Functional survival after acute care for severe head injury at a designated trauma center in Hong Kong.

BACKGROUND: Severe head injury is known to be a major cause of early mortalities and morbidities. Patients' long-term outcome after acute care, however, has not been widely studied. We aim to review the outcome of severely head-injured patients after discharge from acute care at a designated trauma center in Hong Kong. MATERIALS AND METHODS: This is a retrospective study of prospectively collected data of patients admitted with severe head injuries between 2004 and 2008. Patients' functional status post-discharge was assessed using the Extended Glasgow Outcome Score (GOSE). RESULTS: Of a total of 1565 trauma patients, 116 had severe head injuries and 41 of them survived acute hospital care. Upon the last follow-up, 23 (56.1%) of the acute-care survivors had improvements in their GOSE, six (11.8%) experienced deteriorations, and 12 (23.5%) did not exhibit any change. The greatest improvement was observed in patients with GOSE of 5 and 6 upon discharge, but two of the 16 patients with GOSE 2 or 3 also had a good recovery. On logistic regression analysis, old age and prolonged acute hospital stay were found to be independent predictors of poor functional outcome after a mean follow-up duration of 42 months. CONCLUSION: Multidisciplinary neurorehabilitation service is an important component of comprehensive trauma care. Despite significant early mortalities, a proportion of severely head-injured patients who survive acute care may achieve good long-term functional recovery.

Using bevacizumab in the fight against malignant glioma: first results in Asian patients.

OBJECTIVES: To investigate the efficacy and safety profile of bevacizumab in combination with irinotecan in Hong Kong Chinese patients with recurrent malignant glioma and to determine whether their response differed from that reported in other populations. DESIGN: Retrospective study. SETTING: Two private clinics and a public hospital in Hong Kong. PATIENTS: Fourteen individuals who presented with recurrent glioma presenting to the hospital between November 2005 and November 2009. INTERVENTION: Salvage therapy with bevacizumab (10 mg/kg) and irinotecan (125 mg/m(2) [340 mg/m(2) for those taking enzyme-inducing antiepileptic drugs]) on a 14-day schedule. RESULTS: A radiological response was observed in 12 (86%) of the patients, four (33%) of whom had a complete response. The median progression-free survival was 6 (range, 1-15) months; 71% remained progression-free at 6 months. The median overall survival was 18 (range, 9-61) months. The most common adverse events during the bevacizumab and irinotecan treatment period were haematological; five patients had grade 2/3 adverse events. Pulmonary embolism occurred in two patients, one of whom died. Intracranial haemorrhage was not detected in any of the 14 treated patients. CONCLUSIONS: Bevacizumab plus irinotecan was at least as effective at treating Chinese patients with recurrent glioma as previously reported in clinical trials in different patient populations.

Deep brain stimulation in a Chinese Tourette's syndrome patient.

A 31-year-old Chinese man with intractable severe, lifelong Tourette's syndrome characterised by forceful self-injurious motor tics and socially embarrassing vocal tics was treated with bilateral deep brain stimulation. Electrodes were implanted into the thalamic targets at the centromedian-parafascicular complex according to Hassler's nomenclature. A dramatic reduction of tics resulted. At 18 months postoperatively, there was an 81% improvement in his total tics count and a 58% improvement in his Yale Global Tic Severity Scale. His modified Rush video scale decreased from 13 to 8 and visual analogue scale from 10 to 3. These data show that bilateral deep brain stimulation of the thalamus can have a favourable immediate effect on severe tics in a selected group of adult patients suffering from intractable Tourette's syndrome and postoperatively the beneficial effects persisted for at least 18 months.

Neuroimaging techniques in epilepsy.

OBJECTIVE: To review state-of-the-art neuroimaging modalities in epilepsy and their clinical applications. DATA SOURCES AND STUDY SELECTION: PubMed literature searches to March 2010, using the following key words: 'epilepsy', 'positron emission tomography (PET)', 'single photon emission computed tomography (SPECT)', 'MR volumetry', 'diffusion tensor imaging', and 'functional MR imaging'. DATA EXTRACTION: All articles including neuroimaging techniques in epilepsy were included in the review. DATA SYNTHESIS: High-field magnetic resonance imaging is fundamental for high-resolution structural imaging. Functional radionuclide imaging (positron emission tomography/single-photon emission computed tomography) can provide additional information to improve overall accuracy, and show good results with high concordance rates in temporal lobe epilepsy. Magnetic resonance spectroscopy is a useful adjunct consistently demonstrating changing metabolites in the epileptogenic region. Magnetic resonance volumetric imaging shows excellent sensitivity and specificity for temporal lobe epilepsy but thus far it has been inconsistent for extratemporal epilepsy. Diffusion tensor imaging with tractography allows visualisation of specific tracts such as connections with the language and visual cortex to enhance preoperative evaluation. Functional magnetic resonance imaging using blood oxygen level-dependent activation techniques is mainly used in presurgical planning for the high-sensitivity mapping of the eloquent cortex. Both contrast-bolus and arterial spin labelling magnetic resonance perfusion imaging show good correlation with clinical lateralisation of seizure disorder. CONCLUSION: Structural imaging is essential in localisation and lateralisation of the seizure focus. Functional radionuclide imaging or advanced magnetic resonance imaging techniques can provide complementary information when an epileptogenic substrate is not identified or in the presence of non-concordant clinical and structural findings.

