Clinical and Computerized Volumetric Analysis of Posterior Fossa Decompression for Space-Occupying Cerebellar Infarction.

Background and Purpose: Surgical decompression of the posterior fossa is often performed in cases with a space-occupying cerebellar infarction to prevent coma and death. In this study, we analyzed our institutional experience with this condition. We specifically attempted to address timing issues and investigated the role of cerebellar necrosectomy using imaging data and conducting volumetric analyses. Methods: We retrospectively studied pertinent clinical and imaging data, including computerized volumetric analyses (preoperative/postoperative infarction volume, necrosectomy volume, and posterior fossa volume), from all 49 patients who underwent posterior fossa decompression surgery for cerebellar infarction in our department from January 2012 to January 2021. Results: Thirty-five (71%) patients had a Glasgow Coma Scale (GCS) of 14-15 at admission vs. only 14 (29%) before vs. 41 (84%) following surgery. Seven (14%) patients had preventive surgery (initial GCS 14-15, preoperative GCS change ≤ 1). Only 18 (37%) patients had an mRS score of 0-3 at discharge. Estimated overall survival was 70.5% at 1 year. Interestingly, 18/20 (90%) surviving cases had a modified Rankin Scale (mRS) outcome of 0-3 (mRS 0-2: 12/20 [60%]) 1 year after surgery. Surgical timing, including preventive surgery and mass effect of the infarct, in the posterior fossa assessed semi-quantitatively (Kirollos grade) and with volumetric parameters that were not predictive of the patients' (functional) outcomes. Conclusion: Posterior fossa decompression for cerebellar infarction is a life-saving procedure, but rapid recovery of the GCS after surgery does not necessarily translate into good functional outcome. Many patients died during follow-up, but long-term mRS outcomes of 4-5 are rare. Surgery should probably aim primarily at pressure relief, and our clinical as well as volumetric data suggest that the impact of removing an infarcted tissue may be limited. It is presumably relatively safe to initially withhold surgery in cases with a GCS of 14-15.

Impact of COVID-19 on Continuing Medical Education-Results of an Online Survey Among Users of a Non-profit Multi-Specialty Live Online Education Platform.

Background: The Coronavirus Disease-2019 (COVID-19) pandemic accelerated digitalization in medical education. Continuing medical education (CME) as a substantial component of this system was relevantly affected. Here, we present the results of an online survey highlighting the impact on and the role of online CME. Methods: An online survey of 44 questions was completed by users of a German online CME platform receiving an invitation via newsletter. CME habits, requirements, personal perception, and impact of the pandemic were inquired. Standard statistical methods were applied. Results: A total of 2,961 responders took the survey with 2,949 completed surveys included in the final analysis. Most contributions originated from Germany, Austria, and Switzerland. Physicians accounted for 78.3% (57.5% hospital doctors) of responses followed by midwives (7.3%) and paramedics (5.7%). Participating physicians were mainly board-certified specialists (69%; 55.75% hospital specialists, 13.25% specialists in private practice). Frequent online lectures at regular intervals (77.8%) and combined face-to-face and online CME (55.9%) were favored. A duration of 1-2 h was found ideal (57.5%). Technical issues were less a major concern since the pandemic. Conclusion: A shift from face-to-face toward online CME events was expectedly detected since the outbreak. Online CME was accelerated and promoted by the pandemic. According to the perception of users, the CME system appears to have reacted adequately to meet their demand but does not replace human interaction.

Unequal Impact of COVID-19 on Private and Academic Neurosurgical Workforce: Results of an International Survey.

