| 1. |
- Eriksdotter-Jönhagen, Maria, et al.
(författare)
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Encapsulated cell biodelivery of nerve growth factor to the Basal forebrain in patients with Alzheimer's disease.
- 2012
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Ingår i: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1421-9824 .- 1420-8008. ; 33:1, s. 18-28
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Tidskriftsartikel (refereegranskat)abstract
- Degeneration of cholinergic neurons in the basal forebrain correlates with cognitive decline in patients with Alzheimer's disease (AD). Targeted delivery of exogenous nerve growth factor (NGF) has emerged as a potential AD therapy due to its regenerative effects on the basal forebrain cholinergic neurons in AD animal models. Here we report the results of a first-in-man study of encapsulated cell (EC) biodelivery of NGF to the basal forebrain of AD patients with the primary objective to explore safety and tolerability.
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| 2. |
- Asplund, Pär, et al.
(författare)
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One hundred eleven Percutaneous Balloon Compressions for Trigeminal Neuralgia in a Cohort of 66 Patients with Multiple Sclerosis
- 2019
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Ingår i: Operative Neurosurgery. - : Oxford University Press. - 2332-4252 .- 2332-4260. ; 17:5, s. 452-459
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Trigeminal neuralgia associated with multiple sclerosis (MS-TN) is comparatively rare and larger series of percutaneous balloon compression (PBC) in such cases are few in the literature.OBJECTIVE: To evaluate the results after PBC for MS-TN with regards to therapeutic effect, side effects, and complications.METHODS: One hundred eleven procedures with PBC performed in 66 cases of MS-TN were analyzed. Therapeutic effect was measured as postoperative time to pain recurrence without medication. All complications were compiled and the sensory function was evaluated in a subgroup of cases.RESULTS: The initial pain free rate was 67% and the median time to pain recurrence was 8 mo. Thirty-six patients were treated with PBC only, and among them, the results were worse if treated 3 to 4 times before, compared to first treatment (P = .009-.034). Patients who had several PBCs had worse results already after the first surgery (P < .001). A significant number of patients had impaired sensation to light touch directly after surgery, which was normalized at the late follow-up. Sensimetric testing showed raised thresholds for perception and pain directly after surgery (P = .004-.03), but these were also normalized at the late follow-up.CONCLUSION: PBC is a treatment that can be effective for many patients with MS-TN. Repeated previous surgeries is a risk factor for an unsatisfactory outcome. However, the patients with multiple surgeries had less satisfactory results already at the first procedure, indicating that a therapy resistant disease can be predicted after the first two PBCs. Postoperative sensory deficits were common but not lasting.
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| 3. |
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| 4. |
- Bergenheim, A Tommy, et al.
(författare)
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Diplopia after balloon compression of retrogasserian ganglion rootlets for trigeminal neuralgia : technical case report.
- 2008
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Ingår i: Neurosurgery. - : Ovid Technologies (Wolters Kluwer Health). - 1524-4040 .- 0148-396X. ; 62:2, s. E533-4; discussion E534
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Balloon compression of the rootlets behind the trigeminal ganglion for the treatment of trigeminal neuralgia has become an increasingly popular method among neurosurgeons. However, the method has recognized complications, including double vision. Although occurring infrequently, diplopia may cause the patient significant disability. To minimize the risk for this complication, we analyzed our patients with respect to the surgical technique. METHODS: We reviewed our joint consecutive series of 193 patients with trigeminal neuralgia treated with balloon compression. The medical records and the intraoperative x-ray images were analyzed. RESULTS: We identified six patients with double vision postoperatively. In analyzing these occurrences, we found that the balloon was inflated outside Meckel's cave in four patients, the balloon was initially inflated too deeply in one patient, and the anatomy of Meckel's cave was probably aberrant in one patient. In five of the six patients, the symptoms resolved within 5 months. CONCLUSION: By meticulous surgical technique with close attention to the anatomic position and the shape of the inflated balloon, most cases of postcompression diplopia should be avoided.
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| 5. |
- Bergenheim, Tommy, et al.
