Efstathios Boviatsis

Hypoxia-inducible factor 1α/vascular endothelial growth factor axis in astrocytomas. Associations with microvessel morphometry, proliferation and prognosis

Hypoxia‐inducible factor (HIF)‐1α is a transcription factor that promotes ischaemia‐driven angiogenesis. The aim of this study was to determine the relation of HIF‐1α to vascular endothelial growth factor (VEGF; an important angiogenic molecule in brain tumours), p53 expression, angiogenesis, proliferative potential and clinical outcome in a large series of diffuse astrocytomas. Expression of HIF‐1α, VEGF, Ki‐67 (a proliferation‐associated marker) and p53 was determined immunohistochemically in 83 adult patients with supratentorial diffuse astrocytomas. Microvessels, highlighted by means of anti‐CD34 immunohistochemistry, were enumerated with computer‐assisted image analysis. Although HIF‐1α and VEGF were expressed in the majority of cases, their levels increased significantly with increasing grade and proliferative potential. HIF‐1α positively correlated with microvessel counts and VEGF with total vascular area and the presence of rounder vessel sections. There was a positive correlation of VEGF with p53 expression in astrocytomas and anaplastic astrocytomas. In univariate analysis, both VEGF and HIF‐1α were associated with shortened survival in the entire cohort, but lost significance when grades II/III and grade IV were analysed separately. Multivariate analysis revealed that the combination of HIF‐1α with grade was a significant prognostic indicator. HIF‐1α expression may be used to refine the prognostic information provided by grade in patients with diffuse astrocytomas. Its adverse prognostic effect is most likely mediated by hypoxia, the driving force for HIF‐1α accumulation.

Elevated Serum S-100B Protein as a Predictor of Failure to Short-Term Return to Work or Activities after Mild Head Injury

Protein S-100B is an established serum marker of primary and secondary brain damage and stroke. A group of patients after mild head injury (MHI) develop post-concussion symptoms that interfere with the ability in the short-term to return to work or undertake certain activities. The aim of this study was to examine the correlation of serum S-100B with short-term outcome after MHI. We studied 100 subjects who were referred to the Emergency Department (ED) after a MHI. All subjects had a GCS of 15 either with or without loss of consciousness (LOC) and/or post-traumatic amnesia (PTA). Serum S-100B was collected within 3 h from the injury and a value of > or = 0.15 microg/L was considered as abnormal. Subjects with other injuries, including scalp or cervical spine, were excluded, as well as those with alcohol/narcotic drug consumption or history of serious physical/mental illness. An independent observer measured the return to work/activities within one week. Thirty-two (32%) subjects had elevated S-100B. The failure to return to work/activities was significantly correlated with elevated S-100B: subjects with increased S-100B had a failure rate of 37.5% versus 4.9% of those with normal values (p = 0.0001). In MHI, the elevated S-100B seemed to correlate with an unfavorable short-term outcome. This might be useful in (1) selecting patients who need closer observation, hospitalization, and further investigations (such as CT scan or MRI), and (2) the prognosis of genuine post-concussion symptoms, that interfere with return to work or activities, versus other causes such as premorbid personality, labyrinthine dysfunction, whiplash syndrome, postinjury stress, occupational injury, litigation, and malingering.

CT-guided stereotactic biopsies of brain stem lesions: personal experience and literature review

Abstract.Appropriate therapy of brain stem lesions should be guided by an accurate diagnosis. Clinical evaluation combined with modern neuroimaging techniques may nowadays approach the diagnosis but not always with accuracy, thus leading to erroneous treatment. We report a series of 11 patients who underwent stereotactic biopsy for brain stem lesions. In 8 patients, the lesion was approached transfrontally. In the remaining 3 patients, the lesion was approached via the suboccipital transcerebellar route. There was no surgical mortality. Precise histological diagnosis was achieved in all patients. Three patients (27.2%) suffered complications attributed to the procedure and were successfully treated conservatively. Histological results were in accordance with preoperative diagnosis in 9 patients (81.8%). Despite the limited number of patients, our data suggest that stereotactic biopsy of brain stem lesions is a safe technique that can obtain adequate tissue for histological diagnosis, thus providing each patient with the best available treatment.

