Clinical management guidelines for subarachnoid haemorrhage. Diagnosis and treatment.

OBJECTIVE: To update the Spanish Society of Neurology's guidelines for subarachnoid haemorrhage diagnosis and treatment. MATERIAL AND METHODS: A review and analysis of the existing literature. Recommendations are given based on the level of evidence for each study reviewed. RESULTS: The most common cause of spontaneous subarachnoid haemorrhage (SAH) is cerebral aneurysm rupture. Its estimated incidence in Spain is 9/100 000 inhabitants/year with a relative frequency of approximately 5% of all strokes. Hypertension and smoking are the main risk factors. Stroke patients require treatment in a specialised centre. Admission to a stroke unit should be considered for SAH patients whose initial clinical condition is good (Grades I or II on the Hunt and Hess scale). We recommend early exclusion of aneurysms from the circulation. The diagnostic study of choice for SAH is brain CT (computed tomography) without contrast. If the test is negative and SAH is still suspected, a lumbar puncture should then be performed. The diagnostic tests recommended in order to determine the source of the haemorrhage are MRI (magnetic resonance imaging) and angiography. Doppler ultrasonography studies are very useful for diagnosing and monitoring vasospasm. Nimodipine is recommended for preventing delayed cerebral ischaemia. Blood pressure treatment and neurovascular intervention may be considered in treating refractory vasospasm. CONCLUSIONS: SAH is a severe and complex disease which must be managed in specialised centres by professionals with ample experience in relevant diagnostic and therapeutic processes.

Tinnitus and quality of life following vestibular schwannoma surgery.

OBJECTIVE: This study on patients undergoing surgery for vestibular schwannoma investigated tumour (i) the effect of pre-operative factors on tinnitus, (ii) the effect of translabyrinthine or hearing preservation surgical approaches on tinnitus, and (iii) the effect of postoperative tinnitus status on the patient's quality of life (QOL). METHODOLOGY: Seventy-nine patients who underwent vestibular schwannoma (VS) excision between 2001 and 2005 were selected. Postoperative tinnitus status was evaluated using a standard questionnaire for tinnitus, and QOL was measured using the Glasgow Benefit Inventory (GBI). RESULTS: Overall, 58% of patients noted tinnitus before tumour removal. Pre-operative tinnitus was not associated with age, gender, tumour size, or hearing thresholds. The total percentage of patients suffering postoperative tinnitus was 64%. Hearing preservation approaches showed no difference in terms of changes in tinnitus compared to the translabyrinthine approach. Twenty-one patients (30%) reported better QOL, 40 patients (56%) reported worse QOL, and 10 patients (14%) reported the same QOL. A significant association was found between tinnitus worsening as measured by GBI score and QOL. CONCLUSIONS: Most patients do not report significant changes in their tinnitus status after surgery. Tinnitus evolution is unpredictable and not related to the type of surgical approach. Thus, tinnitus should not be used as a criterion for selecting the surgical approach. Tinnitus worsening appears to influence QOL following surgery for VS.

How to repair an ischemic brain injury? Value of experimental models in search of answers.

The major aim of experimental models of cerebral ischemia is to study the cerebral ischemic damage under controlled and reproducible conditions. Experimental studies have been fundamental in the establishment of new concepts regarding the mechanisms underlying the ischemic brain injury, such as the ischemic penumbra, the reperfusion injury, the cell death or the importance of the damage induced on mitochondria, glial cells and white matter. Disagreement between experimental and clinical studies regarding the benefit of drugs to reduce or restore the cerebral ischemic damage has created a growing controversy about the clinical value of the experimental models of cerebral ischemia. One of the major explanations for the failure of the clinical trials is the reductionist approach of most therapies, which are focused on the known effect of a single molecule within a specific pathway of ischemic damage. This philosophy contrasts to the complex morphological design of the cerebral tissue and the complex cellular and molecular physiopathology underlying the ischemic brain injury. We believe that the main objective of studies carried out in experimental models of cerebral ischemic injury must be a better understanding of the fundamental mechanisms underlying progression of the ischemic injury. Clinical trials should not be considered if the benefit obtained in experimental studies is limited or weak.