(författare)
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Percutaneous retrogasserian balloon compression for trigeminal neuralgia : review of critical technical details and outcomes
- 2013
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Ingår i: World Neurosurgery. - : Elsevier BV. - 1878-8750 .- 1878-8769. ; 79:2, s. 359-368
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To describe percutaneous balloon compression (PBC) of the trigeminal rootlets as treatment for trigeminal neuralgia (TN), including history, operative techniques, outcomes, side effects, and some recent findings increasing the likelihood of a positive outcome.METHODS: PBC is indicated in patients with TN in whom microvascular decompression is considered less suitable. The procedure is simplified by the use of biplanar fluoroscopy, although it is usually carried out with C-arm fluoroscopy to facilitate the introduction of the needle and the visualization of the inflated catheter. In the right position, a clearly defined pear shape usually appears after injection of 0.5-0.7 mL of contrast material. The balloon is kept inflated for 1.5-3 minutes. It is crucial to obtain a pear shape because this probably is the most significant factor for obtaining good, long-lasting pain relief.RESULTS: An analysis of 100 consecutive PBC procedures showed an initial success rate of 90% and a median pain-free time without medication of 28 months. Subdividing these patients into primary TN (n = 77) and TN secondary to multiple sclerosis (a = 23), the median pain-free times were 33 months and 24 months (P = 0.2), indicating that the outcome may depend on the preoperative conditions.CONCLUSIONS: Complications and side effects include cardiovascular stress during the procedure, local hemorrhages in the cheek, postoperative sensory disturbance, masseter weakness, infections, and transitory diplopia after surgery. Measures to minimize side effects are proposed. With meticulous technique, PBC is a straightforward, effective, and fast procedure that compares well with other percutaneous therapies for TN.
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| 6. |
- Blomstedt, Patric, 1972-
(författare)
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Analysis of deep brain stimulation and ablative lesions in surgical treatment of movement disorders : with emphasis on safety aspects
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background The last decade has witnessed a renaissance of functional stereotactic neurosurgery in the treatment of patients with movement disorders, especially advanced Parkinson’s disease (PD), essential tremor (ET) and dystonia. Ablative lesions such as thalamotomy and pallidotomy have been gradually replaced by the technique of chronic deep brain stimulation (DBS) applied to targets in the basal ganglia and thalamus, and assumed to be more lenient to the brain than stereotactic radiofrequency lesions. Since the aim of functional neurosurgery is to alleviate symptoms of these chronic, progressive, non-fatal diseases, and to improve life quality of the patients, it is imperative that the surgical procedures remain safe and do not result in complications mitigating any anticipated positive effect of the surgery on the symptoms of the disease.Aim The aim of this thesis is to evaluate, compare and analyse the safety of various surgical procedures used to treat patients with movement disorders, and to document side effects and complications both peri operatively and in a long term follow-up. Further to compare the effects of pallidotomy and pallidal DBS, and to evaluate the longterm efficacy of Vim-DBS.Method 256 consecutive surgical procedures, 129 DBS and 127 stereotactic lesions, were reviewed with respect to complications in 197 treated patients. In a series of 119 patients operated on with DBS during a 10 year period, the occurrence of hardware related complications (infection, breakage, erosion etc) was documented and analysed. Additionally, the interference of external magnetic field with the stimulation was documented. In one patient operated on with subthalamic nucleus DBS, a highly unusual and unexpected psychiatric side effect was carefully analysed. In 5 patients operated on with both methods (lesion and DBS) on each hemisphere, respectively, the effect and side effects of each method were compared. The long term effect and side effects of thalamic DBS was analysed in a series of patients with ET followed for 7 years.Results There were no deaths and few severe neurological complications in this material. Unilateral ablative lesions in the pallidum were well tolerated by patients with advanced PD, while for tremor, thalamic DBS was much safer than thalamotomy, even if its effect on certain aspects of tremor could show some decrease of efficacy over time. Some of the side effects of lesioning are transient while most but not all side effects of DBS are reversible. Hardware-related complications were not uncommon especially in the early “learning curve” period, and the DBS technique, being a life-long therapy, will necessitate a life long follow up of patients. Provided safety protocols are followed and provided patient’s and carer’s education and awareness, external electromagnetic interference should not constitute a risk for patients with DBS. PD patients undergoing STN DBS should be carefully selected to avoid psychiatric or cognitive side effects, due to this brain target´s proximity to, and involvment in, non-motor associative and limbic circuitry.Conclusions In terms of mortality and morbidity, modern stereotactic neurosurgery for movement disorders, both ablation and DBS, is a safe procedure even in advanced stages of disease. Symptoms of PD, ET and dystonia can be alleviated mainly with DBS and even unilaterally with pallidal lesions, at the expense of, in most cases, minor side-effects.
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| 7. |
- Ferreira, Daniel, et al.
