Interobserver variability in the classification of childhood maculopapular cutaneous mastocytosis.

BACKGROUND: Maculopapular cutaneous mastocytosis (MPCM) in children is classified in two variants: (i) monomorphic variant, presenting with the small macules or papules typically seen in adult patients; and (ii) polymorphic variant with larger lesions of variable size and shape, typically seen in children. The definition of polymorphic and monomorphic variants is mostly intuitive, and a validation of this classification has not been done. OBJECTIVE: To study interobserver variability in the classification of MPCM in two groups of observers: mastocytosis experts and general dermatologists. MATERIALS AND METHODS: Nineteen cases of childhood MPCM were shown blindly, for classification as monomorphic or polymorphic type, to 10 independent observers (eight dermatologists, one allergist and one haematologist) from Europe and North America with a vast experience in the management of paediatric mastocytosis. Also, the same cases were shown on a screen to 129 general dermatologists attending a meeting; their votes were registered by remote controls. The interobserver variability kappa coefficient (with 95% confidence interval) was calculated to measure the reliability of the correlation. RESULTS: The value of kappa interobserver variability coefficient for the group of 10 experts (95% confidence interval) was 0.39 (0.18-0.63), which is considered as 'fair'. The value of kappa interobserver variability coefficient for the group of 129 general dermatologists (95% confidence interval) was 0.17 (0.06-0.39), which is considered as 'slight'. A complete agreement of all 10 experts was achieved in only four of 19 cases (21.1%) The most voted choice was concordant between the two groups in only 11 of the 19 cases. CONCLUSIONS: We failed to validate the classification system of childhood MPCM in monomorphic and polymorphic types. While the rate of agreement was low for mastocytosis experts, it was nearly the agreement expected by chance in general dermatologists.

Cytoreductive nephrectomy in metastatic renal cell carcinoma: outcome of patients treated with a multidisciplinary, algorithm-driven approach.

PURPOSE: Metastatic renal cell carcinoma (mRCC) represents a significant and rising burden of disease, with rapidly evolving treatment modalities. The role of cytoreductive nephrectomy (CN) is controversial in this setting. As such, London Cancer has pursued a multidisciplinary team (MDT) approach when assessing suitability for surgery. METHODS: A retrospective analysis of treatment-naive synchronous mRCC patients, managed via a renal-specialist MDT, was conducted between January 2015 and December 2018. An MDT selection algorithm for CN-using the International Metastatic Renal Cell Carcinoma Database Consortium score (IMDC), performance status and metastatic disease burden-was developed. RESULTS: 87 treatment-naive synchronous mRCC patients received either CN (n = 18), Systemic therapy (ST) alone (n = 43) or Best supportive care (BSC) (n = 26). Progression free survival (PFS) and overall survival (OS) were assessed. 51% and 39% were IMDC intermediate and poor risk. Median PFS was 28.6 months and 4.5 months in the CN group and ST alone group, respectively, Hazard Ratio for death was 3.63 [(95% CI 1.68-7.83) p < 0.05]. OS remains immature for the CN group, but a median OS of 12.8 months was observed in the ST group and 5.0 months for BSC. 1-year OS rate for CN, ST and BSC groups was 77.8%, 55.8% and 23.10%, respectively. CONCLUSION: These findings describe outcomes of an unselected series of patients treated via an MDT-driven, protocolised treatment pathway. MDT pathway-based decision making may improve patient selection for CN. Further research is needed to evaluate the role of CN amongst a growing landscape of treatment strategies, including immune checkpoint inhibitors and combination therapies. Multi-disciplinary team, pathway-based treatment strategy may improve patient selection for cytoreductive nephrectomy in patients with metastatic renal cell carcinoma.

Impaired implicit learning and feedback processing after stroke.