[Experimental models of traumatic brain injury]. / Modelos experimentales de traumatismo craneoencefálico.

AIM: To provide a summary of the different experimental models of traumatic brain injury (TBI) designed under both in vivo and in vitro conditions. A comprehensible review of the specific types of brain lesions induced, as well as the technical details to reproduce each model at the laboratory is given. DEVELOPMENT: Outcome of patients suffering from a TBI has significantly improved with the rapid application of vital supporting measures in addition to a strict control of blood and intracranial pressure at the intensive care units. However no specific treatment for post-traumatic brain lesions has proven as efficacious in the clinical settings. A deeper knowledge of the physiopathological events associated with TBI is necessary for the development of new specific therapies. Due to the heterogeneity of the human TBI, each experimental model has been designed to reproduce a different type of brain lesion. Experimental TBI models allow the study of the dynamic evolution of brain injuries under controlled conditions. Usefulness of experimental models is limited by their reliability and reproducibility among different researchers. Small rodents have been the preferred animals to reproduce TBI injuries, mainly due to the similar cerebral physiology shared by these animals and the human beings. CONCLUSION: The use of experimental models of TBI is the most appropriate tool to study the mechanisms underlying this type of injury. However their simplicity precludes an exact reproduction of the heterogeneous cerebral damage observed in clinical settings. This could be the main reason for the discrepancies observed in the therapeutic effects of treatments between experimental and clinical studies.

Update on the pathophysiology and management of syringomyelia unrelated to Chiari malformation. / Siringomielia no secundaria a Chiari. Actualización en fisiopatología y manejo.

INTRODUCTION: Much has been published on syringomyelia related to Chiari malformation. In contrast, little is known about the condition when it is not associated with this malformation, but this presentation of syringomyelia constitutes a different entity and therefore requires specific management. We conducted a literature review to summarise the most accepted and widespread ideas about the pathophysiology, management and other aspects of syringomyelia unrelated to Chiari malformation. DEVELOPMENT: We reviewed the most relevant literature on this condition, focusing on the pathophysiology, clinical presentation, diagnosis, and treatment. CONCLUSIONS: Syringomyelia unrelated to Chiari malformation is a distinct entity that must be well understood to guarantee correct diagnosis, monitoring, and management. When the disease is suspected, a thorough study should be conducted to identify its aetiology. Treatment must aim to eliminate the cause of the disease; symptomatic treatment should remain a second-line option.

Third ventricle glioblastoma. Case report and review of literature.

UNLABELLED: A glioblastoma presenting as a solitary third ventricle mass is exceptional. CASE DESCRIPTION: We report the case of a 29-year-old woman who lost consciousness, was taken to hospital and referred a previous history of depression and diabetes insipidus. Magnetic resonance imaging study revealed a heterogeneous anterior third ventricle mass with ring enhancement after contrast administration. It was approached and subtotally resected by a transcortical-transventricular route and histological diagnosis proved it to be a glioblastoma. There are only two other similar well-described cases and another nine have been previously reported in surgical series of high grade gliomas and glioblastomas. The possible origin of this lesion is discussed.

Nonhistological diagnosis of human cerebral tumors by 1H magnetic resonance spectroscopy and amino acid analysis.