(författare)
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Brain changes in Alzheimer's disease patients with implanted encapsulated cells releasing nerve growth factor
- 2015
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Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 43, s. 1059-1072
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Tidskriftsartikel (refereegranskat)abstract
- © 2015-IOS Press and the authors. New therapies with disease-modifying effects are urgently needed for treating Alzheimer's disease (AD). Nerve growth factor (NGF) protein has demonstrated regenerative and neuroprotective effects on basal forebrain cholinergic neurons in animal studies. In addition, AD patients treated with NGF have previously shown improved cognition, EEG activity, nicotinic binding, and glucose metabolism. However, no study to date has analyzed brain atrophy in patients treated with NGF producing cells. In this study we present MRI results of the first clinical trial in patients with AD using encapsulated NGF biodelivery to the basal forebrain. Six AD patients received the treatment during twelve months. Patients were grouped as responders and non-responders according to their twelve-months change in MMSE. Normative values were created from 131 AD patients from ADNI, selecting 36 age-and MMSE-matched patients for interpreting the longitudinal changes in MMSE and brain atrophy. Results at baseline indicated that responders showed better clinical status and less pathological levels of cerebrospinal fluid (CSF) Aβ1-42. However, they showed more brain atrophy, and neuronal degeneration as evidenced by higher CSF levels of T-tau and neurofilaments. At follow-up, responders showed less brain shrinkage and better progression in the clinical variables and CSF biomarkers. Noteworthy, two responders showed less brain shrinkage than the normative ADNI group. These results together with previous evidence supports the idea that encapsulated biodelivery of NGF might have the potential to become a new treatment strategy for AD with both symptomatic and disease-modifying effects.
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| 8. |
- Fåk, Frida, et al.
(författare)
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Age-related Effects of the Probiotic Bacterium Lactobacillus plantarum 299v on Gastrointestinal Function in Suckling Rats
- 2008
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Ingår i: Digestive Diseases and Sciences. - : Springer Science and Business Media LLC. - 1573-2568 .- 0163-2116. ; 53:664-671, s. 664-671
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Tidskriftsartikel (refereegranskat)abstract
- The effect of a probiotic bacterium on gut function was studied in neonatal animals by using a model with suckling rats. Lactobacillus plantarum 299v (Lp299v) or saline (controls) was fed (3.0 x 10(6) CFU/g b.wt per day) for one week to rats aged either 3, 7 or 14 days, after which bacterial colonization, gut growth, and functional parameters were analyzed. In rats fed with Lp299v from 3 to 10 days of age, an increase in ceacal lactobacilli was correlated with reduced intestinal macromolecular permeability and increased mucosal protein compared to age-matched controls. Pups treated from 7 to 14 days of age showed a decrease in pancreas weight and protein content, whereas pups treated from 14 to 21 days of age showed little effect of the Lp299v treatment. The results indicated that the bacterial exposure affected the gut function, where the effects were age-related and the youngest rats appeared most sensitive.
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| 9. |
- Karami, Azadeh, et al.
(författare)
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Changes in CSF cholinergic biomarkers in response to cell therapy with NGF in patients with Alzheimer's disease
- 2015
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Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 11:11, s. 1316-1328
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The extensive loss of central cholinergic functions in Alzheimer's disease (AD) brain is linked to impaired nerve growth factor (NGF) signaling. The cardinal cholinergic biomarker is the acetylcholine synthesizing enzyme, choline acetyltransferase (ChAT), which has recently been found in cerebrospinal fluid (CSF). The purpose of this study was to see if EC-NGF therapy will alter CSF levels of cholinergic biomarkers, ChAT, and acetylcholinesterase. Method: Encapsulated cell implants releasing NGF (EC-NGF) were surgically implanted bilaterally in the basal forebrain of six AD patients for 12 months and cholinergic markers in CSF were analyzed. Results: Activities of both enzymes were altered after 12 months. In particular, the activity of soluble ChAT showed high correlation with cognition, CSF tau and amyloid-beta, in vivo cerebral glucose utilization and nicotinic binding sites, and morphometric and volumetric magnetic resonance imaging measures. Discussion: A clear pattern of association is demonstrated showing a proof-of-principle effect on CSF cholinergic markers, suggestive of a beneficial EC-NGF implant therapy.
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| 10. |
- Lagerlöf, Ingemar, et al.