The ability to learn is assumed to support successful recovery and rehabilitation therapy after stroke. Hence, learning impairments may reduce the recovery potential. Here, the hypothesis is tested that stroke survivors have deficits in feedback-driven implicit learning. Stroke survivors (n=30) and healthy age-matched control subjects (n=21) learned a probabilistic classification task with brain activation measured using functional magnetic resonance imaging in a subset of these individuals (17 stroke and 10 controls). Stroke subjects learned slower than controls to classify cues. After being rewarded with a smiley face, they were less likely to give the same response when the cue was repeated. Stroke subjects showed reduced brain activation in putamen, pallidum, thalamus, frontal and prefrontal cortices and cerebellum when compared with controls. Lesion analysis identified those stroke survivors as learning-impaired who had lesions in frontal areas, putamen, thalamus, caudate and insula. Lesion laterality had no effect on learning efficacy or brain activation. These findings suggest that stroke survivors have deficits in reinforcement learning that may be related to dysfunctional processing of feedback-based decision-making, reward signals and working memory.

Predictors of important neurological causes of dizziness among patients presenting to the emergency department.

OBJECTIVES: Dizziness is a common presenting complaint in the emergency department (ED). This prospective study describes the incidence, causes and outcome of ED patients presenting with dizziness and tries to identify predictors of central neurological causes of dizziness. METHODS: Single-centre prospective observational study in a university teaching hospital ED in Hong Kong. All ED patients (> or = 18 years old) presenting with dizziness were recruited for 1 month. Symptoms, previous health, physical findings, diagnosis and disposition were recorded. The outcome at 3 months was evaluated using hospital records and telephone interviews. Follow-up was also performed at 55 months using computerised hospital records to identify patients with subsequent stroke and those who had died. RESULTS: 413 adults (65% female, mean 57 years) were recruited. The incidence of dizziness was 3.6% (413/11 319). Nausea and/or vomiting (46%) and headache (20%) were the commonest associated findings. Hypertension (33%) was the commonest previous illness. Central neurological causes of dizziness were found in 6% (23/413) of patients. Age > or = 65 years (OR=6.13, 95% CI 1.97 to 19.09), ataxia symptoms (OR=11.39, 95% CI 2.404 to 53.95), focal neurological symptoms (OR=11.78, 95% CI 1.61 to 86.29), and history of previous stroke (OR=3.89, 95% CI 1.12 to 13.46) and diabetes mellitus (OR=3.57, 95% CI 1.04 to 12.28) predicted central causes of dizziness. CONCLUSIONS: Most dizzy patients had benign causes. Several clinical factors favoured a diagnosis of central neurological causes of dizziness.

Pre- and postoperative fMRI and clinical memory performance in temporal lobe epilepsy.

OBJECTIVE: The present study aimed to examine and compare memory processing in patients with unilateral temporal lobe epilepsy (TLE) before and after surgery using functional magnetic resonance imaging (fMRI). METHODS: Seventeen preoperative patients with unilateral TLE (nine left, eight right) and eight healthy controls were recruited. They performed a complex visual scene-encoding task during fMRI to measure memory activation in the mesial temporal lobe. Their memory performance was evaluated using standardised neuropsychological tests. After unilateral temporal lobe resection (either temporal lobectomy, selective amygdalohippocampectomy or lesionectomy), the same fMRI paradigm and neuropsychological tests were administered to the patient group. RESULTS: Left-TLE patients demonstrated a decline in verbal memory after left temporal lobe resection. Their postoperative verbal and visual memory performance was positively associated with postoperative functional activation in the right mesial temporal lobe, whereas the postoperative memory performance of right-TLE patients was positively associated with postoperative functional activation in the left mesial temporal lobe, contralateral to their respective side of resection. CONCLUSION: Postoperative memory performance was significantly associated with functional activation contralateral to the side of resection in patients with unilateral TLE, and the function of the contralateral mesial temporal lobe might play an important role in supporting memory performance after temporal lobe resection.

Management of spinal injury.

Spinal injury often affects young adults and results in debilitating neurological status, which in turn places a significant burden on society. This review article describes the current practice and controversies surrounding the management of spinal injury. General principles of pre-hospital management, resuscitation, medical treatment, surgical intervention and future advancement are reviewed.

Aneurysm recurrence after treatment of paraclinoid/ophthalmic segment aneurysms--a treatment-modality assessment.

