Multicentre study of hospitalised patients with sports- and recreational cycling-related traumatic brain injury in Hong Kong.

INTRODUCTION: Cycling is associated with a greater risk of traumatic brain injury (TBI) than other recreational activities. This study aimed to investigate the epidemiology of sports-related TBI in Hong Kong and to examine predictors for recreational cycling-induced intracranial haemorrhage. METHODS: This retrospective multicentre study included patients diagnosed with sports-related TBI in public hospitals in Hong Kong from 2015 to 2019. Computed tomography scans were reviewed by an independent assessor. The primary endpoint was traumatic intracranial haemorrhage. The secondary endpoint was an unfavourable Glasgow Outcome Scale (GOS) score at discharge from hospital. RESULTS: In total, 720 patients were hospitalised with sports-related TBI. The most common sport was cycling (59.2%). The crude incidence of cycling-related TBI was 1.1 per 100 000 population. Cyclists were more likely to exhibit intracranial haemorrhage and an unfavourable GOS score, compared with patients who had TBI because of other sports. Although 47% of cyclists had intracranial haemorrhage, only 15% wore a helmet. In multivariate analysis, significant predictors for intracranial haemorrhage were age ≥60 years, antiplatelet medication, moderate or severe TBI, and skull fracture. Among 426 cyclists, 375 (88%) had mild TBI, and helmet wearing was protective against intracranial haemorrhage, regardless of age, antiplatelet medication intake, and mechanism of injury. Of 426 cyclists, 31 (7.3%) had unfavourable outcomes on discharge from hospital. CONCLUSIONS: The incidence of sports-related TBI is low in Hong Kong. Although cycling-related head injuries carried greater risks of intracranial haemorrhage and unfavourable outcomes compared with other sports, most cyclists experienced good recovery. Helmet wearing among recreational cyclists with mild TBI was protective against intracranial haemorrhage and skull fracture.

Feasibility and safety of extended adjuvant temozolomide beyond six cycles for patients with glioblastoma.

INTRODUCTION: Temozolomide is the first chemotherapeutic agent proven effective for patients with newly diagnosed glioblastoma. The drug is well tolerated for its low toxicity. The current standard practice is concomitant chemoradiotherapy for 6 weeks followed by 6 cycles of adjuvant temozolomide. Some Caucasian studies have suggested that patients might benefit from extended adjuvant cycles of temozolomide (>6 cycles) to lengthen both progression-free survival and overall survival. In the present study, we compared differences in survival and toxicity profile between patients who received conventional 6-cycle temozolomide and those who received more than 6 cycles of temozolomide. METHODS: Patients with newly diagnosed glioblastoma without progressive disease and completed concomitant chemoradiotherapy during a 4-year period were studied. Progression-free survival was compared using Kaplan-Meier survival curves. t Test, U test, and correlation were chosen accordingly to examine the impact of age, extent of resection, MGMT promoter methylation status and adjuvant cycles on progression-free survival. For factors with a P value of <0.05 in univariate analyses, Cox regression hazard model was adopted to determine the strongest factors related to progression-free survival. RESULTS: The median progression-free survival was 17.0 months for patients who received 6 cycles of temozolomide (n=7) and 43.4 months for those who received more than 6 cycles (n=7) [P=0.007, log-rank test]. Two patients in the former group and one in the latter group encountered grade 1 toxicity and recovered following dose adjustment. Cycles of adjuvant temozolomide were correlated with progression-free survival (P=0.016, hazard ratio=0.68). CONCLUSION: Extended cycles of temozolomide are safe and feasible for Chinese patients with disease responsive to temozolomide.

Ten-year review of survival and management of malignant glioma in Hong Kong.