(författare)
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No excess long-term mortality in stage I-IIA Hodgkin lymphoma patients treated with ABVD and limited field radiotherapy
- 2020
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Ingår i: British Journal of Haematology. - : John Wiley & Sons. - 0007-1048 .- 1365-2141. ; 188:5, s. 685-691
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Tidskriftsartikel (refereegranskat)abstract
- When treating limited stage classical Hodgkin lymphoma (cHL), balancing treatment efficacy and toxicity is important. Toxicities after extended-field radiotherapy are well documented. Investigators have aimed at reducing toxicity without compromising efficacy, mainly by using combined modality treatment (CMT), i.e. chemotherapy and limited-field radiotherapy. In some clinical trials, radiotherapy has been omitted. We evaluated 364 patients with stage I-IIA cHL treated between 1999 and 2005. Patients were treated with two or four cycles of doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) according to presence of risk factors, followed by 30 Gy limited-field (reduced compared to involved-field) radiotherapy. After a median follow-up of 16 years for survival, freedom from progression at five and ten years was 93% and overall survival at 5 and 10 years was 98% and 96%, respectively. Only two relapses, out of 27, occurred after more than 5 years. There was no excess mortality compared to the general population. Of the analysed subgroups, only patients with progression within five years showed significant excess mortality. The absence of excess mortality questions the concept of omitting radiotherapy after short-term chemotherapy, a strategy that has been associated with an elevated risk of relapse but not yet with a proven reduced long-term excess mortality.
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| 11. |
- Lind, Goran, et al.
(författare)
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Therapeutic value of spinal cord stimulation in irritable bowel syndrome : a randomized crossover pilot study
- 2015
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Ingår i: American Journal of Physiology. Regulatory Integrative and Comparative Physiology. - : American Physiological Society. - 0363-6119 .- 1522-1490. ; 308:10, s. R887-R894
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Tidskriftsartikel (refereegranskat)abstract
- Irritable bowel syndrome (IBS) is characterized by abdominal pain and changed bowel habits. Spinal cord stimulation (SCS) has been used for treatment of chronic pain syndromes. Animal studies have shown SCS to reduce the reaction to colonic balloon distension, known to be increased in IBS patients. To elucidate the potential for SCS as treatment for IBS, a pilot study was performed. Ten IBS patients (age 26-56 yr) were recruited. A SCS system with a four-polar electrode was implanted at the T5-T8 level. After a 2-wk run-in, a randomized, crossover design SCS during 6 wk was compared with no stimulation, with an ensuing stimulation period for 12 wk; total study period 28 wk. Patients recorded pain level, pain attacks, diarrheas, and global quality of life in a diary. At end of the study patients could choose to retain their SCS system or have it removed. Nine patients completed the whole trial. During stimulation periods the median pain scores were significantly reduced from visual analogue scale (VAS) 7 (4-8) to 3 (2.5-7) and to 4 (2-6) during early and late stimulation periods, respectively (P < 0.03-0.04). Pain attacks were numerically reduced. A few patients reported reduced number of diarrheas. After study termination, six patients chose to retain their SCS system. To conclude, SCS is a minimally invasive treatment option for pain in IBS. With SCS the pain level was reduced though with merely a trend for number of attacks and diarrheas. The efficacy of SCS in IBS pain indicates a possible usefulness in other painful bowel disorders.
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| 12. |
- Linderoth, Bengt, et al.
(författare)
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Bjorn Meyerson 1933-2019 OBITUARY
- 2020
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Ingår i: Neuromodulation. - : John Wiley & Sons. - 1094-7159 .- 1525-1403. ; 23:1, s. 1-2
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 13. |
- Odenstedt, Jacob, 1968, et al.
(författare)
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Spinal cord stimulation effects on myocardial ischemia, infarct size, ventricular arrhythmia, and noninvasive electrophysiology in a porcine ischemia-reperfusion model.
