Igor Fischer

5-ALA fluorescence of cerebral metastases and its impact for the local-in-brain progression

Aim of the present study was to analyze the oncological impact of 5-ALA fluorescence of cerebral metastases. A retrospective analysis was performed for 84 patients who underwent 5-ALA fluorescence-guided surgery of a cerebral metastasis. Dichotomized fluorescence behavior was correlated to the histopathological subtype and primary site of the metastases, the degree of surgical resection on an early postoperative MRI within 72 hours after surgery, the local in-brain-progression rate and the overall survival. 34/84 metastases (40.5%) showed either strong or faint and 50 metastases (59.5%) no 5-ALA derived fluorescence. Neither the primary site of the cerebral metastases nor their subtype correlated with fluorescence behavior. The dichotomized 5-ALA fluorescence (yes vs. no) had no statistical influence on the degree of surgical resection. Local in-brain progression within or at the border of the resection cavity was observed in 26 patients (30.9%). A significant correlation between 5-ALA fluorescence and local in-brain-progression rate was observed and patients with 5-ALA-negative metastases had a significant higher risk of local recurrence compared to patients with 5-ALA positive metastases. After exclusion of the 20 patients without any form of adjuvant radiation therapy, there was a trend towards a relation of the 5-ALA behavior on the local recurrence rate and the time to local recurrence, although results did not reach significance anymore. Absence of 5-ALA-induced fluorescence may be a risk factor for local in-brain-progression but did not influence the mean overall survival. Therefore, the dichotomized 5-ALA fluorescence pattern might be an indicator for a more aggressive tumor.

Efficacy of adjunctive vagus nerve stimulation in patients with Dravet syndrome: A meta-analysis of 68 patients

RATIONALE Dravet Syndrome (DS) is a severe epileptic encephalopathy of childhood involving intractable seizures, recurrent status epilepticus and cognitive decline. Because DS is a rare disease, available data is limited and evidence-based treatment guidelines are lacking. Vagus nerve stimulation (VNS) is an established neurostimulation treatment for intractable epilepsy, however little evidence is published on its efficacy in patients with DS. METHODS We performed a meta-analysis of all peer-reviewed English language studies reporting seizure outcomes of patients with DS treated with adjunctive vagus nerve stimulation. The primary and secondary outcome measures were ≥50% reduction of seizures or of the most-debilitating seizure type and seizure reduction per patient. RESULTS 13 studies comprising 68 patients met the inclusion criteria of which 11 were single-center retrospective case series, one was a multi-center retrospective analysis and one was a case report. 52.9% of patients experienced a ≥50% reduction of seizures and the average seizure reduction, which could only be assessed in n=28 patients was 50.8%. 7 out of 13 studies reported additional benefits of VNS, however this could not be assessed systematically. CONCLUSION Vagus nerve stimulation appears to reduce seizure frequency in patients with DS. Based on this preliminary analysis, controlled trials of VNS in this rare condition using patient-centric outcome measures are indicated.

Predictive anatomical factors for rupture in middle cerebral artery mirror bifurcation aneurysms

OBJECTIVE The aim of this study was to define predictive factors for rupture of middle cerebral artery (MCA) mirror bifurcation aneurysms. METHODS The authors retrospectively analyzed the data in patients with ruptured MCA bifurcation aneurysms with simultaneous presence of an unruptured MCA bifurcation mirror aneurysm treated in two neurosurgical centers. The following parameters were measured and analyzed with the statistical software R: neck, dome, and width of both MCA aneurysms-including neck/dome and width/neck ratios, shape of the aneurysms (regular vs irregular), inflow angle of both MCA aneurysms, and the diameters of the bilateral A1 and M1 segments and the frontal and temporal M2 trunks, as well as the bilateral diameter of the internal carotid artery (ICA). RESULTS The authors analyzed the data of 44 patients (15 male and 29 female, mean age 50.1 years). Starting from the usual significance level of 0.05, the Sidak-corrected significance level is 0.0039. The diameter of the measured vessels was statistically not significant, nor was the inflow angle. The size of the dome was highly significant (p = 0.0000069). The size of the neck (p = 0.0047940) and the width of the aneurysms (p = 0.0056902) were slightly nonsignificant at the stated significance level of 0.0039. The shape of the aneurysms was bilaterally identical in 22 cases (50%). In cases of asymmetrical presentation of the aneurysm shape, 19 (86.4%) ruptured aneurysms were irregular and 3 (13.6%) had a regular shape (p = 0.001). CONCLUSIONS In this study the authors show that the extraaneurysmal flow dynamics in mirror aneurysms are nonsignificant, and the aneurysmal geometry also does not seem to play a role as a predictor for rupture. The only predictors for rupture were size and shape of the aneurysms. It seems as though under the same conditions, one of the two aneurysms suffers changes in its wall and starts growing in a more or less stochastic manner. Newer imaging methods should enable practitioners to see which aneurysm has an unstable wall, to predict the rupture risk. At the moment one can only conclude that in cases of MCA mirror aneurysms the larger one, with or without shape irregularities, is the unstable aneurysm and that this is the one that needs to be treated.