Functional outcome of intrathecal baclofen administration for severe spasticity

PURPOSE To estimate the functional benefit in patients with severe spasticity treated with intrathecal baclofen infusion through an implantable pump and to stress the need for functional assessment of these patients with a functional scale. PATIENTS AND METHODS Between 1999 and 2003, 22 patients with a long history of severe and disabling pharmaceutically intractable spasticity, underwent implantation of a pump for continuous intrathecal baclofen infusion. The patients were subdivided into two categories according to the aetiology of spasticity: 15 had Multiple Sclerosis and seven had suffered a Spinal Cord Injury at different levels (from C4 to T11). Clinical status was assessed with the Ashworth and Penn spasm scales. Functional benefits were evaluated with the Barthel index score and pain relief with a self-reported visual analogue pain scale. RESULTS Postoperatively, all patients presented improvement in spasticity, reduction of spasm frequency, significant improvement in functional status, enhancement of life comfort and reduction of pain. CONCLUSION Reduction of spasticity and spasms achieved with intrathecally delivered baclofen, leads to functional improvement and pain relief.

Intensive blood pressure reduction in acute intracerebral hemorrhage: A meta-analysis

Objective: The aim of the present systematic review and meta-analysis was to evaluate the safety and efficacy of intensive blood pressure (BP) reduction in patients with acute-onset intracerebral hemorrhage (ICH) using data from randomized controlled trials. Methods: We conducted a systematic review and meta-analysis according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines of all available randomized controlled trials that randomized patients with acute ICH to either intensive or guideline BP-reduction protocols. Results: We identified 4 eligible studies, including a total of 3,315 patients (mean age 63.4 ± 1.4 years, 64% men). Death rates were similar between patients randomized to intensive BP-lowering treatment and those receiving guideline BP-lowering treatment (odds ratio = 1.01, 95% confidence interval: 0.83–1.23; p = 0.914). Intensive BP-lowering treatment tended to be associated with lower 3-month death or dependency (modified Rankin Scale grades 3–6) compared with guideline treatment (odds ratio = 0.87, 95% confidence interval: 0.76–1.01; p = 0.062). No evidence of heterogeneity between estimates (I2 = 0%; p = 0.723), or publication bias in the funnel plots (p = 0.993, Egger statistical test), was detected. Intensive BP reduction was also associated with a greater attenuation of absolute hematoma growth at 24 hours (standardized mean difference ± SE: −0.110 ± 0.053; p = 0.038). Conclusions: Our findings indicate that intensive BP management in patients with acute ICH is safe. Fewer intensively treated patients had unfavorable 3-month functional outcome although this finding did not reach significance. Moreover, intensive BP reduction appears to be associated with a greater attenuation of absolute hematoma growth at 24 hours.

Infected CNS infusion pumps. Is there a chance for treatment without removal

SummaryBackground. Intrathecal baclofen administration by means of an implantable pump is nowadays a safe and effective method in the treatment of spasticity. One of the rare but devastating complications of this technique is pump infection, with a variety of Gram (−) and Gram (+) organisms being involved. Treatment of these infections, according to international literature, requires removal of the device and appropriate antibiotic therapy. Method. This article reports the authors experience in treating 3 patients with severe, medically intractable spasticity, suffering from infection of the intrathecally-delivering pump. A decision was made not to replace the device, but to treat this complication with pump disinfection and with a new treatment modality that has never been used before, the intra-pocket administration of antibiotics. Findings. In all cases the infection was eradicated and the integrity of the pump maintained. None of the patients required a procedure under general anesthesia. Conclusions. Removal should no longer be considered the first treatment option in infections of intrathecally delivering pumps, especially those due to non-adherent bacteria, with mild clinical symptomatology. An initial attempt should always be made for conservative treatment. Intra-pocket administration of antibiotics helps in achieving high drugs levels locally, and may prove an important element in our armamentarium against such infections.

Phosphorylated 4E-binding protein 1 (p-4E-BP1): a novel prognostic marker in human astrocytomas.