Background: Since the COVID-19 outbreak several manuscripts regarding neurosurgical practice during this pandemic have been published. Qualitative studies on how the pandemic affected neurosurgeons, with additional focus on their practice, are still scarce. This study's objective was to investigate the impact of COVID-19 on various aspects of the professional and private life of a homogeneous group of international neurosurgeons affiliated to the European Association of Neurosurgical Societies (EANS). Methods: Neurosurgeons from Europe and abroad were invited to participate in an online survey endorsed by the Individual Membership Committee of the EANS. The survey captured a subjective snapshot of the impact of the first wave of the COVID-19 pandemic on EANS members and was advertised through its Institutional website. In addition to departmental data, personal feeling of safety, financial security, local precautions, number of surgeries performed, changes in daily routine, and other practice-related information were inquired. Differences among practice types were closely reviewed. Results: The survey was distributed between April and May 2020: 204 neurosurgeons participated. Participants were typically active EANS members (73%), consultants (57.9%), from university hospitals (64.5%). Elective surgical practice was still ongoing only for 15% of responders, whereas 18.7% of them had already transitioned to COVID-19 and emergency medical services. While 65.7% of participants thought their institutions were adequately prepared, lack of testing for SARS-CoV-2, and scarcity of personal protective equipment were still a matter of concern for most of them. Overall surgical activity dropped by 68% (cranial by 54%, spine by 71%), and even emergencies decreased by 35%. COVID-19 prompted changes in communication in 74% of departments, 44% increased telemedicine by >50%. While most neurosurgeons had concerns about personal and families' health, financial outlook appeared to be gloomy only for private practitioners. Conclusion: The lockdown imposed in many countries by the COVID-19 outbreak called for immediate modification of working routine and resulted in a dramatic decrease of elective surgical procedures. Neurosurgeons share common concerns but were not equally exposed to the personal health and financial dangers of the ongoing pandemic.

Health Economic Aspects of Aneurysmal Subarachnoid Hemorrhage: Factors Determining First Year In-Hospital Treatment Expenses.

BACKGROUND: Spontaneous aneurysmal subarachnoid hemorrhage (SAH) is a common neurosurgical emergency with a high case fatality rate. The clinical course of SAH generates high health economic expenses. Here we highlight possible cost-driving factors for in-hospital care expenses for the first year. Furthermore, results are compared with ischemic stroke treatment. METHODS: One hundred and one patients with aneurysmal SAH treated in our hospital from 2007 through 2009 were included. The Hunt and Hess (HH) scale, World Federation of Neurosurgical Societies (WFNS) scale, Fisher Scale, and further outcome-relevant data were recorded. Expenses were calculated using the German fixed case rate classification system consisting of Diagnosis-Related Groups (DRG) and the Operation and Procedure catalogue (OPS). Overall acute length of stay (LOS) and LOS on the intensive care unit (ICU) were separately evaluated. Expenses were compared with formerly published first-year costs of ischemic stroke. RESULTS: Fifty-four percent of the patients (median age 52 years, 69% females) received coiling and 46% clipping. Acute in-hospital treatment accounted for 82% of total in-hospital expenses, while consequential in-hospital treatment accounted only for 18%. Altogether, the total first-year in-hospital expenses for all patients were as high as €2,650,002, resulting in average SAH in-hospital treatment expenses of €26,238 per patient for the first year. Poor clinical condition on admission and longer stay in ICU are the main cost-driving factors. The impact of the aneurysm treatment method is debatable. Only a poor HH grade and longer ICU stay are independent cost-driving factors. SAH treatment expenses are far higher than treatment costs for ischemic stroke in the literature (€6,731 for first-year inpatient and €3,287 for outpatient treatment). CONCLUSIONS: Clinical condition and LOS determine in-hospital expenses after SAH. Aneurysmal SAH prevalently results in a relevant economic impact on the health system exceeding formerly published treatment expenses for ischemic stroke.

Interleukin 6 in cerebrospinal fluid is a biomarker for delayed cerebral ischemia (DCI) related infarctions after aneurysmal subarachnoid hemorrhage.

