| 1. |
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| 2. |
- Bartley, Andreas, et al.
(author)
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Effect of Irrigation Fluid Temperature on Recurrence in the Evacuation of Chronic Subdural Hematoma A Randomized Clinical Trial
- 2023
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In: Jama Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157.
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Journal article (peer-reviewed)abstract
- ImportanceThe 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.ObjectiveTo explore whether irrigation fluid temperature has an influence on cSDH recurrence.Design, Setting, and ParticipantsThis 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.InterventionsThe 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 MeasuresThe primary end point was recurrence requiring reoperation within 6 months. Secondary end points were mortality, health-related quality of life, and complication frequency.ResultsAt 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 RelevanceIn 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.
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| 3. |
- Bartley, Andreas, et al.
(author)
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The Swedish study of Irrigation-fluid temperature in the evacuation of Chronic subdural hematoma (SIC!) : study protocol for a multicenter randomized controlled trial
- 2017
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In: Trials. - : BIOMED CENTRAL LTD. - 1745-6215. ; 18
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Journal article (peer-reviewed)abstract
- 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.
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| 4. |
- Elf, Kristin, et al.
(author)
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Continuous EEG monitoring after brain tumor surgery
- 2019
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In: Acta Neurochirurgica. - : Springer Science and Business Media LLC. - 0001-6268 .- 0942-0940. ; 161:9, s. 1835-1843
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Journal article (peer-reviewed)abstract
- BackgroundProlonged seizures generate cerebral hypoxia and increased intracranial pressure, resulting in an increased risk of neurological deterioration, increased long-term morbidity, and shorter survival. Seizures should be recognized early and treated promptly.The aim of the study was to investigate the occurrence of postoperative seizures in patients undergoing craniotomy for primary brain tumors and to determine if non-convulsive seizures could explain some of the postoperative neurological deterioration that may occur after surgery.MethodsA single-center prospective study of 100 patients with suspected glioma. Participants were studied with EEG and video recording for at least 24 h after surgery.ResultsSeven patients (7%) displayed seizure activity on EEG recording within 24 h after surgery and another two patients (2%) developed late seizures. One of the patients with early seizures also developed late seizures. In five patients (5%), there were non-convulsive seizures. Four of these patients had a combination of clinically overt and non-convulsive seizures and in one patient, all seizures were non-convulsive. The non-convulsive seizures accounted for the majority of total seizure time in those patients. Non-convulsive seizures could not explain six cases of unexpected postoperative neurological deterioration. Postoperative ischemic lesions were more common in patients with early postoperative seizures.ConclusionsEarly seizures, including non-convulsive, occurred in 7% of our patients. Within this group, non-convulsive seizure activity had longer durations than clinically overt seizures, but only 1% of patients had exclusively non-convulsive seizures. Seizures were not associated with unexpected neurological deterioration.
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| 5. |
- Hallin, Karin, 1977-, et al.
(author)
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Pneumolabyrinth following cochlear implantation resolved after shunt adjustment
- 2020
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In: ACTA OTO-LARYNGOLOGICA CASE REPORTS. - : TAYLOR & FRANCIS LTD. - 2377-2484. ; 5:1, s. 81-85
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Journal article (peer-reviewed)abstract
- We present a case of a male with a history of repeated surgeries for a cerebellar astrocytoma, leading to profound deafness and facial paresis on the left side. A ventriculoperitoneal (VP) shunt was inserted to manage hydrocephalus. At the age of 46 the hearing suddenly disappeared on the right side, where he received a cochlear implant (CI). At implant activation, impedances showed atypical high values. One month later impedance levels had further increased and the patient had no benefit from the CI. A computed tomography (CT) scan suggested air in the cochlea (pneumolabyrinth). The shunt was adjusted to elevate the cerebrospinal fluid (CSF) pressure and the pressure in the perilymph to prevent air from entering the cochlea via the round window. One year after activation the electrode impedances were normal and the hearing outcome from the implant was successful.
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| 6. |
- Herman, Stephanie, et al.
(author)
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Alterations in the tyrosine and phenylalanine pathways revealed by biochemical profiling in cerebrospinal fluid of Huntington's disease subjects
- 2019
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In: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 9
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Journal article (peer-reviewed)abstract
- Huntington's disease (HD) is a severe neurological disease leading to psychiatric symptoms, motor impairment and cognitive decline. The disease is caused by a CAG expansion in the huntingtin (HTT) gene, but how this translates into the clinical phenotype of HD remains elusive. Using liquid chromatography mass spectrometry, we analyzed the metabolome of cerebrospinal fluid (CSF) from premanifest and manifest HD subjects as well as control subjects. Inter-group differences revealed that the tyrosine metabolism, including tyrosine, thyroxine, L-DOPA and dopamine, was significantly altered in manifest compared with premanifest HD. These metabolites demonstrated moderate to strong associations to measures of disease severity and symptoms. Thyroxine and dopamine also correlated with the five year risk of onset in premanifest HD subjects. The phenylalanine and the purine metabolisms were also significantly altered, but associated less to disease severity. Decreased levels of lumichrome were commonly found in mutated HTT carriers and the levels correlated with the five year risk of disease onset in premanifest carriers. These biochemical findings demonstrates that the CSF metabolome can be used to characterize molecular pathogenesis occurring in HD, which may be essential for future development of novel HD therapies.