Korkolopoulou P, Levidou G, El‐Habr E A, Piperi C, Adamopoulos C, Samaras V, Boviatsis E, Thymara I, Trigka E‐A, Sakellariou S, Kavantzas N, Patsouris E & Saetta A A 
(2012) Histopathology 61, 293–305

CT-guided stereotactic aspiration of brain abscesses.

The effective treatment of intracranial abscess remains controversial. Progress in technology, linked with the development of neuronavigational systems, has made stereotactic aspiration and drainage of intracerebral abscesses effective and valid alternatives to traditional methods, namely, conservative medical treatment or open surgical excision. Between 1995 and 2002, 12 patients at our hospital underwent drainage of intracerebral abscesses under stereotactic guidance. Ten patients had solitary lesions and two had multiple abscesses. The appropriate antibiotic schemes were administered following culture of the aspirated material. The size of the abscess, the mass effect, and response to antibiotic treatment were followed up by repeated CT scans. All patients showed improvement and, at the end of treatment, returned to their previous activities. There were neither deaths nor any postoperative complication. A second aspiration was required in one patient due to recurrence of the abscess. The CT-guided stereotactic aspiration of brain abscesses helps achieve all treatment goals. It drains the contents of the abscess, reduces mass effect, and confirms diagnosis. It is minimally invasive, carries minimal morbidity and mortality, and can be performed on compromised patients under local anesthesia.

Technical aspects and considerations of deep brain stimulation surgery for movement disorders.

Deep brain stimulation (DBS) represents one of the more recent advancements in Neurosurgery. Even though its most successful applications evolved in movement disorders (MDs), indications now include pain, psychiatric disorders, epilepsy, cluster headaches and Tourette syndrome. As this type of surgery gains popularity and the indications for DBS surgery increase, so it will certainly increase the number of neurosurgeons who will use this neuromodulatory technique. A detailed description of the technical aspects of the DBS procedure, as it is performed in our department, is presented. In our opinion, our method is a good combination of all the well-established necessary techniques in a cost-effective way. This technical article may be helpful to neurosurgeons considering to start performing this type of surgery. It could also prompt others who perform DBS regularly to express their views, and hence, lead to further refinement of this demanding procedure.

Statin pretreatment is associated with better outcomes in large artery atherosclerotic stroke

Objective: Even though statin pretreatment is associated with better functional outcomes and lower risk of mortality in acute ischemic stroke, there are limited data evaluating this association in acute ischemic stroke due to large artery atherosclerosis (LAA), which carries the highest risk of early stroke recurrence. Methods: Consecutive patients with acute LAA were prospectively evaluated from 7 tertiary-care stroke centers during a 3-year period. Statin pretreatment, demographics, vascular risk factors, and admission and discharge stroke severity were recorded. The outcome events of interest were neurologic improvement during hospitalization (quantified as the relative decrease in NIH Stroke Scale score at discharge in comparison to hospital admission), favorable functional outcome (FFO) (defined as modified Rankin Scale score of 0–1), recurrent stroke, and death at 1 month. Statistical analyses were performed using univariable and multivariable Cox regression models adjusting for potential confounders. All analyses were repeated following propensity score matching. Results: Statin pretreatment was documented in 192 (37.2%) of 516 consecutive patients with LAA (mean age: 65 ± 13 years; 60.8% men; median NIH Stroke Scale score: 9 points, interquartile range: 5–18). Statin pretreatment was associated with greater neurologic improvement during hospitalization and higher rates of 30-day FFO in unmatched and matched (odds ratio for FFO: 2.44; 95% confidence interval [CI]: 1.07–5.53) analyses. It was also related to lower risk of 1-month mortality and stroke recurrence in unmatched and matched analyses (hazard ratio for recurrent stroke: 0.11, 95% CI: 0.02–0.46; hazard ratio for death: 0.24, 95% CI: 0.08–0.75). Conclusion: Statin pretreatment in patients with acute LAA appears to be associated with better early outcomes regarding neurologic improvement, disability, survival, and stroke recurrence.