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Biomedical subjects

A David Mendelow

Publications and source records attributed to A David Mendelow.

17 recordsLinked to original sources

Intracranial aneurysms treated with endovascular coils: detection of recurrences using unenhanced and contrast-enhanced transcranial color-coded duplex sonography.

BACKGROUND AND PURPOSE: Because neck recurrence after endovascular treatment of intracranial aneurysms (IAs) is not uncommon, surveillance to assess long-term stability of occlusion is clearly important. This study evaluated unenhanced and contrast-enhanced transcranial color-coded duplex sonography (TCCS) in detecting refilling of IAs treated with detachable coils. METHODS: Patients with coiled IAs were imaged before and after contrast enhancement. The results were compared with those of a surveillance digital subtraction angiogram (DSA). The operator was blinded to the results of the DSA. Aneurysms were classed as either occluded or with residual flow and quantified as minor, moderate, or extensive. There were 208 studies performed in 4 neurosurgical centers. Of those, 141 studies received ultrasonic contrast enhancement with Levovist, and 68 had an additional enhanced study with SonoVue. RESULTS: We excluded 44 studies. Of the 164 unenhanced studies, TCCS correctly identified 52 of 67 cases defined as completely occluded by DSA (sensitivity 78%; specificity 77%), 13 of 50 aneurysms with minor refilling (sensitivity 26%; specificity 88%), 15 of 27 aneurysms with moderate refilling (sensitivity 56%; specificity 95%), and 9 of 20 aneurysms with extensive refilling (sensitivity 45%; specificity 100%). TCCS correctly identified an additional 10 aneurysms with minor refilling after Levovist enhancement and 3 with SonoVue. Both SonoVue and Levovist enhancement identified an additional 1 aneurysm with moderate refilling and 3 with extensive refilling. CONCLUSIONS: TCCS could be used to selectively monitor IAs, which would reduce the requirement for long-term invasive monitoring. The detection of neck refilling is improved with contrast enhancement.

Adult↗

Supraorbital eyebrow minicraniotomy for anterior circulation aneurysms.

BACKGROUND: We report our experience with the minimally invasive supraorbital approach to aneurysms of the ipsilateral anterior cerebral circulation. METHODS: A prospective review of all patients who underwent operations to clip aneurysms in Newcastle between 1993 and 2002. RESULTS: Fifty-six aneurysms were clipped via minicraniotomy in 47 patients. Six patients presented with acute subarachnoid hemorrhage (SAH), 40 patients were admitted for elective clipping, and 1 patient presented with an SAH, had the responsible aneurysm clipped and was readmitted later for elective clipping of a further aneurysm. Bilateral supraorbital craniotomies were performed in 3 patients. In 6 patients, multiple aneurysms were clipped via a single craniotomy. All aneurysms were well visualized with the microscope. Endoscopic assistance was not found necessary. All were successfully clipped. Two aneurysms ruptured while being clipped. There was no direct mortality from surgery. One patient died later from a separate posterior circulation aneurysm. One patient had a significant long-term deficit but remained independent, and 1 had 3 seizures over the 12 months after surgery. This represents a 4% morbidity at 1 year. CONCLUSION: Selected anterior cerebral circulation aneurysms can be clipped with low morbidity, using an ipsilateral minicraniotomy preserving the orbital rim, and without using an endoscope. The types of aneurysm selection criteria and operative equipment used are described.

Adult↗

Surgery for malignant gliomas: mechanistic reasoning and slippery statistics.

Current surgical treatment of malignant gliomas largely depends on mechanistic reasoning and data collected in non-randomised studies. Technological advance has enabled more accurate resection of tumours and preservation of eloquent brain areas but ethical considerations have restricted randomised trials on the efficacy of surgery to one small trial that found a 3 month survival advantage for patients over age 65 years who received surgery and interim analysis of a larger trial. There is an argument for surgery as a palliative measure in patients with symptoms caused by mechanisms that are surgically remediable. Whether there is any survival advantage from surgery in patients other than those with immediately life-threatening, surgically remediable complications, such as raised intracranial pressure, is unclear. The available data show that if such an advantage does exist, it is modest at best. Adjuvant treatments given surgically are being studied. Chemotherapy wafers are the most prominent of the adjuvant treatments but the evidence available is insufficient to recommend their use in routine practice. In this review we examine the prevailing mechanistic model and observational data; we assess how these are applied and the priorities they indicate for future research.