INTRODUCTION: Surgical resection used to be the mainstay of treatment for glioma. In the last decade, however, opinion has changed about the goal of surgical resection in treating glioma. Ample evidence shows that maximum safe resection in glioblastoma improves survival. Neurosurgeons have therefore revised their objective of surgery from diagnostic biopsy or limited debulking to maximum safe resection. Given these changes in the management of glioma, we compared the survival of local Chinese patients with glioblastoma multiforme over a period of 10 years. METHODS: We retrospectively reviewed the data of the brain tumour registry of the CUHK Otto Wong Brain Tumour Centre in Hong Kong. Data of patients with glioblastoma multiforme were reviewed for two periods, during 1 January 2003 to 31 December 2005 and 1 January 2010 to 31 December 2012. Overall survival during these two periods of time was assessed by Kaplan-Meier survival estimates. Risk factors including age, type and extent of resection, use of chemotherapy, and methylation status of O6-methylguanine-DNA methyltransferase were also assessed. RESULTS: There were 26 patients with glioblastoma multiforme with a mean age of 52.2 years during 2003 to 2005, and 42 patients with a mean age of 55.1 years during 2010 to 2012. The mean overall survival during these two periods was 7.4 months and 12.7 months, respectively (P<0.001). The proportion of patients who underwent surgical resection was similar: 69.2% in 2003 to 2005 versus 78.6% in 2010 to 2012 (P=0.404). There was a higher proportion of patients in whom surgery achieved total removal in 2010 to 2012 than in 2003 to 2005 (35.7% and 7.7%, respectively; P=0.015). During 2010 to 2012, patients who were given concomitant chemoradiotherapy showed definitively longer survival than those who were not (17.9 months vs 4.5 months; P=0.001). The proportion of patients who survived 2 years after surgery increased from 11.5% in 2003 to 2005 to 21.4% in 2010 to 2012. CONCLUSIONS: Hong Kong has made substantial improvements in the management of glioblastoma multiforme over the last decade with corresponding improved survival outcomes. The combination of an aggressive surgical strategy and concomitant chemoradiotherapy are probably the driving force for the improvement.

Topical Therapy with Mesenchymal Stem Cells Following an Acute Experimental Head Injury Has Benefits in Motor-Behavioral Tests for Rodents.

BACKGROUND: The neuroprotective effects of mesenchymal stem cells (MSCs) have been reported in rodent and in preliminary clinical studies. MSCs are usually transplanted to patients by systemic infusion. However, only a few of the infused MSCs are delivered to the brain because of pulmonary trapping and the blood-brain barrier. In this study, MSCs were topically applied to the site of traumatic brain injury (TBI) and the neuroprotective effects were assessed. MATERIALS AND METHODS: TBI was induced in Sprague-Dawley (SD) rats with an electromagnetically controlled cortical impact device after craniotomy was performed between the bregma and lambda, 1 mm lateral to the midline. We applied 1.5 million MSCs, derived from the adipose tissue of transgenic green fluorescent protein (GFP)-SD rats, to the exposed cerebral cortex at the injured site. The MSCs were held in position by a thin layer of fibrin. Neurological function in the test (n = 10) and control (n = 10) animals was evaluated using the rotarod test, the water maze test, and gait analysis at different time points. RESULTS: Within 5 days following topical application, GFP-positive cells were found in the brain parenchyma. These cells co-expressed with markers of Glial fibrillary acidic protein (GFAP), nestin, and NeuN. There was less neuronal death in CA1 and CA3 of the hippocampus in the test animals. Neurological functional recovery was significantly improved. CONCLUSION: Topically applied MSCs can migrate to the injured brain parenchyma and offer neuroprotective effects.

Primary ventriculoperitoneal shunting outcomes: a multicentre clinical audit for shunt infection and its risk factors.