Peak flow rate during induced cough: a predictor of successful decannulation of a tracheotomy tube in neurosurgical patients.

BACKGROUND: An accurate predictor of successful decannulation in neurosurgical patients that indicates the best time for tracheotomy decannulation would minimize the risks of continued cannulation and unsuccessful decannulation. OBJECTIVE: To determine whether the peak flow rate during induced cough is an appropriate predictor of successful decannulation. METHODS: A total of 32 neurosurgical patients with a tracheotomy were enrolled. The highest peak expiratory flow rate during 3 induced coughs, the total volume of tracheal secretions collected in 6 hours, and scores on the Glasgow Coma Scale were recorded. Logistic regression analysis was applied to determine the relationship between these variables and successful decannulation (reintubation not required within 72 hours). RESULTS: Decannulation was attempted in 23 of 32 patients. The remaining 9 patients were considered clinically inappropriate for the procedure. Of the 23 patients decannulated, 2 required reinsertion of the tracheotomy tube. Analysis revealed that peak flow rate during induced cough (odds ratio, 1.12; 95% confidence interval, 1.02-1.23) was independently associated with successful decannulation (accuracy, 75%; sensitivity, 85.7%; specificity, 54.5%). The receiver operating characteristic curve indicated an optimal cutoff point of 29 L/min. CONCLUSION: Measurement of peak flow rate during induced cough is a simple and reproducible intervention that improves predictability of successful decannulation in patients with tracheotomy.

Perioperative deep vein thrombosis in Chinese patients undergoing craniotomy.

BACKGROUND: We attempted to determine the incidence of perioperative deep vein thrombosis (DVT) in Chinese patients undergoing elective craniotomy for brain tumors and to assess the efficacy of clinical and serial calf circumference assessment in detecting DVT. METHODS: Between June 1999 and February 2001, 100 consecutive patients who underwent elective craniotomy for brain tumors at the Department of Neurosurgery, University of Hong Kong Medical Centre were examined for perioperative DVT. The demographic data, Glasgow coma score (GCS), mobility status, and the operative details were recorded. Graduated compression stockings and intermittent pneumatic compression were applied perioperatively as prophylaxis against DVT. Serial duplex scans were performed before and after operation. Clinical examination was also performed daily to look for signs of DVT. The calf circumference was measured at fixed levels for both limbs before each duplex scan surveillance. RESULTS: The study group consisted of 44 males and 56 females, with a mean age of 54 +/- 15 years (range, 20-81 years). There was no preoperative DVT. Postoperative DVT was detected on duplex scan in four patients (4%), two of whom had bilateral involvement. The thrombosis was confined to the calf veins in two limbs. The demographic data, neurologic status and operative details of patients with and without DVT were similar. Patients with DVT had no clinically recognizable signs. The change in calf circumference measurement was also not predictive of DVT. CONCLUSIONS: The incidence of perioperative DVT in Chinese patients undergoing elective craniotomy for brain tumors appears to be low with the present mechanical prophylactic measures. Given the low incidence of proximal DVT as detected by duplex scan, the use of heparin prophylaxis may not be justified because of the increased risk of intracranial bleeding. Clinical assessment with calf circumference measurement is unreliable in the diagnosis of DVT.

Salvage treatment for persistent and recurrent T1-2 nasopharyngeal carcinoma by stereotactic radiosurgery.

