Publications by authors named "Ake Seiger"

62 Publications

Transplantation of Human Neural Precursor Cells Reverses Syrinx Growth in a Rat Model of Post-Traumatic Syringomyelia.

Neurotherapeutics 2021 Jan 19. Epub 2021 Jan 19.

Division of Neurogeriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.

Posttraumatic syringomyelia (PTS) is a serious condition of progressive expansion of spinal cord cysts, affecting patients with spinal cord injury years after injury. To evaluate neural cell therapy to prevent cyst expansion and potentially replace lost neurons, we developed a rat model of PTS. We combined contusive trauma with subarachnoid injections of blood, causing tethering of the spinal cord to the surrounding vertebrae, resulting in chronically expanding cysts. The cysts were usually located rostral to the injury, extracanalicular, lined by astrocytes. T2*-weighted magnetic resonance imaging (MRI) showed hyperintense fluid-filled cysts but also hypointense signals from debris and iron-laden macrophages/microglia. Two types of human neural stem/progenitor cells-fetal neural precursor cells (hNPCs) and neuroepithelial-like stem cells (hNESCs) derived from induced pluripotent stem cells-were transplanted to PTS cysts. Cells transplanted into cysts 10 weeks after injury survived at least 10 weeks, migrated into the surrounding parenchyma, but did not differentiate during this period. The cysts were partially obliterated by the cells, and cyst walls often merged with thin layers of cells in between. Cyst volume measurements with MRI showed that the volumes continued to expand in sham-transplanted rats by 102%, while the cyst expansion was effectively prevented by hNPCs and hNESCs transplantation, reducing the cyst volumes by 18.8% and 46.8%, respectively. The volume reductions far exceeded the volume of the added human cells. Thus, in an animal model closely mimicking the clinical situation, we provide proof-of-principle that transplantation of human neural stem/progenitor cells can be used as treatment for PTS.
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http://dx.doi.org/10.1007/s13311-020-00987-3DOI Listing
January 2021

Cognitive challenges in persons with spina bifida: Bearing on urological dysfunctions?

Neurourol Urodyn 2020 11 22;39(8):2139-2145. Epub 2020 Sep 22.

Rehab Station Stockholm, Karolinska Institutet, Stockholm, Sweden.

Aim: To evaluate if adult persons with spina bifida (SB) who have urinary tract complications have cognitive difficulties that can be identified by neuropsychological tests.

Methods: All individuals with SB ≥ 18 years of age registered at a regional outpatient clinic (n = 219) were invited, of which, 154 persons were included. Neuropsychological assessment of their cognitive status was performed with Wechsler Adult Intelligence Scale®-Fourth Edition: Coding, Block design, Arithmetic's, FAS (word generation), Rey Auditory Verbal Test for learning, and delayed recall 30 min. Bladder and bowel function were assessed with questions used by the Nordic Spinal Cord Injury Registry (NSCIR) in structured interviews, by questionnaires, and by chart reviews.

Results: Average neuropsychological test results for this SB population was shown to be approximately 1 SD under the median for the general population. The Coding test showed significantly lower test results as compared with the whole SB group in persons with urinary tract complications, especially urinary tract infections, reduced kidney function, dependent emptying of the bladder, and the bowel and accidental bowel leakage. The Arithmetic's test showed a significant difference between subgroups in all parameters except reduced kidney function whereas the other neuropsychological tests were significantly correlated with some but not all urological parameters.

Conclusion: We propose neuropsychological testing with primarily two tests to find those persons with SB who, due to cognitive challenges, might need extra support to minimize urological complications.
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http://dx.doi.org/10.1002/nau.24515DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7702031PMC
November 2020

A health concept with a social potential: an interview study with nursing home residents.

BMC Geriatr 2020 09 4;20(1):324. Epub 2020 Sep 4.

Stockholms Sjukhem R&D unit, Stockholm, Sweden.

Background: A qualitative, interview-based study was embedded in a randomized intervention trial, the Older People Exercise and Nutrition (OPEN) study. Participants in the OPEN study were encouraged to conduct sessions of sit-to-stand (STS) exercises combined with Oral Nutritional Supplements (ONS) intake. The aim was to describe the older persons' perceptions and experiences of being given the daily opportunity to perform the STS exercise and drink ONS.

Methods: In-depth interviews were conducted in six nursing homes with the participants using a semi-structured interview guide. One or two individual interviews were performed with each included participant. Twenty-three NH residents (16 women and 7 men) participated in the qualitative study. Their ages ranged between 76 and 96 years, and their Mini Mental State Examination (MMSE) scored between 8 and 29. The transcribed interviews and field notes written during the visits were analyzed inductively following a constant comparative method described in Grounded Theory.

Results: The exercise and nutritional intervention was described as highly practical by the NH residents, who claimed it also had a social aspect as they felt acknowledged and empowered to engage others in the combined intervention. Experiences of the intervention ranged from neutral to mainly positive and could be sorted into 5 categories: 1. Perceived hopes and expectations, 2. Health-related driving forces, 3. Appreciated daily activities, 4. A concept easy to perform and integrate into daily life, 5. A beneficial health concept for all. The intervention created perceived benefits on various health aspects due to participants feeling energized and stronger. An overall theme was identified as A health concept with a social potential, as participants feel acknowledged and strong enough to help others.

