Synchronous versus metachronous spinal metastasis: a comparative study of survival outcomes following neurosurgical treatment.

PURPOSE: Patients with spinal metastases (SM) from solid neoplasms typically exhibit progression to an advanced cancer stage. Such metastases can either develop concurrently with an existing cancer diagnosis (termed metachronous SM) or emerge as the initial indication of an undiagnosed malignancy (referred to as synchronous SM). The present study investigates the prognostic implications of synchronous compared to metachronous SM following surgical resection. METHODS: From 2015 to 2020, a total of 211 individuals underwent surgical intervention for SM at our neuro-oncology facility. We conducted a survival analysis starting from the date of the neurosurgical procedure, comparing those diagnosed with synchronous SM against those with metachronous SM. RESULTS: The predominant primary tumor types included lung cancer (23%), prostate cancer (21%), and breast cancer (11.3%). Of the participants, 97 (46%) had synchronous SM, while 114 (54%) had metachronous SM. The median overall survival post-surgery for those with synchronous SM was 13.5 months (95% confidence interval (CI) 6.1-15.8) compared to 13 months (95% CI 7.7-14.2) for those with metachronous SM (p = 0.74). CONCLUSIONS: Our findings suggest that the timing of SM diagnosis (synchronous versus metachronous) does not significantly affect survival outcomes following neurosurgical treatment for SM. These results support the consideration of neurosurgical procedures regardless of the temporal pattern of SM manifestation.

Functional outcome after late cranioplasty after decompressive craniectomy: a single-center retrospective study.

OBJECTIVE: The best time for cranioplasty (CP) after decompressive craniectomy (DC) is controversial, and there are no authoritative guidelines yet. Both complications as well as outcome may depend on the timing of CP. The aim of this single-center study was to evaluate the impact of late CP on procedural safety as well as on patient outcome. METHODS: All patients receiving CP at a tertiary university medical center between 01/2015 and 12/2022 were included retrospectively. Patients' conditions were assessed according to the modified Rankin Scale (mRS) prior to CP and 6 months after. Baseline characteristics, indication for DC, time from DC to CP, and postoperative complications according to the Landriel Ibañez Classification were analyzed. RESULTS: CP was performed in 271 patients who previously underwent DC due to traumatic brain injury (25.5%), ischemic stroke (29.5%), aneurysmal subarachnoid hemorrhage (26.9%), or intracerebral hemorrhage (18.1%). The median interval between DC and CP was 143 days (interquartile range 112-184 days). Receiver operating characteristic analysis revealed a cut-off of 149 days, where CP performed within 149 days after DC led to an improvement on mRS after CP (p = 0.001). In multivariate analysis, additional rehabilitation after and better mRS before CP were independently associated with improvement of outcome. The rate of complications was similar between early and late CP (24.8% and 25.4%, respectively, p = 0.562). CONCLUSIONS: Late cranioplasty is a safe procedure. The outcome was improved when additional rehabilitation was performed after cranioplasty and was not associated with the timing of cranioplasty.

Frequency and Characteristics of Spinal Bleeding Sources in Nontraumatic Angiogram-Negative Subarachnoid Hemorrhage.

INTRODUCTION: Angiogram-negative subarachnoid hemorrhage (AN-SAH) accounts for 5-15% of spontaneous SAH. This study aims to analyze the frequency and characteristics of spinal bleeding sources in patients with AN-SAH. METHODS: 140 patients suffering from AN-SAH treated at our institution from 2012 to 2022 were included in this retrospective cohort study. RESULTS: 52.1% were diagnosed with perimesencephalic SAH, 35.0% with non-perimesencephalic, SAH and 12.9% with CT-negative SAH (diagnosed by lumbar puncture). Additional magnetic resonance imaging (MRI) identified a spinal bleeding source in 4 patients (2.86%). These patients presented with local spine pain or neurological deficits (relative risk: 3.9706 [95% confidence interval [CI]: 0.7272-21.6792]; p < 0.001) and were younger (mean difference 14.85 years [95% CI: 0.85-28.85; p = 0.038]) compared to patients without a spinal bleeding source. CONCLUSIONS: AN-SAH caused by spinal pathology is rare. This study indicates that craniocervical and holospinal MRI should be considered in AN-SAH, especially for young patients with AN-SAH who present with back pain or neurological deficits.

