Predictive ability of hand-grip strength and muscle mass on functional prognosis in patients rehabilitating from stroke.

OBJECTIVES: This study aimed to investigate the association between muscle strength and adjusted appendicular skeletal muscle mass (ASM) in patients who have had strokes with the Functional Independence Measure (FIM) and the probability of being discharged. METHODS: A retrospective cohort study was conducted for older patients who have had strokes admitted to convalescent rehabilitation wards between January 2017 and October 2020. Hand-grip strength (HGS) was used to assess muscle strength. ASM was measured with a bioelectrical impedance analysis, and then divided by height-squared, body weight, body mass index (BMI), body fat mass (BFM), and body fat percentage (BFP) to calculate the adjusted ASM. The primary outcome was FIM at the time of discharge, and the secondary outcome was the probability of being discharged to their home. Multivariate analyses were conducted to adjust for confounding effects. RESULTS: The data of 699 participants (female: 47%; median age, 79 y) were analyzed. HGS was independently associated with FIM at the time of discharge in men (partial regression coefficient [B] = 0.482; 95% confidence interval [CI], 0.225-0.740) and women (B = 0.664; 95% CI, 0.263-1.065) and also was independently associated with being discharged to their home in men (odds ratio [OR]: 1.070; 95% CI, 1.030-1.100) and women (OR: 1.070; 95% CI, 1.000-1.130). Conversely, none of the adjusted ASM indices were associated with the outcomes. The cutoff value of HGS for discharge to home was 15.1 kg for men and 9.5 kg for women. CONCLUSIONS: In patients who have had strokes, HGS independently predicted FIM at the time of discharge and the probability of being discharged to their home. The adjusted ASM methods had less predictive value for functional and discharge outcomes.

Pseudohypoxic Brain Swelling after Unilateral Burr Hole Drainage: A Novel Case Report.

An 85-year-old man underwent emergency right trepanation and drainage for a symptomatic chronic subdural hematoma. Pseudohypoxic brain swelling (PHBS) was suspected because magnetic resonance imaging revealed diffuse brain swelling. Although cerebrospinal fluid (CSF) leakage was not obvious during or after surgery, most of the reported PHBS cases have leaked CSF during craniotomy or spine surgery. PHBS has not been previously reported in patients without obvious CSF leakage or after unilateral burr hole drainage. Herein, we report an extremely rare case with a literature review investigating its pathogenesis and clinical features.

Impact of Pre-operative Embolization With Onyx for Brain Arteriovenous Malformation Surgery.

Objective: To clarify the safety and efficacy of pre-operative embolization using Onyx liquid embolic agent (Onyx; ev3) compared with N-butyl cyanoacrylate (NBCA; Cordis Neurovascular, Inc.) or coils in cerebral arteriovenous malformation (AVM) surgery. Methods: This was a retrospective review of a prospectively collected clinical database of brain AVMs treated at our institute from January 2005 to March 2021. A total of 38 consecutive patients who underwent AVM resection after pre-operative embolization were included. Based on pre-operative embolization materials, the patients were divided into the pre-Onyx group (n = 16), in which NBCA or coils were used for embolization, and the Onyx group (n = 22). Patient characteristics and treatment results were compared between the two groups. Results: Patient characteristics were comparable between the two groups in terms of age, sex, and rupture status. While the Spetzler-Martin grade was also similar between the two groups, the location of the AVM nidus in the eloquent area was slightly higher in patients in the Onyx group (72.7%) than in patients in the pre-Onyx group (43.8%) (P = 0.09). The embolization rate was higher in the pre-Onyx group (mean: 63.0%; range: 12.7-100%) than in the Onyx group (mean: 50.0%; range: 15.8-100%), but the difference was not statistically significant (P = 0.06). The time needed for surgical removal was shorter in the Onyx group (mean: 354.8 min; range: 144-884 min) than in the pre-Onyx group (mean: 457.9 min; range: 240-1,294 min); however, this difference was not statistically significant (P = 0.13). The amount of intraoperative bleeding was significantly lower in the Onyx group (mean: 129.8 ml; range: 20-540 mL) than in the pre-Onyx group (mean: 448.8 mL; range: 120-1,550 ml) (P = 0.0008). The surgical complication rates were comparable between the two groups (pre-Onyx group, 18.8%; Onyx group, 4.5%; P = 0.29). Conclusions: Pre-operative embolization with Onyx can significantly reduce the amount of intraoperative bleeding in AVM resection and may contribute to safe AVM surgery.

