Impact of the per-operatory application of GLIADEL wafers (BCNU, carmustine) in combination with temozolomide and radiotherapy in patients with glioblastoma multiforme: Efficacy and toxicity

Purpose

For the last few years wafers of Gliadel have been inserted into the operation cavity in patients with glioblastoma multiforme. This is followed by concurrent radio-chemotherapy with temozolomide (TMZ) according to the Stupp protocol. Only a few studies have investigated this kind of treatment regimen and the impact in terms of survival and toxicity of the combination of Gliadel with TMZ and radiotherapy.

Methods and materials

From November 2006 to January 2010, 24 patients with a newly diagnosed glioblastoma have undergone a tumour resection which was considered to be macroscopically complete in 12 cases and with tumour residue in another 12 cases. The mean age at the moment of diagnosis was 60.25 years and the median age 63.Twenty-three patients underwent subsequently concurrent radio-chemotherapy with TMZ followed by cycles of elevated doses of TMZ as an adjuvant treatment. One patient had adjuvant radiotherapy alone followed by adjuvant chemotherapy. Thirteen were able to receive 6 or more cycles of adjuvant TMZ. Seven patients had received less than 6 cycles of TMZ as an adjuvant therapy. Two patients did not receive adjuvant TMZ at all.

Results

The median overall survival of our group was 19.2 months and the median progression free survival was 12.3 months. Overall survival for the macroscopically complete-resection patients was 14 months, and 12.85 months in subtotal-resection patients. The median OS was 14.25 months for patients PS 0 – 1 at the moment of diagnosis and 12.65 for PS 2 patients. Chemotherapy with TMZ had to be stopped prematurely in 10 cases due to haematotoxicity, digestive toxicity or early relapse.

Conclusions

The concomitant use of surgery with implantation of BCNU wafers and radio-chemotherapy seems to be well tolerated. Despite the small number of patients treated in our group, particular attention should be paid to the potential haematological consequences of this multimodal treatment regimen.     

Efficacy of temozolomide as adjuvant chemotherapy after postsurgical radiotherapy alone for glioblastomas

Objectives

The aim of this study was to assess the efficacy of adjuvant TMZ chemotherapy for newly diagnosed GBM patients who were treated with surgery followed by radiotherapy alone.

Material and methods

Between January 2003 and April 2005, 59 consecutive GBM patients underwent radiation therapy after surgical resection and subsequently received TMZ chemotherapy. For the comparative analysis, we selected 60 clinically matched GBM patients who underwent radiotherapy followed by nitrosourea-based chemotherapy (NUBC), at the same institution between June 1995 and April 2005. The study cohort was divided into two groups, those with adjuvant TMZ treatment and with NUBC.

Results

59 patients with adjuvant TMZ treatment were assigned to the treatment group and 60 patients with NUBC to the control group. The median overall survival for the treatment group was 18.2 months (95% CI, 11.7–24.7 months), compared with the survival of 14.5 months (95% CI, 11.2–17.7 months) for the control group (p = 0.019). The progression-free survival for the treatment group was 5.6 months (95% CI, 4.4–6.7 months), while the control group showed progression-free survival of 3.3 months (95% CT, 3.2–6.0 months) (p = 0.030). Uni- and multivariate analysis revealed that extent of surgical resection, age ≥55 years and postoperative KPS were significantly associated with survival.

Conclusion

Adjuvant TMZ chemotherapy provided a clinically relevant benefit of survival, as compared with NUBC. Thus, we suggest that adjuvant TMZ chemotherapy may be effective even for patients who did not receive concomitant chemoradiotherapy for GBM.     

Concomitant and adjuvant temozolomide of newly diagnosed glioblastoma in elderly patients

Objective

The effect of concomitant and adjuvant temozolomide in glioblastoma patients above the age of 65 years lacks evidence. However, after combined treatment became standard at our center all patients were considered for combined therapy. We retrospectively analyzed the effect of temozolomide focused on elderly patients.

