Prediction of 60 day case-fatality after aneurysmal subarachnoid haemorrhage: results from the International Subarachnoid Aneurysm Trial (ISAT).

Aneurysmal subarachnoid haemorrhage (aSAH) is a devastating event with substantial case-fatality. Our purpose was to examine which clinical and neuro-imaging characteristics, available on admission, predict 60 day case-fatality in aSAH and to evaluate performance of our prediction model. We performed a secondary analysis of patients enrolled in the International Subarachnoid Aneurysm Trial (ISAT), a randomised multicentre trial to compare coiling with clipping in aSAH patients. Multivariable logistic regression analysis was used to develop a prognostic model to estimate the risk of dying within 60 days from aSAH based on clinical and neuro-imaging characteristics. The model was internally validated with bootstrapping techniques. The study population comprised of 2,128 patients who had been randomised to either endovascular coiling or neurosurgical clipping. In this population 153 patients (7.2%) died within 60 days. World Federation of Neurosurgical Societies (WFNS) grade was the most important predictor of case-fatality, followed by age, lumen size of the aneurysm and Fisher grade. The model discriminated reasonably between those who died within 60 days and those who survived (c statistic = 0.73), with minor optimism according to bootstrap re-sampling (optimism corrected c statistic = 0.70). Several strong predictors are available to predict 60 day case-fatality in aSAH patients who survived the early stage up till a treatment decision; after external validation these predictors could eventually be used in clinical decision making.

Unruptured intracranial aneurysms: their illusive natural history and why subgroup statistics cannot provide normative criteria for clinical decisions or selection criteria for a randomized trial.

There is currently no evidence that treatment of unruptured aneurysms is beneficial. Confronted with the uncertainty, many clinicians are attracted by an individual calculus of risks using numbers extracted from subgroup statistics of observational studies or natural history data. The so-called natural history of unruptured aneurysms refers to a purely man-made ratio of events divided by the number of untreated patients identified by imaging, a ratio heavily influenced by referral patterns and arbitrary clinical decisions. Available studies lacked prespecified hypotheses, exposing all analyses to sampling error and bias, and sample sizes were too small to provide reliable subgroup statistics. Far from being "natural kinds" of aneurysms, subgroups were post-hoc creations. Resulting data-driven statistics can only be exploratory, the error too uncontrollable to serve for clinical decisions. A randomized trial is in order, but selection according to fixed size criteria is ill-advised, given the imprecision of imaging, the influence of other factors such as location, previous history, multiplicity of lesions, risks of treatment, age and the danger of arbitrarily excluding from a long trial a large segment of the population with aneurysms for whom the research question is most pertinent.

Change in incidence and aetiology of intracerebral haemorrhage in Oxfordshire, UK, between 1981 and 2006: a population-based study.

BACKGROUND: UK stroke mortality data suggest that the incidence of haemorrhagic stroke has fallen in the past 20 years, but these data do not include deaths of individuals aged 75 years or over. Trends in the older population might differ, since cause varies with age. Our aim was to investigate changes in the population-based incidence of intracerebral haemorrhage according to age and likely aetiology. METHODS: We used data from the Oxford Community Stroke Project (OCSP; 1981-86) and the Oxford Vascular Study (OXVASC; 2002-06) to investigate changes in the incidence of intracerebral haemorrhage with time, above and below age 75 years, together with associated risk factors and premorbid medications. Incidences were standardised to the 2001 census population of England and Wales. FINDINGS: In the population aged under 75 years the incidence of intracerebral haemorrhage decreased substantially (rate ratio 0.53, 95% CI 0.29-0.95; p=0.03), but the number of cases of intracerebral haemorrhage at all ages were similar in OXVASC and OCSP (52 vs 55 cases) as the proportion of cases occurring at 75 years and over tended to increase (2.0, 0.8-4.6; p=0.09). The incidence of intracerebral haemorrhage associated with premorbid hypertension (blood pressure >or=160/100 mm Hg) fell overall (0.37, 0.20-0.69; p=0.002), but the incidence of intracerebral haemorrhage associated with antithrombotic use was increased (7.4, 1.7-32; p=0.007). Above age 75 years the proportion of cases who were non-hypertensive with lobar bleeds and presumed to have had mainly amyloid-related haemorrhages, also increased (4.0, 1.1-17; p=0.003). INTERPRETATION: There has been a substantial fall in hypertension-associated intracerebral haemorrhage over the past 25 years, but not in the overall number of cases of intracerebral haemorrhage in older age-groups, in part due to a rise in intracerebral haemorrhage associated with antithrombotic use. These trends, along with the expected increase in prevalence of amyloid angiopathy with the ageing population, suggest that, in contrast to projections based on mortality data below age 75 years, absolute number of cases of intracerebral haemorrhage might increase in future.

