to indicate metastatic brain tumors, although cortical atrophy and ventricular dilation were recognized. Left parietal craniotomy was performed under stereotactic targeting to obtain a definitive diagnosis. During manipulation at the center of the targeted lesion, a white, tape-like body was found and recognized to be a live worm. Serological testing revealed strong immunopositivity against Spirometra mansoni. The infection route in the present case was probably through eating raw chicken meat. Cerebral sparganosis is extremely rare but should be considered in the differential diagnosis of metastatic brain tumors, especially in endemic areas.
Central Nervous System Helminthiasis↗
Predictors of outcome of surgery for cervical compressive myelopathy: retrospective analysis and prospective study.
The outcomes of surgical treatment in 80 patients with cervical compressive myelopathy were retrospectively reviewed to examined the correlations between surgical outcomes and the following seven predictive factors: age at surgery, duration of symptoms, severity of myelopathy, number of compressed segments, intramedullary high intensity segments on T(2)-weighted magnetic resonance (MR) imaging, surgical method, and the type of disease. The recovery rates were evaluated at 3 months after the surgery. Significant correlations were observed between recovery rate and duration of symptoms, severity of myelopathy, and high intensity segments on T(2)-weighted MR imaging. No statistical correlation was observed with the other factors. Multivariate analysis revealed significant correlations between recovery rate and duration of symptoms and number of high intensity segments on T(2)-weighted MR imaging. The multiple regression equation was expressed as follows: recovery rate = 82.981 + 0.101 x (age) - 0.675 x (duration) - 1.452 x (number of compressed segments) - 1.451 x (preoperative Neurosurgical Cervical Spine Scale) - 13.826 x (number of high intensity segments). Based on this predicted formula, we compared the predicted and actual recovery rates for 17 patients treated recently. The two values were similar except in two patients with long duration of symptoms. We conclude that the surgical outcome can be predicted to a certain extent and this information could be provided to patients considering surgery for cervical compressive myelopathy.
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Long-term outcome of unruptured giant cerebral aneurysms.
The long-term outcome of 39 patients with unruptured giant aneurysm (>2.5 cm) treated during the last 12 years was retrospectively reviewed. The 7 male and 32 female patients, aged 32 to 81 years, presented with symptoms related to compression of the surrounding structures by the aneurysm in 28 cases, cerebral infarction in one, and asymptomatic in 10. The locations were the internal carotid artery (ICA) in 27 cases, middle cerebral artery in three, anterior cerebral artery in one, and basilar artery in eight. Therapeutic modalities were direct clipping in 11 patients, ICA occlusion combined with extracranial-intracranial bypass in 15, and conservative treatment in 13. The follow-up period ranged from 16 to 128 months (mean 54.0 months). The mortality was 9% (1/11), 0% (0/15), and 31% (4/13), and morbidity was 18% (2/11), 20% (3/15), and 8% (1/13), respectively. Surgery reduced the mortality (from 31% to 4%) but increased the morbidity (from 8% to 19%) as compared with conservatively treated patients (p < 0.05). Giant intracranial aneurysm has a poor prognosis if left untreated, but these lesions are difficult to treat with the present management options.
Adult↗
Sequential and spatial profiles of apoptosis in ischemic penumbra after two-vein occlusion in rats.
OBJECT: The two-vein occlusion model is known to be useful for ischemic penumbra studies in vivo. It was applied here to examine sequential changes in the expression of Bax and Bcl-2 proteins and in apoptotic cells to assess the relationship between penumbra and apoptosis. METHODS: Two cortical veins were occluded photochemically by using rose bengal dye in 27 Wistar rats. The animals were killed with perfusion fixation at the following intervals: 4, 12, 24, 48, 96, and 168 hours after vein occlusion (four at each interval; three additional rats were sham-treated). Immunohistochemical analysis for the Bcl-2 family of proteins was performed along with the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) assay to examine the relationship to single-cell death. Cells positive for antiapoptotic proteins began to appear in the TUNEL assay for animals killed 24 hours after vein occlusion, with a peak at 48 hours. These cells were localized in the core of infarction. Immunohistochemical staining for Bax protein showed an increased presence around ischemic lesions at 4 hours after vein occlusion, and the amounts continued to rise until 24 hours, when the localization was diffuse around the core of infarction. Negative findings on immunohistochemical studies for Bcl-2 protein were seen at the early phase after two-vein occlusion. CONCLUSIONS: After vein occlusion, apoptosis appeared sequentially and widely in cortical lesions considered to be the penumbra. Therefore, control of apoptosis would be expected to offer a therapeutic window for treatment of venous infarction.