Comparison of a special designed high intensity coil to a standard round coil-TMS-setting

BACKGROUND Routine diagnostic Transcranial Magnetic Stimulation (TMS) is performed with a round coil (RC) for cranial and spinal root stimulation, being less successful for motor evoked potentials (MEP) of lower limb muscles. MEP elicited with a special configured flat figure-of-eight coil designed for high intensity stimulation (HI-coil) were compared to RC with regard to handling, efficiency, and physiological properties of MEP. NEW METHODS MEP elicited with HI-coil and 9-cm diameter RC for cortical, spinal and peripheral stimulation (PES) were compared for Motor threshold (MT), latencies and amplitudes of bilateral Abductor pollicis brevis (APB) and Abductor hallucis muscles (AH). RESULTS AND COMPARISON WITH EXISTING METHODS MT for HI-coil were significantly lower for cortical and spinal root stimulation compared to RC (APB: 37% vs. 48%; AH: 58% vs. 72%). MEP-latencies elicited with HI-coil and RC were without significant difference. AH-MEP amplitudes were significantly larger for HI-coil cortical (705±980μV vs. 370±280μV) and root stimulation (260±210μV vs. 151±100μV). Amplitudes elicited by PES compared to HI-coil were always significantly larger. CONCLUSION Results for cortical and spinal root stimulation with regards to latencies and amplitudes for APB were equivalent between HI-coil and RC. PES was superior in achieving supramaximal stimulation in terms of amplitudes. The use of the HI-coil might be advantageous for MEP of lower extremity muscles with emphasis on pathologic conditions requiring higher stimulation intensities.

Aneurysm wall enhancement in black blood MRI correlates with aneurysm size. Black blood MRI could serve as an objective criterion of aneurysm stability in near future

The increasing number of incidental intracranial aneurysms creates a dilemma of which aneurysms to treat and which to observe. Clinical scoring systems consider risk factors for aneurysm rupture however objective parameters for assessment of aneurysms stability are needed. We retrospectively analysed contrast enhancing behaviour of un-ruptured aneurysms in the black blood magnetic resonance imaging (MRI) in N=71 patients with 90 aneurysms and assessed correlation between aneurysm wall contrast enhancement (AWCE) and aneurysm anatomy and clinical scoring systems. AWCE is associated with aneurysm height and height to width ratio in ICA aneurysms. AWCE is correlated to larger aneurysms in every anatomical location evaluated. However the mean size of the contrast enhancing aneurysms is significantly different between anatomical localizations indicating separate analyses for every artery. Clinical scoring systems like PHASES and UIATS correlate positively with AWCE in black blood MRI. MRI aneurysm wall contrast enhancement is a positive predictor for aneurysm instability and should be routinely assessed in follow up of incidental aneurysms. Aneurysms smaller than 7 mm with AWCE should be followed closely with focus on growth, as they may be prone to growth and rupture.

Volume of cerebrospinal fluid drainage as a predictor for pretreatment aneurysmal rebleeding

OBJECTIVE Initiation of external CSF drainage has been associated with a significant increase in rebleeding probability after aneurysmal subarachnoid hemorrhage (aSAH). However, the implications for acute management are uncertain. The purpose of this study was to evaluate the role of the amount of drained CSF on aneurysmal rebleeding. METHODS Consecutive patients with aSAH were analyzed retrospectively. Radiologically confirmed cases of aneurysmal in-hospital rebleeding were identified and predictor variables for rebleeding were retrieved from hospital records. Clinical predictors were identified through multivariate analysis, and logistic regression analysis was performed to ascertain the cutoff value for the rebleeding probability. RESULTS The study included 194 patients. Eighteen cases (9.3%) of in-hospital rebleeding could be identified. Using multivariate analysis, in-hospital rebleeding was significantly associated with initiation of CSF drainage (p = 0.001) and CSF drainage volume (63 ml [interquartile range (IQR) 55-69 ml] vs 25 ml [IQR 10-35 ml], p < 0.001). Logistic regression showed that 58 ml of CSF drainage within 6 hours results in a 50% rebleeding probability. The relative risk (RR) for rebleeding after drainage of more than 60 ml in 6 hours was 5.4 times greater compared with patients with less CSF drainage (RR 5.403, 95% CI 2.481-11.767; p < 0.001, number needed to harm = 1.687). CONCLUSIONS Volume of CSF drainage was highly correlated with the probability of in-hospital aneurysmal rebleeding. These findings suggest that the rebleeding probability can be affected in acute management should the placement of an external ventricular catheter be necessary. This finding necessitates meticulous control of the amount of drained CSF and the development of a definitive treatment protocol for this group of patients.