Methods

293 patients with newly diagnosed glioblastoma treated single-centered between 1998 and 2010, by radiation alone or concomitant and adjuvant radiochemotherapy, were included. Treatment groups were analyzed by multi- and univariate analysis. Matched pairs for age, by a 5-year-caliper, extent of resection and general state was generated for all patients and elderly subgroups.

Results

103 patients received radiation only and 190 combined treatment. Multivariate and matched pair analysis revealed a benefit due to combined temozolomide (HR 1.895 and 1.752, respectively). For patients older than 65 years median survival was 3.6 (95% CI 3.2–4.7) and 8.7 months (6.3–11.8) for radiotherapy only and combined treatment (HR 3.097, p < 0.0001, n = 90). Over the age of 70 and 75 years median survival was 3.2 (2.3–4.2) vs. 7.5 (5.1–10.9, HR 4.453, p < 0.0001, n = 62) and 3.2 (1.4–3.9) vs. 9.2 months (4.7–13.5; HR 9.037, p < 0.0001, n = 24), respectively. In 8/56 (14%) patients over the age of 70 years temozolomide was terminated due to toxicity.

Conclusion

Retrospective matched pair analysis gives class 2b evidence for prolonged survival due to concomitant and adjuvant temozolomide in elderly glioblastoma patients. Until prospective data for combined radiochemotherapy in elderly patients will be available concomitant and adjuvant temozolomide therapy should not be withheld.     

Factors affecting the diagnostic delay in amyotrophic lateral sclerosis

Background

Although amyotrophic lateral sclerosis (ALS) is a relentlessly progressive disorder, early diagnosis allows a prompt start with the specific drug riluzole and an accurate palliative care planning. ALS at onset may however mimic several disorders, some of them treatable (e.g., multifocal motor neuropathy) or epidemiologically more frequent (e.g., cervical myelopathy).

Objective

To study the delay from onset to diagnosis in a cohort of ALS patients and to the variables that may affect it.

Methods

We performed a retrospective analysis of the diagnostic delays in a cohort of 260 patients affected by ALS (M/F = 1.32) followed at our tertiary referral ALS Center between 2000 and 2007.

Results

The median time from onset to diagnosis was 11 months (range: 6–21) for the whole ALS cohort, 10 months (range: 6–15) in bulbar-onset (n = 65) and 12 months (range: 7–23) in spinal-onset (n = 195) patients (p = 0.3). 31.1% of patients received other diagnoses before ALS and this led to a significant delay of the correct diagnosis in this group (other diagnoses before ALS, n = 81: median delay, 15 months [9.75–24.25] vs ALS, n = 179, median delay, 9 months [6–15.25], p < 0.001).

Conclusions

The diagnostic delay in ALS is about one year, besides the growing number of tertiary centres and the spread of information about the disease through media and internet. Cognitive errors based on an incorrect use of heuristics might represent an important contributing factor. Furthermore, the length of the differential diagnosis from other disorders and delays in referral to the neurologist seems to be positively associated with the delay in diagnosis.     

Glioblastoma: clinical characteristics, prognostic factors and survival in 492 patients

Objective

Glioblastoma is the most common and most malignant primary brain tumor in adults. The only overall accepted independent prognostic factors are patient age and performance. We present a large single institution patient series examined for prognostic factors using uni- and multivariate survival analysis.

Methods

492 patients were included who underwent craniotomy for newly diagnosed glioblastoma WHO grade IV between 1990 and 2007 at our department. The association to patient survival was estimated using log-rank test for univariate analysis and cox regression method for multivariate analysis.