Interleukin 6 (IL-6) is a prominent proinflammatory cytokine and has been discussed as a potential biomarker for delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage. In the present study we have analyzed the time course of serum and cerebrospinal fluid (CSF) IL-6 levels in 82 patients with severe aneurysmal subarachnoid hemorrhage (SAH) requiring external ventricular drains in correlation to angiographic vasospasm, delayed cerebral ischemia, secondary infarctions and other clinical parameters. We observed much higher daily mean IL-6 levels (but also large interindividual variations) in the CSF than the serum of the patients with a peak between days 4 and 14 including a maximum on day 5 after SAH. Individual CSF peak levels correlated significantly with DCI (mean day 4-14 peak, DCI: 26,291 ± 24,159 pg/ml vs. no DCI: 16,184 ± 13,163 pg/ml; P = 0.023). Importantly, CSF IL-6 levels differed significantly between cases with DCI and infarctions and patients with DCI and no infarction (mean day 4-14 peak, DCI with infarction: 37,209 ± 26,951 pg/ml vs. DCI, no infarction: 15,123 ± 11,239 pg/ml; P = 0.003), while findings in the latter patient group were similar to cases with no vasospasm (mean day 4-14 peak, DCI, no infarction: 15,123 ± 11,239 vs. no DCI: 15,840 ± 12,979; P = 0.873). Together, these data support a potential role for elevated CSF IL-6 levels as a biomarker for DCI with infarction rather than for DCI in general. This fits well with a growing body of evidence linking neuroinflammation to ischemia and infarction, but (together with the large interindividual variations observed) limits the diagnostic usefulness of CSF IL-6 levels in SAH patients.

Delayed Leukoencephalopathy and Foreign Body Reaction After Endovascular Treatment in Patients With Intracranial Aneurysms and Aneurysmal Subarachnoid Hemorrhage-A Systematic Review of the Literature.

Background: Delayed leukoencephalopathy and foreign body reaction are rare complications after endovascular treatment of intracranial aneurysms. However, cases are increasingly being described, given the rising case numbers and complexity. Methods: Clinical presentation, differentials, diagnostics, treatment, and formerly published data were reviewed in light of available cases. A systematic search of the literature was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Results: This article provides an extensive literature review of previously described cases, and discusses the causes and management of this rare and delayed complication by referring to 17 articles on this topic, with a total of 50 cases with sufficient data in the literature. Furthermore, we present the case of a 53-year-old female patient with subarachnoid hemorrhage from a large anterior communicating artery aneurysm with tortuous cervical vessels who was treated with endovascular coiling and has suffered delayed leukoencephalopathy 6 weeks after discharge. Diagnostics, treatment, and clinical course of this rare complication are presented on this case and based on formerly published literature. The patient timely recovered under high dose corticosteroid treatment and follow up MRI showed almost complete remission of the described lesions within 10 days in accordance with previously published data. Conclusion: Foreign body reaction might result in delayed leukoencephalopathy, especially following complex endovascular aneurysm treatment. Early high dose followed by low dose ongoing corticosteroid treatment might result in timely remission.

Early postoperative seizures (EPS) in patients undergoing brain tumour surgery.

Early postoperative seizures (EPS) are a common complication of brain tumour surgery. This paper investigates risk factors, management and clinical relevance of EPS. We retrospectively analysed the occurrence of EPS, clinical and laboratory parameters, imaging and histopathological findings in a cohort of 679 consecutive patients who underwent craniotomies for intracranial tumours between 2015 and 2017. EPS were observed in 34/679 cases (5.1%), with 14 suffering at least one generalized seizure. Patients with EPS had a worse postoperative Karnofsky performance index (KPI; with EPS, KPI < 70 vs. 70-100: 11/108, 10.2% vs. 23/571, 4.0%; p = 0.007). Preoperative seizure history was a predictor for EPS (none vs. 1 vs. ≥ 2 seizures: p = 0.037). Meningioma patients had the highest EPS incidence (10.1%, p < 0.001). Cranial imaging identified a plausible cause in most cases (78.8%). In 20.6%, EPS were associated with a persisting new neurological deficit that could not otherwise be explained. 34.6% of the EPS patients had recurrent seizures within one year. EPS require an emergency work-up. Multiple EPS and recurrent seizures are frequent, which indicates that EPS may also reflect a more chronic condition i.e. epilepsy. EPS are often associated with persisting neurological worsening.

