Significance of apolipoprotein E in subarachnoid hemorrhage: neuronal injury, repair, and therapeutic perspectives--a review.

Subarachnoid hemorrhage (SAH) strikes individuals at a young age with devastating neurologic consequences. Classic formulations that correlate complications and outcome with clinical variables do not explain all the heterogeneity that is usually found in clinical practice. The role of genetic predisposition has recently been investigated. Particular attention has been paid to the apolipoprotein E (APOE) genotype that encodes for a polymorphic protein existing as 3 isoforms (apoE2, apoE3, apoE4), products of alleles E2, E3, and E4 at a single gene locus. ApoE is produced by astrocytes and exerts complex neuroprotective functions that make it a hub of the biochemical network of SAH. The neuroprotective effectiveness of the apoE4 isoform is reduced with respect to the others and this has made the E4 allele a risk factor candidate. Recently published observational studies and meta-analyses suggested that the APOE genotype may strongly improve the usual predictive model with the possibility of optimizing clinical decisions according to the individual's needs. Furthermore, the clinical results, together with new biological insights, suggest that SAH may be a possible candidate for the ongoing research on apoE-based neuroprotective therapy. This article reviews the clinical studies, analyzes their methodology, and surveys the biological links between the physiopathology of SAH and apoE and the possible prospects.

Angioplasty and stenting of the cervical carotid bifurcation under filter protection: a prospective study in a series of 53 patients.

The aim of this study is to assess safety, reliability, ease of use and usefulness of filter protection devices during angioplasty and stenting of stenotic lesions of the cervical carotid bifurcation. Over a period of 42 months, 53 patients harboring a cervical carotid bifurcation stenotic lesion were treated, by angioplasty and/or stenting using filter protection devices of different kinds. The stenosis was atherosclerotic in 48 cases, post-surgical in four and post-radiation in one case. In all cases, the treatment was successful, with good restoration of the luminal diameter. There were three major strokes (5.6%) and one minor stroke (1.9%). Two of these (one major, one minor) occurred a few hours after the stenting procedure and both seemed by all evidence due to a hemorrhagic hyperperfusion syndrome. One hemiparesis and dysphasia occurred two days after the procedure, secondary to subacute thrombosis with occlusion of the stent. One patient complained of three episodes of decrease in visual acuity of the eye ipsilateral to the stenting in the two weeks following treatment. In conclusion, in our experience, use of the devices adds only few minutes to the procedure time; direct lesions of the arterial wall, such as dissections or intraluminal thrombi, related to the use of filters were never observed, and spasm of the distal I.C.A. also proved rapidly regressive. The content of all filters, if any, was histologically examined, but plaque material was found only in one case, probably owing to our primary stenting technique without use of pre-dilation. The major technical drawback is in-filter coagulation, which occurred in 16 cases, occluding the membrane of the filter and thus slowing or blocking intracranial flow. Such an event can be counteracted by a more aggressive anti-coagulation protocol, which could, however, be responsible for the two complications with hemorrhagic brain infarction. Furthermore, we observed two other major neurological events, which bring the incidence of neurological complications in this series as high as 7.5%. Therefore, it is our opinion that safety of filters is not yet proven, and consequently great care must be taken in their use.

Microsurgical technique in the treatment of vascular compression of cranial nerves in the posterior fossa.

The authors report on 2 cases: cerebello-pontine syndrome and a trigeminal neuralgia with homolateral facial spasm. In both patients the clinical syndrome was thought to be of vascular origin and the vessels accompanying the nerves showed to be tightly anchored to them by means of arachnoid bridges. Microsurgery allowed for performing section of the arachnoid bridges in order to prevent the nerves from the continuous microtrauma due to the vascular pulsation, this being the pathogenic mechanism responsible for the suffering of the nerves themselves.

Critical evaluation of commissural myelotomy in the treatment of intractable pain.

The Authors describe 6 cases of commissural myelotomy performed on patients suffering from malignant neoplasms at the Neurosurgical Department of Bergamo. A review of all cases reported in the literature has been documented by clinical data supported by anatomophysiological considerations.

[Surgery of the base of the skull]. / La chirurgia della base del cranio.

This is a review of the current status of the surgery of the skull base with special reference to the otolaryngological districts. The main topics are as follow: classification of pathology review of the clinical and surgical anatomy clinical and neuroradiological diagnosis surgical management of the pathology in the occipito-temporal area and in the rhinobase principles of management and operative approaches to the skull base in Neurosurgery principles of management and operative approaches to the skull base in Maxillo-Facial Surgery.