Results

Median patient age was 62 years (mean: 60.4 years, range: 22–93 years), the male: female ratio was 1.26:1. Primary genesis was found in 91.0% of cases. A multifocal tumor was present in 110 cases (22.4%). The median pre- and post-operative Karnofsky Performance Score was 70. Total tumor resection was performed in 288 cases (58.5%), subtotal removal in 134 cases (27.2%). The following parameters were significantly associated with survival in univariate analysis: age, performance, primary genesis, multifocal tumor, neurological deficit, neuropsychological findings, seizures, incidental finding, total or subtotal resection, radiotherapy, chemotherapy, combined radio-/chemotherapy with temozolomide, re-craniotomy, second tumor in patient history. The following parameters were significantly associated with survival in multivariate analysis: age, performance, multifocal tumor, total or subtotal resection, radiotherapy, chemotherapy, combined radio-/chemotherapy with temozolomide.

Conclusion

In addition to patient age and performance, we identified multiple lesions and resection status as independent prognostic factors. Radiotherapy, chemotherapy and combined radio-/chemotherapy with temozolomide were significantly associated with prolonged survival.     

Early clinical and neuroradiological worsening after radiotherapy and concomitant temozolomide in patients with glioblastoma: Tumour progression or radionecrosis?

Objectives

This study investigates the diagnosis and management of patients with resected brain glioblastomas who presented early clinical and neuroradiological worsening after the completion of the Stupp protocol. Its aim is to discuss the occurrence of early radionecrosis.

Methods

Fifty patients with brain glioblastoma treated by surgical resection and Stupp protocol were reviewed; 15 among them (30%) had early clinical and neuroradiological worsening at the 6-month follow-up. The MR spectroscopy and surgical findings of these patients are reviewed.

Results

MR spectroscopy was in favour of tumour recurrence in 14 among 15 patients and showed radionecrosis in one. Among 10 patients who were reoperated on, 7 had histologically verified tumour recurrence or regrowth, whereas in 3 histopathology showed necrosis without evidence of tumour. The 7 patients with tumour progression had prevalence of focal neuroradiological signs (6/7) and a survival of 7.5–12 months (median survival 10 months). The 4 patients with early radionecrosis (including one patient who was not reoperated on) had clinical worsening with mental deterioration, confusion and ataxia, and MR spectroscopy positive for tumour recurrence in 3. Three were alive 24–30 months after the end of the radiotherapy, whereas one died at 40 months.

Conclusion

Early radionecrosis after the Stupp protocol is not a rare event due to the radiosensitization effect of temozolomide. This phenomenon may predict a durable response to radiotherapy. MR spectroscopy may simulate tumour recurrence. A correct diagnosis is necessary to avoid useless reoperations and incorrect withdrawal of temozolomide.     

Temozolomide during and after Radiotherapy for Newly Diagnosed Glioblastomas : A Prospective Multicenter Study of Korean Patients

Objective

This study was performed to determine the safety and outcome of concurrent chemoradiotherapy (CCRT) and adjuvant chemotherapy with temozolomide for Korean patients with a newly diagnosed glioblastoma.

Methods

Patients were recruited from four institutions between 2004 and 2007. The patients received fractionated focal irradiation in daily fractions of 2 Gy given 5 days per week for 6 weeks and daily temozolomide, followed by 6 cycles of adjuvant temozolomide. The primary endpoint was overall survival (OS) and the secondary endpoints were progression-free survival (PFS), response, and safety.

Results

A total of 103 patients were enrolled in this study. Ninety-six patients (93%) completed the CCRT and 54 patients (52%) received 6 cycles of adjuvant temozolomide. The response rate was 73% (53/73) and the tumor control rate was 92% (67/73). Of the 96 patients who completed the CCRT, the median OS was 18.0 months and the 1- and 2-year OS rates were 74 and 38%, respectively. The median PFS was 10.0 months and the 1- and 2-year PFS rates were 33 and 16%, respectively. The only significant prognostic factor of survival was the extent of surgical resection (p<0.05). CCRT resulted in grade 3 or 4 hematologic toxic effects in 8% of patients. No opportunistic infections were noted.