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| 7. |
- Hubers, Anna A M, et al.
(author)
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Suicidal ideation in a European Huntington's disease population
- 2013
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In: Journal of Affective Disorders. - : Elsevier BV. - 1573-2517 .- 0165-0327. ; 151:1, s. 58-248
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Journal article (peer-reviewed)abstract
- BACKGROUND: Previous studies indicate increased prevalences of suicidal ideation, suicide attempts, and completed suicide in Huntington's disease (HD) compared with the general population. This study investigates correlates and predictors of suicidal ideation in HD.METHODS: The study cohort consisted of 2106 HD mutation carriers, all participating in the REGISTRY study of the European Huntington's Disease Network. Of the 1937 participants without suicidal ideation at baseline, 945 had one or more follow-up measurements. Participants were assessed for suicidal ideation by the behavioural subscale of the Unified Huntington's Disease Rating Scale (UHDRS). Correlates of suicidal ideation were analyzed using logistic regression analysis and predictors were analyzed using Cox regression analysis.RESULTS: At baseline, 169 (8.0%) mutation carriers endorsed suicidal ideation. Disease duration (odds ratio [OR]=0.96; 95% confidence interval [CI]: 0.9-1.0), anxiety (OR=2.14; 95%CI: 1.4-3.3), aggression (OR=2.41; 95%CI: 1.5-3.8), a previous suicide attempt (OR=3.95; 95%CI: 2.4-6.6), and a depressed mood (OR=13.71; 95%CI: 6.7-28.0) were independently correlated to suicidal ideation at baseline. The 4-year cumulative incidence of suicidal ideation was 9.9%. Longitudinally, the presence of a depressed mood (hazard ratio [HR]=2.05; 95%CI: 1.1-4.0) and use of benzodiazepines (HR=2.44; 95%CI: 1.2-5.0) at baseline were independent predictors of incident suicidal ideation, whereas a previous suicide attempt was not predictive.LIMITATIONS: As suicidal ideation was assessed by only one item, and participants were a selection of all HD mutation carriers, the prevalence of suicidal ideation was likely underestimated.CONCLUSIONS: Suicidal ideation in HD frequently occurs. Assessment of suicidal ideation is a priority in mutation carriers with a depressed mood and in those using benzodiazepines.
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| 8. |
- Korpela, Sara, et al.
(author)
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Cerebrospinal fluid glial fibrillary acidic protein, in contrast to amyloid beta protein, is associated with disease symptoms in Huntington's disease
- 2024
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In: Journal of the Neurological Sciences. - : Elsevier. - 0022-510X .- 1878-5883. ; 459
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Journal article (peer-reviewed)abstract
- Introduction: Huntington's disease (HD) is a hereditary neurodegenerative disease, currently lacking disease-modifying treatments. Biomarkers are needed for objective assessment of disease progression. Evidence supports both complex protein aggregation and astrocyte activation in HD. This study assesses the 42 amino acid long amyloid beta (Aβ42) and glial fibrillary acidic protein (GFAP) as potential biomarkers in the cerebrospinal fluid (CSF) of HD mutation carriers.Methods: CSF from participants was obtained from three sites in Sweden. Clinical symptoms were graded with the composite Unified Huntington's disease rating scale (cUHDRS). Protein concentrations were measured using ELISA. Pearson correlations were calculated to assess disease progression association. Results were adjusted for age and collection site.Results: The study enrolled 28 manifest HD patients (ManHD), 13 premanifest HD gene-expansion carriers (PreHD) and 20 controls. Aβ42 levels did not differ between groups and there was no correlation with measures of disease progression. GFAP concentration was higher in ManHD (424 ng/l, SD 253) compared with both PreHD (266 ng/l, SD 92.4) and controls (208 ng/l, SD 83.7). GFAP correlated with both cUHDRS (r = -0.77, p < 0.001), and 5-year risk of disease onset (r = 0.70, p = 0.008).Conclusion: We provide evidence that indicates CSF Aβ42 has limited potential as a biomarker for HD. GFAP is a potential biomarker of progression in HD. Validation in larger cohorts measuring GFAP in blood and CSF would be of interest.
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| 9. |
- Lönnemark, Olle, et al.