Animals↗
Use of multifocal visual evoked potential tests in the objective evaluation of the visual field in pediatric epilepsy surgery.
OBJECT: To evaluate objectively the visual fields of patients with pediatric epilepsy who are uncooperative with perimetry and in whom postoperative visual field deficits are expected, the authors investigated the usefulness of the multifocal visual evoked potential (VEP) method. METHODS: Normal waves in multifocal VEP were determined in 21 healthy children (21 eyes) 6 to 15 years of age (mean 11.4 years). Responses from eight sites in each child were divided into four quadrants (superior and inferior temporal and superior and inferior nasal). In each quadrant, two response waves were grouped and averaged. The peak latency and amplitude at approximately 100 msec were used for assessment. In three cases involving patients with epilepsy, multifocal VEP measurements were also recorded and compared with the peak latency and amplitude in the healthy children. In these children, no significant differences were observed in the peak latency of amplitude among four quadrants using one-way analysis of variance. In each patient, multifocal VEP tests showed abnormal waves in the quadrant corresponding to the lesion demonstrated in neuroradiological images. This result was useful in the treatment of choice and the postoperative evaluation. CONCLUSIONS: Multifocal VEP tests can be useful in evaluating the visual field of children objectively. They can also be valuable in assessing preoperative visual field defects and revealing changes in the visual field after treatment.
Adolescent↗
Frequent HRK inactivation associated with low apoptotic index in secondary glioblastomas.
To detect and identify the genetic alterations and methylation status of the HRK gene in human glioblastomas, we analyzed a cohort of astrocytic tumors for hypermethylation, loss of heterozygosity on 12q13.1, and gene expression. Our study examined a series of 36 diffuse low-grade astrocytomas, 32 anaplastic astrocytomas, 64 primary glioblastomas, and 28 secondary glioblastomas that had evolved from either 24 low-grade diffuse astrocytomas or 4 anaplastic astrocytomas. The region around the HRK transcription start site was methylated in 19% of diffuse astrocytomas, in 22% of anaplastic astrocytomas, in 27% of primary glioblastomas, and in 43% of secondary glioblastomas. HRK expression was significantly reduced in 61% of secondary glioblastomas as compared to other types of tumors, and aberrant methylation was closely associated with loss of expression. Reverse transcription-PCR analysis also demonstrated a clear agreement between reduced HRK protein levels and low or absent HRK transcripts. Lack of HRK immunoreactivity was significantly correlated with a low apoptotic index, whereas a strong association between methylation status and apoptosis was found only in secondary glioblastomas. Abnormal methylation of HRK was detected in astrocytic tumors concurrent with methylation of multiple genes, including p16(INK4a) and p14(ARF). Interestingly, these epigenetic changes in secondary glioblastoma were further associated with wild-type p53. Our findings suggest that HRK is inactivated mainly by aberrant DNA methylation in astrocytic tumors and that reduced HRK expression contributes to the loss of apoptotic control in high-grade tumors. Reduced expression of HRK may serve as one important molecular mechanism in progression to secondary glioblastoma.
Apoptosis↗
Expression of ciliary neurotrophic factor (CNTF), CNTF receptor alpha (CNTFR-alpha) following experimental intracerebral hemorrhage in rats.
Ciliary neurotrophic factor (CNTF) is known as a neuro-survival factor in the developing and developed CNS, as well as in the CNS following injury. However, little is known about the expression of CNTF or that of its receptor (CNTFR-alpha) in cases of intracerebral hemorrhage (ICH). We investigated the temporal and spatial profiles of CNTF and CNTFR-alpha expression using a collagenase-induced ICH rat model. CNTF expression was up-regulated from the day following ICH induction and reached a peak level at 5 to 14 days, with increased expression observed in brain tissue surrounding the hematoma lesion and white matter structures in association with astroglial proliferation. Further, CNTFR-alpha was transiently expressed in the cerebral cortex surrounding the hematoma, with a peak at 5 days. Administration of exogenous CNTF into the lesion following initiation of ICH resulted in a prolonged expression of CNTFR-alpha on cortical neurons neighboring the hematoma. Our findings suggest differential regulation of CNTF and CNTFR-alpha, and the possibility of a therapeutic strategy using CNTF administration for ICH.