OBJECTIVES: To determine the frequency of primary ventriculoperitoneal shunt infection among patients treated at neurosurgical centres of the Hospital Authority and to identify underlying risk factors. METHODS: This multicentre historical cohort study included consecutive patients who underwent primary ventriculoperitoneal shunting at a Hospital Authority neurosurgery centre from 1 January 2009 to 31 December 2011. The primary endpoint was shunt infection, defined as: (1) the presence of cerebrospinal fluid or shunt hardware culture that yielded the pathogenic micro-organism with associated compatible symptoms and signs of central nervous system infection or shunt malfunction; or (2) surgical incision site infection requiring shunt reinsertion (even in the absence of positive culture); or (3) intraperitoneal pseudocyst formation (even in the absence of positive culture). Secondary endpoints were shunt malfunction, defined as unsatisfactory cerebrospinal fluid drainage that required shunt reinsertion, and 30-day mortality. RESULTS: A primary ventriculoperitoneal shunt was inserted in 538 patients during the study period. The mean age of patients was 48 years (range, 13-88 years) with a male-to-female ratio of 1:1. Aneurysmal subarachnoid haemorrhage was the most common aetiology (n=169, 31%) followed by intracranial tumour (n=164, 30%), central nervous system infection (n=42, 8%), and traumatic brain injury (n=27, 5%). The mean operating time was 75 (standard deviation, 29) minutes. Shunt reinsertion and infection rates were 16% (n=87) and 7% (n=36), respectively. The most common cause for shunt reinsertion was malfunction followed by shunt infection. Independent predictors for shunt infection were: traumatic brain injury (adjusted odds ratio=6.2; 95% confidence interval, 2.3-16.8), emergency shunting (2.3; 1.0-5.1), and prophylactic vancomycin as the sole antibiotic (3.4; 1.1-11.0). The 30-day all-cause mortality was 6% and none were directly procedure-related. CONCLUSIONS: This is the first Hong Kong territory-wide review of infection in primary ventriculoperitoneal shunts. Although the ventriculoperitoneal shunt infection rate met international standards, there are areas of improvement such as vancomycin administration and the avoidance of scheduling the procedure as an emergency.

MoCA-assessed cognitive function and excellent outcome after aneurysmal subarachnoid hemorrhage at 1 year.

BACKGROUND AND PURPOSE: After aneurysmal subarachnoid hemorrhage (aSAH), cognitive impairment, even mild and relatively isolated, can be devastating, especially in working-age persons. The Montreal Cognitive Assessment (MoCA) is accepted as a valid screening tool for mild cognitive impairment due to cerebral ischaemia. Whether MoCA is independently associated with excellent outcome [a score of 0 on the modified Rankin Scale (mRS) or 18/18 on the Lawton Instrumental Activities of Daily Living (IADL) scale] 1 year after aSAH was assessed. METHODS: Hong Kong Chinese aSAH patients were assessed prospectively by means of the MoCA, Mini-Mental State Examination (MMSE), mRS and IADL scale at 1 year. This multicenter prospective observational study is registered at ClinicalTrials.gov of the US National Institutes of Health (NCT01038193). RESULTS: In all, 194 patients completed the assessments at 1 year. After adjustment for age, both excellent IADL and mRS outcomes were associated with MoCA (OR 1.2, 95% CI 1.1-1.3, P < 0.001, and OR 1.1, 95% CI 1.0-1.2, P = 0.001, respectively). CONCLUSIONS: MoCA-assessed cognitive function is an important determinant for excellent outcomes after aSAH.

Middle cerebral artery infarction in a cancer patient: a fatal case of Trousseau's syndrome.

Trousseau's syndrome is defined as any unexplained thrombotic event that precedes the diagnosis of an occult visceral malignancy or appears concomitantly with a tumour. This report describes a young, previously healthy man diagnosed to have an acute middle cerebral arterial ischaemic stroke and lower-limb deep vein thrombosis, who subsequently succumbed to pulmonary arterial embolism. During the course of his illness, he was diagnosed to have a malignant pleural effusion secondary to an occult adenocarcinoma. This report highlights the need for a high degree of suspicion for occult malignancy and non-bacterial thrombotic endocarditis in young (<60 years old) ischaemic stroke patients with no identifiable conventional cardiovascular risks. In selected patients, transoesophageal echocardiography is the diagnostic investigation of choice, since transthoracic imaging is not sensitive. Screening tests for serum tumour markers and prompt heparinisation of these patients are suggested whenever ischaemic stroke secondary to malignancy-induced systemic hypercoagulability is suspected.

