Jacob Bertram Springborg

A single subcutaneous bolus of erythropoietin normalizes cerebral blood flow autoregulation after subarachnoid haemorrhage in rats

Systemic administration of recombinant erythropoietin (EPO) has been demonstrated to mediate neuroprotection. This effect of EPO may in part rely on a beneficial effect on cerebrovascular dysfunction leading to ischaemic neuronal damage. We investigated the in vivo effects of subcutaneously administered recombinant EPO on impaired cerebral blood flow (CBF) autoregulation after experimental subarachnoid haemorrhage (SAH). Four groups of male Sprague‐Dawley rats were studied: group A, sham operation plus vehicle; group B, sham operation plus EPO; group C, SAH plus vehicle; group D, SAH plus EPO. SAH was induced by injection of 0.07 ml of autologous blood into the cisterna magna. EPO (400 iu kg−1 s.c.) or vehicle was given immediately after the subarachnoid injection of blood or saline. Forty‐eight hours after the induction of SAH, CBF autoregulatory function was evaluated using the intracarotid 133Xe method. CBF autoregulation was preserved in both sham‐operated groups (lower limits of mean arterial blood pressure: 91±3 and 98±3 mmHg in groups A and B, respectively). In the vehicle treated SAH‐group, autoregulation was abolished and the relationship between CBF and blood pressure was best described by a single linear regression line. A subcutaneous injection of EPO given immediately after the induction of SAH normalized autoregulation of CBF (lower limit in group D: 93±4 mmHg, NS compared with groups A and B). Early activation of endothelial EPO receptors may represent a potential therapeutic strategy in the treatment of cerebrovascular perturbations after SAH.

Erythropoietin in patients with aneurysmal subarachnoid haemorrhage: a double blind randomised clinical trial

SummaryBackground. Erythropoietin (EPO) is neuroprotective in experimental models of stroke and subarachnoid haemorrhage (SAH) and possibly in patients with thromboembolic stroke. We studied the efficacy and safety of EPO in patients with SAH. Methods. A larger scale clinical trial was planned but preliminarily terminated because of a lower than expected inclusion rate. However, 73 patients were randomised to treatment with EPO (500 IU/kg/day for three days) or placebo. The primary endpoint was Glasgow Outcome Score at six months. We further studied surrogate measures of secondary ischaemia, i.e. transcranial Doppler (TCD) flow velocity, symptomatic vasospasm, cerebral metabolism (microdialysis) and jugular venous oximetry, biochemical markers of brain damage (S-100β and neuron specific enolase) and blood–brain barrier integrity. Findings. The limited sample size precluded our primary hypotheses being verified and refuted. However, data from this study are important for any other study of SAH and as much raw data as possible are presented and can be included in future meta analyses. On admission the proportion of patients in a poor condition was higher in the EPO group compared with the placebo group but the difference was statistically insignificant. In the EPO-treated patients the CSF concentration of EPO increased 600-fold. Except for a higher extracelullar concentration of glycerol in the EPO group probably caused by the poorer clinical condition of these patients, there were no statistically significant group differences in the primary or secondary outcome measures. EPO was well tolerated. Conclusions. Beneficial effects of EPO in patients with SAH cannot be excluded or concluded on the basis of this study and larger scale trials are warranted.

Erythropoietin improves place learning in fimbria-fornix-transected rats and modifies the search pattern of normal rats.

The acquisition of a water-maze-based allocentric place learning task was studied in four groups of rats: two groups subjected to bilateral transections of the fimbria-fornix and two groups undergoing a sham control operation. At the moment of surgery all animals were given one systemic (intraperitoneal) injection of either human recombinant erythropoietin (EPO) (at a dosage of 5000 IU/kg body weight), given to one of the fimbria-fornix-transected groups and one of the sham-operated groups, or vehicle (saline), given to the two remaining groups. The 25-day task acquisition period (one session/day) began 6 or 7 days after the day of surgery. The fimbria-fornix-transected and saline-injected group exhibited a pronounced and long-lasting impairment of task acquisition. In contrast, the fimbria-fornix-transected and EPO-treated group demonstrated a less pronounced and more transient lesion-associated impairment. The two sham-operated groups did not differ with respect to the proficiency of task acquisition. But administration of EPO to intact animals caused a significant modification of swim patterns-apparently reflecting a somewhat modified strategy of task solution. It is concluded that systemic administration of EPO significantly improves the posttraumatic functional recovery of the presently studied place learning task after transections of the fimbria-fornix. Additionally, administration of EPO influences the strategy, although not quality, of task solution in normal (sham-operated) rats.

Anterior cervical discectomy with or without fusion with ray titanium cage: a prospective randomized clinical study.