OBJECTIVE: To study the efficacy of stereotactic radiosurgery in salvaging early-stage persistent and recurrent nasopharyngeal carcinoma (NPC) after primary radiotherapy. METHODS: A prospective single-arm study evaluating the response and outcome of patients with rT1-2 NPC treated by stereotactic radiosurgery. Eleven patients with rT1-2 were treated by radiosurgery between March 1998 and March 2000. Four patients were treated for persistent disease occurring within 4 months after primary radiotherapy, six were treated for first recurrence, and one for third recurrence. Six patients had rT1 disease and five had rT2 disease. Most patients had disease not amenable to brachytherapy, surgery, or external re-irradiation. The median target volume was 5.8 cc (range, 3.3-16.9). Radiosurgery was performed with multiple noncoplanar arcs of photon, with a median dose of 12.5 Gy delivered to the 80% isodose line (range, 12-14 Gy). Median follow-up time after radiosurgery was 18 months (range, 9-30). RESULTS: Nine patients had complete regression of tumor as assessed by imaging, nasopharyngoscopy, and biopsy; one patient had partial regression of tumor; whereas one patient had static disease. The overall response rate was 91% (10 of 11) and the complete response rate was 82% (9 of 11). Two patients with complete response subsequently had local relapse develop, with one recurrence outside the treated volume 8 months after radiosurgery, and the other within the treated volume 6 months after radiosurgery. One patient with a partial response had neck node recurrence develop. Temporal lobe necrosis occurred in one patient but probably represents sequelae of primary radiation after reviewing the dosimetry. Ten patients are still alive, whereas one patient with local relapse had distant metastases develop and died. The estimated 1-year local control rate after radiosurgery was 82%. CONCLUSIONS: Our preliminary results indicate that stereotactic radiosurgery is an effective treatment modality for persistent and recurrent T1-T2 NPC, and early control rate seems to be comparable to other salvage treatments. More clinical experiences and longer follow-up are still needed to validate our results and to address fully the role of radiosurgery in salvaging local failures of NPC.

Surgical management of Parkinson's disease: a critical review.

Parkinson's disease is a progressive disabling movement disorder that is characterised by three cardinal symptoms: resting tremor, rigidity, and bradykinesia. Before the availability of effective medical treatment with levodopa and stereotactic neurosurgery, the objective of surgical management was to alleviate symptoms such as tremor at the expense of motor deficits. Levodopa was the first effective medical treatment for Parkinson's disease, and surgical treatment such as stereotactic thalamotomy became obsolete. After one decade of levodopa therapy, however, drug-induced dyskinesia had become a source of additional disability not amenable to medical treatment. Renewed interest in stereotactic functional neurosurgery to manage Parkinson's disease has been seen since the 1980s. Local experience of deep-brain stimulation is presented and discussed in this paper. Deep-brain stimulation of the subthalamic nucleus is an effective treatment for advanced Parkinson's disease, although evidence from randomised control trials is lacking.

Chromosomal instability and p53 inactivation are required for genesis of glioblastoma but not for colorectal cancer in patients with germline mismatch repair gene mutation.

We have previously reported high-frequency microsatellite instability (MSI-H) and germ-line mismatch repair gene mutation in patients with unusually young onset of high-grade glioma. Some of these patients developed metachronous MSI-H colorectal cancer and conformed to the diagnosis of Turcot's syndrome. Frameshift mutation of TGFbetaRII was present in all the colorectal carcinomas but not in brain tumours. We further characterized the genetic pathways of tumour evolution in these metachronous gliomas and colorectal carcinomas. All MSI-H glioblastomas had inactivation of both alleles of the p53 gene and showed over-expression of the p53 protein while none of the colorectal carcinomas had p53 mutation or protein over-expression. Flow cytometry and comparative genomic hybridization revealed that all glioblastomas were chromosomal unstable with aneuploid DNA content, and with a variable number of chromosomal arm aberrations. In contrast, the colorectal carcinomas had diploid or near-diploid DNA content with few chromosomal arm aberrations. The pattern of chromosomal aberrations in the two organs was different. Loss of 9p was consistently observed in all glioblastomas but not in colorectal carcinomas. Epidermal growth factor receptor amplification was absent in all glioblastomas and colorectal carcinomas. Our results suggest that both the frequency of p53 mutation and its effects differ greatly in the two organs. Following loss of mismatch repair function, p53 inactivation and chromosomal instability are not necessary for development of colorectal carcinoma, but are required for genesis of glioblastoma. Oncogene (2000) 19, 4079 - 4083.

Stereotactic radiosurgery as a salvage treatment for locally persistent and recurrent nasopharyngeal carcinoma.