Pallidal deep brain stimulation: an effective treatment in Chinese patients with tardive dystonia.

Tardive dystonia is an iatrogenic complication of dopamine receptor antagonist medication such as first-generation antipsychotics. It occurs in up to 2% of patients and only 10% recover after stopping medication. Deep brain stimulation for primary dystonia has proven to be effective and its application for secondary dystonias is gaining acceptance. We report our experience in treating three ethnic Chinese schizophrenia patients with severe medically refractory tardive dystonia by globus pallidus internus deep brain stimulation. Preoperatively, all required assistance with essential activities of daily living and two were bed-bound. The mean Burke-Fahn-Marsden Dystonia Rating Scale score was 61 (range, 44-80) and mean Global Dystonia Rating Scale score was 47 (range, 40-52). No procedure-related complications were encountered. By 3 months all could return to unassisted living and walk with support with a mean of 77% and 66% improvement in the Burke-Fahn-Marsden Dystonia Rating Scale and Global Dystonia Rating Scale scores, respectively. Quality-of-life assessment performed for two patients using the EuroQol-5 dimensions visual analogue scale showed a mean improvement of 86% at 3 months. On clinical follow-up, the effect was well maintained for a period of 3 to 10 years. Pallidal deep brain stimulation is a safe and highly effective form of symptomatic treatment for patients with medically refractory tardive dystonia.

Subthalamic nucleus deep brain stimulation for Parkinson's disease: evidence for effectiveness and limitations from 12 years' experience.

OBJECTIVE: To present the result and experience of subthalamic nucleus deep brain stimulation for Parkinson's disease. DESIGN: Case series. SETTING: Prince of Wales Hospital, Hong Kong. PATIENTS: A cohort of patients with Parkinson's disease received subthalamic nucleus deep brain stimulation from September 1998 to January 2010. Patient assessment data before and after the operation were collected prospectively. RESULTS: Forty-one patients (21 male and 20 female) with Parkinson's disease underwent bilateral subthalamic nucleus deep brain stimulation and were followed up for a median interval of 12 months. For the whole group, the mean improvements of Unified Parkinson's Disease Rating Scale (UPDRS) parts II and III were 32.5% and 31.5%, respectively (P<0.001). Throughout the years, a multidisciplinary team was gradually built. The deep brain stimulation protocol evolved and was substantiated by updated patient selection criteria and outcome assessment, integrated imaging and neurophysiological targeting, refinement of surgical technique as well as the accumulation of experience in deep brain stimulation programming. Most of the structural improvement occurred before mid-2005. Patients receiving the operation before June 2005 (19 cases) and after (22 cases) were compared; the improvements in UPDRS part III were 13.2% and 55.2%, respectively (P<0.001). There were three operative complications (one lead migration, one cerebral haematoma, and one infection) in the group operated on before 2005. There was no operative mortality. CONCLUSIONS: The functional state of Parkinson's disease patients with motor disabilities refractory to best medical treatment improved significantly after subthalamic nucleus deep brain stimulation. A dedicated multidisciplinary team building, refined protocol for patient selection and assessment, improvement of targeting methods, meticulous surgical technique, and experience in programming are the key factors contributing to the improved outcome.

Neurocognitive and psychological profiles of adult patients with epilepsy in Hong Kong.

