Clinical Course in Chronic Subdural Hematoma Patients Aged 18–49 Compared to Patients 50 Years and Above: A Multicenter Study and Meta-Analysis

Objective: Chronic Subdural Hematoma (cSDH) is primarily a disease of elderly, and is rare in patients <50 years, and this may in part be related to the increased brain atrophy from 50 years of age. This fact may also influence clinical presentation and outcome. The aim of this study was to study the clinical course with emphasis on clinical presentation of cSDH patients in the young (<50 years).Methods: A retrospective review of a population-based cohort of 1,252 patients operated for cSDH from three Scandinavian neurosurgical centers was conducted. The primary end-point was difference in clinical presentation between the patients <50 y/o and the remaining patients (≥50 y/o group). The secondary end-points were differences in perioperative morbidity, recurrence and mortality between the two groups. In addition, a meta-analysis was performed comparing clinical patterns of cSDH in the two age groups.Results: Fifty-two patients (4.2%) were younger than 50 years. Younger patients were more likely to present with headache (86.5% vs. 37.9%, p < 0.001) and vomiting (25% vs. 5.2%, p < 0.001) than the patients ≥50 y/o, while the ≥50 y/o group more often presented with limb weakness (17.3% vs. 44.8%, p < 0.001), speech impairment (5.8% vs. 26.2%, p = 0.001) and gait disturbance or falls (23.1% vs. 50.7%, p < 0.001). There was no difference between the two groups in recurrence, overall complication rate and mortality within 90 days. Our meta-analysis confirmed that younger patients are more likely to present with headache (p = 0.015) while the hemispheric symptoms are more likely in patients ≥50 y/o (p < 0.001).Conclusion: Younger patients with cSDH present more often with signs of increased intracranial pressure, while those ≥50 y/o more often present with hemispheric symptoms. No difference exists between the two groups in terms of recurrence, morbidity, and short-term mortality. Knowledge of variations in clinical presentation is important for correct and timely diagnosis in younger cSDH patients

On the actions of neurotrophic factors on the chromaffin cells of the adrenal medulla

Chromaffin cells producing adrenaline or noradrenaline are the predominant celltype in the adrenal medulla, but ganglion cells and Schwann cells are also present. All cells of the adrenal medulla are derived from the neural crest, which is a transient neuroectoderm-derived embryonic structure. During the migration of the pluripotent neural crest cells they differentiate into their mature phenotype. The differentiation is regulated by signal molecules, such as neurotrophic factors and steroid hormones. The pluripotency of the neural crest cells is to some extent maintained in the mature chromaffin cells. In this thesis chromaffin cells were used to study the effects of nerve growth factor (NGF) and other neurotrophic factors on the transformation of adult chromaffin cells into neuronal-like phenotypes, as well as the expression and regulation of neurotrofic factors and their receptors. Furthermore, striatal neuronal responses to intraparenchymal infusion of NGF was studied. In situ hybridization, immunohistochemistry, neurite outgrowth assay, TGFß and NGF assays, and HPLC were used to study the chromaffin cells in situ and the effects of neurotrophic factors on intraocular transplanted and primary cultured adult chromaffin cells. Dose-dependent reinnervation of host irides in response to different concentrations of NGF was shown. Nerve fiber formation was saturated when transplants were treated with NGF (100 [my]g/ml), and the half-maximal effect was achieved when host eyes were injected with 30 [my]g/ml NGF. As a result of the first study a baseline of neurite formation in response to NGF had been documented, and therefore other neurotrophic factors were tested using the same experimental model. The results revealed that ciliary neurotrophic factor (CNTF), basic fibroblast growth factor (bFGF), neurotrophin 4 (NT-4), glial cell line-derived neurotrophic factor (GDNF), at concentrations of 100200 [my]g/ml, stimulated nerve fiber formation from chromaffin grafts. Neurotrophin 3 (NT-3) was the only neurotrophic factor tested that had no effect on neurite outgrowth. In the next series of experiment the relationship between NGF and transforming growth factor-ß (TGFß) was studied on the chromaffin cells. No synergistic effect was found on neurite formation after co-administration of TGFß and NGF in the chromaffin grafts. Instead grafts treated with NGF and antibodies against TGFß resulted in enlarged area of reinnervation. TGFß and NGF had thus antagonistic effects on neurite formation from the chromaffin cells. Using in situ hybridization CNTF receptor alpha (CNTFR[alpha]) mRNA was detected in P1, and adult adrenal medullary cells. Increased level of CNTFR[alpha] mRNA was seen after NGF treatment. Furthermore, GDNF family receptor alpha I (GFR[alpha]1) mRNA was present in the ganglion cells of the adrenal medulla, when adult adrenal medullary tissue was explanted, many chromaffin cells became GFR[alpha]1 mRNA-positive. Factors within cell culture medium were important for the expression of GFR[alpha]1 in the cultured chromaffin cells. GDNF induced neurite formation from intraocular chromaffin grafts, and this neurite-promoting capacity of GDNF, was confirmed in primary cultures of adult chromaffin cells. Intrastriatal transplants of chromaffin tissue as a source of catecholamines, have been proposed as an alternative treatment strategy in Parkinsion's disease. In clinical trials intrastriatal chromaffin transplant have been stimulated by co-administration of NGF. A transient reduction of some typical parkinsonian symptoms was reported. In the last article of this thesis NGF was intraparenchymally infused into the normal rat striatum, to evaluate the role of NGF on the striatal neurons. NGF diffused from the infusion site to the overlying cortex and to the hippocampus. The results revealed that increased levels of mRNA corresponding to trkA, p75, muscarin receptor 2, ChAT and increased levels of acetylcholine esterase in the NGF infused striatum compared to contralateral side were found. Thus, NGF stimulates the cholinergic system, which is believed to be excitatory in the striatum. Surprisingly, a decreased spontaneous firing rate was found in the NGF infused animals, although the cholinergic markers were upregulated. This downregulation of spontaneous activity in the striatum could explain some of the beneficial effects, seen in patients suffering from Parkinson's disease, when NGF was co-administrated to the intra striatal chromaffin graft