Usefulness of the Atherosclerosis Risk Score for Patients With Acute Infarction in the Lenticulostriate Artery Region.

Background and purpose Internal carotid artery intima-media thickness (IMT) and pulse wave velocity (PWV) are risk factors of cerebrovascular disease and coronary artery disease. They are known as independent predictors of arteriosclerotic disease. It has been reported that IMT and PWV are useful factors for predicting stroke subtype and/or outcome. Coronary artery disease onset is proportional to atherosclerosis progression, and the Framingham Risk Score (FRS) and Suita score (SS) are standard risk predictors. This study examined whether FRS and SS can be useful for patient outcomes with acute infarction in the lenticulostriate artery (LSA) region without special tests or invasive procedures while using IMT or PWV as predictive factors. Methods We screened 629 consecutive patients with ischemic stroke and reviewed 84 patients with acute infarction in the LSA region who were admitted between January 2018 and December 2020. An early deterioration (ED) group was defined. In addition, the clinical characteristics, FRS, SS, treatment therapy, and neurovascular findings were evaluated. Results FRS and SS (FRS: 11.6 vs. 8.3, p < 0.01, SS: 58.2 vs. 53.7, p = 0.01, respectively), pre-symptomatic modified Rankin Scale (mRS) (p = 0.03), mRS at discharge (p < 0.01), and deterioration of manual muscle test (MMT) (<0.01) were significantly higher in patients in the ED (34 patients) group than in the no-ED group (54 patients). FRS and SS were correlated with mRS deterioration (FRS: r = 0.47; p < 0.01, SS: r = 0.23; p = 0.03). Among the laboratory parameters, total cholesterol (TC) (p < 0.01) and low-density lipoprotein cholesterol (LDL-C) (p < 0.01) were significantly higher in the ED group, and no significant differences in any acute therapeutic interventions. Conclusion Atherosclerosis risk scores, such as FRS and SS, may be useful for predicting outcomes in patients with acute LSA-region infarctions within 48 hours of onset.

Prevalence and Associated Factors of Coexistence of Malnutrition and Sarcopenia in Geriatric Rehabilitation.

Malnutrition and sarcopenia often coexist in rehabilitation patients, although they are often overlooked and undertreated in clinical practice. This cross-sectional study aimed to clarify the prevalence of the coexistence of malnutrition and sarcopenia (Co-MS) and its associated factors in convalescent rehabilitation wards in Japan. Consecutive patients aged ≥ 65 years in convalescent rehabilitation wards between November 2018 and October 2020 were included. Malnutrition and sarcopenia were determined by the Global Leadership Initiative on Malnutrition (GLIM) criteria and the Asian Working Group for Sarcopenia (AWGS 2019) criteria, respectively. Patients who presented both with malnutrition and sarcopenia were classified as Co-MS. Potentially associated factors included age, sex, days from onset to admission of rehabilitation wards, reason for admission, pre-morbid functional dependency, comorbidity, activities of daily living, swallowing ability, and oral function and hygiene. The prevalence of malnutrition, sarcopenia, and Co-MS was calculated. Binary logistic regression analyses were performed to compute odds ratios (ORs) and the 95% confidence interval (CI) of possible associated factors for each condition. Overall, 601 patients were eligible for the analysis (median 80 years old, 355 female patients, 70% cerebrovascular disease). Co-MS, malnutrition, and sarcopenia were found in 23.5%, 29.0%, and 62.4% of the enrolled patients, respectively. After adjustment, onset-admission interval (OR = 1.04; 95% CI = 1.02 to 1.06), hospital-associated deconditioning (OR = 4.62; 95% CI = 1.13 to 18.8), and swallowing ability (Food Intake LEVEL Scale) (OR = 0.83; 95% CI = 0.73 to 0.93) were identified as independent explanatory factors of Co-MS. In conclusion, Co-MS was prevalent in geriatric rehabilitation patients; thus, healthcare professionals should be aware of the associated factors to detect the geriatric rehabilitation patients who are at risk of both malnutrition and sarcopenia, and to provide appropriate treatments.