Cognitive deficits and psychological impairments are often associated with seizures. In order to describe the neuropsychological profiles of adult patients with epilepsy (PWEs) in Hong Kong China, a total of 186 PWEs were recruited with 102 being drug-responsive and 84 being drug-resistant. Symptoms of depression, anxiety, and epilepsy-specific quality of life (QOL) were measured. Cognitive assessments consisted of intelligence, memory, verbal and visual abilities, and executive function. Neurocognitive impairments were prevalent among PWEs, and patients with drug-resistant epilepsy had significantly more impaired psychological and cognitive profiles. Thirty-nine percent and 30% of patients with drug-resistant epilepsy reported moderate to severe levels of anxiety and depression, respectively, versus 16% and 7% of patients with drug-responsive epilepsy. The most commonly occurring cognitive deficit was memory. Thirty-five percent to 47% of patients with drug-resistant epilepsy and 26% to 35% of patients with drug-responsive epilepsy were compromised in verbal recall memory. Our findings also suggested significant correlations between psychological well-being and cognitive performance. Patients who reported more psychological symptoms tended to perform worse in neurocognitive tests. Identification and management of neuropsychological difficulties in PWEs are important and should be included in primary epilepsy care.

The volumetric relationship of white matter lesion and contrast-enhanced lesion in delayed radiation brain injury: an MRI-based study.

PURPOSE: This study investigated the volumetric relationship of white matter lesion (WML) and contrast-enhanced lesion (CEL) in delayed radiation brain injury (RBI) during the course of evolution. MATERIALS AND METHODS: MRI results in 45 patients with RBI after receiving radiation for nasopharyngeal carcinoma were analyzed. In total there were 75 lobes with RBI and 114 MRI examinations in this study. WML and CEL lesion volumes were measured. The lesion volume change of less than 5% or 0.25 cm(3) was regarded as being static. RESULTS: The average WML volume was 16.33 cm(3) (ranging 0.11 cm(3) to 102.83 cm(3)), and the average CEL volume was 3.15 cm(3) (ranging 0.03 cm(3) to 27.85 cm(3)). WML was larger than CEL in 164 measurements, and CEL was larger than WML in 10 measurements. In 64.3% follow-ups WML and CEL evolved in the same pattern; and in most follow-ups (93.8%) WML and CEL did not evolve in the opposite directions. A larger WML volume tended to have a larger CEL volume though this relationship was not linear. CONCLUSION: Evolution of WML and CEL tended to follow the same pattern. WML tended to be larger than CEL, and larger WML tended to be associated with larger CEL.

An uncommon mimic of spontaneous subarachnoid haemorrhage.

We here presented a rare disease entity with a clinical presentation mimicking aneurysmal subarachnoid haemorrhage. A 43-year-old woman presented with a 1-week history of neck pain and dizziness. Computed tomography of brain showed communicating hydrocephalus and subarachnoid hyperintensity suspicious of previous subarachnoid haemorrhage. Investigations revealed no underlying vascular lesion and leptomeningeal biopsy showed diffuse melanocytosis. We go on to discuss the diagnostic features and clinical course of this entity.

Evaluation of cognitive impairment by the Montreal cognitive assessment in patients with aneurysmal subarachnoid haemorrhage: prevalence, risk factors and correlations with 3 month outcomes.

OBJECTIVE: Identification of patients with aneurysmal subarachnoid haemorrhage (aSAH) with cognitive impairment is important for patient management (medical treatment, cognitive rehabilitation and social arrangements). The Montreal cognitive assessment (MoCA) is currently recommended over the mini-mental state examination (MMSE) by the U.S. National Institute of Neurological Disorder, in the chronic post-stroke setting. We hypothesised that the MoCA has a better correlation with functional outcome at 3 months than the MMSE. METHODS: We carried out a prospective observational study in Hong Kong over a 2 year period, recruiting patients aged 21-75 years with aSAH admitted within 96 h of ictus. The assessments included the modified Rankin Scale, Lawton Instrumental Activity of Daily Living (IADL), Short Form-36, MoCA and MMSE at 3 months after ictus. Analyses were carried out to compare MoCA with MMSE. RESULTS: 90 patients completed the 3 month assessments. Cognitive impairment (MoCA <26) was determined in 73% of patients at 3 months. Delayed cerebral infarction explained the 31-38% variance in cognitive outcomes (MMSE and MoCA) at 3 months. MoCA demonstrated good discrimination of favourable neurological and IADL outcomes similar to the MMSE in receiver operating characteristics curve analyses. CONCLUSIONS: MoCA defined cognitive impairment was common at 3 months after aSAH and MoCA correlated with functional outcomes similar, but not superior, to the MMSE. The study is registered at ClinicalTrials.gov of the US National Institutes of Health (NCT01038193).