Study Design. A prospective randomized clinical study. Objective. To compare 2 surgical methods in the treatment of cervical radiculopathy caused by hard or soft disc herniation; namely, simple discectomy versus discectomy with an additional interbody fusion with a Ray titanium cage. Summary of Background Data. Although an interbody fusion after anterior decompressive surgery for hard or soft disc herniation is widely accepted, there is no scientific evidence that convincingly demonstrates that insertion of graft material for interbody fusion is necessary after discectomy and decompression of the nervous elements have been performed. To date, no randomized studies have compared simple discectomy with discectomy followed by an interbody fusion with a titanium cage. Methods. Eighty-six patients with symptoms of nerve root compression at 1 level were randomly allocated to either discectomy followed by fusion with a Ray titanium cage (40 patients) or to discectomy alone (46 patients). Clinical and radiologic follow-up was performed 3, 12, and 24 months after surgery. Results. There was no statistically significant difference between the 2 groups concerning self-reported satisfaction or severity of pain in the neck and arm. Two years after the operation, 86.1% of the patients treated with cage stated a good outcome versus 76.7% in the discectomy group (P = 0.44). The rate of fusion was 83.3% in the cage group versus 81.0% in the discectomy group (P = 0.30). Furthermore, after 2 years, also the rates of new adjacent disc degeneration or spondylosis were the same in both groups. Conclusion. This study showed no statistically significant difference between simple discectomy and discectomy followed by interbody fusion with a titanium cage in the surgical treatment of cervical radiculopathy caused by disc herniation.

Modifiable Risk Factors for Aneurysmal Subarachnoid Hemorrhage

Aneurysmal subarachnoid hemorrhage (aSAH) is bleeding into the subarachnoid space from a cerebral aneurysm, defined as a thin-walled outpouching on one of the cerebral arteries.1 SAH represents 0.8% to 15% of strokes and has a low incidence of 0.03 to 0.2 per 1000 person-years with a female preponderance.2,3 However, SAH usually occurs at a relatively young age and has a high 1-month case fatality rate (32%), leading to a high loss of potential life years.2 Subsequently, primary prevention of aSAH by identifying and addressing modifiable risk factors has been a focus of research for decades.4 Although the main focus has been on identifying modifiable risk factors, less attention has been given to the underlying pathogenic mechanisms. We, therefore, conducted a literature review to identify recognized modifiable risk factors for aneurysm development and aSAH and examined the pathogenesis by which these individual risk factors are suspected to contribute to aneurysm development and rupture. We conducted MEDLINE searches using the PubMed database for relevant articles published between 1980 and 2012 in English. We used search words such as Cerebral Arteries [Majr], Subarachnoid Hemorrhage [Majr], or Intracranial Aneurysm [Majr] combined with Medical Subject Headings (MeSH) search words for different risk factors such as Alcohol drinking, Ethanol, Estrogens, Menopause, Hypertension, Smoking, Cholesterol, Diabetes Mellitus, and Cocaine. The first search was performed in June 2012 and the last in December 2012. Articles were screened by title and abstract, and if relevant the article was reviewed in its entirety. References lists in key publications were hand-searched to reveal additional relevant studies. Initially, the focus was on epidemiological studies that helped establish the different modifiable risk factors for aSAH. Inclusion criteria comprised: (1) SAH analyzed as a separate stroke entity, although in some studies SAH was part of a hemorrhagic stroke …

Nonvestibular Schwannoma Tumors in the Cerebellopontine Angle: A Structured Approach and Management Guidelines

The most common cerebellopontine angle (CPA) tumor is a vestibular schwannoma, but one in five CPA tumors are not vestibular schwannomas. These tumors may require different management strategies. Compared with vestibular schwannomas, symptoms and signs from cranial nerve VIII are less frequent: other cranial nerve and cerebellar symptoms and signs predominate in patients with these less common CPA tumors. Computed tomography and magnetic resonance imaging often show features leading to the correct diagnosis. Treatment most often includes surgery, but a policy of observation or subtotal resection is often wiser. This review provides a structured approach to the diagnosis of nonvestibular schwannoma CPA lesions and also management guidelines.

Outcome after translabyrinthine surgery for vestibular schwannomas: report on 1244 patients.

The objective of this article is to study the outcome after translabyrinthine surgery for vestibular schwannomas, with special focus on the facial nerve function. The study design is a case series from a national centralized database and it is set in two University Hospitals in Denmark. Participants were 1244 patients who underwent translabyrinthine surgery during a period of 33 years from 1976 to 2009. Main outcome measures were tumor removal, intraoperative facial nerve preservation, complications, and postoperative facial nerve function. In 84% patients, the tumor was totally resected and in ~85% the nerve was intact during surgery. During 33 years, 12 patients died from complications to surgery and ~14% had cerebrospinal fluid leakage. Before surgery, 74 patients had facial paresis and 46% of these improved after surgery. In patients with normal facial function, overall ~70% had a good outcome (House-Brackmann grade 1 or 2). The chance of a good outcome was related to tumor size with a higher the chance the smaller the tumor, but not to the degree of tumor removal. In ~78% of the patients with facial paresis at discharge the paresis improved over time, in ~42% from a poor to a good function. The translabyrinthine approach is generally efficient in tumor control and with satisfactory facial nerve outcome. With larger tumors the risk of a poor outcome is evident and more data on patients managed with alternative strategies are warranted.