Biopsy↗

Design and analysis of phase III trials with ordered outcome scales: the concept of the sliding dichotomy.

The conventional approach to the analysis of a Phase III trial in head injury or stroke takes an ordered scale measuring functional outcome and collapses the scale to a binary outcome of favorable versus unfavorable. This discards potentially relevant information which limits statistical power and moreover is not in accord with clinical practice. We propose an alternative approach where a favorable outcome is defined as better than would be expected, taking account of each individual patient's baseline prognosis. This is illustrated through a worked example based on data from a Phase III trial in head injury. The approach is also compared with the proportional odds model, which is another statistical approach that can exploit an ordered outcome scale. The approach raises issues of clinical, statistical, and regulatory importance, and we initiate what we believe needs to become a widespread debate amongst the community involved in clinical research in head injury and stroke.

Clinical Trials, Phase III as Topic↗

Retracing "Ondine's curse".

"Ondine's curse" is a term used to denote a rare neurological condition causing failure of automatic respiration. The patients are no longer capable of breathing spontaneously-they must consciously and voluntarily force themselves to do so. Ondine (also known as "Undine"), a mythological figure of European tradition, was a water nymph or sprite who could become human only when she fell in love with a mortal man. However, if the mortal was unfaithful to her, he was destined to forfeit his life. In the 16th century, Paracelsus coined the term "Undine" to describe the spirit that inhabited the element of water. Baron de la Motte-Fouque wrote the story of Undine in the late 18th century. It has since become a popular subject for theater productions. Jean Giraudoux, the French playwright, introduced the concept of the loss of automaticity of all functions as the "curse of Ondine." The legend was popularized in the form of the fairy tale "The Little Mermaid" by Hans Christian Andersen and as an animated motion picture by Walt Disney Productions. In this study, we look at the origins of this eponymous term, the personalities intertwined with its popularity, and its misrepresentations in the medical literature.

Humans↗

Unruptured intracranial aneurysms: benign curiosity or ticking bomb?

15 years ago, the treatment of incidentally discovered intracranial aneurysms was straightforward with a good evidence base behind it. When intracranial aneurysms were identified, people were referred to neurosurgeons who would offer surgical repair if the patient was in reasonable health and had a good life expectancy. Since that time, several studies have given contradictory evidence for what should be done with these lesions, and a new technique for the repair of aneurysms, endovascular coil embolisation, has been developed. Here we review the research and make several recommendations. First, incidentally discovered aneurysms in the anterior circulation less than 7 mm in size in people with no personal or family history of subarachnoid haemorrhage should be left untreated. Second, people with remaining life expectancy of less than 20 years or so (ie, those over age 60 years) should be informed that from a statistical point of view the benefits of treatment do not outweigh the risks. Third, in all other cases treatment with surgical clipping or coil embolisation should be advised. And finally, if surgical treatment is not feasible then medical hypotensive treatment may be a viable alternative.

Diagnostic Imaging↗

International variations in surgical practice for spontaneous intracerebral hemorrhage.

BACKGROUND AND PURPOSE: Spontaneous intracerebral hemorrhage is a major cause of death and disability, yet there is no convincing evidence of the benefit of any medical treatment and the role of surgery remains controversial. The international randomized Surgical Trial in Intracerebral Hemorrhage (STICH) provided an opportunity to assess the role of surgery within the centers taking part. METHODS: Screening logs were completed to record details of all patients assessed by the department, whether they were included in the trial, the reasons if they were not included, and whether they underwent surgery. RESULTS: Logs were returned by 42 centers and cover 704 months. They include details on 1578 patients with characteristics comparable to STICH inclusion criteria. Neurosurgeons were more likely to express clinical certainty about treatment for older patients, patients with a higher Glasgow Coma Score scale, and patients in whom the hematoma was located on the right or in the basal ganglia or thalamus. Patients for whom the neurosurgeon was certain about treatment were more likely to have the hematoma removed if they were younger (62 versus 68 years of age), had a lower Glasgow Coma Scale score (10 versus 13), and had a lobar hematoma (49% versus 40%). The operation rate varied between 74% in Lithuania and 2% in Hungary. CONCLUSIONS: The difference in operation rates could not be explained by differences in patient characteristics alone. This finding demonstrates the need for further evidence to ensure that treatment for intracerebral hemorrhage is not governed by local custom.