OBJECT: The treatment of 21 paraclinoid/ophthalmic segment internal carotid artery aneurysms (PCOSAs) over a seven year period in a regional neurosurgical center was reviewed to assess the degree of obliteration and recurrence rate of these aneurysms after treatment by surgical and endovascular methods. METHOD AND RESULT: An assessment of the clinical notes, operation records and cerebral angiograms was made to evaluate the rate of residual and recurrent aneurysms after treatment and at follow-up. In the coiling group, the aneurysm recurrence rate was eight out of fifteen aneurysms (53%). Four recurrences were from previously totally occluded aneurysms. Out of the six surgical cases, five had follow-up angiography performed. All had stable occlusions of their aneurysms including one with subtotal occlusion. Two clipping procedures after previous coiling achieved total occlusion of aneurysm on follow-up angiography. CONCLUSION: Based on our case series we conclude that PCOSAs frequently recur after primary treatment. GDC coiling was associated with a higher rate of recurrent aneurysms when compared with surgical treatment. A review of the literature on the surgical and endovascular treatment of PCOSAs support this observation.

Cerebral blood flow (CBF)-directed management of ventilated head-injured patients.

OBJECTIVE: Ischaemic brain damage has been shown to be an important contributing factor causing head injury fatality. Maintenance of an adequate cerebral perfusion pressure is difficult in patients with elevated intracranial pressure (ICP) and deranged cerebral vasoreactivity. Thirty-five cases of ventilated moderate-to-severe head-injured patients were prospectively studied, correlating their cerebral haemodynamic abnormalities, neurochemical disturbances (using microdialysis methodology) and clinical outcome. METHODS: Cerebral haemodynamic abnormalities were defined and classified by transcranial Doppler ultrasonography (TCD) and stable xenon-CT cerebral blood flow measurements (XeCT) into their status of CO2 reactivity, pressure autoregulation, hyperaemia or non-hyperaemia. Two-hour episodes of these abnormalities with and without haemodynamic intervention were followed in their changes in ICP, CPP, intracerebral metabolites and finally their clinical outcome. RESULTS: Loss of CO2 reactivity was associated with a significantly higher ICP, increasing intracerebral metabolites (lactate, glutamate and glycerol) and invariably a fatal outcome. Impaired pressure autoregulation was also associated with an elevated ICP, but no significant difference in intracerebral metabolites and incidence of favourable clinical outcome. Patients with intact CO2 reactivity and impaired pressure autoregulation were treated with an elevated CPP in 32 episodes, resulting in a significant reduction in ICP, intracerebral glutamate and glycerol and non-survival. In patients with intact CO2 reactivity and impaired pressure autoregulation, eleven episodes of hyperaemia were identified by XeCT. A modest 20%, blood pressure reduction resulted in a trend towards a reduction of ICP, intracerebral glutamate and glycerol and non-survival. CONCLUSIONS: The need for haemodynamic intervention in this group of ventilated patients with moderate-to-severe head inury can be made logical when these abnormalities are identified daily. The success of management was reflected by a stable or improved ICP, CPP, intracerebral metabolic deranagement and survival.

Re-defining the ischemic threshold for jugular venous oxygen saturation--a microdialysis study in patients with severe head injury.

Neurological change is more likely to occur when jugular venous oxygen saturation (SjvO2) is less than 50%. However, the value indicating cellular damage has not been clearly defined. We determined the critical SjvO2 value below which intracerebral extracellular metabolic abnormalities occurred in 25 patients with severe head injury. All patients received standard treatment with normoventilation and maintenance of intracranial pressure < 20 mmHg. SjvO2 was measured from the dominant jugular bulb using a calibrated fibreoptic catheter. Intracerebral metabolic monitoring was performed by collecting perfusate from a microdialysis probe placed in the frontal lobe anterior to the intracranial catheter. Excitotoxin (glutamate) and other extracellular metabolites (lactate, glucose and glycerol) were measured frequently using enzymatic and colorimetric methods. We observed biphasic relationships between SjvO2 and all intracerebral metabolites. Analysis of variance showed that there were rapid increases in glutamate, glycerol and lactate when SjvO2 dropped below 40, 43 and 45% respectively. Extracellular glucose decreased when SjvO2 dropped below 42%. Our findings suggested that the ischemic threshold for SjvO2 in patients with severe head injury is 45%, below which secondary brain damage occurred.