First Report of Extraspinal Lead Migration Along a Thoracic Spinal Nerve After Spinal Cord Stimulation.

BACKGROUND: Spinal cord stimulation for failed back surgery syndrome and chronic pain is a well-established treatment regimen today. Lead migration is the most common complication; mainly epidural caudal more than cranial electrode migration from the primary position is described repeatedly throughout the literature. CASE DESCRIPTION: A 60-year-old male patient with failed back surgery syndrome was eligible for spinal cord stimulation. Surgery had been performed 4 weeks before readmission with proper lead positioning of both electrodes in the midline of the epidural space. The electrode fixation mechanism at L2/3 had to be revised and was replaced with multiple ligature fixations due to the patient's slim build. He presented to our outpatient clinic with thoracic right-sided pain matching T5 with signs of overstimulation of the paravertebral muscles. X-ray imaging revealed cranial migration of 1 lead to T4 and a right-sided extraspinal migration of the other lead along a spinal nerve in T5 exiting the neuroforamen and following beneath the corresponding rib dorsally. Revision surgery was performed using a thoracic paddle electrode. CONCLUSIONS: Lead migration remains a challenge in spinal cord stimulation regardless of the fixation method. Rare unusual migration patterns in addition to simple caudal or cranial migration might pose a challenge for revision surgery and thus might reduce overall treatment efficacy.

Safety and Efficacy of Negative Pressure Wound Therapy for Deep Spinal Wound Infections After Dural Exposure, Durotomy, or Intradural Surgery.

BACKGROUND: Negative pressure wound therapy (NPWT) for deep spinal wound infections after exposure or opening of the dura can carry significant risks (i.e., cerebrospinal fluid infections and fistulas). In the present study, we reviewed a fairly large and recent experience with such patients. METHODS: We identified 25 patients with exposure and/or incision of the dura who had undergone NPWT from January 2014 to June 2018 for deep spinal wound infections. The demographic data, specifics of primary surgery and NPWT (i.e., dressing changes, duration, time required for wound healing), patients' clinical course, outcomes, and microbiological findings were studied. Application of a Granufoam vacuum dressing with a continuous negative pressure of 60 mm Hg was performed after proper debridement. RESULTS: Of the 25 patients, 13 were women and 12 were men (median age, 69 years). They had primarily undergone treatment for spinal tumors (n = 7), infections and degenerative disease (n = 8 each), or fractures (n = 2), with instrumentation in 18 patients (72%). The dura was exposed in all 25 patients and had been incised in 10 (40%) patients (intended incision, 3; accidental incision, 7). Most patients had been treated for a lumbar wound infection (64%). A microorganism was detected in 84% of the cases, with Staphylococcus aureus accounting for most of the infections (48%). NPWT was concluded after a median of 4 dressing changes (range, 2-14) and 19 days (range, 10-70), with no implant removal required in any patient. NPWT application was observed to be safe without cerebrospinal fluid-related complications. The presence of comorbidities (28% had diabetes) had no effect on the treatment results. CONCLUSIONS: NPWT can be safely applied for deep spinal wound infections after dura exposure or durotomy during previous spine surgery.

Cardiac Arrest in Patients with Poor-Grade Aneurysmal Subarachnoid Hemorrhage: A Single-Center Experience.

