Neuronal laterality in Parkinson's disease with unilateral symptom by in vivo 1H magnetic resonance spectroscopy.

RATIONALE AND OBJECTIVES: The authors investigate whether there is a lateral effect of 1H-magnetic resonance spectroscopy (MRS) observable metabolite ratios between the symptomatic and the asymptomatic side in Parkinson's disease with unilateral symptoms. METHODS: Localized in vivo 1H MRS was used to measure the metabolite levels in the symptomatic and the asymptomatic sides of the substantia nigra (SN) and putamen-globus pallidus (PG) in Parkinson's disease with unilateral symptom (n = 15). The metabolite ratios of N-acetylasparatate (NAA)/creatine (Cr), and choline-containing compounds (Cho)/Cr in the symptomatic side were compared with those in the asymptomatic side. According to the symptomatic duration, the authors evaluated whether there was a specific correlation between laterality and the clinical stage. RESULTS: Significant metabolic lateral effect of NAA/Cr ratio was established between the symptomatic and the asymptomatic sides of SN and PG in Parkinson's disease with unilateral symptoms (P = 0.03). The decreased NAA/Cr ratio was calculated in at least one of the selected regions in SN and PG, indicating neuronal loss. The main observations were that NAA/Cr ratios were reduced in the left symptomatic side (n = 7; P = 0.001) and reduced to a lesser degree in the right symptomatic side (n = 8; P = 0.03 [PG], P = 0.21 [SN]) and that there was no significant laterality of other metabolite ratios. CONCLUSIONS: On the basis of NAA/Cr ratios between the symptomatic and the asymptomatic sides, the present 1H MRS study shows a significant neuronal laterality in Parkinson's disease with unilateral symptoms. In vivo 1H MRS may provide a diagnostic marker for neuronal dysfunction in Parkinson's disease with unilateral symptoms.

Expression of vascular endothelial growth factor mRNA following transient forebrain ischemia in rats.

Using a reproducible two-vessel occlusion model for forebrain ischemia in rats, we investigated the temporal and spatial changes of vascular endothelial growth factor (VEGF) expression after transient forebrain ischemia with Northern blot analysis and in situ hybridization. Northern blot analysis revealed that VEGF mRNA of the hippocampus was increased from 12 h after reperfusion, with a peak at 1 day. In situ hybridization and double labeling for VEGF mRNA and glial fibrillary acidic protein showed a transient induction of VEGF mRNA in the neurons of the hippocampus from 12 h of reperfusion with a peak at 1 day, and in the astrocytes of the hippocampus, caudoputamen, thalamus and cortical regions at 1 day. After 3 days, no more VEGF signal was detected. Our results demonstrate that astrocytes and neurons each upregulate VEGF mRNA in different temporal and spatial patterns after transient forebrain ischemia in the rat, and these patterns appear to be different from those in transient focal cerebral ischemia.

Metabolic changes in pericontusional oedematous areas in mild head injury evaluated by 1H MRS.

In order to define metabolic brain changes associated with mild traumatic brain injury, proton magnetic resonance spectroscopy (MRS) was performed in patients with regional brain contusion and 13-15 of initial GCS score. The authors measured N-acetylaspartate(NAA)/creatine(Cr) ratio and lactate signal on in vivo proton MRS, which indicated cell loss and ischaemic dAmage respectively, in pericontusional oedematous areas (region of interest; ROI) adjacent to traumatic brain contusion on brain MRI to determine possible metabolic changes. The metabolic ratio of NAA/Cr and lactate/Cr peaks was measured both in the ROI and a corresponding region of the contralateral hemisphere (ROC) in seven patients and twenty-five normal control. In initial NAA/Cr ratios, the values of ROIs were significantly lower than those of the control (p = 0.009), but there was no difference either between ROI and ROC (p = 0.410) or between ROC of patients and the control (p = 0.199). In lactate/Cr ratios, the ROI in all seven patients and the ROC in two showed increased lactate signals. The lacate/Cr ratios of the ROIs were significantly elevated as compared to those of the ROCs (p = 0.02) and the control (p = 0.015). In 2-month follow up, lactate signals were absent or significantly reduced (p = 0.015). In no patients, clinical or radiological deterioration has been observed. Our results demonstrate that there is significant neuronal dysfunction in pericontusional oedematous areas as indicated by NAA/Cr ratios in the patients with mild head injury at both early and late stages. And there are significant ischaemic changes as indicated by increase of lactate level in ROI at early stage. These findings suggest that pericontusional oedematous areas can be vulnerable to secondary brain insults even in the patients with mild head injury.