(author)
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Cranioplasty in Brain Tumor Surgery : A Single-Center Retrospective Study Investigating Cranioplasty Failure and Tumor Recurrence
- 2023
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In: World Neurosurgery. - : Elsevier. - 1878-8750 .- 1878-8769. ; 170, s. e313-e323
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Journal article (peer-reviewed)abstract
- OBJECTIVE: Cranioplasty with synthetic implant can be performed to restore function and form of the skull after resection of malignancy infiltrating the bone. The aim of this study was to examine the rate of implant failure and tumor recurrence in patients undergoing nonautologous cranioplasty and tumor resection.METHODS: In this retrospective single-center study, 48 patients were identified who had undergone cranioplasty with synthetic implants after tumor resection between 2010 and 2020. The medical records were analyzed to investigate patient demographics, surgery data, cranioplasty failure rates, and rate of tumor recurrence.RESULTS: Cranioplasty failed in 8 patients. The median time to implant failure was 220 days with most failures occurring within 1 year (5 of 8). There was no significant difference in rate or time to failure between the different cranioplasty materials (P = 0.39). Low body mass index (P < 0.05), previous craniectomy/cranioplasty (P < 0.05), previous radiation therapy to the brain/skull (P < 0.05), and skin closure with sutures (P < 0.05) were associated with an increased risk of implant failure. Tumors recurred in 15 patients.CONCLUSIONS: Cranioplasty surgery with synthetic implants carries a relatively high risk of failure, regardless of type of cranioplasty material used. Skin closure with staples may be beneficial in these patients.
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| 10. |
- McNulty, Paul, et al.
(author)
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Reduced Cancer Incidence in Huntington's Disease : Analysis in the Registry Study.
- 2018
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In: Journal of Huntington's disease. - 1879-6400. ; 7:3, s. 209-222
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Journal article (peer-reviewed)abstract
- BACKGROUND: People with Huntington's disease (HD) have been observed to have lower rates of cancers.OBJECTIVE: To investigate the relationship between age of onset of HD, CAG repeat length, and cancer diagnosis.METHODS: Data were obtained from the European Huntington's disease network REGISTRY study for 6540 subjects. Population cancer incidence was ascertained from the GLOBOCAN database to obtain standardised incidence ratios of cancers in the REGISTRY subjects.RESULTS: 173/6528 HD REGISTRY subjects had had a cancer diagnosis. The age-standardised incidence rate of all cancers in the REGISTRY HD population was 0.26 (CI 0.22-0.30). Individual cancers showed a lower age-standardised incidence rate compared with the control population with prostate and colorectal cancers showing the lowest rates. There was no effect of CAG length on the likelihood of cancer, but a cancer diagnosis within the last year was associated with a greatly increased rate of HD onset (Hazard Ratio 18.94, p < 0.001).CONCLUSIONS: Cancer is less common than expected in the HD population, confirming previous reports. However, this does not appear to be related to CAG length in HTT. A recent diagnosis of cancer increases the risk of HD onset at any age, likely due to increased investigation following a cancer diagnosis.
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| 11. |
- Niemelä, Valter, et al.
(author)
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Cerebrospinal fluid sCD27 levels indicate active T cell-mediated inflammation in premanifest Huntington's disease
- 2018
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In: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 13:2
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Journal article (peer-reviewed)abstract
- Introduction Huntington's disease (HD) is a neurodegenerative disorder, but evidence also suggests neuroinflammation in the pathogenesis. The immune mechanisms involved and the timing of their activation need further clarification. A clinically well-characterized HD cohort and gene negative controls were enrolled. YKL-40 reflecting innate immunity and sCD27, a marker of adaptive immunity, were measured across disease stages. Comparisons were made with markers of neurodegeneration: neurofilament light (NFL), total-tau (T-tau), and phospho-tau (P-tau). 52 cross-sectional cerebrospinal fluid samples and 23 follow-up samples were analyzed. sCD27 was elevated in manifest HD and premanifest gene expansion carriers, whereas controls mostly had undetectable levels. YKL-40 showed a trend toward increase in manifest HD. sCD27 correlated with YKL-40 which in turn was closely associated to all included markers of neurodegeneration. YKL-40, NFL, and both forms of tau could all independently predict HD symptoms, but only NFL levels differed between groups after age adjustment. Increased sCD27 in premanifest HD is a sign of T cell-mediated neuroinflammation. This finding is novel since other reports almost exclusively have found early involvement of innate immunity. Validation of sCD27 in a larger HD cohort is needed. The role of adaptive immunity in HD needs further clarification, as it may hasten disease progression.
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| 12. |
- Niemelä, Valter, et al.
(author)
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CSF Proenkephalin decreases with the progression of Huntington's disease
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Other publication (other academic/artistic)abstract
- Identifying molecular changes that contribute to the onset and progression of Huntington's disease (HD) is of importance for the development and evaluation of potential therapies. We conducted an unbiased mass-spectrometry proteomic analysis on the cerebrospinal fluid of 12 manifest HD patients (ManHD), 13 presymptomatic gene expansion carriers (pGEC) and 38 controls. In ManHD compared to pGEC 10 proteins were downregulated, and 43 upregulated. Decreased levels of proenkephalin (PENK) and transthyretin along with upregulated proteins (VASN, STC2, SGCE and C7) were all closely linked to HD symptom severity. The decreased PENK levels were replicated in a separate cohort of 23 ManHD and 23 controls where absolute quantitation was performed. We hypothesize that declining PENK levels reflect the degeneration of medium spiny neurons (MSNs) that produce PENK, and that assays for PENK may serve as a surrogate marker for the state of MSNs in HD.