Monitoring of autoregulation using intracerebral microdialysis in patients with severe head injury.

We evaluated the performance of continuous intracerebral microdialysis to indicate the autoregulatory reserve in 36 severely head-injured patients. All patients received standard treatment with intracranial pressure (ICP) monitoring. A microdialysis probe was placed in the frontal cortex anterior to the ICP catheter. Perfusate was collected frequently and extracellular concentration of glutamate was measured online using enzymatic method. Autoregulatory index was calculated by comparing glutamate concentration with CPP using Pearson's correlation. A correlation coefficient (r) < 0.5 is considered as loss of autoregulation, whereas r values approach 0 indicate preserved autoregulation. The change of autoregulatory status over time was correlated with outcome at 6 months. Three patterns of autoregulatory profiles were identified. Patients with intact autoregulation had satisfactory outcome. Transient impairment of autoregulation may result in favorable outcome if patients responded to treatment. However, persistent loss of autoregulation was associated with poor outcome (P < 0.001). The correlation between extracellular glutamate concentration (by microdialysis) and CPP is a useful index of autoregulation in head-injured patients. It predicts clinical outcome and may be used to guide therapy.

A review of isolated third nerve palsy without subarachnoid hemorrhage using computed tomographic angiography as the first line of investigation.

INTRODUCTION: Digital subtraction angiography is recognized as the standard investigation for isolated third nerve palsy thought to be caused by an expanding aneurysm. We reviewed our experience in using computed tomographic angiography (CTA) as the first line investigation for patients presenting with isolated third nerve palsy without subarachnoid hemorrhage. METHOD: We retrieved the medical records of 34 patients who had presented with isolated third nerve palsy without associated subarachnoid hemorrhage to our institution between January 1998 and July 2001. The clinical history, course and outcome as well as the radiological data was reviewed. RESULTS: A total of nine structural lesions (26%) were noted as the etiology of the third nerve palsy. All of the five posterior communicating artery aneurysms were picked up by the CTA. Neither the presence nor the absence of painful complete third nerve palsy was of diagnostic value for intracranial aneurysm. CONCLUSION: A good quality CTA is sufficient to detect a compressive aneurysm and may detect other structural lesions. This allows neurosurgeons to plan the management of patients with isolated third nerve palsy. Patients in whom CTA results are inconclusive should be further investigated with catheter angiography.

Consensus statement on ischaemic stroke care in Hong Kong.

OBJECTIVE: To issue guidelines for the care of acute stroke in Hong Kong, with the target audience of all health care professionals who are involved in acute stroke care. PARTICIPANTS: The Hong Kong Neurological Society and the Hong Kong Stroke Society. EVIDENCE: The panel applied the 'rule of evidence' used by the United States Agency for Health Care Policy and Research. When there is insufficient evidence, the recommendation was based on customary practice and was circulated among the members and fellows of the two societies before coming to a consensus. CONSENSUS PROCESS: Group meetings were held in 2002 to review the literature about acute care for patients with ischaemic stroke and to issue a consensus statement with reference to the local health care system. Participants of the meetings were appointed by the councils of The Hong Kong Neurological Society and the Hong Kong Stroke Society. The draft statement was circulated among the members and fellows of the two societies for comments before it was finalized. CONCLUSIONS: Ischaemic stroke is a heavy health care burden to Hong Kong. The current consensus statement provides a framework to establish a multidisciplinary approach towards its acute management.

The surgical treatment of intracranial aneurysms based on computer tomographic angiography alone--streamlining the acute mananagement of symptomatic aneurysms.