Hearing preservation surgery in acoustic neuroma. Slow progress and new strategies.

Quality and rate of preserved hearing are crucial to make hearing preservation surgery a viable treatment. A long-term experience with hearing preservation surgery, with tumour size and hearing as admission criteria, was evaluated to assess which size and hearing allowed a high rate of success. The hearing outcome in relation to size of tumour and pre-operative hearing was retrospectively reviewed in a consecutive series of 115 cases of sporadic acoustic neuroma which were operated on with hearing preservation surgery. Inclusion criteria were hearing with ≤ 30 dB pure tone average and ≥ 70% Speech Discrimination Score. The size was ≤ 15 mm in the first series of 51 cases, and ≤ 10 mm in the second series of 64 cases. Pre-operative and post-operative pure tone average were measured at 0.5 to 4.0 KHz, and speech discrimination score at ≤ 40 dB above perception. Post-operative hearing within 30 dB pure tone average and 70% speech discrimination score was considered socially useful hearing and successful outcome. The change to 40 dB pure tone average and 60% speech discrimination score from a pre-operative 30 pure tone average/70% speech discrimination score was considered an acceptable outcome. Patients with a tumour of ≤ 10 mm size in the cerebello-pontine-angle and hearing within 20 dB pure tone average/80% speech discrimination score had a success rate of 76%. Patients with hearing between the 20 dB pure tone average/80% speech discrimination score and 30 dB pure tone average/ 70% speech discrimination score had a success rate of 41%, which increased to 53% if the limit to success was set at 40 dB pure tone average/60% speech discrimination score. Patients with a tumour larger than 10 mm or hearing worse than 30 dB pure tone average/70% speech discrimination score had a poor preservation rate. In conclusion, hearing preservation surgery on a ≤ 10 mm acoustic neuroma with good hearing had a high rate of success and appeared to be a realistic treatment option which could be integrated with observation and radiotherapy in updated guidelines of treatment.

Meta-analysis of APOE genotype and subarachnoid hemorrhage: clinical outcome and delayed ischemia.

BACKGROUND: Emerging evidence suggests that the APOE4 allele may increase the risk of a negative outcome in patients with aneurysmal subarachnoid hemorrhage (SAH), but the results are conflicting. A genetic variable predicting the individual clinical course is currently lacking. OBJECTIVE: To examine the association between the APOE4 allele and a negative outcome. A secondary objective was to investigate the association between the APOE4 allele and delayed ischemia, a major complication of SAH. METHODS: We searched MEDLINE, EMBASE, the Cochrane Library, CINHAL, LILACS, and www.google.it through March 2006. We hand-searched journals, international conference proceedings, and reference lists of retrieved articles. Individual patient data were requested from the corresponding authors of the original articles. Information on study design, participant characteristics, clinical outcome, delayed ischemia, and confounder distribution were independently abstracted by two investigators. RESULTS: We included eight observational studies (696 patients for the clinical outcome and 600 for the delayed ischemia analyses). The corresponding authors of all the retrieved publications but one gave their original data. Summary odds ratios (ORs) were calculated by means of the random-effect model. The risk of a negative outcome (OR = 2.558; 95% CI 1.610 to 4.065) and delayed ischemia (OR = 2.044; 95% CI 1.269 to 3.291) were increased in the E4 carriers. CONCLUSIONS: In patients with subarachnoid hemorrhage, the expression of the E4 allele is associated with a higher risk of a negative outcome and delayed ischemia.

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.

Large demyelinating brain lesion mimicking a herniating tumor.

We describe the case of a large brain lesion whose computed tomography appearance and clinical evolution mimicked a herniating tumor. The patient progressed to coma within 6 days of hospitalization despite high-dose steroid treatment. Emergency excision of the lesion was carried out. Histological analysis showed massive demyelination, axon preservation and no tumor cells. No lesion recurrence was seen during a 55-month follow-up. Recognition of such lesions through magnetic resonance imaging or spectroscopy may spare unnecessary surgery or biopsy. However, our case shows that such lesions may still require resection in the face of a rapid clinical progression and poor response to medical treatment.

[Surgical treatment of fracture-luxations between C3 and C7 vertebrae]. / Trattamento chirurgico delle fratture-lussazioni da C3 a C7.