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| 13. |
- Niemelä, Valter
(author)
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Mapping the Huntington's disease process using cerebrospinal fluid analysis
- 2019
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Doctoral thesis (other academic/artistic)abstract
- Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder, caused by a CAG-repeat expansion in the HTT-gene. Today there are no disease-modifying therapies (DMTs), but several promising clinical trials are underway, including therapies that reduce mutant huntingtin expression.Reliable biomarkers could empower such trials and guide the timing for initiation of future DMTs.Neurofilament light (NFL) and tau, which are cerebrospinal fluid markers of neuronal death, have been implicated as markers of disease progression. Increased levels of the inflammatory marker YKL-40 have also been reported in HD.The aim was to validate and compare the above biomarker candidates by targeted analyses, while explorative liquid chromatography-mass spectrometry (LC-MS) was used to identify new candidates. Clinically well-characterized HD patients, premanifest gene expansion carriers (pGECs), and controls were enrolled from Uppsala University Hospital in Sweden.In contrast to tau, NFL levels differed between all three groups and NFL had stronger correlations with symptom severity compared with total-tau and phospho-tau. Longitudinally, only NFL maintained intergroup differences and rose with disease progression.Soluble CD27, a marker of T cell-mediated inflammation, differed between all three groups, with the highest levels in manifest HD, and mostly undetectable levels in controls. YKL-40 showed a non-significant trend toward increase in manifest HD. We applied LC-MS metabolomics and discovered a metabolite signature unique to manifest HD, with deranged tyrosine metabolism including L-DOPA, dopamine, and thyroxine. Utilizing LC-MS we also identified altered proteins in manifest HD, including proenkephalin that was decreased and associated with symptom severity. In conclusion, NFL may be used as a pharmacodynamic marker in intervention trials. Interestingly, elevated sCD27 implies a role of adaptive immunity before disease onset, but validation is needed. YKL-40 is not suitable as an early marker in HD. The CSF metabolome constitutes a new compartment of potential biomarkers but challenges in metabolite identification should be addressed in future studies. Proenkephalin levels potentially reflect the remaining number of striatal medium spiny neurons and hold promise as a marker of disease progression.
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| 14. |
- Niemelä, Valter, et al.
(author)
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Proenkephalin Decreases in Cerebrospinal Fluid with Symptom Progression of Huntington's Disease
- 2021
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In: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257. ; 36:2, s. 481-491
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Journal article (peer-reviewed)abstract
- Objective Identifying molecular changes that contribute to the onset and progression of Huntington's disease (HD) is of importance for the development and evaluation of potential therapies. Methods We conducted an unbiased mass-spectrometry proteomic analysis on the cerebrospinal fluid of 12 manifest HD patients (ManHD), 13 pre-manifest (preHD), and 38 controls. A biologically plausible and significant possible biomarker was validated in samples from a separate cohort of patients and controls consisting of 23 ManHD patients and 23 controls. Results In ManHD compared to preHD, 10 proteins were downregulated and 43 upregulated. Decreased levels of proenkephalin (PENK) and transthyretin were closely linked to HD symptom severity, whereas levels of 15 upregulated proteins were associated with symptom severity. The decreased PENK levels were replicated in the separate cohort where absolute quantitation was performed. Conclusions We hypothesize that declining PENK levels reflect the degeneration of medium spiny neurons (MSNs) that produce PENK and that assays for PENK may serve as a surrogate marker for the state of MSNs in HD. (c) 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society
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| 15. |
- Oosterloo, Mayke, et al.
(author)
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Clinical and genetic characteristics of late-onset Huntington's disease
- 2019
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In: Parkinsonism & Related Disorders. - : Elsevier BV. - 1353-8020 .- 1873-5126. ; 61, s. 101-105
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Journal article (peer-reviewed)abstract
- BACKGROUND: The frequency of late-onset Huntington's disease (>59 years) is assumed to be low and the clinical course milder. However, previous literature on late-onset disease is scarce and inconclusive.OBJECTIVE: Our aim is to study clinical characteristics of late-onset compared to common-onset HD patients in a large cohort of HD patients from the Registry database.METHODS: Participants with late- and common-onset (30-50 years)were compared for first clinical symptoms, disease progression, CAG repeat size and family history. Participants with a missing CAG repeat size, a repeat size of ≤35 or a UHDRS motor score of ≤5 were excluded.RESULTS: Of 6007 eligible participants, 687 had late-onset (11.4%) and 3216 (53.5%) common-onset HD. Late-onset (n = 577) had significantly more gait and balance problems as first symptom compared to common-onset (n = 2408) (P < .001). Overall motor and cognitive performance (P < .001) were worse, however only disease motor progression was slower (coefficient, -0.58; SE 0.16; P < .001) compared to the common-onset group. Repeat size was significantly lower in the late-onset (n = 40.8; SD 1.6) compared to common-onset (n = 44.4; SD 2.8) (P < .001). Fewer late-onset patients (n = 451) had a positive family history compared to common-onset (n = 2940) (P < .001).CONCLUSIONS: Late-onset patients present more frequently with gait and balance problems as first symptom, and disease progression is not milder compared to common-onset HD patients apart from motor progression. The family history is likely to be negative, which might make diagnosing HD more difficult in this population. However, the balance and gait problems might be helpful in diagnosing HD in elderly patients.