We describe a multivariate analysis procedure to classify human cerebral tumors nonhistologically in vitro, combining the use of 1H magnetic resonance spectroscopy (MRS) with automatic amino acid analysis of biopsy extracts. Eighty-one biopsies were obtained surgically and classified histologically in eight classes: high-grade astrocytomas (class 1, n = 19), low-grade astrocytomas (class 2, n = 10), normal brain (class 3, n = 9), medulloblastomas (class 4, n = 4), meningiomas (class 5, n = 18), metastases (class 6, n = 8), neurinomas (class 7, n = 9), and oligodendrogliomas (class 8, n = 4). Perchloric acid extracts were prepared from every biopsy and analyzed by high resolution 1H MRS and automatic amino acid analysis by ionic exchange chromatography. Intensities of 27 resonances and ratios of resonances were measured in the 1H MRS spectra, and 17 amino acid concentrations were determined in the chromatograms. Linear discriminant analysis provided the most adequate combination of these variables for binary classifications of a biopsy between any two possible classes and in multiple choice comparisons, involving the eight possible classes considered. Correct diagnosis was obtained when the class selected by the computer matched the histological diagnosis. In binary comparisons, consideration of the amino acid profile increased the percentage of correct classifications, being always higher than 75% and reaching 100% in many cases. In multilateral comparisons, scores were: high-grade astrocytomas, 80%; low-grade astrocytomas, 74%; normal brain, 100%; medulloblastomas, 100%; meningiomas, 94.5%; metastases, 86%; neurinomas, 100%; and oligodendrogliomas, 75%. These results indicate that statistical multivariate procedures, combining 1H MRS and amino acid analysis of tissue extracts, provide a valuable classifier for the nonhistological diagnosis of biopsies from brain tumors in vitro.

Hemangioblastoma of the lateral ventricle: case report and review of the literature.

We report a unique case of hemangioblastoma of the lateral ventricle in a 73 year-old man with cognitive deficits and fluent dysphasia. He harboured an intraventricular tumor, placed at the trigone of the left lateral ventricle. The tumor was successfully excised, by means of a temporal craniotomy. The patient became mute in the immediate postoperative with restoration of speech within a few days. The literature has been reviewed and only three other similar cases have been reported. Discovery of lesions in such unusual location should raise a high degree of suspicion for von Hippel-Lindau disease.

Hippocampal cell loss in transient global cerebral ischemia in rats: a critical assessment.

The induction of transient global cerebral ischemia by permanent vertebral occlusion and temporary carotid ligation (four-vessel occlusion) is widely accepted as a valid tool for the study of pathogenesis and treatment of ischemia. The neural damage inflicted by this intervention is often assessed by measuring pyramidal cell loss in the CA1 hippocampal field. Nevertheless studies using this model in rats often fail to control variables that are relevant to the outcome, and/or apply biased methods to quantitate histological damage. We have applied unbiased stereological methods to estimate absolute numbers of surviving neurons in CA1 in Wistar rats subjected to either 10 or 20 min global ischemia using the Sugio et al. variant of the original four-vessel occlusion model. Animal mortality was high at both times, with neuron losses averaging 39% and 31%, respectively. Post-operative mortality was reduced substantially by using decompressive craniectomies and, even more effectively, by pre-treating the rats with low doses of phenytoin. Both maneuvers led to a severely increased CA1 neuron loss, which reached 50%, after an ischemia of 10 min. This finding strongly supports that mortality biases the sample. Other noteworthy findings that emerged from this study were a linear relationship between per-ischemic blood pressure increments and animal survival, and a negative correlation between cell survival and preferentially left-sided damage.

Combined nimodipine and citicoline reduce infarct size, attenuate apoptosis and increase bcl-2 expression after focal cerebral ischemia.