Trial on endovascular treatment of unruptured aneurysms (TEAM): study monitoring and rationale for trial interruption or continuation.

Preventive treatment of unruptured intracranial aneurysms is often performed but has never been proved beneficial as compared to conservative management. In a context of uncertainty, the 'best treatment' that can be offered to each individual is a chance to be treated and thus to be protected from rupture of the aneurysm, and an equal chance not to be treated, and hence to be exempted from possible immediate complications, using randomization. Such action is optimal unless or until an independent committee with privileged access to data judges that, given the comparative outcome of the 2 groups, preventive treatment or conservative management, is generally warranted. Potential reasons to interrupt such a study are reviewed, including insufficient recruitment, poor compliance, excessive cross-overs, unacceptable iatrogenia, and treatments being convincingly different or equivalent. We conclude that insufficient recruitment is the sole realistic event that could lead to premature interruption. This review may provide a deeper understanding of the principles justifying the necessity of the study.

The usefulness of tyrosinase in the immunohistochemical assessment of melanocytic lesions: a comparison of the novel T311 antibody (anti-tyrosinase) with S-100, HMB45, and A103 (anti-melan-A).

AIM: To compare the sensitivity and staining pattern of the new immunohistochemical antibody to tyrosinase (T311) with S-100, HMB45, and the recently evaluated antibody to melan-A (A103) in a range of melanocytic lesions. METHOD: Archival, formalin fixed, paraffin wax embedded sections from 50 benign and malignant melanocytic lesions were stained immunohistochemically with anti-tyrosinase, A103, S-100, and HMB45. They were scored semiquantitatively for the distribution and intensity of staining. RESULTS: All melanomas, with the exception of desmoplastic melanoma, showed some staining with all four antibodies. Overall, T311 and A103 showed an intermediate sensitivity compared with that of S-100 and HMB45. T311 stained most benign and malignant lesions strongly and diffusely with minimal background staining. Immunoreactivity was found to be patchy in some naevi, with weak or absent staining of the mature melanocytes. A103 showed strong and diffuse staining of all benign lesions and most melanomas with minimal background staining. S-100 was the most sensitive, with diffuse staining of most lesions, including desmoplastic and metastatic melanoma, but lacked specificity. HMB45 was the least sensitive antibody, frequently demonstrating patchy staining with absent staining in some benign naevi. CONCLUSIONS: S-100 remains the most sensitive marker of melanocytes. However, because of its lack of specificity, it should be used with at least one other more specific antibody. HMB45 is more specific, but lacks sensitivity; T311 is a reliable marker of melanocytes in paraffin wax embedded sections and is worth consideration for use in a staining panel, although it shows no additional benefit over A103.

Mucopolysaccharidosis type VII associated with hydrops fetalis: histopathological and ultrastructural features with genetic implications.