Pseudoprogression of malignant glioma in Chinese patients receiving concomitant chemoradiotherapy.

OBJECTIVES: To investigate the frequency of pseudoprogression of glioblastoma in Chinese patients receiving concomitant chemoradiotherapy and investigate its association with pseudoprogression and tumour molecular marker O(6)-methylguanine-DNA methyltransferase promoter methylation status. DESIGN: Case series with internal comparisons. SETTING: University teaching hospital, Hong Kong. PATIENTS: Patients with glioblastoma treated with concomitant chemoradiotherapy during April 2005 to June 2010 were reviewed. Magnetic resonance imaging brain scans, pre- and post-concomitant chemoradiotherapy and 3-monthly thereafter were reviewed by an independent neuroradiologist according to Macdonald's criteria. Relevant patient information (clinical condition, performance score, development of new neurological deficits, use of steroids, and survival) was retrieved. For each patient, O(6)-methylguanine-DNA methyltransferase methylation status was investigated with genomic DNA from formalin-fixed or paraffin-embedded sections of tumour tissues by methylation-specific polymerase chain reaction. RESULTS: During the study period, 28 primary glioblastoma patients underwent concomitant chemoradiotherapy. The mean age of the patients was 48 (range, 16-71) years. Thirteen patients (13/28, 46%) developed early radiological progression of the tumour after completion of concomitant chemoradiotherapy, of whom five (39%) were subsequently found to have had pseudoprogression. Patients with pseudoprogression showed a trend towards longer survival (22 months in pseudoprogression vs 17 months in all others vs 11 months in those with genuine progression). Among the 27 patients tested for O(6)-methylguanine-DNA methyltransferase promoter status, 12 (44%) were methylated. Two (2/12, 17%) in the methylated group had pseudoprogression, while three (3/15, 20%) in the unmethylated group had pseudoprogression. CONCLUSIONS: Nearly half of all patients (46%) developed early radiological progression (within 3 months of completing concomitant chemoradiotherapy). Moreover, about one in three of such patients had pseudoprogression. Pseudoprogression is an important clinical condition to be aware of to prevent premature termination of an effective treatment.

A venographic operational classification for transvenous embolization of dural carotid-cavernous fistula.

INTRODUCTION: It is hypothesized that a venographic-based operational classification of dural carotid-cavernous fistula (DCCF) will facilitate early selection of the optimal venous route and enhance the efficacy of transvenous catheterization and embolization of the cavernous sinus. METHODS: This was a retrospective study on 97 patients who presented with symptomatic DCCF. Definition of classification type 1: both the anterior and posterior compartments of the cavernous sinus were opacified, type 2: only the anterior compartment was opacified, type 3: only the posterior compartment was opacified. Subtype a: the facial vein (FV) draining the superior ophthalmic vein (SOV) was opacified, subtype b: only the inferior petrosal sinus (IPS) was opacified, subtype c: neither the FV nor the IPS were opacified, subtype d: both the FV and the IPS were opacified. The SOV route was recommended for subtype 1a and type 2. The IPS route was recommended for subtype 1b, 1c, 1d, and type 3. Success rates of catheterization by the recommended routes and non-recommended routes were calculated. RESULTS: Number of DCCF lesions were 20 (1a), 28 (1b), 23 (1c), 26 (1d), 16 (2a), 10 (2c), 2 (3b). Of 145 attempted catheterization, 91 and 54 were performed with a recommended route and un-recommended route, respectively. Success rate for catheterization and embolization performed with the recommended route and un-recommended route was 71/91 (78%) and 20/54 (37%), respectively (Chi-Square test P = 0.0024). CONCLUSIONS: Venographic operational classification is useful for guiding the selection of optimal venous route which enhances the efficacy of transvenous embolization of the DCCF.