- 2011
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Ingår i: Heart Rhythm. - : Elsevier BV. - 1556-3871 .- 1547-5271. ; Jan:18
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Susceptibility to ventricular arrhythmias and sudden cardiac death can be reduced by modulation of autonomic tone. Spinal cord stimulation (SCS) presumably affects autonomic tone and reduces myocardial ischemia. OBJECTIVE: The purpose of this study was to investigate whether SCS could reduce myocardial ischemia, infarct size, and ventricular arrhythmias as well as repolarization alterations in a porcine ischemia-reperfusion model. METHODS: Anesthetized common Landrace pigs were randomized to SCS (n = 10) or sham treatment (n = 10) before, during, and after 45 minutes of coronary occlusion. Area at risk, infarct size, and spontaneous ventricular arrhythmias were analyzed. Continuous three-dimensional vectorcardiograms was recorded and analyzed with respect to ECG intervals, ST-segment, and T-vector and T-vector-loop morphology. RESULTS: SCS was associated with significantly (P <.04) fewer episodes of nonsustained ventricular tachycardia (NSVT) and sustained ventricular tachycardia (SVT), particularly during mid-left anterior descending artery (LAD) occlusion (SCS vs non-SCS; NSVT, mid- and proximal LAD: 0 vs 22 and 45 vs 72; SVT, mid- and proximal LAD: 3 vs 15 and 5 vs 5). No difference in ventricular fibrillation episodes was observed. The SCS group had significantly less ST elevation (P <.03) but similar area at risk, infarct size, and ratio of infarct size/area at risk. Ischemia induced increases of T(amplitude) and T(area) suggesting increased repolarization gradients, which were significantly reduced by SCS (P <.01 for both). CONCLUSION: SCS appears to have an antiarrhythmic effect on spontaneous NSVT and SVT during ischemia-reperfusion in association with a reduction of repolarization alterations. Vectorcardiography signs of myocardial ischemia were reduced by SCS, but this intervention was not accompanied by any effect on infarct size.
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| 14. |
- Paul-Visse, Gesine, et al.
(författare)
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Safety and tolerability of intracerebroventricular PDGF-BB in Parkinson's disease patients
- 2015
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Ingår i: Journal of Clinical Investigation. - 0021-9738 .- 1558-8238. ; 125:3, s. 1339-1346
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND. Recombinant human PDGF-BB (rhPDGF-BB) reduces Parkinsonian symptoms and increases dopamine transporter (DAT) binding in several animal models of Parkinson's disease (PD). Effects of rhPDGF-BB are the result of proliferation of ventricular wall progenitor cells and reversed by blocking mitosis. Based on these restorative effects, we assessed the safety and tolerability of intracerebroventricular (i.c.v.) rhPDGF-BB administration in individuals with PD. METHODS. We conducted a double-blind, randomized, placebo-controlled phase I/IIa study at two clinical centers in Sweden. Twelve patients with moderate PD received rhPDGF-BB via an implanted drug infusion pump and an investigational i.c.v. catheter. Patients were assigned to a dose cohort (0.2, 1.5, or 5 mu g rhPDGF-BB per day) and then randomized to active treatment or placebo (3:1) for a 12-day treatment period. The primary objective was to assess safety and tolerability of i.c.v.-delivered rhPDGF-BB. Secondary outcome assessments included several clinical rating scales and changes in DAT binding. The follow-up period was 85 days. RESULTS. All patients completed the study. There were no unresolved adverse events. Serious adverse events occurred in three patients; however, these were unrelated to rhPDGF-BB administration. Secondary outcome parameters did not show dose-dependent changes in clinical rating scales, but there was a positive effect on DAT binding in the right putamen. CONCLUSION. At all doses tested, i.c.v. administration of rhPDGF-BB was well tolerated. Results support further clinical development of rhPDGF-BB for patients with PD.
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| 15. |
- Wernersson, Ann-Sofie, 1969, et al.
(författare)
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The European technical report on aquatic effect-based monitoring tools under the water framework directive
- 2015
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Ingår i: Environmental Sciences Europe. - : Springer Science and Business Media LLC. - 2190-4715 .- 2190-4707. ; 27:11 March 2015
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Tidskriftsartikel (refereegranskat)abstract
- The Water Framework Directive (WFD), 2000/60/EC, requires an integrated approach to the monitoring and assessment of the quality of surface water bodies. The chemical status assessment is based on compliance with legally binding Environmental Quality Standards (EQSs) for selected chemical pollutants (priority substances) of EU-wide concern. In the context of the mandate for the period 2010 to 2012 of the subgroup Chemical Monitoring and Emerging Pollutants (CMEP) under the Common Implementation Strategy (CIS) for the WFD, a specific task was established for the elaboration of a technical report on aquatic effect-based monitoring tools. The activity was chaired by Sweden and co-chaired by Italy and progressively involved several Member States and stakeholders in an EU-wide drafting group. The main aim of this technical report was to identify potential effect-based tools (e.g. biomarkers and bioassays) that could be used in the context of the different monitoring programmes (surveillance, operational and investigative) linking chemical and ecological status assessment. The present paper summarizes the major technical contents and findings of the report.
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