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| 16. |
- Stienen, Martin N, et al.
(author)
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Procedures performed during neurosurgery residency in Europe.
- 2020
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In: Acta Neurochirurgica. - : Springer Science and Business Media LLC. - 0001-6268 .- 0942-0940. ; 162:10, s. 2303-2311
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Journal article (peer-reviewed)abstract
- BACKGROUND: In a previous article ( https://doi.org/10.1007/s00701-019-03888-3 ), preliminary results of a survey, aiming to shed light on the number of surgical procedures performed and assisted during neurosurgery residency in Europe were reported. We here present the final results and extend the analyses.METHODS: Board-certified neurosurgeons of European Association of Neurosurgical Societies (EANS) member countries were asked to review their residency case logs and participate in a 31-question electronic survey (SurveyMonkey Inc., San Mateo, CA). The responses received between April 25, 2018, and April 25, 2020, were considered. We excluded responses that were incomplete, from non-EANS member countries, or from respondents that have not yet completed their residency.RESULTS: Of 430 responses, 168 were considered for analysis after checking in- and exclusion criteria. Survey responders had a mean age of 42.7 ± 8.8 years, and 88.8% were male. Responses mainly came from surgeons employed at university/teaching hospitals (85.1%) in Germany (22.0%), France (12.5%), the United Kingdom (UK; 8.3%), Switzerland (7.7%), and Greece (7.1%). Most responders graduated in the years between 2011 and 2019 (57.7%). Thirty-eight responders (22.6%) graduated before and 130 responders (77.4%) after the European WTD 2003/88/EC came into effect. The mean number of surgical procedures performed independently, supervised or assisted throughout residency was 540 (95% CI 424-657), 482 (95% CI 398-568), and 579 (95% CI 441-717), respectively. Detailed numbers for cranial, spinal, adult, and pediatric subgroups are presented in the article. There was an annual decrease of about 33 cases in total caseload between 1976 and 2019 (coeff. - 33, 95% CI - 62 to - 4, p = 0.025). Variables associated with lesser total caseload during residency were training abroad (1210 vs. 1747, p = 0.083) and female sex by trend (947 vs. 1671, p = 0.111), whereas case numbers were comparable across the EANS countries (p = 0.443).CONCLUSION: The final results of this survey largely confirm the previously reported numbers. They provide an opportunity for current trainees to compare their own case logs with. Again, we confirm a significant decline in surgical exposure during training between 1976 and 2019. In addition, the current analysis reveals that female sex and training abroad may be variables associated with lesser case numbers during residency.
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| 17. |
- Sundblom, Jimmy, 1981-, et al.
(author)
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A family with discordance between Malignant hyperthermia susceptibility and Rippling muscle disease
- 2013
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In: Journal of Anesthesia. - : Springer Science and Business Media LLC. - 0913-8668 .- 1438-8359. ; 27:1, s. 128-131
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Journal article (peer-reviewed)abstract
- Rippling muscle disease (RMD) is a benign disorder affecting striated muscle.Malignant hyperthermia (MH) susceptibility is a potentially lethal disorder in which otherwise healthy individuals can develop an extreme hypermetabolism and muscle rigidity/rhabdomyolysis during anesthesia with potent inhalational agents and/or succinylcholine. Disturbed calcium homeostasis has been suggested as the cause of RMD symptoms. Uncontrolled increase in intracellular calcium concentration starts a MH reaction.PurposeTo investigate if there is a relation between RMD and MH susceptibility in a family with both RMD and MH susceptibility.Materials and methodsTen members of a family segregating RMD had, prior to RMD diagnosis, been investigated for MH susceptibility. Results from MH and RMD investigations and anesthesia outcomes were cross-referenced and evaluated to find connections or phenotype variations predicted by in vitro contracture test results.ResultsThere was no relation between RMD and MH susceptibility. There were no adverse anesthesia reactions recorded in this family.ConclusionsRMD and MH susceptibility did not co-segregate. RMD patients should probably not be considered at risk for MH reactions.