Cerebral ischemia triggers a multitude of pathophysiological and biochemical events that separately affect the evolution of focal ischemia and, therefore, stroke treatment should logically employ all known neuroprotective agents. We hypothesized that a treatment combining nimodipine and citicoline might have a potential neuroprotective effect. To assess this idea, Sprague-Dawley rats underwent transient bilateral common carotid artery ligation with simultaneous middle cerebral artery occlusion for 60 min. Four treatment groups were established. Animals received either: a) saline (control group); b) intracarotid nimodipine infusion during 30 min in the ischemia-reperfusion (nimodipine group); c) i.p. postischemic citicoline injections once daily for 7 days (citicoline group); or d) intracarotid nimodipine bolus during ischemia-reperfusion plus i.p. postichemic citicoline injections (combination group). They were killed after either 7 or 3 days after reperfusion. In the first case, the volume of the infarcted tissue was studied by a stereological procedure and in the second case, in situ end-labeling of nuclear DNA fragmentation (TUNEL) and Bcl-2 expression were employed to determine the level of apoptosis. The infarct volume was significantly reduced in both the nimodipine and the citicoline treatment groups after 7 days of reperfusion; combination of both drugs produced an additive effect. After 3 days of reperfusion, the number of Bcl-2-positive neurons was significantly increased while that of TUNEL-positive cells significantly decreased at the infarct border in the combined-treatment animals. Our findings demonstrate a neuroprotective effect from an acute single dose of nimodipine during ischemia-reperfusion and prolonged post-ischemic treatment with citicoline in a model of focal cerebral ischemia. These results suggest that a possible mechanism of neuroprotective action would be mediated by increased Bcl-2 expression and decreased apoptosis within the boundary zone of the infarct together with neutralization of the ischemia-reperfusion injury.

Morphometric study of focal cerebral ischemia in rats: a stereological evaluation.

An efficient, unbiased stereological method for estimating and evaluating volumetric parameters of cortical infarction is presented. Long-Evans rats were subjected to a standard procedure for achieving focal cerebral ischemia, consisting of permanent ligation of the right middle cerebral artery and temporary occlusion of both common carotid arteries. Animals were killed 24 h later by perfusion fixation and the brains were embedded in celloidin, serially sectioned at 60 microns and stained with Cresyl violet. All cases showed identifiable areas of infarction of variable extent within the territory of the right middle cerebral artery. Involvement of allocortical or subcortical structures was variable and in three cases there were small foci of infarct in the contralateral hemisphere. The absolute volumes of the infarcted tissue and of the spared cortex of both hemispheres were obtained by means of an unbiased estimator of volume based on Cavalieri's principle. The best estimate of the actual amount of infarcted cortex was found to be given by the volume ratio between the spared cortex of the right (infarcted) hemisphere and the total cortex of the left (control) hemisphere. This approach avoided the error introduced by the accompanying edema and decreased the observed interanimal variance. Sample size predictions for therapeutic-pharmacological trials show that relatively few animals would be needed using the model of ischemia and quantitative morphometry presented here to detect a 30-40% change in infarct volume.

Thyroid hormones in human tumoral and normal nervous tissues.

We have studied T4 and T3 concentrations, DNA and protein concentrations and 5' and 5 deiodinases in samples of brain tumors obtained at surgery from 49 patients, and, in most cases, also from surrounding normal tissue. T4 concentrations in normal cortical tissue (6.19+/-0.45 ng/g) were lower than in white matter, but the difference disappeared when referred to the DNA content (2.26+/-0.27 ng/mg DNA). No other differences were found between cortical and white matter, or among cortical lobes. T4 in normal tissue was higher than previously reported, mostly from autopsy samples, whereas T3 (0.99+/-0.07 ng/g) was similar. 5'D-I activity was negligible as compared to 5'D-II (8.11+/-1.09 fmol/h/mg protein). When expressed in relation to the different DNA contents of normal vs. tumoral tissue, 5'D-II activities were the same for both. 5D activity was highly variable in the tumoral tissue, with negligible activities in meningiomas and pituitary adenomas. When referred to the DNA content, T4 and 5'D-II were the same, but T3 concentrations were lower in the tumor (0.24+/-0.03 ng/mg DNA) as compared to normal (0.35+/-0.04 ng/mg DNA) tissue samples. Whether or not this decrease of T3 affects the expression of T3-sensitive processes remains to be studied.

Serpentine aneurysm: regrowth after a superficial temporal artery-middle cerebral artery bypass and internal carotid artery ligation: case report.