Conclusion

This study is the first prospective multi-institutional report of CCRT and adjuvant chemotherapy with temozolomide for patients with a newly diagnosed glioblastoma in Korea. The current protocol may prolong the survival of Korean patients with a glioblastoma and may be tolerable in terms of toxicity.     

An analysis of related factors of surgical results for patients with craniopharyngiomas

Objective

The objective of this study was to retrospectively review the surgical results following gross total resection and partial resection with or without radiotherapy for craniopharyngiomas and analyze the related factors of surgical results.

Methods

From 1994 to 2009, 214 patients underwent 219 procedures for craniopharyngiomas. We retrospectively reviewed the pre- and postoperative data of patients, reported the perioperative and long-term surgical results and analyzed the influencing factors and the relationship between hypothalamic involvement and postoperative quality of life.

Results

Gross total resection was achieved in 154 procedures (70.3%). Perioperative mortality was 5%. Perioperative hyperpyrexia was the most significant risk factor for perioperative mortality. A total of 151 patients were followed from 6 months to 190 months. There were significant differences in recurrence rate and overall survival between gross total resection and limited resection (P < 0.05). There was significant difference in recurrence rate between limited resection and limited resection with radiotherapy (P < 0.01), but it did not reach statistical difference between gross total resection and gross total resection with radiotherapy. The factors strongly influencing overall survival include old patients, partial resection and recurrent tumors. The preoperative hypothalamic involvement negatively correlates with the postoperative quality of life in patients with craniopharyngiomas.

Conclusion

The preoperative CT/MR imaging provides clues of the relationship between tumor and surrounding structures. Gross total resection should be achieved in the treatment of craniopharyngiomas on the condition that hypothalamus is preserved. The patients who undergo limited resection should receive conventional radiotherapy or gamma knife surgery.     

Radiation induced early necrosis in patients with malignant gliomas receiving temozolomide

Background

Temozolomide is the major drug in the treatment of malignant gliomas. Radiation induced necrosis can behave radiologically and clinically like a recurrent tumor. The major problem is the differentiation between recurrence and radiation injury especially in early phases of treatment. The aim of this study was to evaluate the patients receiving temozolomide showing early clinical or radiological progression and impact of early necrosis on follow-up.

Patients and methods

We retrospectively evaluated medical records of 67 patients with malignant glioma receiving temozolomide. All patients received concomitant radiotherapy and temozolomide followed by adjuvant temozolomide. In case of any radiological or clinical progression, MRI spectroscopy evaluation was used to confirm tumoral progression.

Results

Radiological or clinical progression was observed in 17 (25.4%) patients. Early radiation induced necrosis was diagnosed in 4 of 17 patients (23.5%) by surgery (n = 3) and MRI spectroscopy (n = 1). The observed incidence of pseudoprogression was 4 in 67 (6%) patients. Patients with diagnosis of early radiation injury had median progression-free survival of 7 months compared to 5 months in patients without radiation damage (p = 0.004). However, there was no statistically significant difference in terms of overall survival between groups.

Conclusion

Temozolomide can cause early radiation induced injury which can mimic progressive tumor. Although the discrimination between two entities results in the accurate evaluation of response to therapy and benefits those patients, it did not affect overall survival. MRI spectroscopy is a valuable tool to define early radiation necrosis and should be further evaluated in larger prospective studies.     

Single brain metastasis: resection followed by whole-brain irradiation and a boost to the metastatic site compared to whole-brain irradiation plus radiosurgery

Objective

The most appropriate treatment for a single brain metastasis is still controversial. This matched-pair analysis compared whole-brain irradiation plus radiosurgery (WBI + RS) to neurosurgical resection followed by whole-brain irradiation and a boost to the metastatic site (NR + WBI + B).

Methods

The data of 46 patients treated with WBI + RS were matched 1:1 to 46 patients treated with NR + WBI + B with respect to age, gender, Karnofsky performance score (KPS), tumor type, extracerebral metastases, and interval from first diagnosis of cancer to treatment of the metastasis, RPA class, and GPA score. Both groups were compared for local control of the treated metastasis, intracerebral control, and survival.