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| 18. |
- Sundblom, Jimmy, 1981-
(author)
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Autosomal Dominant Leukodystrophy with Autonomic Symptoms and Rippling Muscle Disease : Translational Studies of Two Neurogenetic Diseases
- 2011
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Doctoral thesis (other academic/artistic)abstract
- There is a large variety of diseases caused by single-gene mutations. Although most of these conditions are rare, together they impose a significant burden to the population. This thesis describes clinical and genetic studies of two single-gene diseases: 1) Adult-onset autosomal dominant leukodystrophy with autonomic symptoms (ADLD) caused by LMNB1 gene duplications, and characterized by autonomic, pyramidal and cerebellar symptoms. Spinal cords of patients with ADLD were studied by MRI and found to be thin, with high signal intensity in white matter. Histopathology showed loss of myelinated fibres with some reactive gliosis. DNA samples from four different families with ADLD were obtained, and the LMNB1 gene was screened for duplications. Single nucleotide polymorphism array revealed LMNB1 duplications in all ADLD families. LMNB1 mRNA and protein levels were assessed in white blood cells using quantitative polymerase chain reaction and Western blot, and increased levels of LMNB1 mRNA and lamin B1 protein could be demonstrated. We concluded that spinal cord atrophy in patients with ADLD is a valuable differential diagnostic sign, and that increased levels of LMNB1 can be detected in peripheral blood. 2) Rippling muscle disease (RMD) is caused by CAV3 gene mutations. Clinical features are percussion-induced muscle mounding, –rapid contractions and undulating muscle contractions (rippling). The CAV3 gene was sequenced in 38 members of a family with RMD. Twenty-two individuals had clinical features of RMD. No muscle weakness was seen. All patients with signs of RMD carried the p.A46T CAV3 mutation, showing that the p.A46T mutation was benign and that the diagnosis can be made clinically. In vitro contracture test results from 10 of the subjects were collected, but no association between pathological test results and RMD was found.
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| 19. |
- Sundblom, Jimmy, 1981-, et al.
(author)
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Bone formation in custom-made cranioplasty : evidence of early and sustained bone development in bioceramic calcium phosphate implants. Patient series
- 2021
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In: Journal of Neurosurgery: Case Lessons. - : Journal of Neurosurgery Publishing Group (JNSPG). - 2694-1902. ; 1:17
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Journal article (peer-reviewed)abstract
- BACKGROUNDImplant failure (IF) rates in cranioplasty remain high despite efforts to reduce the incidence. New biomaterials may be part of the solution for this problem. Formation of autologous bone in implants may reduce rates of infection and subsequent failure.OBSERVATIONSFour patients with calcium phosphate implants supported by titanium mesh and undergoing surgery for reasons unrelated to IF were included in this series. Samples from the implants were microscopically examined. Pathological studies proved the formation of autologous bone in the calcium phosphate implants.LESSONSBone and blood vessel formation in the implants and diminished foreign body reaction to autologous bone may reduce the rates of IF.
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| 20. |
- Sundblom, Jimmy, 1981-, et al.
(author)
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Central nervous system hemangioblastomas in von Hippel-Lindau disease : Total growth rate and risk of developing new lesions not associated with circulating VEGF levels
- 2022
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 17:11
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Journal article (peer-reviewed)abstract
- BACKGROUND: Hemangioblastomas of the central nervous system are a prominent feature of von Hippel-Lindau-disease (vHL). Hemangioblastomas are known to secrete vascular endothelial growth factor (VEGF), suggesting a potential role of VEGF as a biomarker for tumor growth.METHODS: Plasma VEGF samples from 24 patients with von Hippel-Lindau disease were analyzed by solid-phase proximity ligation assay (PLA). Levels were monitored over time together with numeric and volumetric CNS tumor burden, and compared to plasma VEGF levels in healthy controls.RESULTS: The mean yearly progression in tumor volume was 65.5%. Yearly risk of developing one or several new CNS tumor(s) was 50%. No significant correlation between tumor burden and levels of VEGF was seen. VEGF levels in patients (31.55-92.04; mean 55.83, median 56.41) as measured by immunodetection in a solid-phase PLA did not differ significantly from controls (37.38-104.56; mean 58.89, median 54.12) (p = 0,266).CONCLUSION: The increase in total CNS tumor volume in vHL occurred in a saltatory manner. The risk of developing a new lesion was 50% per year. We found no evidence for VEGF secretion from CNS hemangioblastomas in vHL in circulating blood. Other potential biomarkers should be explored to assess progression of tumor burden in vHL.
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| 21. |
- Sundblom, Jimmy, 1981-, et al.