Effect of Irrigation Fluid Temperature on Recurrence in the Evacuation of Chronic Subdural Hematoma : A Randomized Clinical Trial

Importance: The effect of a physical property of irrigation fluid (at body vs room temperature) on recurrence rate in the evacuation of chronic subdural hematoma (cSDH) needs further study. Objective: To explore whether irrigation fluid temperature has an influence on cSDH recurrence. Design, Setting, and Participants: This was a multicenter randomized clinical trial performed between March 16, 2016, and May 30, 2020. The follow-up period was 6 months. The study was conducted at 3 neurosurgical departments in Sweden. All patients older than 18 years undergoing cSDH evacuation during the study period were screened for eligibility in the study. Interventions: The study participants were randomly assigned by 1:1 block randomization to the cSDH evacuation procedure with irrigation fluid at room temperature (RT group) or at body temperature (BT group). Main Outcomes and Measures: The primary end point was recurrence requiring reoperation within 6 months. Secondary end points were mortality, health-related quality of life, and complication frequency. Results: At 6 months after surgery, 541 patients (mean [SD] age, 75.8 [9.8] years; 395 men [73%]) had a complete follow-up according to protocol. There were 39 of 277 recurrences (14%) requiring reoperation in the RT group, compared with 16 of 264 recurrences (6%) in the BT group (odds ratio, 2.56; 95% CI, 1.38-4.66; P < .001). There were no significant differences in mortality, health-related quality of life, or complication frequency. Conclusions and Relevance: In this study, irrigation at body temperature was superior to irrigation at room temperature in terms of fewer recurrences. This is a simple, safe, and readily available technique to optimize outcome in patients with cSDH. When irrigation is used in cSDH surgery, irrigation fluid at body temperature should be considered standard of care. Trial Registration: ClincalTrials.gov Identifier: NCT02757235

The Swedish study of Irrigation-fluid temperature in the evacuation of Chronic subdural hematoma (SIC!) : study protocol for a multicenter randomized controlled trial

Background: Chronic subdural hematoma (cSDH) is one of the most common conditions encountered in neurosurgical practice. Recurrence, observed in 5-30% of patients, is a major clinical problem. The temperature of the irrigation fluid used during evacuation of the hematoma might theoretically influence recurrence rates since irrigation fluid at body temperature (37 degrees C) may beneficially influence coagulation and cSDH solubility when compared to irrigation fluid at room temperature. Should no difference in recurrence rates be observed when comparing irrigation-fluid temperatures, there is no need for warmed fluids during surgery. Our main aim is to investigate the effect of irrigation-fluid temperature on recurrence rates and clinical outcomes after cSDH evacuation using a multicenter randomized controlled trial design. Methods: The study will be conducted in three neurosurgical departments with population-based catchment areas using a similar surgical strategy. In total, 600 patients fulfilling the inclusion criteria will randomly be assigned to either intraoperative irrigation with fluid at body temperature or room temperature. The power calculation is based on a retrospective study performed at our department showing a recurrence rate of 5% versus 12% when comparing irrigation fluid at body temperature versus fluid at room temperature (unpublished data). The primary endpoint is recurrence rate of cSDH analyzed at 6 months post treatment. Secondary endpoints are mortality rate, complications and health-related quality of life. Discussion: Irrigation-fluid temperature might influence recurrence rates in the evacuation of chronic subdural hematomas. We present a study protocol for a multicenter randomized controlled trial investigating our hypothesis that irrigation fluid at body temperature is superior to room temperature in reducing recurrence rates following evacuation of cSDH

Amino acid tracers in PET imaging of diffuse low-grade gliomas : a systematic review of preoperative applications

Positron emission tomography (PET) imaging using amino acid tracers has in recent years become widely used in the diagnosis and prediction of disease course in diffuse low-grade gliomas (LGG). However, implications of preoperative PET for treatment and prognosis in this patient group have not been systematically studied. The aim of this systematic review was to evaluate the preoperative diagnostic and prognostic value of amino acid PET in suspected diffuse LGG. Medline, Cochrane Library, and Embase databases were systematically searched using keywords "PET," "low-grade glioma," and "amino acids tracers" with their respective synonyms. Out of 2137 eligible studies, 28 met the inclusion criteria. Increased amino acid uptake (lesion/brain) was consistently reported among included studies; in 25-92% of subsequently histopathology-verified LGG, in 83-100% of histopathology-verified HGG, and also in some non-neoplastic lesions. No consistent results were found in studies reporting hot spot areas on PET in MRI-suspected LGG. Thus, the diagnostic value of amino acid PET imaging in suspected LGG has proven difficult to interpret, showing clear overlap and inconsistencies among reported results. Similarly, the results regarding the prognostic value of PET in suspected LGG and the correlation between uptake ratios and the molecular tumor status of LGG were conflicting. This systematic review illustrates the difficulties with prognostic studies presenting data on group-level without adjustment for established clinical prognostic factors, leading to a loss of additional prognostic information. We conclude that the prognostic value of PET is limited to analysis of histological subgroups of LGG and is probably strongest when using kinetic analysis of dynamic FET uptake parameters