Additive prognostic impact of the cerebrospinal fluid arginine/ornithine ratio to established clinical scores in aneurysmal subarachnoid hemorrhage.

Cerebrospinal fluid (CSF) metabolites are increasingly recognized as prognostic factors in aneurysmal subarachnoid hemorrhage (SAH). The CSF arginine/ornithine ratio (Arg/Orn) was shown to predict cerebral vasospasms and clinical outcome in SAH. The additive prognostic value of Arg/Orn over established prognostic scores has not been investigated. CSF Arg/Orn and the established prognostic scores SAH, FRESH, SAH-PDS, HAIR, Rosen-McDonald, Hunt and Hess, WFNS and modified Fisher scale were determined in a prospective cohort of patients with aneurysmal SAH. Logistic regression models to predict a favorable outcome, defined as a modified Rankin Scale score of 0-3 at 3 months follow-up, were constructed for each score, both with and without the addition of Arg/Orn. The impact of Arg/Orn was assessed comparing logistic regression models containing the respective score with and without Arg/Orn with the likelihood ratio chi-squared test. CSF Arg/Orn and clinical scores were determined in 38 SAH patients. Arg/Orn was an independent predictor of clinical outcome when added to established prognostic scores (p < 0.05) with the exception of HAIR (p = 0.078). All models were significantly improved if Arg/Orn was added as a covariable (p < 0.05). The results of this study confirm Arg/Orn as an independent prognostic factor and its addition improves established prognostic models in SAH.

Correlation between Blood Type 0 and Risk of Chronic Subdural Hematoma Recurrence: A Single Center Retrospective Cohort Study.

Chronic subdural hematoma (cSDH) is a common disease in the neurological and neurosurgical world. The recommended treatment for cSDH patients with moderate or severe neurological symptoms is surgical evacuation, but cSDH frequently recurs. The patient's ABO blood type may influence the outcome. This study aims to evaluate the correlation between cSDH recurrence and blood type O. We performed a retrospective analysis of the data of patients with cSDH who were surgically treated. Recurrence was defined as the need for re-operation within the first 12 weeks after the initial surgery. We analyzed standard demographic data, duration and type of surgery, ABO blood types, and the re-operation rate. Univariate and multivariate analyses were conducted. A total of 229 patients were included. The recurrence of hematoma was identified in 20.5% of patients. Blood type O was found to be significantly associated with cSDH recurrence leading to re-operation within 12 weeks (p = 0.02, OR 1.9, 95% CI 1.1-3.5). Thrombocyte aggregation inhibition and oral anticoagulants were not predictors of cSDH recurrence. Patients with blood type O in our cohort were identified to be at higher risk of cSDH recurrence and may, therefore, be a more vulnerable patient group. This finding needs further evaluation in larger cohorts.

Size of Craniectomy Predicts Approach-Related Shear Bleeding in Poor-Grade Subarachnoid Hemorrhage.

Decompressive craniectomy is an option to decrease elevated intracranial pressure in poor-grade aneurysmal subarachnoid hemorrhage (SAH) patients. The aim of the present study was to analyze the size of the bone flap according to approach-related complications in patients with poor-grade SAH. We retrospectively analyzed poor-grade SAH patients (WFNS 4 and 5) who underwent aneurysm clipping and craniectomy (DC or ommitance of bone flap reinsertion). Postoperative CT scans were analyzed for approach-related tissue injury at the margin of the craniectomy (shear bleeding). The size of the bone flap was calculated using the De Bonis equation. Between 01/2012 and 01/2020, 67 poor-grade SAH patients underwent clipping and craniectomy at our institution. We found 14 patients with new shear bleeding lesion in postoperative CT scan. In patients with shear bleeding, the size of the bone flap was significantly smaller compared to patients without shear bleeding (102.1 ± 45.2 cm2 vs. 150.8 ± 37.43 cm2, p > 0.0001). However, we found no difference in mortality rates (10/14 vs. 23/53, p = 0.07) or number of implanted VP shunts (2/14 vs. 18/53, p = 0.2). We found no difference regarding modified Rankin Scale (mRS) 6 months postoperatively. In poor-grade aneurysmal SAH, the initial planning of DC-if deemed necessary -and enlargement of the flap size seems to decrease the rate of postoperatively developed shear bleeding lesions.