Level of headaches after surgical aneurysm clipping decreases significantly faster compared to endovascular coiled patients

In incidental aneurysms, endovascular treatment can lead to post-procedural headaches. We studied the difference of surgical clipping vs. endovascular coiling in concern to post-procedural headaches in patients with ruptured aneurysms. Sixty-seven patients with aneurysmal subarachnoidal haemorrhage were treated in our department from September 1st 2015 - September 1st 2016. 43 Patients were included in the study and the rest was excluded because of late recovery or high-grade subarachnoid bleedings. Twenty-two were surgical treated and twenty-one were interventionally treated. We compared the post-procedural headaches at the time points of 24 h, 21 days, and 3 months after treatment using the visual analog scale (VAS) for pain. After surgical clipping the headache score decreased for 8.8 points in the VAS, whereas the endovascular treated population showed a decrease of headaches of 3.3 points. This difference was highly statistical significant and remained significant even after 3 weeks where the pain score for the surgically treated patients was 0.68 and for the endovascular treated 1.8. After 3 months the pain was less than 1 for both groups with surgically treated patients scoring 0.1 and endovascular treated patients 0.9 (not significant). Clipping is relieving the headaches of patients with aneurysm rupture faster and more effective than endovascular coiling. This effect stays significant for at least 3 weeks and plays a crucial role in stress relieve during the acute and subacute ICU care of such patients.

Response to the Letter to the Editor Surgery for high-grade unruptured arteriovenous malformations: era for a new paradox? by Bervini and Morgan.

We appreciate the comments by Bervini and Morgan regarding our publication BMicrosurgical resection of Spetzler–Martin grades 1 and 2 unruptured brain arteriovenous malformations results in lower long-term morbidity and loss of quality-adjusted life-years (QALY) than conservative managementResults of a single group series^. They challenge our somewhat-simplified conclusion that at present a benefit of microsurgical treatment of Spetzler–Martin (SM) grade 1 and 2 arteriovenous malformation (AVMs) can be accepted with certainty while this is not the case for SM grades 3 and 4. They argue that, despite its high morbidity, microsurgical treatment mortality for unruptured SM grade 3 AVM is likely lower than the long-term mortality resulting from the natural history. In general, it is somewhat difficult to compare a onetime risk (i.e., treatment-related morbidity) with a longterm risk (natural history of AVMs) as these are two different quantities: Is it better for a 40-year-old patient to live with a permanent neurological deficit without the threat of hemorrhage and premature death, or to live and work normally up to the age of 50 or 60 and then possibly suffer a hemorrhage and die suddenly? We tried to partially solve this dilemma by normalizing morbidity and mortality in terms of lost qualityadjusted life-years (QALY). Although with this approach SM grade 3 as a whole group did not benefit from microsurgery, patients younger than 39 years did. A clear benefit of surgical treatment was seen in the younger patients with SM grade 3 AVMs. The surgical risk in these patients with respect to lost QALY was negated by the natural course within 5–7 years. However, statistical uncertainty due to the small sample size precluded us from drawing more definitive conclusions regarding the potential benefit of microsurgical resection in younger patients with SM grade 3 AVM. Thus, we agree that the appropriate management of AVM patients requires careful and nuanced assessment of risks and benefits of both invasive and conservative treatment for every patient individually until more data in this respect become available. * Hans-Jakob Steiger steiger@uni-duesseldorf.de

Reply to: accelerometer-based goniometer for smartphone and manual measurement on photographs: do they agree?

We appreciate the opportunity to answer the letter by Ferriero et al. [1] concerning our paper “Monitoring recovery after elbow surgery using smartphones” [2]. Before delving into details, we would like to point out that the purpose of our study was not to establish a more precise goniometric method (there are certainly more exact ones than one that is accelerometer-based), but a convenient and cost-efficient method for documenting progress during physical therapy. Now, turning to the specific points raised by Ferriero et al.: The elbow range of motion was measured during physical therapy. While the therapy is inherently dynamic, the relevant measurements, at maximum attainable flexion/extension are essentially static, as the movement is halted. Especially at the early stage of the therapy, when a full flexion/extension cycle takes almost 10 s, the difference between static and dynamic measurement should be negligible. We made only two photography-based measurements to ensure plausibility of the accelerometer-based values and did not perform a statistical analysis of the

Monitoring Recovery after Elbow Surgery Using Smartphone.

Inexpensive, accelerometer-equipped smartphone is used for monitoring and documenting recovery progress after elbow surgery. We can identify four distinct recovery phase.