Comparison of frame-based and frameless stereotactic hematoma puncture and subsequent fibrinolytic therapy for the treatment of supratentorial deep seated spontaneous intracerebral hemorrhage.

OBJECTIVE: This study compared the technical implications and clinical outcome of patients treated for an intracerebral hemorrhage using two minimally invasive procedures: frame-based stereotactic hematoma aspiration and frameless navigation-guided hematoma aspiration followed by fibrinolysis. METHODS: Thirty patients with a spontaneous supratentorial intracerebral hemorrhage, which was treated by a frame-based (n=15) and frameless (n=15) hematoma aspiration followed by subsequent fibrinolysis with urokinase, were retrospectively reviewed. The data for the two subsets of patients were analyzed with regard to hematoma reduction, Glasgow Coma Scale (GCS), and degree of weakness. RESULTS: In the frame-based stereotactic hematoma aspiration group, the volume of the hematoma was 15.4-100.0 mL (mean: 40.7+/-24.4), the GCS upon admission was 4-15 (mean: 10.1+/-3.0), and the grade of weakness upon admission was 1-5 (mean: 2.1+/-0.9). On the other hand, in the frameless navigation-guided hematoma aspiration group, the hematoma volume was 15.2-62.0 mL (mean: 30.0+/-15.2), the GCS upon admission was 7-15 (mean: 13.0+/-2.4), and the grade of weakness upon admission was 1-4 (mean: 2.3+/-1.2). The drainage catheter was in place for a mean duration of 5.1+/-2.4 days (range: 1-12 days). In the frame-based group, the initial hematoma was reduced by -115-88.5% (mean: 52+/-31.5) immediately after surgery, and 90.5% (41-100%) of the initial volume 14 days after surgery. In the frameless group, the initial hematoma was reduced by 11.7-90.8% (mean 57.3+/-25.1) immediately after surgery and 95.8% (87.7-100%) 14 days after surgery. The GCS score and the degree of weakness were evaluated 14 days after surgery, and the Glasgow outcome scale (GOS) score was evaluated at discharge. There were no statistically significant differences between the two groups. CONCLUSION: The frame-based group and the frameless group followed by fibrinolysis had similar outcomes, and both procedures effectively reduced the intracerebral hemorrhage volume within a short period of time. In addition, these procedures are simple, precise, safe, and brief with a very low rebleeding rate and mortality.

Delayed occurrence of intracranial supratentorial chondroma following compound depressed skull fracture.

We describe an exceptional case of a frontal convexity chondroma arising at the site of a compound depressed skull fracture operated on 12 years earlier. We conclude that intracranial chondroma should be included in the differential diagnosis of a calcified mass for the patients who had had a compound, depressed skull fracture along the suture line, especially in cases of dural laceration by the fragmented bone.

Vim thalamotomy for Holmes' tremor secondary to midbrain tumour.

Holmes' (rubral or midbrain) tremor is an unusual combination of 2 Hz to 5 Hz rest, postural, and kinetic tremors of an upper extremity. This tremor has been considered to result from the lesions in the vicinity of the red nucleus in the midbrain. There has been no systematic analysis of the surgical target in the Holmes' tremor so far of nucleus ventrointermedius (Vim) or globus pallidus interna. This 26 year old man gradually developed a disabling midbrain tremor involving both the distal and proximal parts of the left upper arm. Additional neurological findings included oculomotor palsy and ataxia of the left arm. On the radiological studies, a mass lesion (germinoma) was found on the midbrain tegmentum, which was treated by conventional radiation therapy. Although there was improvement in the radiological imaging, his midbrain tremor became intolerable despite medical treatment. The authors performed MR guided stereotactic Vim thalamotomy. With radiofrequency lesioning in the right Vim, his resting, postural, and action tremors were much alleviated in both the distal and proximal parts of the left upper extremity. The authors consider that Vim thalamotomy is still an effective means of controlling midbrain tremors involving the proximal upper limb.

Regional cerebral blood flow changes in patients with intractable obsessive compulsive disorders treated by limbic leukotomy.