BACKGROUND: The purpose of this work was to study the efficacy of stereotactic radiosurgery as a salvage treatment in patients with locally persistent and recurrent nasopharyngeal carcinoma (NPC). METHODS: Between March 1996 and August 1997, 10 patients with locally persistent or recurrent NPC were treated by linac-based stereotactic radiosurgery. Four patients had radiosurgery for persistent disease after a first course of radiotherapy, 3 had radiosurgery as a boost after reirradiation for local recurrence, and 3 had radiosurgery for disease that recurred after reirradiation. The tumor volume ranged from 1.3 to 23.7 cc (median: 5.2). Treatment was prescribed at 80% isodose line and ranged from 12 to 18 Gy (median: 13.4), with a mean tumor surface dose ranged from 10-21 Gy (median: 14). The median clinical follow-up was 10.5 months (range 8-27), and the median imaging follow-up was 9.5 months (range 6-26). RESULTS: One patient had complete regression of tumor after radiosurgery, five had reduction in tumor size, three had no change, and one had progression of tumor. The overall response rate to radiosurgery was 60% (6/10), with 10% (1/10) developing in-field progression. Excluding patients receiving radiosurgery as a boost treatment after reirradiation, the response rate was 57% (4/7) and none developed in-field progression. Only one patient developed a new cranial neuropathy in the absence of disease progression. CONCLUSION: In selected patients with locally persistent or recurrent NPC, stereotactic radiosurgery can be considered as a salvage treatment with good short-term local control. The complications appear to be minimal except for treating recurrence in the cavernous sinus. Early results are encouraging although more experience and longer follow-up are still needed to better define the role of radiosurgery in the management of persistent and recurrent NPC.

Retrograde suction decompression of paraclinoid aneurysm--a revised technique.

BACKGROUND: Aneurysms of the ophthalmic segment of the carotid artery are difficult lesions to handle. Batjer and Samson described the technique of suction decompression of the aneurysm by inserting a needle and aspirating blood from the internal carotid artery in the neck. However, this method carries a risk of arterial dissection and distal embolization. METHOD: We describe a revised technique for suction decompression of paraclinoid aneurysms. The method makes use of the anatomical advantage of the carotid bifurcation. Instead of direct clamping of the internal carotid artery, we isolated the common and external carotid arteries and decompressed the aneurysm via the external carotid artery. We also saved the aspirated blood for autotransfusion. RESULTS: We have used this technique in two elderly patients with good results. CONCLUSION: This technique avoids dissection of the internal carotid artery and minimizes the risk of embolization.

Microsatellite instability and mutation of DNA mismatch repair genes in gliomas.

Microsatellite instability (MSI) has been identified in various human cancers, particularly those associated with the hereditary nonpolyposis colorectal cancer syndrome. Although gliomas have been reported in a few hereditary nonpolyposis colorectal cancer syndrome kindred, data on the incidence of MSI in gliomas are conflicting, and the nature of the mismatch repair (MMR) defect is not known. We established the incidence of MSI and the underlying MMR gene mutation in 22 patients ages 45 years or less with sporadic high-grade gliomas (17 glioblastomas, 3 anaplastic astrocytomas, and 2 mixed gliomas, grade III). Using five microsatellite loci, four patients (18%) had high level MSI, with at least 40% unstable loci. Germline MMR gene mutation was detected in all four patients, with inactivation of the second allele of the corresponding MMR gene or loss of protein expression in the tumor tissue. Frameshift mutation in the mononucleotide tract of insulin-like growth factor type II receptor was found in one high-level MSI glioma, but none was found in the transforming growth factor beta type II receptor and the Bax genes. There was no family history of cancer in three of the patients, and although one patient did have a family history of colorectal carcinoma, the case did not satisfy the Amsterdam criteria for hereditary nonpolyposis colorectal cancer syndrome. Three patients developed metachronous colorectal adenocarcinomas, fitting the criteria of Turcot's syndrome. Thus, MSI and germline MMR gene mutation is present in a subset of young glioma patients, and these patients and their family members are at risk of developing other hereditary nonpolyposis colorectal cancer syndrome-related tumors, in particular colorectal carcinomas. These results have important implications in the genetic testing and management of young patients with glioma and their families.

Solution structure of duplex DNA containing an extrahelical abasic site analog determined by NMR spectroscopy and molecular dynamics.

Translesional DNA synthesis past abasic sites proceeds with the preferential incorporation of dAMP opposite the lesion and, depending on the sequence context, one or two base deletions. High-resolution NMR spectroscopy and molecular dynamics simulations were used to determine the three-dimensional structure of a DNA heteroduplex containing a synthetic abasic site (tetrahydrofuran) residue positioned in a sequence that promotes one base deletions. Analysis of NMR spectra indicates that the stem region of the duplex adopts a right-handed helical structure and the glycosidic torsion angle is in anti orientation for all residues. NOE interactions establish Watson-Crick alignments for all canonical base pairs of the duplex. Measurement of distance interactions at the lesion site shows the abasic residue excluded from the helix. Restrained molecular dynamics simulations generated three-dimensional models in excellent agreement with the spectroscopic data. These structures show a regular duplex region and a slight bend at the lesion site. The tetrahydrofuran residue extrudes from the helix and is highly flexible. The model reported here, in conjunction with a previous study performed on abasic sites, explains the structural bias of one-base deletion mutations.