BACKGROUND: Poor-grade aneurysmal subarachnoid hemorrhage (SAH), in particular Hunt and Hess (H&H) grade 5 SAH, still has a high case-fatality rate. Recent studies regarding the clinical outcome of such patients and the influence of comorbidities, especially cardiac arrest (CA) requiring additional cardiopulmonary resuscitation (CPR), on the outcome of these patients are scant. Our primary objective was to assess the outcome of SAH H&H grade 5 patients and the influence of additional CA and requirement for CPR. METHODS: All patients with spontaneous aneurysmal SAH H&H grade 5 admitted to our hospital from 2001 to 2010 were enrolled in the study. Data were extracted from the hospital's clinical records and electronic database. The patients' clinical outcome at time of discharge was represented by the Glasgow Outcome Score and modified Rankin Scale (mRS). The influence of CA and additional CPR on patient outcome was analyzed. RESULTS: Of 80 SAH H&H grade 5 patients (median age 55 years), 21 patients (median age 50 years) experienced CA and received additional CPR. Mortality in SAH H&H grade 5 patients was 85% with CA and 68% without CA (p = 0.158). Overall, 22 of 59 patients with no CA survived, 4 with a good clinical outcome (mRS 0-3). Of the 21 with CA, only 3 survived, none with a good outcome (mRS 4-5). Due to the small subgroup surviving additional CA, a statistical difference could not be found between the groups. Aneurysm occlusion (p < 0.001) and aneurysm of the posterior circulation (p = 0.010) resulted in a more favorable clinical outcome. CONCLUSIONS: Patients with SAH H&H grade 5 do survive and in 5% of cases even with a good outcome. Surviving an additional CA resulted in a less favorable outcome without statistical significance. Thus SAH H&H grade 5 patients with or without CA and additional CPR should not be excluded from appropriate neurosurgical treatment.

Spontaneous Aneurysmal Subarachnoid Hemorrhage and Related Cortisol and Immunologic Alterations: Impact on Patients' Health-related Quality of Life.

OBJECTIVE: To highlight the impact of aneurysmal subarachnoid hemorrhage (SAH) on surviving patients' health-related quality of life (HRQoL) with respect to cortisol and interleukin (IL)-6 alterations and also to identify possible clinical predictors for a better HRQoL. METHODS: Fifty surviving patients treated in our hospital for aneurysmal SAH in a 2-year period with sufficient HRQoL data were enrolled. A good clinical outcome was represented by the modified Rankin Scale (mRS) 0 to 2. The patient's HRQoL was assessed using the Short Form health survey questionnaire, the Beck Depression Inventory, and the Daily Fatigue Impact Scale at 6 and 12 months. The results were analyzed regarding possible correlation to 24-hour urinary free cortisol, serum, and cerebrospinal fluid IL-6 levels. RESULTS: A reduction of HRQoL in up to 35% of survivors was observed at 6 months and in a high proportion of patients (47.2%) with an assumable good outcome (mRS 0-2). Reduced HRQoL in survivors was found in terms of SF-36 (34.9%), depression (26.8%), and fatigue (14%) at 6 months and 18.4%, 39.4%, and 18.9% at 12 months, respectively. Improvement was recorded at 12 months, mainly in SF-36. Early elevated 24-hour urinary free cortisol and IL-6 levels showed a significant positive impact on HRQoL. CONCLUSIONS: Early cortisol and IL-6 levels may predict patients' HRQoL after SAH. Twelve months after SAH, a considerable percentage of patients with a presumably good outcome (mRS 0-2) had a lower HRQoL compared with the general population. Implementing corresponding tests at discharge and 12-month follow-up is recommended.

Hyponatremia After Spontaneous Aneurysmal Subarachnoid Hemorrhage-A Prospective Observational Study.