Effect of Improvement in Sarcopenia on Functional and Discharge Outcomes in Stroke Rehabilitation Patients.

This cross-sectional study investigated the proportion of patients' recovery from sarcopenia status and the relationship between improvement in sarcopenia (IS) and function and discharge outcome in hospitalized patients with stroke. This study included patients with stroke, aged 65 years or more, with a diagnosis of sarcopenia, who were admitted to a convalescent rehabilitation ward. Sarcopenia was diagnosed according to the Asian Working Group for Sarcopenia 2019 criteria. Patients were divided according to the presence or absence of sarcopenia at discharge: IS group and non-improvement in sarcopenia (NIS) group. Among the 227 participants (mean age: 80.5 years; 125 females), 30% (69/227) of the patients were in the IS group, while 70% (158/227) were in the NIS group. The IS group showed a higher Functional Independence Measure (FIM) than the NIS group (median 112 vs. 101, p = 0.003). The results demonstrated that IS was independently associated with higher FIM (partial regression coefficient, 5.378; 95% confidence interval (CI), 0.709-10.047). The IS group had higher odds of home discharge than the NIS group (odds ratio, 2.560; 95% CI, 0.912-7.170). In conclusion, recovery from sarcopenia may be associated with better function in patients with stroke.

Moyamoya Disease Associated with Graves' Disease and Down Syndrome: A Case Report and Literature Review.

BACKGROUND: Moyamoya vessels are cerebral vasculopathies characterized by net-like collateral vessel formation at the cerebral basal area and stenosis of the terminal internal carotid artery, proximal middle cerebral artery, and anterior cerebral artery. A diagnosis of Moyamoya disease depends on the bilateral presence of Moyamoya vessels. Moyamoya disease associated with Graves' disease has rarely been reported to be a cause of ischemic events due to hyperthyroidism. However, there are extremely rare cases of Moyamoya disease with concurrent Graves' disease and Down syndrome. We aimed to report such a case, and to compare these cases' clinical features, pathogenesis, and treatment effects to those of the cases of concurrent Moyamoya disease and Graves' disease alone. METHODS: We performed an English literature search using the PubMed database and the keywords Moyamoya, quasi-Moyamoya, Graves' disease, thyrotoxicosis, Down syndrome, and trisomy 21. RESULTS: Only five cases of Moyamoya disease with Graves' disease and Down syndrome have been reported, including our own. Four patients were female (80%), and all underwent antithyroid therapy and experienced ischemic episodes, including transient ischemic attacks. At the time of their vascular accident, two patients were in a thyrotoxic state; only our patient was in a euthyroid state. The mean age was 15.6 years (standard deviation: 6.1), which was younger than the mean age of 31.4 years (standard deviation: 13) in patients with Moyamoya disease and Graves' disease alone. Down syndrome is commonly associated with abnormal vascular networks due to increased endostatin concentrations or immunological abnormalities such as those that occur in Graves' disease. Graves' disease accelerates the progression of Moyamoya disease and ischemic attacks due to atherosclerosis, enhances sympathetic nervous system activity and immunological changes. As compared to Moyamoya disease patients, patients with concurrent Graves' disease only and Moyamoya disease patients with concurrent Graves' disease and Down syndrome may experience accelerated disease progression or more frequent ischemic attacks. CONCLUSION: Early imaging follow-ups and strict control of thyroid function are necessary in such cases; if ischemic attacks have already occurred, revascularization surgery may be effective.

A Case of Cerebral Hyperperfusion Showing Unique Characteristics on Susceptibility-weighted MR Imaging after Carotid Endarterectomy.