The object of this study is to assess the changes in regional cerebral blood flow (rCBF) following stereotactic limbic leukotomy in patients with medically intractable Obsessive-Compulsive Disorder (OCD). Technetium-99-Hexa Methyl Propylene Amine Oxime (99mTc-HMPAO) Single Photon Emission Computed Tomography (SPECT) data obtained before and after limbic leukotomy were subjected to image fusion with MRI images. Eight samples were obtained from healthy voluteers. After localization of the ROI (Region Of Interest) in anatomical area, rCBF measurements were obtained by METLAB. The results of this study show a change of rCBF following limbic leukotomy in intractable OCD. Postoperative 99mTc-HMPAO SPECT findings implicate the medial frontal cortex, cingulate and striatum, which culd be linked to limbic leukotomy that blocks the functional connection of corticolimbic loop.

Shunt-independent surgical treatment of middle cranial fossa arachnoid cysts in children.

The best operative intervention for children with arachnoid cysts remains the subject of controversy. Recent reports stress that craniotomy for cyst fenestration is associated with a low incidence of morbidity and mortality and may leave the child shunt-independent. Among a total of 66 intracranial arachnoid cysts operated on in the authors' department from 1985 to 1997, 44 cases (67%) were located in the middle cranial fossa. A higher incidence in the first decade of life (53 cases) and a marked male predominance (45 cases) were recognized. Headache, cranial deformities, symptoms of raised intracranial pressure, and seizures constituted the most frequent features of the clinical presentation. To determine which treatment provides the greatest benefit with the lowest incidence of complications, the records of the 44 patients with arachnoid cysts in the middle cranial fossa were reviewed. The mean age of these patients was 4.6 years (range 0-16 years). Different types of initial surgical procedures were performed. In 33 patients with middle cranial fossa arachnoid cysts (MCFAC) the initial surgery took the form of craniotomy with excision of the cyst walls and fenestration into the basal cisterns. Shunting procedures were performed in 9 patients: cysto-peritoneal shunts (CPS) were placed in 4 patients and ventriculo-peritoneal shunts (VPS), in 3 patients, and cyst excision was performed in addition to CPS in 2 patients. Excision of the cyst membrane alone without fenestration was performed in 2 patients. The initial treatment was successful in terms of reduced symptoms and decreased cyst size, with no additional treatment needed for the cyst, in 79% (26/33) of patients who had undergone excision of the cyst walls and fenestration into the basal cisterns, compared with 66% (6/9) of patients who had undergone shunting procedures. Cyst membrane excision was not successful in any of the patients who underwent this procedure alone. No significant difference in morbidity was noted between these different treatment options. On follow-up CT scan and MRI, cysts of types I and II (Galassi classification) exhibited a steady tendency to reduction or obliteration. These results confirm that radical excision of the outer and inner membranes of the cyst wall with fenestration into the basal cistern is a safe and effective shunt-independent procedure for MCFAC, especially for those of types I and II.

Perioperative specific management of blood volume loss in craniosynostosis surgery.

Accurate assessment and replacement of blood loss and fluid-electrolyte deficit during craniosynostosis repair is difficult owing to patient size and the diversity of surgical technique. Forty-three patients undergoing primary craniosynostosis repair over a 10-year period were studied retrospectively to determine blood loss and fluid deficit and to assess blood transfusion practices during both intraoperative and postoperative periods. Blood loss was calculated on the basis of estimated red cell mass (ERCM) and fluid-electrolyte imbalance was investigated with blood samplings. Blood transfusion was considered appropriate if the postoperative or posttransfusion ERCM was within 12% of the preoperative value. Estimated fluid requirement (EFR) was used in 4 ml kg(-1) h(-1) except for neonates. Intraoperatively, 80% of all patients were appropriately managed with respect to blood transfusion and EFR. Postoperatively only 20% of the patients receiving transfusions were transfused appropriately. In 23.3% of these patients (10/43) unexpected respiratory distress developed immediately after their recovery from the anesthesia. With the measurement of estimated blood volume and allowable blood loss, appropriate transfusion could be achieved for the successful treatment of the primary craniosynostosis.

Experience with pineal region tumors.