Results

The 1-year local control rates were 85% after WBI + RS and 78% after NR + WBI + B (p = 0.35). The 1-year intracerebral control rates were 74% and 68% (p = 0.33), respectively. The 1-year survival rates were 64% and 58% (p = 0.70), respectively. A multivariate analysis was not performed for local and intracerebral control, because no factor achieved significance on univariate analyses for these endpoints. Improved survival was associated with KPS > 70 (p = 0.032), absence of extracerebral metastases (p = 0.003), RPA-class 1 (p = 0.014), and GPA score of 3.0–4.0 (p = 0.010).

Conclusion

Treatment outcomes were not significantly different after WBI + RS or NR + WBI + B. Because WBI + RS is less invasive, it may be preferable for many patients with a single brain metastasis.     

The incidence of pulmonary embolism (PE) after spinal fusions

Background

Pulmonary embolism (PE) is a rare but serious event that may occur after spinal surgery.

Objective

To correlate PE incidence after spinal arthrodesis with surgical approach, region of spine operated, and primary spinal pathology. To identify PE incidence trends in this population.

Methods

The Nationwide Inpatient Sample was queried using ICD-9 codes (81.01–81.08) for spinal fusion procedures over a 21-year period (1988–2008). Other data points included PE occurrence, surgical approach, spinal region, surgical indication, and mortality. Multivariate and relational analyses were performed.

Results

4,505,556 patients were identified and 9530 had PE (incidence = 0.2%). PE patients had higher odds of combined A/P surgical approaches than posterior approaches (OR = 1.97; 95% CI = 1.66–2.33), and PE incidence was higher in thoracic versus cervical or lumbar fusions (OR = 2.54; 95% CI = 2.14–3.02). PE was more likely with vertebral fracture (OR = 1.85; 95% CI = 1.53–2.23) and SCI with vertebral fracture (OR = 4.59; 95% CI = 3.72–5.70) than without trauma. Between 1988 and 2008, the PE incidence remained stable for patients with intervertebral disk degeneration and scoliosis, but increased for patients with vertebral fracture, and SCI with vertebral fracture. There was greater inpatient mortality with occurrence of a PE (OR = 12.92; 95% CI = 10.55–14.41).

Conclusion

Although the incidence of PE in spinal arthrodesis patients is only 0.2%, there is a higher incidence after combined A/P approaches, thoracic procedures, and trauma surgical procedures. Despite the overall PE incidence remaining stable since 1988, incidence steadily increased among trauma patients. Further research is needed to explain these trends, given the context of changing patient populations and improving surgical techniques and prophylaxis measures. Greater caution and prophylaxis among trauma patients may be warranted.     

Malignant glioma grade 3 and 4: How relevant is timing of radiotherapy?

Aims and background

The aim of this study is to determine prognostic factors that influence further outcome in patients with glioma.

Methods

Between 01/2002 and 08/2008, 153 patients with malignant gliomas of WHO-grade 3 or 4 who were treated with external beam radiotherapy with or without chemotherapy.

Results

In univariate analysis, following factors were ascertained as statistically significant prognostic parameters: grade (p = 0.000), time between operation and radiotherapy >24 days (p = 0.044) for progression-free survival; grade (p = 0.000), age < 58 years (p = 0.001), extent of surgery (p = 0.011), time between operation and radiotherapy >24 days (p = 0.009), overall treatment time >68 days (p = 0.003), use of chemotherapy (p = 0.015) for overall survival. A longer time period between resection and start of radiotherapy showed to be associated with improved outcome. After multivariate analysis, only grade (p = 0.000) remained a statistically significant factor for progression-free and grade (p = 0.000) and use of chemotherapy (p = 0.031) for overall survival.

Conclusions

We were able to recognize grade and use of chemotherapy as statistically significant prognostic determinants, but not time intervals or overall treatment time.     