OBJECTIVE: Hyponatremia has been frequently observed after aneurysmal subarachnoid hemorrhage (SAH), and some data have suggested a correlation with symptomatic cerebral vasospasm and poor outcomes. The present prospective study investigated sodium and water disturbances after aneurysmal SAH with regard to symptomatic vasospasm and patient outcomes. METHODS: Data from all patients with aneurysmal SAH treated in our department during a 2-year period were collected. Daily natriuresis, sodium levels, water balance, and serum and urine osmolality were measured at 4 different points: day 1 of admission or bleeding, day 3, day 7, and day 14-21 or discharge. The clinical parameters (i.e., Hunt and Hess grade, aneurysm location and treatment, onset of vasospasm) were reviewed. The patients' outcome was assessed using the Glasgow outcome score and modified Rankin scale. RESULTS: A total of 101 patients (70 women; median age, 52 years) were enrolled in the present study. Of these 101 patients, 59.4% had a good grade SAH (Hunt and Hess grade 1-3). The most common aneurysm location was the anterior communicating artery (37%). The results from an electrolyte analysis were available for ≤91 patients at days 1 and 78 at discharge. In 33 patients (32.7%), hyponatremia had been diagnosed at any time point. Hyponatremia was most frequently observed at day 1 and later at days 7-10. A location in the anterior communicating artery resulted in hyponatremia more frequently only at day 1 (P = 0.007). The main causes of hyponatremia were cerebral salt-wasting syndrome (early onset) and syndrome of inappropriate antidiuretic hormone secretion (early and late onset). CONCLUSION: Distinguishing early- and late-onset hyponatremia is of major relevance, because different therapeutic approaches are required. Only hyponatremia at discharge resulted in less favorable outcomes.

Surgical Treatment of Chronic Subdural Hematoma: Predicting Recurrence and Cure.

BACKGROUND: Chronic subdural hematoma (CSDH) is a common neurosurgical condition, especially among elderly patients. Here we have analyzed our institutional experience with surgical management of CSDH. We aimed at identifying predictors of hematoma recurrence and cure, and the respective time course. METHODS: Pertinent data were collected from all 208 patients (136 males; median age, 78 years) treated for unilateral CSDH in our department from 2014 to 2016 after exclusion of cases with CSDH following previous head surgery or missing postoperative imaging. Pre- and postoperative neuroimaging studies were subjected to computer-assisted volumetric analyses. CSDH composition and anatomy were assessed using a modified Nakaguchi classification. RESULTS: A total of 67.8% of the patients presented with neurologic deficits, and 51.4% were at least on 1 anticoagulant agent. Burr hole trephinations were performed in 94.7%. The median residual hematoma volume was 35.0 mL (44.1 mL including air). Surgical recurrences were seen in 17.8%. The median time to repeat surgery was 17 days, and 91.9% of recurrences occurred within 60 days. Recurrence rates varied between 36.4% (separated or trabecular subtypes and postoperative CSDH volume ≥35.0 mL) and 3.7% (all other subtypes and postoperative CSDH volume <35.0 mL). A neuroimaging proven cure could be documented in an estimated 90% of cases at 145 days after first surgery. CONCLUSIONS: Postoperative CSDH volume and the Nakaguchi classification subtypes proved the most powerful predictors of recurrence, cure, and the time to recurrence and cure. Although our results demonstrate the important impact of CSDH volume, composition, and anatomy, they also show that other so far unknown factors play a significant role as well.

Health Care Costs of Spontaneous Aneurysmal Subarachnoid Hemorrhage for Rehabilitation, Home Care, and In-Hospital Treatment for the First Year.