A case of mucopolysaccharidosis type VII (MPS VII, beta glucuronidase deficiency) causing fatal hydrops fetalis in the third trimester is presented. The diagnosis was suspected on histopathological examination by the presence of foam cells in many of the viscera and foamy change in the placental Hofbauer cells. Electron microscopy showed empty cytoplasmic inclusion bodies within macrophages and in the Hofbauer cells. Enzyme assay of cultured fibroblasts showed markedly deficient beta glucuronidase activity, thus confirming the diagnosis. A detailed and thorough histopathological examination of hydrops fetalis cases is important to detect subtle features of inherited metabolic disorders. Use of a structured necropsy protocol is recommended for cases of non-immune hydrops. Electron microscopy is a useful adjunct to light microscopy in cases where an inherited metabolic disorder is suspected. Precise necropsy diagnosis is important as there are implications for genetic counselling and possible prenatal diagnosis in subsequent pregnancies.

Thrombosis in giant basilar tip aneurysms during coil embolization.

Two patients with giant basilar tip aneurysms underwent coil embolization, one with both platinum fiber and platinum Guglielmi detachable coils and the other with Guglielmi detachable coils only. In both cases, spontaneous intraaneurysmal thrombosis occurred outside the coil mass, presumably a result of disruption of the intraaneurysmal flow pattern.

Factors influencing successful angiographic occlusion of aneurysms treated by coil embolization.

BACKGROUND AND PURPOSE: Coil embolization of berry aneurysms is a relatively new treatment whose long-term efficacy has yet to be established. The purpose of this study was, first, to attempt to identify factors that might be important in predicting success both at the time of treatment and at the time of follow-up angiography, and, second, to study changes in the aneurysm between treatment and follow-up to determine the frequency of these changes. METHODS: The pretreatment, posttreatment, and follow-up angiograms of the first 63 aneurysms (in 58 patients) treated at our institution between June 1992 and April 1995 were analyzed, and the percentage of occlusion of each aneurysm was calculated. The size of any rest was noted for the posttreatment and follow-up angiograms. Treatment success was defined as a residue of less than 2 mm. Aneurysms were said to have changed if the percentage of occlusion had altered by more than 2.5% or if the difference in rest size was greater than 0.25 mm. Possible factors influencing primary and follow-up success rates were correlated against these calculations. RESULTS: Success rates at treatment and follow-up were 71% and 65%, respectively. No change occurred in 41% of aneurysms, and 20% had a decrease in size of the residue. Twenty-eight percent had coil compaction, and 11% had aneurysmal growth. Neck size was the only significant variable in primary treatment success. Success at follow-up correlated significantly with neck size, initial treatment success, vasospasm at the time of treatment, and clinical presentation. CONCLUSION: Best long-term angiographic results are obtained when the primary treatment is successful, when the aneurysm is small and narrow-necked, when the acutely ruptured aneurysm is treated within 15 days of ictus, and with anterior communicating and basilar-tip aneurysms.

Selective amygdalohippocampectomy for hippocampal sclerosis: postoperative MR appearance.

PURPOSE: To analyze the anatomic consequences of selective amygdalohippocampectomy (AH) in patients with hippocampal sclerosis and to correlate the clinical outcome with the MR appearance. METHODS: Seventeen patients were examined with clinical and neuropsychologic examination and cranial MR after AH (7 transcortical AH, 10 trans-Sylvian AH). The clinical and neuropsychologic outcomes after AH were compared with those of anterior lobectomy (ATL). RESULTS: There was no significant difference in seizure cure between transcortical or trans-Sylvian AH and ATL. However, patients with left AH fared significantly better in terms of verbal IQ and nonverbal memory when compared with those with left ATL. Verbal memory and cognition were not significantly different in the two AH groups. Variable amounts of hippocampal and amygdala remnants were found in both AH groups and did not correlate with seizure cure. White matter change consistent with gliosis probably secondary to wallerian degeneration was demonstrated in the anterior temporal lobe to a mean distance of 4.5 cm after transcortical AH and to a lesser degree as a consequence of trans-Sylvian AH. Nine patients (53%) (4 transcortical All, 5 trans-Sylvian AH) demonstrated wallerian degeneration in the optic radiations after surgery. All had incomplete contralateral quadrantanopia. CONCLUSIONS: There is more secondary damage to the temporal lobe after AH than was previously recognized. The extent of hippocampal and amygdala resection in AH do not seem to be directly related to seizure cure. Visual field defects are common in AH because of the anterior but variable course of the optic radiations

Effects of timing of coil embolization after aneurysmal subarachnoid hemorrhage on procedural morbidity and outcomes.