Comparison of two methods for the detection of oligoclonal bands in a large number of clinically isolated syndrome and multiple sclerosis patients

Objective

A novel oligoclonal band (OB) assay which consists of isoelectric focusing (IEF) and IgG immunodetection by alkaline phosphatase-labeled anti IgG antibody was reported to be very sensitive. It also accurately predicted conversion to MS in patients with CIS. The aim of our study was to compare sensitivity of a novel and the standard procedure with peroxidase immunodetection in a large number of CIS and MS patients.

Methods

OB were determined in serum and CSF samples in 161 patients (104 females), 47 with CIS and 114 with MS with median age 38 years (range 19–68) using both methods.

Results

Eighty-three percent of patients had CSF OB with the standard and 89% with the novel method. Median number of OB was 5 (range 0–17) with the peroxidase and 8 (range 0–18) with the alkaline phosphatase method; p = 0.001. Twenty-one percent of patients had ≥10 OB with the standard and 37% with the novel method of the detection; p = 0.021. Subjective impression of band clarity showed that 20% of patients had sharper and stronger bands when the peroxidase and 65% when the alkaline phosphatase method was used; p < 0.0001.

Conclusion

The alkaline phosphatase method is more sensitive than the peroxidase method and at the same time cheaper, easy to perform and less time consuming.     

Gamma knife radiosurgery for orbital tumors

Objective

This study was performed to investigate the radiological and functional outcomes of patients with orbital tumors treated by gamma knife radiosurgery (GKS).

Patients and methods

Fifteen patients with orbital tumors (7 meningiomas, 3 cavernous hemangiomas, 2 schwannomas, 2 metastatic tumors and 1 adenoid cystic carcinoma of the lacrimal gland) were treated. Seven patients with preserved vision and tumors located near the optic nerve were treated with multisession (3 or 4 fractions) radiosurgery. The mean tumor volume was 3695 mm³ (737–13,300). The median marginal dose was 14 Gy (13–20) in single-session radiosurgery, and the median cumulative marginal dose was 20 Gy (15–20) in multisession radiosurgery.

Results

After a mean follow-up of 20.9 months (6–50), tumor control was confirmed in 12 of 15 patients. Three patients with malignant lesions had to undergo another operation due to tumor progression. Of the 13 patients whose preoperative vision was preserved, 6 patients showed improvement in visual acuity and/or visual field, 4 patients showed no change in vision, and 3 patients showed deterioration (2 related to tumor progression).

Conclusions

As with intracranial tumors with similar pathologies, GKS may be an effective treatment option for orbital tumors. Multisession radiosurgery may be a good strategy for increasing the possibility of visual function preservation in selected cases in which the lesion is adjacent to the optic apparatus.     

Anti-aquaporin-4 antibody in Chinese patients with central nervous system inflammatory demyelinating disorders

Objective

To determine seroprevalence of aquaporin-4 (AQP4) antibody in Chinese patients with central nervous system (CNS) inflammatory demyelinating disorders.

Methods

AQP4 antibody was detected by anti-AQP4 antibody assay. We measured seroprevalence in 200 patients with neuromyelitis optica (NMO, n = 44), multiple sclerosis (MS, n = 46), transverse myelitis (TM, n = 44), optic neuritis (ON, n = 13), acute disseminated encephalomyelitis (ADEM, n = 2), and other neurological diseases (OND, n = 51).

Results

AQP4 antibody seropositivity was 88.6% in patients with NMO, 4.3% in patients with MS, 30.8% in patients with ON and 51.7% in patients with LETM (longitudinally extensive TM). No patients with acute partial TM, ADEM, OND were positive for AQP4 antibody. Sensitivity of the test was 88.6% (95% CI 80–95) in patients with NMO. Specificity is 97.9% (95% CI 95.1–100) in 46 MS patients, with 51 OND patients as the control group. If the patients with recurrent ON, LETM were considered high risk for NMO (n = 37) and the remaining patients (n = 119) were considered controls, the sensitivity of this assay would be 48.6% (95% CI 33.4–64.1) and the specificity 97.5% (95% CI 94.7–100).