Acute Disease↗

Predicting clinical ischaemia during awake carotid endarterectomy: use of the SJVO2 probe as a guide to selective shunting.

Stroke is a major cause of disability within the western world. About 20% of strokes are a consequence of atheromatous narrowing of the origin of the internal carotid artery. Carotid endarterectomy has been shown to be an effective treatment for those with symptomatic and severe stenosis, provided the risk of death and peri-operative stroke is less than 7%. The aim of this study was to investigate the clinical value of jugular venous oxygen saturation (SJVO2) monitoring in identifying patients who develop cerebral ischaemia whilst undergoing an awake carotid endarterectomy by comparison with a simple neurological assessment. Each patient underwent a standard awake carotid endarterectomy. Peri-operatively a SJVO2 catheter was inserted, and the jugular oxygen saturation was correlated with the presence or absence of cerebral ischaemia. Data from 34 patients were analysed using time-series plots and by calculating a receiver operator characteristic (ROC) curve. The optimal sensitivity and specificity for this technique were found to be 1.0 and 0.8, respectively, when a 25% change in SJVO2 was used as a threshold. Although a small observational study, we have shown that percentage change in SJVO2 correlates well with the development of clinically apparent cerebral ischaemia. This technique may improve the safety of carotid endarterectomy under general anaesthesia when used with other more established monitoring methods.

Awareness↗

Aneurysmal subarachnoid hemorrhage in young adults.

OBJECT: The authors reviewed the management protocols for young adults who presented with subarachnoid hemorrhage (SAH) at the Regional Neurosurgery Unit in Newcastle during a study period of 9 years. Aneurysmal SAH is uncommon in the age group selected (18-39 years) and, therefore, the performance of these patients has not been extensively reported in the literature. The authors also evaluated the good-grade rebleed rate (an index of management efficiency) in this cohort of patients. METHODS: The Newcastle neurosurgical unit serves a population of close to 3 million people, and an average of 180 patients with SAH are seen each year. The majority of patients are transferred from other hospitals in the region. This study includes patients admitted between January 1990 and December 1998. A total of 1,609 patients were admitted during this period, of whom 295 (18.4%) between the ages of 18 and 39 years constituted the study population of young adults. Two hundred ninety-five young adults presented with SAH; 181 (61.4%) were women and 114 (38.6%) were men, a ratio of 3:2. Of 246 patients in whom this value was recorded, 15 (6.1%) presented with a history of hypertension, and there was an association between hypertension and the occurrence of multiple aneurysms (Fisher two-tailed exact test, p = 0.008). Thirty-five patients (11.9%) presented with a hematoma on computerized tomography scans; of these, 20 (57%) were women and 15 were men. In six patients the lesion had rebled before treatment. The good-grade rebleed rate was three (1.7%) of 178. The overall favorable outcome rate was 83.8% (Glasgow Outcome Scale [GOS] 4 and 5) and unfavorable outcome occurred in 16.2% (GOS 1-3), with a total of 40 deaths in this group (13%). Age had no influence on outcome in young adults. Comparing the outcome at discharge with the follow-up evaluation at 6 months revealed that patients in the moderate and severe disability groups continued to improve and many achieved good recovery. CONCLUSIONS: In this report the authors detail the outcome of a large number of young adults with SAH. The incidence of SAH was higher in the female population, although the ratio was not as high as previously reported. The authors have also demonstrated a progressive increase in the incidence of aneurysmal SAH with age, even in young adults. Hypertension but not age influenced the occurrence of multiple aneurysms. The good-grade rebleed rate is low, although it is not zero. Generally, a satisfactory outcome was obtained and significant continuing improvements were noted between discharge and follow-up evaluation. This reflects the power of recovery in young adults. These are people whose economic productivity and fertility are at peak levels and therefore the financial and social burden occasioned by less-than-perfect outcomes is large.

Adolescent↗

Computed tomography angiography for the evaluation of carotid atherosclerotic plaque: correlation with histopathology of endarterectomy specimens.