OBJECTIVE: To elucidate the effect of treatment timing on procedural clinical outcomes after aneurysmal subarachnoid hemorrhage (SAH) for patients treated by endosaccular coil embolization. METHODS: A group of 327 patients who were consecutively treated, during a 46-month period, for ruptured intracranial aneurysms by coil embolization within 30 days after SAH were evaluated. Outcomes were assessed by comparing immediate pretreatment World Federation of Neurological Surgeons (WFNS) grades, 72-hour posttreatment WFNS grades, and modified Glasgow Outcome Scale scores at 6 months for patients treated within 48 hours (Group 1), 3 to 10 days (Group 2), or 11 to 30 days (Group 3) after SAH. RESULTS: The three interval-to-treatment groups included 33, 38, and 29% of the patients, respectively. Before treatment, 70% of the patients in Group 1, 78% of those in Group 2, and 83% of those in Group 3 were in good clinical grades (i.e., WFNS Grade 1 or 2). After coil embolization, the WFNS grades were either unchanged or improved for 93.5% of the patients in Group 1, 89.5% of those in Group 2, and 91.5% of those in Group 3. After 6 months, 81.3% of the patients in Group 1 experienced good outcomes (modified Glasgow Outcome Scale scores of 1 or 2), as did 84% of those in Group 2 and 80% of those in Group 3. No statistical difference was demonstrated between the three groups when they were compared for these two variables. CONCLUSION: The interval between endovascular treatment and SAH did not affect periprocedural morbidity rates or 6-month outcomes. Coil embolization should therefore be performed as early as possible after aneurysmal SAH, to prevent aneurysmal rerupture.

Embolization of spinal cord arteriovenous malformations with an ethylene vinyl alcohol copolymer dissolved in dimethyl sulfoxide (Onyx liquid embolic system). Report of two cases.

In this paper the authors describe the first use of a new liquid embolic agent (Onyx) to treat spinal cord arteriovenous malformations (AVMs). Because its properties make it more predictable to use than currently available liquid agents, the authors believe that this material has great potential in the endovascular management of both spinal cord and brain AVMs. This very promising agent merits further clinical study.

Histological findings in giant aneurysms treated with Guglielmi detachable coils. Report of two cases with autopsy correlation.

The authors report the pathological and histological findings in two patients with giant partially thrombosed aneurysms who were treated by means of Guglielmi detachable coils with subtotal occlusion of the aneurysms. Autopsies of these patients were performed 2 and 6 months after endovascular treatment. The histological findings revealed coils embedded in largely unorganized thrombus in the aneurysms; there was no clear reduction in size of the aneurysms over the period. There was no evidence of endothelialization of the aneurysm neck demonstrated in either case. The significance of these findings is discussed.

Five-year experience in using coil embolization for ruptured intracranial aneurysms: outcomes and incidence of late rebleeding.

OBJECT: During a 5-year period 317 patients presenting with aneurysmal subarachnoid hemorrhage were successfully treated by coil embolization within 30 days of hemorrhage. The authors followed patients to assess the stability of aneurysm occlusion and its longer-term efficacy in protecting patients against rebleeding. METHODS: Patients were followed for 6 to 65 months (median 22.3 months) by clinical review, angiography performed at 6 months posttreatment, and annual questionnaires. Stable angiographic occlusion was evident in 86.4% of small and 85.2% of large aneurysms with recurrent filling in 38 (14.7%) of 259 aneurysms. Rebleeding was caused by aneurysm recurrence in four patients (between 11 and 35 months posttreatment) and by rupture of a coincidental untreated aneurysm in one patient. Annual rebleeding rates were 0.8% in the 1st year, 0.6% in the 2nd year, and 2.4% in the 3rd year after aneurysm embolization, with no rebleeding in subsequent years. Rebleeding occurred in three (7.9%) of 38 recurrent aneurysms and in one (0.4%) of 221 aneurysms that appeared stable on angiography. CONCLUSIONS: Periodic follow-up angiography after coil embolization is recommended to identify aneurysm recurrence and those patients at a high risk of late rebleeding.