Animals↗
Frequent LOH on 22q12.3 and TIMP-3 inactivation occur in the progression to secondary glioblastomas.
Frequent allelic losses on the long arm of chromosome 22 (22q) in gliomas indicate the presence of tumor suppressor gene (TSG) at this location. However, the target gene(s) residing in this chromosome are still unknown and their putative roles in the development of astrocytic tumors, especially in secondary glioblastoma, have not yet been defined. To compile a precise physical map for the region of common deletions in astrocytic tumors, we performed a high-density loss of heterozygosity (LOH) analysis using 31 polymorphic microsatellite markers spanning 22q in a series of grade II diffuse astrocytomas, anaplastic astrocytomas, primary glioblastomas, and secondary glioblastomas that had evolved from lower grade astrocytomas. LOH was found at one or more loci in 33% (12/36) of grade II diffuse astrocytomas, in 40% (4/10) of anaplastic astrocytomas, in 41% (26/64) of primary glioblastomas, and in 82% (23/28) of secondary glioblastomas. Characterization of the 22q deletions in primary glioblastomas identified two sites of minimally deleted regions at 22q12.3-13.2 and 22q13.31. Interestingly, 22 of 23 secondary glioblastomas affected shared a deletion in the same small (957 kb) region of 22q12.3, a region in which the human tissue inhibitor of metalloproteinases-3 (TIMP-3) is located. Investigation of the promoter methylation and expression of this gene indicated that frequent hypermethylation correlated with loss of TIMP-3 expression in secondary glioblastoma. This epigenetic change was significantly correlated to poor survival in eight patients with grade II diffuse astrocytoma. Our results suggest that a 957 kb locus, located at 22q12.3, may contain the putative TSG, TIMP-3, that appears to be relevant to progression to secondary glioblastoma and subsequently to the prognosis of grade II diffuse astrocytoma. In addition, the possibility of other putative TSGs on 22q12.3-13.2 and 22q13.31 that may also be involved in the development of primary glioblastomas cannot be ruled out.
Adult↗
Tetanic stimulation of the peripheral nerve before transcranial electrical stimulation can enlarge amplitudes of myogenic motor evoked potentials during general anesthesia with neuromuscular blockade.
BACKGROUND: Neuromuscular blockade can suppress myogenic motor evoked potentials (MEPs). The authors hypothesized that tetanic stimulation (TS) of the peripheral nerve before transcranial stimulation may enhance myogenic MEPs during neuromuscular blockade. In the current study, the authors evaluated MEP augmentations by TS at different levels of duration, posttetanic interval, neuromuscular blockade, and stimulus intensity. METHODS: Thirty-two patients undergoing propofol-fentanyl-nitrous oxide anesthesia were examined. Train-of-five stimulation was delivered to C3-C4, and MEPs were recorded from the abductor hallucis muscle. In study 1, TS with a duration of 1, 3, or 5 s was delivered at 50 Hz to the tibial nerve 1, 3, or 5 s (interval) before transcranial stimulation, and the effects of TS on MEP amplitude were evaluated. In study 2, TS-induced MEP augmentations were evaluated at the neuromuscular blockade level (%T1) of 50% or 5%. In study 3, MEP augmentations by TS at stimulus intensities of 0, 5, 25, and 50 mA were evaluated. RESULTS: The application of TS significantly enlarged the amplitudes of MEPs at the combinations of duration (3, 5 s) and interval (1, 3, 5 s) compared with those without TS. TS-induced MEP augmentations were similarly observed at %T1 of both 50% and 5%. TS-induced MEP augmentations were observed at stimulus intensities of 25 and 50 mA. CONCLUSIONS: The results indicate that TS of the peripheral nerve before transcranial stimulation can enlarge the amplitude of MEPs during general anesthesia with neuromuscular blockade. TS of the peripheral nerve can be intraoperatively applied as a method to augment myogenic MEP responses.
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