BACKGROUND AND PURPOSE: The goal of this study was to determine the efficacy of CT angiography for the characterization of plaque morphology and composition in carotid atherosclerotic disease. METHODS: Fifty-five patients undergoing carotid endarterectomy were imaged preoperatively with single-slice spiral CT angiography. One hundred sixty-five endarterectomy sections were examined histologically at selected levels through the distal common and proximal internal carotid arteries. Plaque density was measured (in Hounsfield units) on axial CT sections, and the presence or absence of ulceration was noted. These observations were compared with the histological findings at corresponding levels. Data were analyzed with 2-sample t tests and 1-way analysis of variance (ANOVA). RESULTS: ANOVA testing showed a statistically significant decrease in CT attenuation values with increasing plaque lipid but with a very high standard deviation of values. No other histological factor showed a statistically significant link with CT attenuation. Plaque ulceration was detected by CT with a sensitivity of 60% and a specificity of 74%. CONCLUSIONS: Analysis of plaque attenuation with single-slice spiral CT does not give useful information concerning plaque composition. The predictive value of CT for the detection of plaque ulceration was moderate. Single-slice CT angiography is insufficiently robust to be a useful tool for the characterization of carotid plaque composition and morphology.

Analysis of Variance↗

Co-existing cholesteatoma and vestibular schwannoma.

A 69-year-old man presented with a cholesteatoma in the right mastoid process and a vestibular schwannoma at the left internal acoustic meatus. Cholesteatoma co-existing with a vestibular schwannoma has not been documented previously in the contemporary literature. The clinical dilemma in the management of his progressive bilateral hearing loss is discussed. He presented with dizziness and bilateral hearing loss worse on the right side. Pressure over the mastoid process elicited vertigo and nystagmus. He had no history of previous operation or infection in the ear canal. Audiograms confirmed high-tone hearing loss. Radiological investigations revealed a symptomatic cholesteatoma on the right side and an incidental vestibular schwannoma on the left. We have elected to manage both lesions conservatively. Bilateral cholesteatoma and bilateral vestibular schwannomas have been previously reported. Co-existing lesions, as in our patient have, however, not been reported previously. The management options of his hearing loss are discussed.

Aged↗

Comparative study of traumatic and spontaneous intracerebral hemorrhage.

OBJECT: Spontaneous intracerebral hemorrhage (SICH) and traumatic intracerebral hemorrhage (TICH) are common disorders. The authors planned to study how these two types of hemorrhage behave pathologically and clinically to gain further insight into their causes, pathogeneses, indications for surgical intervention, and prognoses. METHODS: Prospectively filled databases of demographic, clinical, radiological, and outcome details have been maintained for all patients admitted to the Regional Neurosciences Centre with head injury since 1987 and with SICH since 1993. Of the 5686 patients whose case information was included in the head-injury database, 90 were found to suffer from an isolated intracerebral hemorrhage (ICH) as the only major abnormality observed on computerized tomography scans (subdural and extradural hematomas were excluded). Case details on these 90 patients and the 440 patients from the SICH database were extracted and analyzed using a statistical software program. The median age of patients with TICH was lower than the median age of patients with SICH (51 years compared with 65 years, respectively), but it was much higher than the median age of the entire head-injury group (21 years). Among patients younger than 45 years of age, 0.8% of patients who experienced trauma suffered from an ICH compared with 4.3% of patients older than 45 years of age. Irrespective of intervention, much better outcomes were achieved by patients with TICH compared with those with SICH (67% favorable outcomes compared with 24% in patients with SICH). Following trauma, there was no significant relationship between the severity of injury and the development of ICH. At presentation the median Glasgow Coma Scale (GCS) score for both groups was 13. Younger age and higher GCS score at presentation were strongly related to a favorable outcome for both types of hemorrhage. There was no significant difference in patient age, presenting GCS score, or outcomes of patients who underwent surgery compared with those who did not for either type of hemorrhage. No conclusions can be drawn about the efficacy of surgery from such observational studies. CONCLUSIONS: On the basis of these data the authors suggest that TICH and SICH have different features: TICH affects a slightly younger age group and carries a much better prognosis compared with SICH. In addition, indications for surgical intervention are not well defined for either type of hemorrhage. Practice is subjective and inconsistent. The International Surgical Trial in Intracerebral Haemorrhage may resolve the dilemma for SICH. A similar trial in which surgery is compared with conservative management should be considered for cases of TICH.

Adult↗

Reversible ischemia around intracerebral hemorrhage: a single-photon emission computerized tomography study.