Conclusion

This study confirms that AQP4 antibody is a sensitive and specific biomarker for discrimination between NMO and other CNS autoimmune diseases.     

Diffusion tensor and dynamic susceptibility contrast MRI in glioblastoma

Objective

We prospectively investigated the correlation between diffusion tensor (DTI), dynamic susceptibility contrast (DSC) perfusion MRI metrics and Ki-67 labelling index in glioblastomas.

Methods

We studied seventeen patients who were operated on for glioblastoma. DTI and DSC MRI were performed within a week prior to surgical excision. Lesion/normal ratios were calculated for the apparent diffusion coefficient (ADC), fractional anisotropy (FA), relative cerebral blood volume (rCBV), relative cerebral blood flow (rCBF) and relative mean transit time (rMTT) ratio. In the excised tumour specimens Ki-67 antigen expression was evaluated by the MIB-1 immunostaining method.

Results

A significant correlation was observed between Ki-67 index and ADC ratio (r = −0.528, p = 0.029) and FA ratio (r = 0.589, p = 0.012). rCBV and rMTT presented a trend towards significant correlation with Ki-67 index (r = 0.628, p = 0.07 and r = 0.644, p = 0.06 respectively). There was a trend towards better survival for patients with gross total tumour excision and FA values lower than 0.48 (p = 0.1 and p = 0.09 respectively). No significant correlation was found between ADC ratio, rCBV, rCBF, rMTT and overall survival.

Conclusion

ADC ratio, FA ratio, rCBV and rMTT tumour/normal tissue ratios may represent indicators of glioma proliferation. FA values may hold promise for predicting survival in patients with glioblastoma.     

Systemic arterial inflammation, measured with 18FDG-PET, is common amongst subjects with both recent and prior cerebrovascular disease

Objective

To compare systemic arterial inflammation in subjects with recent ischaemic stroke or TIA and controls with prior cerebrovascular disease.

Methods

Systemic arterial inflammation was prospectively measured by ¹⁸F-fluorodeoxygluose positron emission tomography in 11 cases with recent ischaemic stroke or TIA, and 11 sex matched controls with prior cerebrovascular disease.

Results

Hot spots (both carotid and non-carotid) of localised ¹⁸FDG uptake were found in more than half of all patients with either recent (n = 6) or prior (n = 8) cerebrovascular disease. There was no significant difference in the total number of hotspots, or hotspots at specific sites, in cases compared with controls. Mean standard uptake values (SUV) were similar in the carotid arteries and aorta of cases and controls, and showed a trend toward higher values in the femoral arteries of the controls (median 1.8; IQR 1.6–2.2) compared to cases (median 1.5; IQR 1.4–1.7).

Conclusion

Arterial inflammation was common, and appeared similar, in patients with recent stroke/TIA, and controls with stroke/TIA more than two years previously.     

Usefulness of thallium-201 SPECT for prediction of early progression in low-grade astrocytomas diagnosed by stereotactic biopsy

Objective

To establish the value of thallium-201 single-photon emission computed tomography (²⁰¹Tl-SPECT) as a predictor of early progression in low-grade astrocytomas (LGAs).

Methods

We studied 57 consecutive patients who underwent 201 Tl-SPECT before stereotactic biopsy (n = 33) or surgical resection (n = 24). The value of radiologic and histopathological variables (²⁰¹Tl index and MIB-1 index) in predicting progression free survival (PFS) was examined in each group of patients.