BACKGROUND: We aimed to prospectively assess the usefulness of computer tomographic angiography (CTA) in streamlining the management of symptomatic intracranial aneurysms in a tertiary neurosurgical unit, from admission to surgery. METHODS: We performed a prospective evaluation over a 2-year period of all symptomatic intracranial aneurysms managed according to a standardized departmental protocol, to assess how CTA has impacted the decision-making process pertaining to the suitability of this investigation to proceed directly to surgery. FINDINGS: A total of 90 patients with intracranial aneurysms were treated over the 2-year period. 23 (26%) underwent endovascular occlusion while 67 (74%) patients underwent a surgical clipping procedure. In the surgical group, 22 (33%) patients had their aneurysms clipped based on CTA alone, while 45 (67%) required additional conventional angiography prior to surgery. Thus around one quarter of all patients treated for symptomatic intracranial aneurysms in our unit had their aneurysm secured surgically based solely on CTA. INTERPRETATION: CTA significantly influences the acute management of symptomatic intracranial aneurysms by streamlining the decision-making process during the early and acute management of these lesions.

Role of magnetic resonance imaging for preoperative evaluation of patients with refractory epilepsy.

OBJECTIVE: To investigate the magnetic resonance imaging characteristics of patients with refractory epilepsy and the relationship to progression to surgery. DESIGN: Prospective observational study. SETTING: University teaching hospital, Hong Kong. PATIENTS: Patients undergoing preoperative evaluation for epilepsy surgery. MAIN OUTCOME MEASURE: Cranial magnetic resonance imaging findings, correlation with electroencephalographic results, and percentage of patients who were considered suitable candidates for surgery. RESULTS: Structural abnormalities associated with refractory epilepsy in 100 consecutive patients were mesial temporal sclerosis (30%), neocortical sclerosis (23%), vascular malformation (7%), neuronal migration disorders (7%), and tumours (5%). Normal brain scans were found for 28% of patients. Fourteen of 30 (46%) patients with medial temporal lobe lesions at magnetic resonance imaging were suitable candidates for surgery compared with 8/42 (19%) patients with extrahippocampal lesions (odds ratio=3.7; 95% confidence interval, 1.3-10.6; P<0.012). CONCLUSION: Mesial temporal sclerosis was the most common pathology in patients with refractory epilepsy. At the Prince of Wales Hospital, for patients who have undergone a basic magnetic resonance imaging protocol and surface electroencephalography, the result of cranial magnetic resonance imaging is an important determinant for whether patients will undergo surgery.

Failure of regular external ventricular drain exchange to reduce cerebrospinal fluid infection: result of a randomised controlled trial.

BACKGROUND: It is controversial whether regular changes of external ventricular drains can reduce cerebrospinal fluid (CSF) infection. OBJECTIVE: To carry out a randomised controlled clinical trial over a two year period to determine whether a regular change of ventricular catheter every five days could reduce CSF infection and improve outcome. METHODS: 103 patients requiring external ventricular drains for more than five days and with no evidence of concurrent CSF infection were studied. The patients were randomised to regular change of ventricular catheter (every five days) and no change unless clinically indicated. RESULTS: The CSF infection rates were 7.8% for the catheter change group and 3.8% for the no change group, respectively (rate ratio = 1.80, 95% confidence interval 0.33 to 9.81, p = 0.50). No significant difference was found in intensive care unit stay, ward stay, or clinical outcome between the two groups. CONCLUSIONS: Regular changes of ventricular catheter at five day intervals did not reduce the risk of CSF infection. A single external ventricular drain can be employed for as long as clinically indicated.

Is transcranial Doppler ultrasonography (TCD) good enough in determining CO2 reactivity and pressure autoregulation in head-injured patients?

Disturbance of cerebral haemodynamic status, cerebral vasoreactivity (CVR) to carbon dioxide (CO2) and pressure autoregulatory response (PAR) have been shown to be associated with severity of head injury and to correlate with neurological condition and clinical outcome. Information regarding impaired CVR and/or lost PAR has been shown to be of prognostic value in treating head-injured patients. The classic method of evaluating cerebral haemodynamic status requires an invasive measurement of cerebral blood flow (CBF) such as the technique of Kety and Schmidt or by the 133Xe inhalation method. Transcranial Doppler ultrasonography (TCD) is a simple and non-invasive method for its assessment. In this study, cerebral haemodynamic status as determined by TCD was compared with that of stable xenon-enhanced cerebral blood flow (XeCBF) which is generally regarded as a gold standard in CBF measurement with minimal complication, suggesting that employing CO2 and blood pressure challenge with TCD measurement to assess the CVR and PAR in head-injured patients, provides a relatively less invasive method and can be repeated at least daily to assess the cerebrovascular autoregulatory reserve.