OBJECT: A zone of perilesional ischemia has been demonstrated around intracerebral hemorrhage (ICH) in numerous experimental models and in human studies. There is potential for perfusion recovery in the zone of perilesional oligemia around ICH. The authors sought to demonstrate, quantify, and study the chronological evolution of perilesional ischemic change in ICH in humans by measuring cerebral blood flow. METHODS: Eleven patients with spontaneous supratentorial ICH underwent two technetium-99m hexamethylpropyleneamine oxime single-photon emission computerized tomography (SPECT) scanning, one in the acute stage (within days of ictus) and the other in the late stage (6-9 months postictus). All patients in this study were treated nonsurgically. Methods of SPECT data analysis based on count differences in regions of interest can be difficult to apply to images with large space-occupying lesions such as ICH, because of the distortion of intracranial anatomy, midline shift, and alterations in the three-dimensional (3D) characteristics of the lesion over time (that is, absorption of the hematoma on the later studies). The authors used the following method: the late and early images were registered and aligned to a common 3D orientation and were normalized to maximal counts. The late images were then compared voxel by voxel with the early ones. The region-growing algorithm was used to discern the difference between the two images, outlining voxels in the perihematoma region, with a signal improvement of at least 15% on the late image. Discrete brain regions around the hematoma with at least a 15% improvement in radiotracer uptake (and hence perfusion) in the late images were observed in all cases. The mean volume of brain with a greater than 15% improvement in perfusion between the two studies was 34.8 cm3 (range 7.2-71.3 cm3). These volumes represent regions of the brain that were poorly perfused in the initial studies. This may represent a zone of reversible perilesional oligemia (penumbra) in ICH in humans. CONCLUSIONS: This is the first study in which it is documented that some of the perilesional hypoperfused tissue around human ICH regains its perfusion in the long term, leading the authors to suggest that there may be a penumbra in human ICH. Medical or surgical therapeutic interventions could increase the volume of perilesional brain that recovers after the initial insult. The results of this study therefore support the concept that intervention in ICH has the potential to reduce the ultimate neurological deficit and improve outcome.

Adult↗

Subarachnoid haemorrhage.

Aneurysmal SAH is a devastating condition arising suddenly and usually without warning. The best outcomes may be facilitated by prompt recognition/suspicion and immediate referral to the neurosurgical unit. Many contentious issues surround this subject and the ISAT trial should resolve many of these. Modern developments alongside evidence-based practice should hopefully optimise results.

Algorithms↗

Early surgery versus initial conservative treatment in patients with spontaneous supratentorial intracerebral haematomas in the International Surgical Trial in Intracerebral Haemorrhage (STICH): a randomised trial.

BACKGROUND: Spontaneous supratentorial intracerebral haemorrhage accounts for 20% of all stroke-related sudden neurological deficits, has the highest morbidity and mortality of all stroke, and the role of surgery remains controversial. We undertook a prospective randomised trial to compare early surgery with initial conservative treatment for patients with intracerebral haemorrhage. METHODS: A parallel-group trial design was used. Early surgery combined haematoma evacuation (within 24 h of randomisation) with medical treatment. Initial conservative treatment used medical treatment, although later evacuation was allowed if necessary. We used the eight-point Glasgow outcome scale obtained by postal questionnaires sent directly to patients at 6 months follow-up as the primary outcome measure. We divided the patients into good and poor prognosis groups on the basis of their clinical status at randomisation. For the good prognosis group, a favourable outcome was defined as good recovery or moderate disability on the Glasgow outcome scale. For the poor prognosis group, a favourable outcome also included the upper level of severe disability. Analysis was by intention to treat. FINDINGS: 1033 patients from 83 centres in 27 countries were randomised to early surgery (503) or initial conservative treatment (530). At 6 months, 51 patients were lost to follow-up, and 17 were alive with unknown status. Of 468 patients randomised to early surgery, 122 (26%) had a favourable outcome compared with 118 (24%) of 496 randomised to initial conservative treatment (odds ratio 0.89 [95% CI 0.66-1.19], p=0.414); absolute benefit 2.3% (-3.2 to 7.7), relative benefit 10% (-13 to 33). INTERPRETATION: Patients with spontaneous supratentorial intracerebral haemorrhage in neurosurgical units show no overall benefit from early surgery when compared with initial conservative treatment.

Aged↗