Urgent referral for suspected CNS cancer: which clinical features are associated with a positive predictive value of 3 % or more?

Background Urgent referral for suspected central nervous system (CNS) cancer is recommended, but little analysis of the referral criteria diagnostic performance has been conducted. New 2015 NICE guidance recommends direct brain imaging for patients with symptoms with positive predictive values (PPV) of 3 %, but further guidance is needed. Methods A 12-month retrospective evaluation of 393 patients referred under previous 2005 NICE 2-week rule criteria was conducted. Analysis was based on the three groups of symptoms forming the referral criteria, (1) CNS symptoms, (2) recent onset headaches, (3) rapidly progressive subacute focal deficit/cognitive/behavioural/personality change. Comparison was made with neuroimaging findings. Results Twelve (3.1 %) of 383 patients who attended clinic had CNS cancer suggesting the combination of clinical judgement and application of 2005 criteria matched the 2015 guideline’s PPV threshold. PPVs for the three groups of symptoms were (1) 4.1 % (95 % CIs 2.0 to 7.4 %), (2) 1.2 % (0.1 to 4.3 %) and (3) 3.7 % (0.1 to 19.0 %). Sensitivities were (1) 83.3 % (95 % CIs 51.6 to 97.9 %), (2) 16.7 % (2.1 to 48.4 %), and (3) 8.3 % (0.2 to 38.5 %); specificities were (1) 37.2 % (32.3 to 42.3 %), (2) 55.5 % (50.3 to 60.7 %) and (3) 93.0 % (89.9 to 95.4 %). Of 288 patients who underwent neuroimaging, 59 (20.5 %) had incidental findings, most commonly cerebrovascular disease. Conclusions The 2015 guidance is less prescriptive than previous criteria making clinical judgement more important. CNS symptoms had greatest sensitivity, while PPVs for CNS symptoms and rapidly progressive subacute deficit/cognitive/behavioural/personality change were closest to 3 %. Recent onset headaches had the lowest sensitivity and PPV

Pediatric Moyamoya Disease and Syndrome in Italy: A Multicenter Cohort

Background: Moyamoya is a rare progressive cerebral arteriopathy, occurring as an isolated phenomenon (moyamoya disease, MMD) or associated with other conditions (moyamoya syndrome, MMS), responsible for 6–10% of all childhood strokes and transient ischemic attacks (TIAs). Methods: We conducted a retrospective multicenter study on pediatric-onset MMD/MMS in Italy in order to characterize disease presentation, course, management, neuroradiology, and outcome in a European country. Results: A total of 65 patients (34/65 women) with MMD (27/65) or MMS (38/65) were included. About 18% (12/65) of patients were asymptomatic and diagnosed incidentally during investigations performed for an underlying condition (incMMS), whereas 82% (53/65) of patients with MMD or MMS were diagnosed due to the presence of neurological symptoms (symptMMD/MMS). Of these latter, before diagnosis, 66% (43/65) of patients suffered from cerebrovascular events with or without other manifestations (ischemic stroke 42%, 27/65; TIA 32%, 21/65; and no hemorrhagic strokes), 18% (12/65) of them reported headache (in 4/12 headache was not associated with any other manifestation), and 26% (17/65) of them experienced multiple phenotypes (≥2 among: stroke/TIA/seizures/headache/others). Neuroradiology disclosed ≥1 ischemic lesion in 67% (39/58) of patients and posterior circulation involvement in 51% (30/58) of them. About 73% (47/64) of patients underwent surgery, and 69% (45/65) of them received aspirin, but after diagnosis, further stroke events occurred in 20% (12/61) of them, including operated patients (11%, 5/47). Between symptom onset and last follow-up, the overall patient/year incidence of stroke was 10.26% (IC 95% 7.58–13.88%). At last follow-up (median 4 years after diagnosis, range 0.5–15), 43% (26/61) of patients had motor deficits, 31% (19/61) of them had intellectual disability, 13% (8/61) of them had epilepsy, 11% (7/61) of them had behavioral problems, and 25% (13/52) of them had mRS > 2. The proportion of final mRS > 2 was significantly higher in patients with symptMMD/MMS than in patients with incMMS (p = 0.021). Onset age <4 years and stroke before diagnosis were significantly associated with increased risk of intellectual disability (p = 0.0010 and p = 0.0071, respectively) and mRS > 2 at follow-up (p = 0.0106 and p = 0.0009, respectively). Conclusions: Moyamoya is a severe condition that may affect young children and frequently cause cerebrovascular events throughout the disease course, but may also manifest with multiple and non-cerebrovascular clinical phenotypes including headache (isolated or associated with other manifestations), seizures, and movement disorder. Younger onset age and stroke before diagnosis may associate with increased risk of worse outcome (final mRS > 2)

Shc3 affects human high-grade astrocytomas survival

A selective switch from expression of Shc1 gene to Shc3 occurs with maturation of neuronal precursors into postmitotic neurons. Previous studies showed that in the embryo, Shc1 is maximally expressed in dividing CNS stem cells while it is silenced in mature neurons, where it is replaced by Shc3. Under normal conditions Shc3 is never expressed by glial cells. We now show that in human astrocytomas and glioblastomas, the normal pattern of expression of Shc1/Shc3 is totally subverted, both proteins being present at the same time and in the same cells. Our data indicate that Shc3 is maximally expressed, together with Shc1, in glioblastoma, a highly proliferative tumor with little, if any, indication of neuronal differentiation. In primary cultures of glioblastoma, tumor cells maintain Shc1 expression but downregulate Shc3. Analysis of the phosphorylation status of Shc3 in human glioblastoma tumor samples in vivo indicates that it is tyrosine phosphorylated. Finally, we found that the expression of truncated variants of Shc3 with dominant-negative effects in human high-grade glioma cells that maintain Shc3 expression in vitro leads to a decreased Akt posphorylation and increased apoptosis, thus resulting in impaired survival of the transfected cells. These data suggest that Shc molecules play an important role in glioblastoma cell growth and survival