Pain management with epidural catheter and epidural analgesia after spinal dorsal instrumentation of lumbar spine.

Spinal dorsal instrumentation (SDI) is an established treatment for degenerative spinal diseases. Adequate and immediate postoperative pain control is important for patient recovery and may be compromised by uncertainty about its efficacy and concern about early postoperative surgical complications or adverse events. The aim of the current study was to compare the use of epidural analgesia (EA) with systemic analgesia (SA) as regards pain reduction and early postoperative complications after SDI. Pain management with epidural or systemic analgesia in patients undergoing SDI by posterior approach between January 2019 and July 2020 was evaluated by clinical functional testing, measuring total opioid amounts used, and evaluating numerical rating scale values 24 and 96 hours postoperatively. The following were also monitored: demographic data, number of affected segments, length of hospital stay, inflammatory markers (leukocytes and serum C-reactive protein), early postoperative surgical complication rates, and adverse events. In total 79 patients were included (33 in the EA and 46 in the SA group). The SA group had significantly lower numerical rating scale values at days 1 to 4 after surgery (P ≤ .001) and lower cumulative opioid use than the EA group (P < .001). We found no difference in infection parameters, length of hospital stay or surgery-related complication rates. Our data demonstrate that epidural anesthesia was inferior to an opioid-based SA regime in reducing postoperative pain in patients undergoing spinal surgery. There is no benefit to the use of epidural catheters.

Early fusion outcome after surgical treatment of single-level and multi-level pyogenic spondylodiscitis: experience at a level 1 center for spinal surgery-a single center cohort study.

STUDY DESIGN: Retrospective single center cohort study. PURPOSE: Spinal instrumentation in combination with antibiotic therapy is a treatment option for acute or chronic pyogenic spondylodiscitis (PSD). This study compares the early fusion outcome for multi-level and single-level PSD after urgent surgical treatment with interbody fusion in combination with fixation. METHODS: This is a retrospective cohort study. Over a 10 year period at a single institution, all surgically treated patients received surgical debridement, fusion und fixation of the spine to treat PSD. Multi-level cases were either adjacent to each other on the spine or distant. Fusion rates were assessed at 3 and 12 months after surgery. We analyzed demographic data, ASA status, duration of surgery, location and length of spine affected, Charlson comorbidity index (CCI), and early complications. RESULTS: A total of 172 patients were included. Of these, 114 patients suffered from single-level and 58 from multi-level PSD. The most frequent location was the lumbar spine (54.0%) followed by the thoracic spine (18.0%). The PSD was adjacent in 19.0% and distant in 81.0% of multi-level cases. Fusion rates at the 3 month follow-up did not differ among the multi-level group (p = 0.27 for both adjacent and distant sites). In the single-level group, sufficient fusion was achieved in 70.2% of cases. Pathogen identification was possible 58.5% of the time. CONCLUSIONS: Surgical treatment of multi-level PSD is a safe option. Our study demonstrates that there was no significant difference in early fusion outcomes between single-level and multi-level PSD, whether adjacent or distant.

Non-Convulsive Status Epilepticus in Aneurysmal Subarachnoid Hemorrhage: A Prognostic Parameter.