Neurochemical changes in ventilated head-injured patients with cerebral perfusion pressure treatment failure.

The goal of intensive care management of patients with head injury is to provide them with a favourable physiological and metabolic environment for recovery of injury-compromised cells, and to prevent secondary brain insults. Clinical intracerebral microdialysis has enabled documentation of the metabolic derangement after head injury. Treatment targeted at this derangement has emphasized maintenance of optimal cerebral perfusion pressure (CPP). To determine the relationships between CPP and five clinically relevant intracerebral extracellular metabolites (glucose, lactate, glycerol, glutamate and pyruvate) in relation to different therapy intensities, 23 moderate to severe head-injury patients with hourly microdialysis samples were studied. These five metabolites were correlated with CPP and showed a biphasic relation at CPP of 65 to 67 mmHg, which was believed to be the critical CPP indicating irreversible brain damage. Relationship between intracerebral metabolites and CPP in relation to different therapy intensities was studied and suggests the critical CPP threshold in head-injured patients with high ICP and maximum therapy is elevated and should be maintained above 70 mmHg to prevent irreversible brain damage.

Prevalence of yeasts in saliva and root canals of teeth associated with apical periodontitis.

AIMS: To determine: (i) the relative prevalence and diversity of yeasts in salivary and root canal samples from the same patients; and (ii) the clinical factors associated with their presence in saliva and root canals. METHODOLOGY: Sixty root canal samples from teeth associated apical periodontitis and the corresponding whole unstimulated saliva samples were obtained from 55 patients. The medical history including antibiotic therapy and clinical/radiographic data on the teeth were recorded. The samples were serially diluted and cultured on yeast & fungi-selective sabouraud dextrose agar. Isolates were characterized and speciated by the germ tube formation test, hyphal morphology and a commercial biochemical test kit (Rapid ID32C(R) system). RESULTS: Twenty-three yeast isolates were recovered from 19 saliva samples and eight isolates from six root canal samples. Candida albicans (17/23 & 3/8) and Rodotorula mucilaginosa (2/23 & 4/8) were the most prevalent isolates from saliva and root canal samples. It was significantly (13.8 times) more probable that yeasts would be recovered from root canals when they were also present in the saliva (P = 0.021). The effect of coronal restoration leakage (P = 0.08) and previous root canal treatment (P = 0.123) were equivocal. The history of antibiotic therapy had no association with the presence of yeasts in saliva (OR = 1.1). CONCLUSIONS: Yeasts occurred relatively infrequently (10%) in root canals. Their presence in root canals was significantly associated with their presence in saliva. The role of yeasts in the initiation and perpetuation of periapical disease remains to be determined.

The use of stereotactic navigation guidance in minimally invasive transnasal nasopharyngectomy: a comparison with the conventional open transfacial approach.

The purpose of this paper is to study the efficacy of applying stereotactic navigation guidance to nasopharyngectomy via a minimally invasive transnasal approach as compared with the conventional open transfacial approaches. The nasopharynx is the centre of the anterior skull base, which is remote from the surface of the facial skeleton. It is well known that there are several surgical approaches for access to resect tumours from the nasopharynx. However, the open techniques have been associated with much morbidity and only provide access to, and identification of, the ipsilateral internal carotid artery that forms the lateral boundary and resection limit of the nasopharynx. The coupling of stereotactic navigation guidance and a minimally invasive transnasal approach for nasopharyngectomy allows the surgeon to identify and protect the internal carotid artery bilaterally at the nasopharynx. This technique reduces operating time and morbidity to a minimum and yet is oncologically sound for resecting nasopharyngeal lesions. We compare 15 patients who underwent the stereotactic navigation guidance approach with 20 patients who received a conventional open transfacial approach.