Common variants of the ACE gene and aneurysmal subarachnoid hemorrhage in a Danish population: a case-control study.

Objective The intron 16 insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme (ACE) gene has been associated with rupture of intracranial aneurysms, but the effect of haplotypes within ACE has not been studied. This study investigated whether ACE haplotypes including the I/D polymorphism are associated with aneurysmal subarachnoid hemorrhage. Methods The hypothesis was tested with a case-control design in 176 patients with aneurysmal subarachnoid hemorrhage and with 498 hospital controls. Through the pairwise tagging principle, single nucleotide polymorphisms (rs4291 A/T, rs4295 C/G, rs4305 C/T, rs4311 C/T, rs4331 T/C, rs4343 C/T) in the ACE gene were genotyped along with the I/D polymorphism. Haplotypes were estimated using the PHASE software. Results Fifty-five haplotypes were identified with 3 of these having a frequency above 5%: ACCCCIT (41.6±0.4%), TGTTTDC (32.1±0.5%), and ACCTTDC (9.5±0.2%). No significant difference in distribution of alleles, genotypes, haplotypes, or haplotype pairs between the 2 populations was found. Specifically, we could not reproduce previously reported associations between the ACE I genotype and intracranial aneurysms. When subdivided into groups of aneurysm location, we found a trend toward an association between homozygotes of the ACCCCIT haplotype and middle cerebral artery aneurysms, odds ratio=2.9 (1.0 to 7.6), which however proved insignificant (P=0.22) after correction for multiple testing. Conclusion In this Danish population, ACE haplotypes and the I/D polymorphism did not contribute significantly to the overall risk of intracranial aneurysm rupture. Larger studies are needed to delineate the association between ACE polymorphism and ruptured middle cerebral artery aneurysms.

Accuracy of tunnelated vs. bolt-connected external ventricular drains

BACKGROUND Ventriculostomy is one of the most common neurosurgical procedures and an important tool in the treatment and monitoring of elevated intracranial pressure. Low accuracy has frequently been reported in the literature with risk of drain misplacement over 20% and with a need for reinsertion in up to 40%. As an alternative to the tunnelated EVD technique we often use a bolt-connected EVD. The aim of the present study was to investigate whether the use of bolt-connected EVDs would lead to higher accuracy, fewer passes and reoperations due to poor placement compared to tunnelated EVDs. PATIENTS AND METHODS We retrospectively identified all patients who received an EVD from January 1st 2008 to December 31st 2010. Postoperative images were evaluated for anatomical placement of the EVD-tip, distance from tip to optimal placement and were categorized as optimal, suboptimal and undesired. Patient files were evaluated for EVD technique, number of passes and postoperative complications and handling. RESULTS 147 patients with 154 separate EVDs met the inclusion criteria. We found a statistical significant higher accuracy in the bolt-group compared to the tunnelated-group (p=0.023). Eleven patients were reoperated following ventriculostomy and we found a statistical significant 11.9% reduction in reoperations due to poor placement in the bolt-group (p=0.006). CONCLUSIONS We have showed in this study that by using a bolt-connected EVD and maintaining the freehanded technique we can significantly increase precision and decrease the number of reoperations due to poor placement.

Outcome after surgical treatment for lumbar spinal stenosis: the lumbar extension test is not a predictive factor.

Study Design. A prospective clinical study. Objectives. To investigate the predictive value of the lumbar extension test for outcome after surgical treatment of lumbar spinal stenosis (LSS). Summary of Background Data. Studies have indicated that aggravation of the symptoms from LSS by extension of the lumbar spine has predictive value for the outcome after decompression. The aim of this study was to investigate this theory in a larger group of patients. Methods. One hundred forty-six consecutive patients surgically treated for LSS were included in the study. The clinical condition was recorded before surgery and at 3, 6, 12, and 24 months after surgery using 3 different scoring systems: Swiss Spinal Stenosis Questionnaire, Neurogenic Claudication Outcome Score, and Oswestry Disability Index. The group of patients with preoperative aggravation of the symptoms by the lumbar extension test, (positive extension test), was compared with the group of patients without aggravation by the test, (negative extension test). Results. Before surgery, patients with a positive extension test scored significantly worse on all disability scoring systems than patients with a negative test. However, the extension test itself had no prognostic value for the overall outcome after lumbar decompression. Using regression models with the 2-year Oswestry Disability Index as dependent variable, only before surgery self-reported health and age were found to have prognostic significance. Conclusion. The lumbar extension test has no predictive value for the outcome after surgical treatment of LSS.