A randomized blind trial of Iopamidol and meglumine calcium metrizoate (Triosil 280, Isopaque Cerebral) in cerebral angiography.

A randomized blind trial of iopamidol and meglumine calcium metrizoate (Triosil 280, Isopaque Cerebral) for cerebral angiography was performed in 20 patients. The Iopamidol was better tolerated and caused significantly less discomfort in patients than metrizoate. There was no difference in the quality of the radiographs. A further 13 patients also received Iopamidol for cerebral angiography with similar results. No adverse effects were observed in any of the patients. Our evidence suggests that Iopamidol has significant advantages over currently available contrast media for cerebral angiography.

A comparative trial of sodium meglumine ioxaglate (Hexabrix) and iopamidol (Niopam) for cerebral angiography.

We have carried out a randomized blind trial comparing iopamidol (Niopam) and sodium meglumine ioxaglate (Hexabrix) in cerebral angiography in 50 patients. There was no significant difference in the degree of pain or movement produced by the contrast media. The degree of heat felt was slightly greater with iopamidol than with ioxaglate. Both were very well tolerated by patients, producing only a mild or moderate sensation of heat, and in only a few instances slight pain during the injections. No difference in radiographic quality was observed. We conclude that both media are a significant advance over the conventional ionic media and the choice between them will be determined by factors of neurotoxicity, ease of use and cost.

An investigation into the deposition of inhalation aerosol particles as a function of air flow rate in a modified 'Kirk Lung'.

The effect of air flow rate on the deposition of inhalation aerosol particles in a modified 'Kirk Lung' has been studied. Two commercial products were used. The amount depositied in the mouthpiece and throat regions decreases with increasing flow rate. The amount in the collector rises to maximum of approximately 50%. This material represents the therapeutically available portion. Such an apparatus would be useful for routine quality control of the size distribution ratios for inhalation aerosol particles.

Atypical carcinoid tumour of the larynx.

The case of an atypical carcinoid tumour of the larynx is described in a 65-year-old man. This rare tumour may present diagnostic difficulties, but the diagnosis should be considered in a patient presenting with symptoms of local or referred pain and an apparently small, non-ulcerating supraglottic tumour. Immunocytochemistry has an important role in establishing the diagnosis. A very unusual feature of this case was positive staining for S-100 protein by sustentacular cells. Atypical carcinoid tumours do not respond well to radiotherapy so the primary treatment should be surgical resection.

Differences in the angiographic evaluation of coiled cerebral aneurysms between a core laboratory reader and operators: results of the Cerecyte Coil Trial.

BACKGROUND AND PURPOSE: Independent evaluation of angiographic images is becoming widely applied in the assessment of treatment outcomes of cerebral aneurysms. In the current study, we assessed the agreement between an independent core laboratory and the operators regarding angiographic appearance in a recent randomized, controlled trial. MATERIALS AND METHODS: Data were derived from the Cerecyte Coil Trial. Angiographic images of each coiled aneurysm, taken immediately after embolization and at 5- to 7-month follow-up, were evaluated by the operator at the treating center and by an independent neuroradiologist at the core laboratory. For the purpose of this study, images were interpreted on a 3-point scale to provide uniformity for analysis; grade 1: complete occlusion, grade 2: neck remnant; and grade 3: sac filling. "Unfavorable angiographic appearance" was defined as grade 3 at follow-up or interval worsening of grade between the 2 time points. RESULTS: The study included 434 aneurysms. Immediately after embolization, grade 3 was reported by operators in 39 (9%) compared with 52 (12%) by the core laboratory (P = .159). On follow-up, grade 3 was reported by operators in 44 (10%) compared with 81 (19%) by the core laboratory (P < .0001). Overall, operators noted unfavorable angiographic appearance in 78 (18%) compared with 134 (31%) by the core laboratory (P < .0001). At every time point, agreement between the core laboratory and the operators was slight. CONCLUSIONS: Unfavorable angiographic appearance was noted almost twice as frequently by an independent core laboratory as compared with the operators. Planning of trials and interpretation of published studies should be done with careful attention to the mode of angiographic appearance interpretation.