Cerebral hyperperfusion syndrome (CHS) is a potentially devastating complication of carotid endarterectomy (CEA). Early detection and treatment of hyperperfusion are important before the condition develops into CHS. We herein present a case involving a 65-year-old female with severe right internal carotid artery (ICA) stenosis, who experienced hyperperfusion after right CEA. During the postoperative course, changes in the resting cerebral blood flow (rCBF) were evaluated using single-photon emission computed tomography (SPECT), and were found to correlate with the changes in the signal intensity of cortical arteries, cortical veins, and perilateral ventricular veins of the right middle cerebral artery (MCA) territory on susceptibility-weighted imaging (SWI). SWI showed a prominent hyperintensity of cortical arteries in the right MCA territory at postoperative day 1 (POD1), but the hyperintensity gradually decreased over time and became indistinct by POD48. As for cortical veins and perilateral ventricular veins, SWI showed an increased signal intensity of these veins during the peak of rCBF on POD1, but later, the signal intensity decreased as rCBF decreased on POD5. The signal intensity of cortical veins and perilateral ventricular veins finally returned to normal on POD9. Those SWI findings could be related to an impairment of cerebral autoregulation and the resulting hyperperfusion. SWI could be potentially useful as an additional tool in the evaluation of hyperperfusion.

[A case report of dolichoectasia of the anterior cerebral artery].

Dolichoectasia of the intracranial arteries is a rare condition, and the vertebrobasilar system and the internal carotid artery is most commonly involved. We describe a rare case of a 60-year-old man with dolichoectasia of the anterior cerebral artery (ACA). The patient presented with continuous vertigo and nausea. CT and MR imaging showed a prominent serpentine structure with calcification and flow void in the region of the interhemispheric fissure, findings which were suspicious for arteriovenous malformation (AVM) or fistula (AVF). A cerebral angiogram demonstrated an extensive dilatation of the ACA above the level of the anterior communicating artery. There was no evidence of AVM or AVF. Although SPECT study revealed a decrease of cerebral blood flow (CBF) in the right frontal lobe, cerebrovascular reserve, as demonstrated by acetazolamide challenge was sufficient for maintenance. Decrease of CBF may have resulted from diaschisis or selective neural cell elimination by old cerebral infarction. The patient was treated with an anti-platelet agent conservatively and the symptoms gradually improved. Cerebral angiography may be needed for definitive diagnosis because cerebral dolichoectasia may mimic CT and MR imaging findings of AVF or AVM. Cerebral hemodynamics must be examined strictly in addition to demonstrating vascular disease by angiography, and SPECT study may play a role in the detection of hemodynamic change induced by dolichoectasia.

[A case of cerebral amyloid angiopathy in which a restricted subarachnoid hemorrhage recurred in the cortical sulcus following a subcortical hemorrhage].

Cerebral amyloid angiopathy (CAA) is predominantly recognized in elderly people and repeatedly causes a huge subcortical hemorrhage. Some cases of CAA can cause secondary subarachnoid hemorrhage (SAH), but cases in which it causes primary SAH is very rare. We describe a valuable reference case of a 75-year-old man in whom a restricted SAH recurred in the cortical sulcus following a huge subcortical hemorrhage. He presented with an unknown restricted SAH in the left frontal sulcus twice before neck clipping for a right IC-PC unruptured aneurysm. Postoperative computed tomography (CT) revealed a recurrent SAH in the left frontal lobe, and it spread gradually. T2(*) weighted imaging (T2(*)WI) revealed subarachnoid hemosiderosis and superficial cortical hemosiderosis in the frontal and parietal lobe. On the 21st postoperative day, he suddenly presented right hemiplegia and a huge subcortical hemorrhage was observed in the left frontal lobe on CT. Emergent removal of the hematoma was performed, but the patient had become bedridden. Pathological diagnosis of CAA was made. A recurrent restricted SAH in the frontal sulcus might have been a warning sign of a huge subcortical hemorrhage. In the aging society, a radiological prediction of CAA is very important. Although it is generally thought to be very difficult, T2(*)WI may be useful for predicting CAA. When we plan surgery for elderly people, we must always take CAA into consideration.

[Subclavian steal phenomenon associated with hypervascular thyroid tumor].