Results

During a median follow up of 55 months (range, 11–101), progression of the primary lesion was identified in 46 patients (80.7%). Based on Cox's proportional hazards model, the increased thallium uptake was associated with a short PFS in both biopsy and resection groups, whereas the MIB-1 index was significant only in the resection group. Considering the cut-off value, ²⁰¹Tl index > 1.7 was statistically significant for reduced PFS in the biopsy group; however, MIB-1 index was not directly related to the PFS at any level. For the surgical resection group, both a ²⁰¹Tl index > 1.9 and a MIB-1 index > 6% were associated with short PFS.

Conclusion

²⁰¹Tl SPECT may play a role in prediction of early tumor progression not only in resected LGAs, but also in biopsy-proven LGAs. Therefore, we suggest that patients with LGAs established from biopsy should be considered as high-risk groups for early progression if the tumor shows a high ²⁰¹Tl uptake, even if the tumor demonstrates low proliferative activity on histopathologic examination.     

Mismatch negativity and low frequency oscillations in schizophrenia families

Objective

Theta-alpha range oscillations have been associated with MMN in healthy controls. Our previous studies showed that theta-alpha activities are highly heritable in schizophrenia patients’ families. We aimed to test the hypothesis that theta-alpha activities may contribute to MMN in schizophrenia patients and their family members.

Methods

We compared MMN and single trial oscillations during MMN in 95 patients, 75 first-degree relatives, 87 controls, and 34 community subjects with schizophrenia spectrum personality (SSP) traits.

Results

We found that (1) MMN was reduced in patients (p < 0.001) and SSP subjects (p = 0.047) but not in relatives (p = 0.42); (2) there were augmented 1–20 Hz oscillations in patients (p = 0.02 to <0.001) during standard and deviant stimuli; (3) theta-alpha (5–12 Hz) oscillations had the strongest correlation to MMN in controls and relatives (ΔR² = 21.4–23.9%, all p < 0.001), while delta (<5 Hz) showed the strongest correlation to MMN in schizophrenia and SSP trait subjects; and, (4) MMN (h² = 0.56, p = 0.002) and theta-alpha (h² = 0.55, p = 0.004) were heritable traits.

Conclusions

Low frequency oscillations have a robust relationship with MMN and the relationship appears altered by schizophrenia; and schizophrenia patients showed augmented low frequency activities during the MMN paradigm.

Significance

The results encourage investigation of low frequency oscillations to elucidate the neurophysiological pathology underlying MMN abnormalities in schizophrenia.     

Effectiveness of home rehabilitation program for ischemic stroke upon disability and quality of life: a randomized controlled trial

Background

To develop and examine the effectiveness of individual 6-month home rehabilitation program in ischemic stroke patients upon disability and quality of life at 2 years.

Methods

This is a prospective randomized controlled trial (RCT) in 60 patients with recent ischemic stroke. They were randomly assigned to receive either home rehabilitation program once a month for 6 months with audiovisual materials (intervention group) or usual care (control group). We collected outcome data after discharge from the hospital until 2 years. The Barthel index (BI), the modified Rankin Scale (mRS) and utility index (EQ-5D) were measured for function, disability and quality of life respectively.

Results

At 2 years, the BI was significantly improved in the intervention group more than the control group: 97.2 ± 2.8 vs. 76.4 ± 9.4, p < 0.001. The good outcome, defined as BI 95–100, or mRS 0 or 1. For BI, there were 29 patients (96.7%) in intervention group vs 12 patients (42.9%) in usual care group (95% CI, 42.0, 85.0, p = 0.03). For mRS, there were 28 patients (93.3%) in intervention group vs 9 patients (32.1%) in usual care group (95% CI, 38.2, 87.0, p = 0.02). Number needed to treat for good outcome in mRS was 2.0 (95% CI: 1.0, 1.3). The mean (SD) of utility index in intervention group and control group were 0.9 ± 0.02 and 0.7 ± 0.04 respectively (p = 0.03). There was no significant interaction in baseline characteristics and treatment outcome.

Conclusions

Early home rehabilitation program in the first 6 months period after ischemic stroke leads to more rapid improvement in function, reducing disability and increase quality of life than usual care.