The results are reported of a retrospective review of the presentation and outcome of 43 pineal region tumors treated from 1982 to 1996, including 20 identified tumors: 5 germinomas, 8 teratomas, 2 embryonal carcinomas, 1 endodermal sinus tumor, 2 pineocytomas and 2 pineoblastomas. Of the 43 tumors reviewed, 36 were located in the pineal region, 5 in the suprasellar, and 2 in both the pineal and suprasellar regions. Twenty patients underwent surgical resection: total in 6 and partial in 10, while only a biopsy was taken in 4 cases. Fifteen patients were managed on the basis of serum CSF tumor markers and radiation response. Twenty-three patients with germinomas received radiotherapy (RT) and had a 5-year survival rate of 87%. Fifteen patients with non-germinomatous germ cell tumors received RT and chemotherapy following direct surgery, and 5 died (mortality rate of 33.3%). The overall survival rate of the 43 patients with pineal tumors was 79.1% (34/43) and the death rate was 20.9% (9/43). It is now recognized that the wide variety of tumor types found in the pineal region necessitates different modes of treatment, and improved microsurgical and stereotactic surgical techniques have made mortality and morbidity rates acceptably low. Because the radiation response and CSF cytology are not enough to determine optimum treatment, a tissue diagnosis should be obtained in all patients.

Proton magnetic resonance chemical shift imaging (1H CSI)-directed stereotactic biopsy.

INTRODUCTION: To add metabolic information during stereotactic biopsy target selection, the authors adopted proton chemical shift imaging (1H CSI)-directed stereotactic biopsy. Currently, proton single voxel spectroscopy (SVS) technique has been reported in stereotactic biopsy. We performed 1H CSI in combination with a stereotactic headframe and selected targets according to local metabolic information, and evaluated the pathological results. PATIENTS AND METHOD: The 1H CSI-directed stereotactic biopsy was performed in four patients. 1H CSI and conventional Gd-enhancement stereotactic MRI were performed simultaneously after the fitting of a stereotactic frame. After reconstructing the metabolic maps of N-acetylaspartate (NAA)/phosphocreatine (Cr), phosphocholine (Cho)/Cr, and Lactate/Cr ratios, focal areas of increased Cho/Cr ratio and Lac/Cr ratios were selected as target sites in the stereotactic MR images. RESULTS: 1H CSI is possible with the stereotactic headframe in place. No difficulty was experienced performing 1H CSI or making a diagnosis. Pathological samples taken from areas of increased Cho/Cr ratios and decreased NAA/Cr ratios provided information upon increased cellularity, mitoses and cellular atypism, and facilitated diagnosis. Pathological samples taken from areas of increased Lac/Cr ratio showed predominant feature of necrosis. CONCLUSION: 1H CSI was feasible with the stereotactic headframe in place. The final pathological results obtained were concordant with the local metabolic information from 1H CSI. We believe that 1H CSI-directed stereotatic biopsy has the potential to significantly improve the accuracy of stereotactic biopsy targeting.

Potentials and limitations of adenovirus-p53 gene therapy for brain tumors.

We investigated the antineoplastic potentials of recombinant adenovirus containing wild-type p53 cDNA (Ad5CMV-p53) for malignant gliomas. In four human glioma cell lines (U-251 and LG expressing endogenous mutant p53, and U-87 and EFC-2 expressing wild-type p53) and two rat glioma cell lines (9L and C6, each expressing mutant and wild-type p53), gene transfer efficiency determined by X-gal staining and Western blotting was varied (10-99% at 10-500 multiplicity of infection, MOI). Growth inhibitory effect was drastic (>90% at 100 MOI) in U-251 cells and only moderate or minimal in other cell lines harboring wild-type p53 or low gene transfer efficiency. Ex vivo transduction of U-251 cells with Ad5CMV-p53 suppressed the in vivo tumorigenicity of the cells. Histopathologic examination for Ad5CMV-p53 toxicity to rat brains showed inflammatory reactions in half of the tested brains at 10(8) MOI. U-251 cells were inoculated intracerebrally in nude mice and injected Ad5CMV-p53 into the tumor, in which neither the tumor suppression nor the survival benefit was observed. In conclusion, heterogeneity of the cellular subpopulations of malignant glioma in p53 status, variable and insufficient gene delivery to tumor, and adenoviral toxicity to brain at higher doses may be limiting factors to be solved in developing adenovirus-p53 gene therapy for malignant gliomas.