Giant serpentine aneurysms (GSAs) are infrequent. We present a 37-year-old patient with a giant serpentine aneurysm of the left middle cerebral artery that was treated with a superficial temporal artery to middle cerebral artery bypass and ligature of the left internal carotid artery. After 2 years, the patient presented new symptoms of neurological deterioration and the computed tomographic scan and arteriography showed regrowth of the aneurysm, which was excised. Enlargement of a giant serpentine aneurysm once it has been treated with ipsilateral carotid ligation and/or bypass anastomosis is rare, and only two cases have been described previously.

Malignant and atypical meningiomas: a reappraisal of clinical, histological, and computed tomographic features.

A series of 21 patients with atypical and malignant meningiomas is presented. Histological criteria such as high cellularity, typical and atypical mitosis, necrosis, infiltration of the underlying brain, poor differentiation, and distant metastasis define nonbenign meningiomas. Male predominance in this nonbenign group is significant when compared to a group of 205 benign meningiomas, which were also operated on. The malignant and atypical meningiomas are compared with the benign meningiomas, and special emphasis is placed on their computed tomographic features. The presence of tumor fringes (suggesting invasion of the brain substance) and intratumoral hypodense areas were both significant signs of malignancy of atypia. Radical surgical excision is still considered the treatment of choice.

Intracranial cavernous angioma in the dura.

Cavernous malformations located in the dura are rare. We present a case of a large cavernous malformation located in the anterior fossa and implanted in the dura of a pregnant woman. It showed great vascularization on an angiogram, and resembled a meningioma on computed tomographic scan. The operation was difficult because of the tumor's great vascularity and profuse bleeding.

Intradural herniated dorsal disc: case report and review of the literature.

A 67-year-old man with a 1 1/2-month history of spastic paraparesis caused by a dorsal intradural disc herniation underwent surgical treatment via a posterior approach. Dorsal herniated discs are rare, and intradural dorsal disc herniations are even more infrequent. Including this case, the medical literature reviewed describes only four such cases.

Multiple intraspinal low-grade astrocytomas mixed with lipoma (astrolipoma). Case report.

Multiple intraspinal low-grade astrocytomas without neurofibromatosis stigmata and low-grade astrocytoma with intermingled areas of adipose tissue have not been reported previously. The authors present the case of a 48-year-old woman with a 7-month history of paraparesis. When she underwent surgery, multiple intraspinal mixed tumors made up of astrocytes mingled with adipose cells were found and excised. In this report, the authors refer to this tumor as an "astrolipoma" and discuss its characteristics.

Experimental model for induction of cerebral aneurysms in rats.

Two groups of rats with induced arterial hypertension were studied. One group underwent section of the left common carotid artery with an end-to-side anastomosis of the proximal segment to the right common carotid artery. The second group was subjected to ligation of the left common carotid artery. The number of aneurysms caused by the procedure in the first group was higher, the difference being statistically significant (p less than 0.05, chi-square).

Hangman's fracture with complete dislocation of C-2 on C-3. Case report.

A patient with a complete fracture-dislocation of C-2 on C-3 without dysfunction of the spinal cord is presented. The patient was treated conservatively, and immobilization resulted in good alignment of the cervical spine and solid healing of the fracture.

Encapsulated intracerebral hematomas: a defined entity. Case report.

Encapsulated intracerebral hematoma is an interesting and not widely appreciated entity. It can be defined as an intraparenchymal hematoma found in normotensive patients, usually caused by histologically confirmed vascular malformations, characterized by a gradual clinical onset, and presenting a well-defined capsule at operation. One case is presented and 25 previously reported cases are reviewed, all reflecting the above-mentioned characteristics. The hematomas reviewed here occurred in relatively young patients with a mean age of 35 years and a clear male predominance (19 males, seven females). A ring of contrast enhancement around a lesion of variable density, usually with mass effect and perifocal edema, is the most relevant feature on computerized tomography. Findings on magnetic resonance images are described for the first time in the reported case. A vascular malformation was the most frequent cause found on histological examination (12 of the 26 total cases). No proven cause was found in the remaining 14 cases, although a small vascular malformation, destroyed or thrombosed after rupturing and bleeding, is the most likely etiology in these patients.