APOE influences vasospasm and cognition of noncomatose patients with subarachnoid hemorrhage

OBJECTIVE: To determine the influence of the APOE genotype on functional and cognitive outcome and on the incidence and prognosis of clinical vasospasm (delayed ischemic neurologic deficit [DIND]) in noncomatose patients with aneurysmal subarachnoid hemorrhage (SAH). METHODS: The authors reviewed the data of patients admitted for SAH to the Neurosurgical Departments of the San Gerardo Hospital of Monza (January 1996 to December 2001) and the Ospedali Riuniti of Bergamo (January 2002 to September 2003). The authors considered only noncomatose patients and evaluated outcome by means of the Rankin Disability Index and the Mini-Mental State Examination at least 6 months after the SAH. Statistical analysis: Uni- and multivariate logistic regression. RESULTS: The authors included 101 patients. They found the epsilon4 allele in 26 patients (25.7%). The presence of the epsilon4 allele negatively affected the overall outcome (functional morbidity or cognitive morbidity, or both) (p = 0.0087) and, particularly, cognitive morbidity (p = 0.0028). Those with an epsilon4 allele had delayed ischemic neurologic deficit DINDs more frequently (p = 0.024) and, in the presence of DIND, they were more likely to show permanent neurologic deficits (p = 0.0051). CONCLUSIONS: ApoE4 negatively affects cognitive morbidity and delayed ischemic neurologic deficit recovery. The presence of an epsilon4 allele increases the risk of delayed ischemic neurologic deficit

Mortality and morbidity in patients operated on for ruptured intracranial aneurysms

It is generally agreed, mortality and morbidity rates, in patients operated on for ruptured intracranial aneurysm, strictly depend upon the state at admission. Nevertheless, a precise definition of surgical mortality is still not available. Even the term morbidity still remains rather controversial for the lack of accurate evaluation scales. The wide range of parameters, affecting the composition of sample and outcome of patients, such as age, blood at CT scan and atherosclerosis at angiography, makes harder a correct statistical analysis of mortality and morbidity. Moreover, the gap between bleeding and admission, the management and choice of treatment, the selection of unicentric or multicentric studies, the level of the hospital introduce even more striking bias errors. Recent papers reported concrete improvements obtained by means of both aggressive therapeutical behaviour and adequate intensive care management. Among factors, producing improvement of the overall outcome, have to be also reported the encouraging preliminary results supplied by the interventional neuroradiological techniques. However, the overall mortality rate of SAH remains high. Thus, a coded scheme for detection and prevention of risk factors significatively associated to mortality and outcome can be only worked out by employing an appropriate therapeutical behaviour and an adequate intensive care management. Furthermore, employment of feasible evaluation scales will be essential to point out the most accurate procedure for management and treatment of patients with intracranial ruptured aneurysm. We think CESE, developed by one of the authors, to be considered as an adequate method for the assessment of results at follow-up

Stenting of atherosclerotic stenoses of the extracranial carotid artery

BACKGROUND: Percutaneous transluminal angioplasty (PTA) and stenting seems to be, at present, the treatment of choice for early restenosis after endarterectomy and for atherosclerotic stenoses of supra-aortic trunks near or at the ostium. In contrast, the role of PTA and stenting for treatment of symptomatic and asymptomatic atherosclerotic stenosis of carotid bifurcation is still debated. METHODS: The present study comprises 27 consecutive cases of atherosclerotic lesions of the carotid bifurcation treated with PTA and stenting. All patients were symptomatic, except for 2 suffering from asymptomatic stenosis with contralateral carotid occlusion. There were 23 stenoses occluding 70% or more of the lumen according to the NASCET criteria and 4 mild stenoses (50-60% of the lumen) with large type C ulcers. Criteria for exclusion from surgery in these cases were aged >79 years, previous neck surgery for laryngeal cancer, carotid bifurcation at C2, association with intracranial aneurysms, occlusion of the contralateral carotid artery, and heart, lung and kidney diseases. All procedures were performed under local anaesthesia associated with mild sedation in a few cases. In all cases, self-expandable stents (Wallstent) were used. Follow-up ranged from 6 to 37 months. FINDINGS: Transient neurological deficit occurred in 3 cases (11%). One case (3.7%) experienced a minor stroke at three months. Asymptomatic tight restenosis due to intimal hyperplasia occurred in one case (3.7%). In 8 cases (40%) of complex stenosis involving common and internal carotid arteries there was some loss of contact of the stent with the wall of the common carotid artery in the late follow-up. One case (3.7%) experienced severe and prolonged hypotension and bradycardia during the release of the stent. INTERPRETATION: From literature data and our results it emerges that periprocedural catastrophic embolism is unlikely to occur. The best results are undoubtedly obtained when treating stenosis limited to the internal carotid artery. Nevertheless, the ideal stent to treat vessels of different calibre, as occurs at the carotid bifurcation, is not yet available. The problem of periprocedural cerebral protection has not been resolved. Reported series are heterogeneous and retrospective, and an adequate follow-up of cases is still lacking