Subclavian steal syndrome (SSS) is caused by hypoplasia of a vertebral artery or stenosis or occlusion of the subclavian artery or the brachiocephalic artery with subsequent retrograde filling of the subclavian artery via the contralateral vertebral artery. Symptoms of SSS are due to vertbrobasilar insufficiency or ischemia of the ipsilateral upper extremity, and they may include dizziness, syncope, ataxia, arm claudication, hand numbness or a decrease in brachial blood pressure on the affected side. However, most SSS cases are asymptomatic and they are classified as subclavian steal phenomenon (SSP). Atherosclerosis is the common cause of SSS, and Takayasu arteritis, neurofibromatosis, trauma, embolization, congenital vascular anomalies and surgical interruption of the subclavian artery can be identified among the other causes. We describe a rare case of hypervascular thyroid nodule presenting with features of SSP. The patient was hospitalized with acute cerebral infarction due to middle cerebral artery (MCA) severe stenosis. The patient had conservative therapy in the acute stage, and underwent STA-MCA anastomosis for MCA stenosis in the chronic stage. SSS was asymptomatic although there was laterality in blood pressure in the patient's bilateral upper limbs. Thyroid tumor was regarded as benign by radiological findings, laboratory data, and physical examination. If SSS becomes symptomatic, removal of the thyroid tumor may be indicated.

De novo basilar head aneurysms--two case reports.

We describe two rare cases of de novo basilar head aneurysms. The first patient presented with a ruptured basilar tip aneurysm, which developed de novo 5 years after the clipping of a left middle cerebral artery aneurysm. The second patient presented with a right basilar artery-superior cerebellar artery aneurysm, which developed de novo 3 years after the clipping of a right A(1) aneurysm. The formation of de novo aneurysm in the posterior circulation has significant implications for screening. Patients must be carefully examined not only at the sites of the initial aneurysm, but also at separate sites, including the posterior circulation, to evaluate the possibility of de novo appearance of another aneurysm.

[A case of rapidly growing dumbbell-shaped convexity meningioma].

We have had more opportunities to treat incidental meningiomas owing to the recent development of neuroradiological imaging. Generally, most of them are treated conservatively unless they grow rapidly or change to symptomatic. Rapidly growing meningiomas are unusual because meningiomas are generally benign and slow-growing tumors. Particularly, the indication of surgery in elderly patients with asymptomatic meningiomas must be considered very carefully because of the higher risks of complications or postoperative neurological deficits. The author describes a rare case of a rapidly growing dumbbell-shaped convexity meningioma in an elderly patient. The tumor was removed completely (Simpson grade II), and the pathological diagnosis was atypical meningioma. There was a difference of MIB-1 LI within the tumor, which suggests that the difference of proliferation within the meningioma may have changed it into "dumbbell-shaped". The only factor we could identify to explain the rapid growth was the high MIB-1LI. This represents an interesting example of a rapidly growing meningiomas. Although the indication of aggresive surgery in elderly patients with symptomatic meningiomas should be considered, the postoperative deterioration of quality of life must be avoided. And earlier postoperative rehabilitation can be regarded as indispensable for elderly patients.

Reversible clinical and magnetic resonance imaging of central pontine myelinolysis following surgery for craniopharyngioma: serial magnetic resonance imaging studies.

An 18-year-old girl presented with central pontine myelinolysis (CPM) following surgery for craniopharyngioma. Postoperatively, the patient developed diabetes insipidus with remarkable fluctuation of serum sodium level, suffered a seizure, and developed mental state changes and quadriparesis. Magnetic resonance (MR) imaging obtained soon after the development of the symptoms showed no significant abnormalities. MR imaging obtained 2 months later demonstrated typical trident or bat-like signal abnormalities in the center of the pons, compatible with CPM. Serial MR imaging obtained at 7 and 10 months showed the lesion had decreased in size or almost completely resolved and the patient almost completely recovered. CPM is well known, but neurosurgeons should consider the possibility following surgery for craniopharyngioma.

[Case of reversible ischemic neurological deficit presented as hemiballism].