(author)
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Gentamicin loading of calcium phosphate implants : implications for cranioplasty
- 2019
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In: Acta Neurochirurgica. - : SPRINGER WIEN. - 0001-6268 .- 0942-0940. ; 161:6, s. 1255-1259
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Journal article (peer-reviewed)abstract
- BackgroundSurgical site infections (SSI) are a significant risk in cranioplasty, with reported rates of around 8-9%. The most common bacteria associated with these nosocomial infections are of the Staphylococcus species, which have the ability to form biofilm. The possibility to deliver antibiotics, such as gentamicin, locally rather than systemically could potentially lower the early postoperative SSI. Various antibiotic dosages are being applied clinically, without any true consensus on the effectiveness.MethodsDrug release from calcium phosphate (CaP), polyetheretherketone (PEEK), and titanium (Ti) samples was evaluated. Microbiological studies with Staphylococcus aureus (SA) and Staphylococcus epidermidis (SE) including strains from clinical infection were used to establish clinically relevant concentrations.ResultsThe CaP samples were able to retain and release gentamicin overtime, whereas the Ti and PEEK samples did not show any drug uptake or release. A gentamicin loading concentration of 400g/ml was shown to be effective in in vitro microbiological studies with both SA and SE.ConclusionsOut of the three materials studied, only CaP could be loaded with gentamicin. An initial loading concentration of 400g/ml appears to establish an effective gentamicin concentration, possibly translating into a clinical benefit in cranioplasty.
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| 22. |
- Sundblom, Jimmy, 1981-, et al.
(author)
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High frequency of intermediary alleles in the HTT gene in Northern Sweden - The Swedish Huntingtin Alleles and Phenotype (SHAPE) study
- 2020
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In: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 10:1
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Journal article (peer-reviewed)abstract
- Trinucleotide (CAG) repeat expansions longer than 39 in the huntingtin (HTT) gene cause Huntington's disease (HD). The frequency of intermediate alleles (IA) with a length of 27-35 in the general population is not fully known, but studied in specific materials connected to the incidence of HD. The Swedish Huntingtin Alleles and Phenotype (SHAPE) study aims to assess the frequency of trinucleotide repeat expansions in the HTT gene in north Sweden. 8260 individuals unselected for HD from the counties of Norr- and Vasterbotten in the north of Sweden were included. DNA samples were obtained and analysis of the HTT gene was performed, yielding data on HTT gene expansion length in 7379 individuals. A high frequency of intermediate alleles, 6.8%, was seen. Also, individuals with repeat numbers lower than ever previously reported (<5) were found. These results suggest a high frequency of HD in the norther parts of Sweden. Subsequent analyses may elucidate the influence of IA:s on traits other than HD.
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| 23. |
- Sundblom, Jimmy, 1981-, et al.
(author)
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Removal of giant intraosseous meningioma followed by cranioplasty using a custom-made bioceramic implant : case report
- 2019
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In: Journal of Neurosurgery. - 0022-3085 .- 1933-0693. ; 131:3, s. 735-739
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Journal article (peer-reviewed)abstract
- Intraosseous meningioma of the chordoid type is a rare clinical entity. Radical surgical removal and subsequent cranioplasty is the treatment of choice. Here, the authors report a severe case involving more than 70% of the calvarial surface area, which was removed and repaired using a prefabricated custom-made, titanium-reinforced, bioceramic implant and bone-cutting guides. Tumor removal and good esthetic outcome were achieved, along with a 17.1% increase of intracranial volume. Bioceramic implants have shown promising initial results and may represent an important new tool in the surgeon's armamentarium.
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| 24. |
- Sundblom, Jimmy, 1981-, et al.
(author)
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Trauma Mechanisms and Surgical Outcomes in the Elderly Patient with Chronic Subdural Hematoma
- 2022
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In: CANADIAN GERIATRICS JOURNAL. - : Canadian Geriatrics Society. - 1925-8348. ; 25:1, s. 40-48
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Journal article (peer-reviewed)abstract
- Background Chronic subdural hematoma is the preeminent neurosurgical condition in the older population. This retrospective single-centre study focuses on outcome after surgery of chronic subdural hematoma in patients over 70 years. Methods Patients treated at a single neurosurgical referral centre between 2010 and 2014 were screened. Included patients were assessed for comorbid conditions, lifestyle factors, and outcomes including recurrence, mortality, and postoperative complications. Results A total of 511 patients (70-97 yrs) were identified. 50.7% of patients were treated with anticoagulants and/or antiplatelet therapy. A known probable cause for the hematoma was found in 68.1% of patient's histories. Mortality rate was 3.1% and recurrence was seen in 49 patients (9.6%). Postoperative complications were more common in patients with excessive use of alcohol (p value =.02). Neurological function was improved in 78.1% of patients after the initial surgery. A strategy of delayed contralateral surgery in bilateral hematomas showed low rates of recurrence. Conclusion Fall injuries are the most common underlying trauma mechanism in the elderly with chronic subdural hematoma. Recurrence is not more common in the elderly patient group compared to the general population. Excessive alcohol use is a risk factor for post-operative complications.
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| 25. |
- Svedung-Wettervik, Teodor, et al.