Endovascular treatment of 300 consecutive middle cerebral artery aneurysms: clinical and radiologic outcomes.

BACKGROUND AND PURPOSE: There is controversy as to the best mode of treating MCA aneurysms. We report the results of a large endovascular series of patients treated at our center. MATERIALS AND METHODS: This study was a retrospective analysis of a prospectively acquired data base. All patients with saccular MCA aneurysms treated between November 1996 and June 2012 were included. World Federation of Neurosurgical Societies grade, aneurysm site, size, and aneurysm neck size were recorded, along with clinical outcome assessed with the Glasgow Outcome Scale and radiographic occlusion assessed with the Raymond classification at 6 months and 2.5 years. RESULTS: A total of 295 patients with 300 MCA aneurysms were treated including 244 ruptured aneurysms (80.7%). The technical failure rate was 4.3% (13 patients). Complete occlusion or neck remnant was achieved in 264 (91.4%). Complications included rupture in 15 patients (5%), thromboembolism in 17 patients (5.7%), and early rebleeding in 3 patients (1%). Overall permanent procedural-related morbidity and mortality were seen in 12 patients (7.8%). Of the ruptured aneurysms, 189 (79.4%) had a favorable clinical outcome (Glasgow Outcome Scale score, 4-5). A total of 33 patients (13.6%) died. On initial angiographic follow-up, aneurysm remnant was seen in 18 aneurysms (8.1%). A total of 13 patients (4.3%) were re-treated. CONCLUSIONS: Our experience demonstrates that endovascular treatment of MCA aneurysms has an acceptable safety profile with low rates of technical failure and re-treatment. Therefore, coiling is acceptable as the primary treatment of MCA aneurysms.

Effects of circle of Willis anatomic variations on angiographic and clinical outcomes of coiled anterior communicating artery aneurysms.

BACKGROUND AND PURPOSE: Anterior communicating artery aneurysms account for one-fourth of all intracranial aneurysms and frequently occur in the context of A1 vessel asymmetry. The purpose of this study was to correlate circle of Willis anatomic variation association to angiographic and clinical outcomes of anterior communicating aneurysm coiling. MATERIALS AND METHODS: The Cerecyte Coil Trial provides a subgroup of 124 cases with anterior communicating artery aneurysms after endovascular coiling. One hundred seventeen of 124 anterior communicating artery aneurysms had complete imaging and follow-up for clinical outcome analysis, stability of aneurysm coil packing, and follow-up imaging between 5 and 7 months after treatment. Clinical outcomes were assessed by the mRS at 6 months. RESULTS: Anterior cerebral artery trunk-dominance was seen in 91 of 124 (73%) anterior communicating artery aneurysms and codominance in 33 of 124 (27%) anterior communicating artery aneurysms. There was no significant difference (P > .5) in treatment success at 5-7 months for anterior communicating artery aneurysms between the anterior cerebral artery trunk-dominant (49 of 86, 57%) and anterior cerebral artery trunk-codominant (19 of 31) groups. Angiographic follow-up demonstrates a statistically significant increase in neck remnants and progressive aneurysm sac filling with the A1 dominant configuration (n = 21, 24% at follow-up versus n = 11, 12% at immediate posttreatment, P = .035). There was no statistically significant difference in clinical outcomes between types of anterior cerebral artery trunk configuration (P > .5). CONCLUSIONS: Anterior communicating artery aneurysms with anterior cerebral artery trunk-dominant circle of Willis configurations show less angiographic stability at follow-up than those with anterior cerebral artery trunk-codominance similar to other "termination" type aneurysms. This supports the hypothesis that anterior cerebral artery trunk-dominant flow contributes to aneurysm formation, growth, and instability after coiling treatment.