Ballism is characterized by continuous, coarse, flinging involuntary movements involving the limbs. Although persistent involuntary movements caused by cerebrovascular diseases mostly in middle-aged patients are well known, transient involuntary movements are an unusual manifestation of cerebrovascular diseases. We describe a rare case of reversible ischemic neurologic deficit (RIND) presented as hemiballism. A 71-year-old man was admitted to our hospital for hemiballism in the right limbs. On magnetic resonance (MR) imagings, there was no evidence of acute ischemic stroke, but MR angiography revealed severe stenosis of left middle cerebral artery. Electroencephalogram showed no epileptic discharge. For hemiballism, chlorpromazine and haloperidol were administered in addition to antiplatelet management for ischemic attack, and the patient completely recovered on the 5 days of hospitalization. Transient ischemic attacks (TIA) or RIND typically present with neurological deficits such as loss of muscle power, reduced sensation, or visual loss. Involuntary movements are not generally regarded to be TIA or RIND. Involuntary movements such as hemiballism, however, can occur as a symptom of TIA or RIND, which should be recognized and differentiated from conditions like partial seizures. Moreover, they may be an indicator of severe carotid stenotic or occlusive diseases, and patients may be at high risk of ischemic events. Early diagnosis and timely treatment are required to prevent ischemic events.

Papillary tumor of the pineal region.

A 48-year-old female presented with an extremely rare primary tumor of the pineal region with papillary features manifesting as morning headaches persisting for 1 month. Magnetic resonance imaging showed a well-defined mass, with some cystic components, in the region of the pineal gland. The tumor was completely removed through an occipital transtentorial approach in the prone position. Histological examination found a distinctive papillary growth pattern in which the vessels were covered by multiple layers of tumor cells. The histological diagnosis was papillary tumor of the pineal region (PTPR), which has recently been described as a distinct clinicopathological entity requiring careful follow up because the prognosis is not well understood. Postoperatively, the patient has continued to do well, with no recurrence at the 8-month follow-up examination. PTPR should be considered in the differential diagnosis of pineal tumors. PTPR may have been frequently misinterpreted in the past as either ependymoma or choroid plexus papilloma due to the similar morphology.

Epstein-Barr virus-based vector improves the tumor cell killing effect of pituitary tumor in HVJ-liposome-mediated transcriptional targeting suicide gene therapy.

Although tissue-specific promoters offer a promising approach to the targeting of gene therapy, the activity of such promoters is generally low, which is thus a major limitation, especially when using non-viral vectors. To establish effective transcriptional targeting gene therapy for growth hormone (GH) producing pituitary tumors, an Epstein-Barr virus (EBV) based vector system expressing herpes simplex virus type 1 thymidine kinase (HSV1-TK) driven by a rat GH promoter (pEBGTK) was developed. This harbors an EBV nuclear antigen-1 (EBNA-1) gene with an origin of the latent viral DNA replication (OriP) gene of EBV. We constructed an EBV-based luciferase plasmid (pEBGL) as a reporter plasmid. We also generated pGTK and pGL, which are non-EBV counterparts. Metastatic GH3 (mGH3) cells were used in this study. The transfection of pEBGL to mGH3 resulted in approximately a 39 times greater luciferase activity than pGL in vitro. Its expression was also prolonged 144 h after transfection. According to the results of pEBGL gene transfer in in vivo experiments, the luciferase activity was only observed in the tumors, but not detected in other normal tissues. The luciferase activities in tumor tissues were found until day 25 post transfection. During in vitro gene therapy, the transfection by pEBGTK using hemmaglutinating virus of Japan (HVJ) liposome enhances the susceptibility of mGH3 to gancyclovir (GCV) 110 times more than that by pGTK. The in vivo anti-tumor effects of pEBGTK on mGH3-tumor-bearing nude mice were evaluated. The intratumoral injection of HVJ anionic lipososme-enveloped pEBGTK followed by the intra-peritoneal injection of GCV demonstrated a significant growth inhibition against tumors without toxicity, while the tumors treated by other treatment modalities grew progressively. These results demonstrated that the EBV-based vector system can therefore contribute to the improvement of the anti-tumor effects for the HVJ-liposome-mediated transcriptional targeting suicide gene therapy, suggesting that this paradigm may thus be a potentially effective approach for the treatment of uncontrollable pituitary tumors.

Inhibition of tumor growth and prolonged survival of rats with intracranial gliomas following administration of clotrimazole.