A non-convulsive status epilepticus (ncSE) is a potentially fatal complication for patients in neurointensive care. In patients with aneurysmal subarachnoid hemorrhage (SAH), ncSE remains scarcely investigated. In this study, we aim to investigate the frequency and influence of non-convulsive status epilepticus on outcome in patients with SAH. We retrospectively analyzed data of consecutive patients with aneurysmal subarachnoid hemorrhage and evaluated clinical, radiological, demographical and electroencephalogram (EEG) data. Outcome was assessed according to the modified Rankin Scale (mRS) at 6 months and stratified into favorable (mRS 0-2) vs. unfavorable (mRS 3-6). We identified 171 patients with SAH, who received EEG between 01/2012 and 12/2020. ncSE was diagnosed in 19 patients (3.7%), only one of whom achieved favorable outcome. The multivariate regression analysis revealed four independent predictors of unfavorable outcome: presence of ncSE (p = 0.003; OR 24.1; 95 CI% 2.9-195.3), poor-grade SAH (p < 0.001; OR 14.0; 95 CI% 8.5-23.1), age (p < 0.001; OR 2.8; 95 CI% 1.6-4.6) and the presence of DIND (p < 0.003; OR 1.9; 95 CI% 1.2-3.1) as independent predictors for unfavorable outcome. According to our study, development of ncSE in patients suffering SAH might correlate with poor prognosis. Even when medical treatment is successful and no EEG abnormalities are detected, the long-term outcome remains poor.

Postoperative Hematoma Expansion in Patients Undergoing Decompressive Hemicraniectomy for Spontaneous Intracerebral Hemorrhage.

Introduction: The aim of the study was to analyze risk factors for hematoma expansion (HE) in patients undergoing decompressive hemicraniectomy (DC) in patients with elevated intracranial pressure due to spontaneous intracerebral hematoma (ICH). Methods: We retrospectively evaluated 72 patients with spontaneous ICH who underwent DC at our institution. We compared the pre- and postoperative volumes of ICH and divided the patients into two groups: first, patients with postoperative HE > 6 cm3 (group 1), and second, patients without HE (group 2). Additionally, we screened the medical history for anticoagulant and antiplatelet medication (AC/AP), bleeding-related comorbidities, age, admission Glasgow coma scale and laboratory parameters. Results: The rate of AC/AP medication was higher in group 1 versus group 2 (15/16 vs. 5/38, p < 0.00001), and patients were significantly older in group 1 versus group 2 (65.1 ± 16.2 years vs. 54.4 ± 14.3 years, p = 0.02). Furthermore, preoperative laboratory tests showed lower rates of hematocrit (34.1 ± 5.4% vs. 38.1 ± 5.1%, p = 0.01) and hemoglobin (11.5 ± 1.6 g/dL vs. 13.13 ± 1.8 g/dL, p = 0.0028) in group 1 versus group 2. In multivariate analysis, the history of AC/AP medication was the only independent predictor of HE (p < 0.0001, OR 0.015, CI 95% 0.001−0.153). Conclusion: We presented a comprehensive evaluation of risk factors for hematoma epansion by patients undergoing DC due to ICH.

Early Serum Creatinine Levels after Aneurysmal Subarachnoid Hemorrhage Predict Functional Neurological Outcome after 6 Months.

Acute kidney injury (AKI) is a known predictor of unfavorable outcome in patients treated at the ICU, irrespective of the disease. However, data on the potential influence of serum creatinine (sCr) on hospital admission on the outcome in patients suffering from aneurysmal subarachnoid hemorrhage (SAH) is scarce. A total of 369 consecutive patients suffering from SAH were included in this retrospective cohort study. Patients were divided into good-grade (WFNS I−III) versus poor-grade (WFNS IV−V). Outcome was assessed according to the modified Rankin Scale (mRS) after 6 months and stratified into favorable (mRS 0−2) versus unfavorable (mRS 3−6). SAH patients with sCr levels <1.0 mg/dL achieved significantly a favorable outcome more often compared to patients with sCr levels ≥1.0 mg/dL (p = 0.003). In the multivariable analysis, higher levels of sCr (p = 0.014, OR 2.4; 95% CI 1.2−4.7), poor-grade on admission (p < 0.001, OR 9.8; 95% CI 5.6−17.2), age over 65 years (p < 0.001, OR 3.3; 95% CI 1.7−6.1), and delayed cerebral ischemia (p < 0.001, OR 7.9; 95% CI 3.7−17.1) were independently associated with an unfavorable outcome. We identified increased sCr on admission as a predictor for unfavorable functional outcome after SAH. Further studies elucidating the pathophysiology of this association are necessary.

Severe white matter damage in SHANK3 deficiency: a human and translational study.