BACKGROUND: Given the young age of onset and high probability of long-term disability after subarachnoid hemorrhage (SAH), the financial impact is expected to be substantial. Our primary objective was to highlight subsequent treatment costs after the acute in-hospital stay, including rehabilitation and home care, compared with costs for ischemic stroke. METHODS: The study included 101 patients (median age 52 years, 70 women) with aneurysmal SAH treated from July 2007 to April 2009. In-hospital costs were calculated using German diagnosis related groups. Rehabilitation costs depended on rehabilitation phase/grade and daily rate. Level of severity of care requirements determined the costs for home care. RESULTS: Of patients, 54% received coiling and 46% received clipping. The clipping group included more poor-grade patients than the coiling group (P = 0.039); 23 patients died. Of 78 surviving patients, 70 received rehabilitation treatment (68 in Germany). Mean rehabilitation costs were €16,030 per patient. Patients in the clipping group generated higher rehabilitation costs and longer treatment periods in rehabilitation facilities (P = 0.001 for costs [€20,290 vs. €11,771] and P = 0.011 for duration (54.4 days vs. 40.5 days). Of surviving patients, 32% needed home care, of whom 52% required constant care. Multivariate regression analysis identified longer intensive care unit stay and poor Hunt and Hess grade as independent predictors of higher costs. CONCLUSIONS: Aneurysmal SAH prevalently affects working individuals with long-term occupational disability necessitating long-term medical rehabilitation for most patients and subsequent nursing care in one third of survivors. Overall, SAH treatment generates far higher costs than reported for ischemic stroke.

Distribution of the hematopoietic growth factor G-CSF and its receptor in the adult human brain with specific reference to Alzheimer's disease.

The granulocyte colony-stimulating factor (G-CSF), being a member of the hematopoietic growth factor family, is also critically involved in controlling proliferation and differentiation of neural stem cells. Treatment with G-CSF has been shown to result in substantial neuroprotective and neuroregenerative effects in various experimental models of acute and chronic diseases of the central nervous system. Although G-CSF has been tested in a clinical study for treatment of acute ischemic stroke, there is only fragmentary data on the distribution of this cytokine and its receptor in the human brain. Therefore, the present study was focused on the immunohistochemical analysis of the protein expression of G-CSF and its receptor (G-CSF R) in the adult human brain. Since G-CSF has been shown not only to exert neuroprotective effects in animal models of Alzheimer's disease (AD) but also to be a candidate for clinical treatment, we have also placed an emphasis on the regulation of these molecules in this neurodegenerative disease. One major finding is that both G-CSF and G-CSF R were ubiquitously but not uniformly expressed in neurons throughout the CNS. Protein expression of G-CSF and G-CSF R was not restricted to neurons but was also detectable in astrocytes, ependymal cells, and choroid plexus cells. However, the distribution of G-CSF and G-CSF R did not substantially differ between AD brains and control, even in the hippocampus, where early neurodegenerative changes typically occur.

Distribution of granulocyte-monocyte colony-stimulating factor and its receptor α-subunit in the adult human brain with specific reference to Alzheimer's disease.

Granulocyte-monocyte colony-stimulating factor (GM-CSF) is a member of the hematopoietic growth factor family, promoting proliferation and differentiation of hematopoietic progenitor cells of the myeloid lineage. In recent years, GM-CSF has also proved to be an important neurotrophic factor in the central nervous system (CNS) via binding to the GM-CSF receptor (GM-CSF R). Furthermore, studies on rodent CNS revealed a wide distribution of both the major binding α-subunit of the GM-CSF R (GM-CSF Rα) and its ligand. Since respective data on the expression pattern of these two molecules are still lacking, the present study has been designed to systematically analyze the protein expression of GM-CSF and GM-CSF Rα in the human brain, with particular emphasis on their regulation in Alzheimer's disease (AD). One major finding is that both GM-CSF and GM-CSF Rα were ubiquitously but not uniformly expressed in neurons throughout the CNS. Protein expression of GM-CSF and GM-CSF Rα was not restricted to neurons but also detectable in astrocytes, ependymal cells and choroid plexus cells. Interestingly, distribution and intensity of immunohistochemical staining for GM-CSF did not differ among AD brains and age-matched controls. Concerning GM-CSF Rα, a marked reduction of protein expression was predominantly detected in the hippocampus although a slight reduction was also found in various cortical regions, thalamic nuclei and some brainstem nuclei. Since the hippocampus is one of the target regions of neurodegenerative changes in AD, reduction of GM-CSF Rα, with consecutive downregulation of GM-CSF signaling, may contribute to in the progressive course of neurodegeneration in AD.