(author)
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Inflammatory biomarkers differentiate the stage of maturation in chronic subdural hematomas
- 2023
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In: Journal of Neuroimmunology. - : Elsevier. - 0165-5728 .- 1872-8421. ; 381
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Journal article (peer-reviewed)abstract
- Objective: Inflammation is a major pathophysiological driver of the development of chronic subdural hematomas (CSDH), but there is still limited knowledge on the key molecular processes and corresponding biomarkers involved in this disease. In this study, the aim was to study a subset of inflammatory biomarkers and their relation to the clinical status of the patient and the radiological characteristics of the CSDH.Methods: In this observational study, 58 patients who were operated on with CSDH evacuation, at the Department of Neurosurgery, Uppsala, Sweden, between 2019 and 2021, were prospectively included. The CSDH fluid was collected peri-operatively and was later analyzed with proximity extension assay (PEA) technique (Olink) for a panel of 92 inflammatory biomarkers. Demographic, neurological (Markwalder), radiological (general (Nakaguchi classification) and focal (septa below the burr holes)), and outcome variables were collected.Results: In 84 of the 92 inflammatory biomarkers, the concentration was above the detection limit in >50% of the patients. There was a significant difference in GDNF, NT-3, and IL-8 depending on the Nakaguchi class, with higher values in the trabeculated CSDH subtype. In addition, those with septa at the focal area of CSDH collection, had higher levels of GDNF, MCP-3, NT-3, CXCL1, CXCL5, IL8, and OSM. There was no association between Markwalder grade and the inflammatory biomarkers.Conclusions: Our findings support the presence of local inflammation in the CSDH, a shift in biomarker pattern as the CSDH matures towards the trabeculated state, potentially differences in biomarker patterns within the CSDH depending on the focal environment with presence of septa, and that the brain might develop protective mechanisms (GDNF and NT-3) in case of mature and long-standing CSDHs.
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| 26. |
- Uche, E. O., et al.
(author)
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Global neurosurgery over a 60-year period : Conceptual foundations, time reference, emerging Co-ordinates and prospects for collaborative interventions in low and middle income countries
- 2022
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In: BRAIN AND SPINE. - : Elsevier BV. - 2772-5294. ; 2
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Journal article (peer-reviewed)abstract
- Introduction: We evaluated salient initiatives invested in global neurosurgery over a 60-year period.Research question: What are the Phases, Achievements, Challenges, and Lessons of Global Neurosurgery.Methods: A 60-year retrospective study from 1960 to 2020 analyzing the major phases, lessons, and progress notes. We reviewed the foundational need questions and innovated tools used to answer them.Results: Three phases defining our study period were identified. In the early phase, birthing academic units and the onset of individual volunteerism were dominant concepts. The 2nd phase is summarized by the rise of volunteerism and surgical camps. The third phase is heralded by advocacy and strategies for achieving care equity.The defining moment is the Lancet commission for global surgery summit in 2015. Lessons include the need for evaluation of the resources of recipient and donor locations using novel global surgery tools.Conclusion: Global neurosurgery over the 60-year study period is summarized by indelible touchstones of personal and group efforts as well as triumphs derived from innovations in the face of formidable challenges.
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| 27. |
- Uche, Enoch Ogbonnaya, et al.
(author)
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Pilot application of Lecture-Panel-Discussion Model (LPDM) in global collaborative neurosurgical education : a novel training paradigm innovated by the Swedish African Neurosurgery Collaboration
- 2022
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In: Acta Neurochirurgica. - : Springer Nature. - 0001-6268 .- 0942-0940. ; 164:4, s. 967-972
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Journal article (peer-reviewed)abstract
- Background Disruptions in global surgery educational routines by the COVID-19 pandemic have elicited demands for alternative formats for rendering qualitative neurosurgical education. This study presents application of a novel model of online neurosurgical course, the Lecture-Panel-Discussion Model (LPDM). Methods This is a cross-sectional survey of participants who attended the Swedish African Neurosurgery Collaboration (SANC)-100A course. Participants evaluated the course through an online self-administered questionnaire using a 5-point Likert scale ranging from very poor-1, poor-2, average (fair)-3, good-4, to excellent-5. SANC-100A comprises a tripod of Lectures, Panel review, and interactive case Discussion. This model (LPDM) was innovated by SANC and applied at the Enugu International Neurosurgery course in February 2021. Results There were 71 attendees, 19 were course faculty, while 52 were participants. Thirty-five attended from Nigeria, 11 from Sweden, 3 from Malawi, 2 from Senegal, and 1 from the UK. Among 44 participants who completed the questionnaire, there were 9 fellows and 35 residents. The overall median course Likert rating was 4.65 +/- 0.1. The median overall rating for course events was similar between day 1 (Likert score = 4.45) and day 2 (Likert score = 4.55), U = 55, Z score = 1.10, P = 0.27. The median rating for lectures was 4.50 +/- 0.2 and varied from 4.40 on day 1 to 4.55 on day 2. The median rating for panel review was 4.60 +/- 0.1 and varied from 4.55 on day 1 to 4.65 on day 2. Interactive case discussions were rated 4.80 on both course days. There was a significant variability in the rating profiles of the course tripod: U = 24.5, P = 0.03. Fifty-one (98%) participants believe LPDM was COVID-19-compliant, while 90% believe the course was beneficial to training and practice. Conclusion Initial application of LPDM is rewarded with both high acceptance and high rating among participants.
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