OBJECTIVE: Heterozygous SHANK3 mutations or partial deletions of the long arm of chromosome 22, also known as Phelan-McDermid syndrome, result in a syndromic form of the autism spectrum as well as in global developmental delay, intellectual disability, and several neuropsychiatric comorbidities. The exact pathophysiological mechanisms underlying the disease are still far from being deciphered but studies of SHANK3 models have contributed to the understanding of how the loss of the synaptic protein SHANK3 affects neuronal function. METHODS AND RESULTS: Diffusion tensor imaging-based and automatic volumetric brain mapping were performed in 12 SHANK3-deficient participants (mean age 19 ± 15 years) versus 14 age- and gender-matched controls (mean age 29 ± 5 years). Using whole brain-based spatial statistics, we observed a highly significant pattern of white matter alterations in participants with SHANK3 mutations with focus on the long association fiber tracts, particularly the uncinate tract and the inferior fronto-occipital fasciculus. In contrast, only subtle gray matter volumetric abnormalities were detectable. In a back-translational approach, we observed similar white matter alterations in heterozygous isoform-specific Shank3 knockout (KO) mice. Here, in the baseline data sets, the comparison of Shank3 heterozygous KO vs wildtype showed significant fractional anisotropy reduction of the long fiber tract systems in the KO model. The multiparametric Magnetic Resonance Imaging (MRI) analysis by DTI and volumetry demonstrated a pathology pattern with severe white matter alterations and only subtle gray matter changes in the animal model. INTERPRETATION: In summary, these translational data provide strong evidence that the SHANK3-deficiency-associated pathomechanism presents predominantly with a white matter disease. Further studies should concentrate on the role of SHANK3 during early axonal pathfinding/wiring and in myelin formation.

Shank3 Transgenic and Prenatal Zinc-Deficient Autism Mouse Models Show Convergent and Individual Alterations of Brain Structures in MRI.

Research efforts over the past decades have unraveled both genetic and environmental factors, which contribute to the development of autism spectrum disorders (ASD). It is, to date, largely unknown how different underlying causes result in a common phenotype. However, the individual course of development and the different comorbidities might reflect the heterogeneous genetic and non-genetic contributions. Therefore, it is reasonable to identify commonalities and differences in models of these disorders at the different hierarchical levels of brain function, including genetics/environment, cellular/synaptic functions, brain regions, connectivity, and behavior. To that end, we investigated Shank3 transgenic mouse lines and compared them with a prenatal zinc-deficient (PZD) mouse model of ASD at the level of brain structural alterations in an 11,7 T small animal magnetic resonance imaging (MRI). Animals were measured at 4 and 9 weeks of age. We identified a decreased total brain volume (TBV) and hippocampal size of Shank3-/- mice but a convergent increase of basal ganglia (striatum and globus pallidus) in most mouse lines. Moreover, Shank3 transgenic mice had smaller thalami, whereas PZD mice had this region enlarged. Intriguingly, Shank3 heterozygous knockout mice mostly showed minor abnormalities to full knockouts, which might reflect the importance of proper Shank3 dosage in neuronal cells. Most reported volume changes seemed to be more pronounced at younger age. Our results indicate both convergent and divergent brain region abnormalities in genetic and non-genetic models of ASD. These alterations of brain structures might be mirrored in the reported behavior of both models, which have not been assessed in this study.

Brain Lateralization in Mice Is Associated with Zinc Signaling and Altered in Prenatal Zinc Deficient Mice That Display Features of Autism Spectrum Disorder.

A number of studies have reported changes in the hemispheric dominance in autism spectrum disorder (ASD) patients on functional, biochemical, and morphological level. Since asymmetry of the brain is also found in many vertebrates, we analyzed whether prenatal zinc deficient (PZD) mice, a mouse model with ASD like behavior, show alterations regarding brain lateralization on molecular and behavioral level. Our results show that hemisphere-specific expression of marker genes is abolished in PZD mice on mRNA and protein level. Using magnetic resonance imaging, we found an increased striatal volume in PZD mice with no change in total brain volume. Moreover, behavioral patterns associated with striatal lateralization are altered and the lateralized expression of dopamine receptor 1 (DR1) in the striatum of PZD mice was changed. We conclude that zinc signaling during brain development has a critical role in the establishment of brain lateralization in mice.