OBJECT: Clotrimazole, an imidazole derivative and inhibitor of cytochrome P-450, inhibits the proliferation of cancer cells by downregulating the movement of intracellular Ca++ and K+ and by interfering with the translation initiation process. Clotrimazole inhibits the proliferation of human glioblastoma multiforme cells; it induces morphological changes toward differentiation and blocks the cell cycle in the G1/G1 phase. In vitro, clotrimazole enhances the antitumor effect of cisplatin by inducing wild-type p53-mediated apoptosis. The authors examined the effect of clotrimazole on tumor growth, sensitivity to cisplatin, and survival of rats with intracranial gliomas. METHODS: Cultured C6 and 9L glioma cells were exposed to clotrimazole, and cell growth was assessed using the 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyl tetrazolium bromide colorimetric assay. Clotrimazole produced a dose- and time-dependent inhibition of cell proliferation. The growth inhibitory effect of clotrimazole could not be overcome by exogenous stimulation with epidermal growth factor. Both C6 and 9L glioma cells were implanted into the rat brain and after 5 days, the animals were treated with a daily single dose of clotrimazole for 8 consecutive days. Clotrimazole treatment caused a significant inhibition of intracranial tumor growth. The survival of rats with 9L gliomas was analyzed after 10 days of treatment with clotrimazole, cisplatin, or a combination of clotrimazole and cisplatin. Rats treated with either drug displayed a significantly prolonged survival time; however, the combination treatment resulted only in an additional survival benefit. CONCLUSIONS: Clotrimazole effectively inhibits cell proliferation and tumor growth, and prolongs survival of rats with intracranial gliomas. Clotrimazole may be considered a potential anticancer drug for treatment of intracranial gliomas.

Immunohistochemical expression of E-cadherin in metastatic brain tumors.

The adhesion molecule E-cadherin has been shown to influence malignant transformation of tumors, including local and distant metastases. We examined the expression of E-cadherin to determine its relationship to the development of metastasis in metastatic brain tumors. Immunohistochemistry for E-cadherin and Ki-67 was carried out in 76 formalin-fixed, paraffin-embedded archival specimens of metastatic brain tumors and in 14 corresponding available primary tumors from patients who received treatment for metastatic brain tumors. The primary tumors were mainly lung cancers (51.3%), followed by gastrointestinal tumors (28.9%). E-cadherin was expressed in 62 (81.5%) of 76 cases examined. In metastatic adenocarcinomas, a consistent tendency for E-cadherin expression was noted, regardless of the degree of differentiation or the extent of spread of the disease (P = 0.04). There was a direct correlation between E-cadherin expression and high MIB-1 index in all metastatic brain tumors (P = 0.0007). Pairwise analysis in 14 primary tumors and the corresponding metastatic specimens revealed high E-cadherin and MIB-1 staining in metastatic brain tumors. These results provide a unique association between E-cadherin, systemic metastasis, and proliferation potential in metastatic brain tumors.

Relationship between expression of O6-methylguanine-DNA methyltransferase, glutathione-S-transferase pi in glioblastoma and the survival of the patients treated with nimustine hydrochloride: an immunohistochemical analysis.

Drug resistance is one of the important factors that determine tumor response to chemotherapy. Several candidates for resistance to various chemotherapeutic agents have been elucidated. O6-methylguanine-DNA methyltransferase (MGMT) removes methylation damage induced by nitrosourea from the O6 position of DNA guanines before cell injury. Glutathione-S-transferase (GST) pi is also involved in nitrosourea resistance. We examined the expression of MGMT and GST pi in 18 glioblastomas (GBM) using immunohistochemistry and compared the results with patients' survival after administration of 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU)-based chemotherapy. According to the Kaplan-Meier's method, although median progression free survival (PFS) of eight patients whose tumors retained high MGMT (3+ approximately 2+), and 10 patients whose tumors showed low MGMT expression (1+ approximately 0) were nine and 15 months, respectively (p = 0.09), median overall survival (OS) of the two groups were 12 and 22 months, respectively, which were significantly different (p = 0.01). GST pi expression in GBM was not a prognostic factor. It is suggested that GBM with strong staining of MGMT activity may show more resistance to ACNU-based chemotherapy compared to that with low MGMT. The simple immunohistochemical analysis of MGMT in GBM can be a useful method to determine whether ACNU or another treatment regimen should be recommended.