Between January 1983 and December 1987, 121 patients who sustained a cervical spine injury were treated at the Neurosurgical Department of Ospedali Riuniti Bergamo. In 55 patients the segment between C3 and C7 was involved. Different techniques and results in the management of these lesions are discussed.

[Single-photon emission-computed tomography (SPECT) during the first 72 hours after subarachnoid hemorrhage: a study of 45 cases]. / Tomographie d'émission mono-photonique (SPECT) au cours des 72 premières heures suivant l'hémorragie sous-arachnoïdienne (HSA): étude de 45 cas.

Forty five patients suffering by S.A.H., with I-III degree according to Hunt-Hess classification, have been studied with SPECT, performed within 72 hours from the hemorrhage, in order to evaluate early alterations of cerebral blood flow and their prognostic value. The patients with a clinical worsening showed an important diminution of C.B.F. detected by SPECT and a great amount of blood in the sub-arachnoidal spaces at the CT scan (III degree, according to Fischer). If these results will be confirmed with further studies, it could be possible to early identify a group of patients with a high risk of developing a cerebral vasospasm.

Extranervous localization of a presumed suprasellar and pineal germinoma. Metastasis or multifocal origin?

The contemporary occurrence of a presumed suprasellar and pineal germinoma and its late association with an extranervous germinoma in the sacral region is reported. Metastatic dissemination versus multifocality of the tumour are discussed with respect to prognosis.

Non-medical treatment of ischemic cerebrovascular disease. Surgical operations and other methods.

Surgical operations on vessels and other methods of treatment are considered as non-medical therapies for ischemic cerebrovascular diseases. Some of these methods are accepted (improvement in lifestyle, rehabilitative measures) and some are not (acupuncture, homeopathic therapy). Considering the surgical operations, the results of microsurgical anastomoses between extra- and intracranial vessels, in particular, are discussed on the basis of experiences with 40 operated patients. The principles of some therapeutic methods like acupuncture and homeopathic therapy are then presented.

[Cerebral pathology and hyponatremia. Cerebral damage with central pontine myelinolysis after rapid correction]. / Patologia cerebrale ed iponatremia. Danno cerebrale con mielinolisi centrale pontina dopo rapida correzione.

Hyponatremia is a state of relatively common observation among neurosurgical patients and it may determine or precipitate a condition of brain swelling in the head-injured. The quick reversal to normal values of serum sodium concentration may cause relevant neurological disturbances: they are related to peculiar neuropathological changes, the most representative of which is central pontine myelonilysis. Two cases (one in pediatric age) of head injured patients with brain damage resulting from rapid correction of a SIADH related hyponatremia are presented.

[Hyponatremia in meningeal hemorrhage]. / L'hyponatremie au cours de l'hémorragie méningée.

One hundred patients affected by S.A.H. have been studied, evaluating the possible correlations between clinical findings and hyponatremia. For a better understanding of hyponatremia during S.A.H., the hematic concentration of A.D.H. and A.N.P. have been determined and correlated with hyponatremia.

[Infective complications of external ventricular shunts]. / Complicanze infettive nelle derivazioni ventricolari esterne.

Since the sixties at our Department of Neurosurgery, we use an original method for external ventricular shunts. To verify the effectiveness for reduction of infections risks the Authors have retrospectively analyzed 95 patients: only 4 cases of meningitis have been observed. The Authors consider the utility of the proper method and the importance of the duration of ventriculostomy placement.

[Tracheal intubation: increase of arterial pressure and cerebral blood flow velocity. Effect of thiopentone and propofol]. / Intubazione tracheale: aumento della pressione arteriosa e della velocità del flusso ematico cerebrale. Ruolo del TPS e del propofol.

Induction of anaesthesia in intracranial surgery, especially for vascular diseases, must minimize haemodynamic changes: blood pressure and cerebral blood flow must not be increased to a high degree. Our work compares increases in blood pressure and in the speed of cerebral blood flow during endotracheal intubation in two groups of patients, who received propofol or thiopentone for the induction of anaesthesia. We studied 30 patients, without intracranial diseases, who underwent lumbar slipped disk surgery. Half of the patients received thiopentone and curare before intubation and the other half propofol and curare. Increase in blood pressure after intubation was lower with propofol than with thiopentone in a statistically significant way. Also the increase in the speed of cerebral blood flow, measured with doppler technique, was lower when induction with propofol was used, though not statistically relevant.