Conclusions: The intervention was described by participants as a health concept that could potentially be beneficial for a broader spectrum of NH residents. The findings indicate that health concepts, such as STS/ONS, might contribute to a more meaningful day for older people, even vulnerable NH residents approaching the end of life.

Trial Registration: ClinicalTrials.govIdentifier: NCT02702037 . Date of trial registration February 26, 2016.
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http://dx.doi.org/10.1186/s12877-020-01731-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7487501PMC
September 2020

Factors associated with self-rated health in a Norwegian population of older people participating in a preventive home visit program: a cross-sectional study.

BMC Geriatr 2020 09 4;20(1):323. Epub 2020 Sep 4.

Department of Neurobiology, Care Sciences and Society, Division of Nursing, Karolinska Institutet, Stockholm, Sweden.

Background: Assessing self-rated health by preventive home visits of older people can provide information about the person's well-being, quality of life and risk of developing illness. The aim of this study was to examine associations between self-rated health and factors related to demographics, lifestyle, health conditions and medical diagnoses by older people participating in a preventive home visit program.

Methods: A cross-sectional study including 233 participants (age 75-79) from three municipalities of Western Norway was conducted. Data were collected through preventive home visits performed by six nurses, using a questionnaire including self-rated health assessment and questions and tests related to demographics (e.g. education and housing), lifestyle (e.g. social activities, alcohol and smoking), health conditions (e.g. sensory impairment, pain and limited by disease) and medical diagnoses. Descriptive and inferential statistics including linear block-wise regression model were applied.

Results: The block-wise regression model showed that the variables Limited by disease and Pain were negatively associated with self-rated health and Use internet was positively associated. The model had a R 0.432. The variable that contributed to largest change in the model was Limited by disease (R Change; 0.297, p-value< 0.001).

Conclusions: In the present study, being limited by disease and pain were strongly associated with poor self-rated health, indicating that these are important factors to assess during a preventive home visit. Also, digital competence (Use internet) was associated with a better self-rated health, suggesting that it could be useful to ask, inform and motivate for the use of digital tools that may compensate for or improve social support, social contact and access to health -related information.
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http://dx.doi.org/10.1186/s12877-020-01733-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7650279PMC
September 2020

Evaluating the feasibility of ReWork-SCI: a person-centred intervention for return-to-work after spinal cord injury.

BMJ Open 2020 08 20;10(8):e036000. Epub 2020 Aug 20.

Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden.

Objectives: To evaluate the feasibility of: (1) ReWork-SCI with regard to adherence and acceptability and (2) a study design for evaluating ReWork-SCI with regard to recruitment, retention and outcome measures.

Design: Pre-test and post-test, single group, feasibility study.

Setting: Spinal cord injury (SCI) unit at a regional rehabilitation centre in Sweden.

Participants: Two women and five men (n=7). Eligible criteria: (1) sustained traumatic or non-traumatic SCI; (2) completed the first acute care episode in a hospital; (3) between 18 to 65 years of age; (4) assessed by a physician as approachable for participation in the intervention; (5) history of permanent or temporary employment; (6) self-reported desire to return to work; and (7) ability to communicate in English or Swedish.

Intervention: ReWork-SCI is a person-centred intervention for return-to-work (RTW), developed and evaluated using the Medical Research Council's guidelines. ReWork-SCI follows a person-centred, structured and coordinated intervention process led by a coordinator within a SCI rehabilitation team.

Outcome Measures: The feasibility of ReWork-SCI and a study design was evaluated using a set of outcome measurement tools, vocational data, logbooks and semi-structured interviews.

Results: All eligible participants accepted enrolment and follow-up. All participants had a plan for RTW after 3 months and four participants had initiated part-time work or work trial 6 months after commencement of intervention. Adherence and acceptability were overall good. Challenges of the intervention related to the person-centred follow-up, staff shortage and rootedness in the SCI team.

Conclusions: ReWork-SCI was feasible and can contribute to a systematic design of an individualised plan, facilitate decision-making and build trust in the RTW process after SCI. Core features of the intervention was the systematic structure, use of a person-centred approach and dialogue with the employer. For the effectiveness of ReWork-SCI, modifications and considerations of study design are needed.
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http://dx.doi.org/10.1136/bmjopen-2019-036000DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7443280PMC
August 2020

Adults with spina bifida: A cross-sectional study of health issues and living conditions.

Brain Behav 2020 08 7;10(8):e01736. Epub 2020 Jul 7.

Rehab Station Stockholm, Spinalis Outpatient Clinic, Solna, Sweden.

Objective: To describe health issues and living conditions in a cohort of adults living with Spina bifida.

Material And Methods: A cross-sectional study was conducted by a multidisciplinary team. Adults with spina bifida (n = 219) were invited to participate. One-hundred-and-ninety-six persons (104 women and 92 men; 18-73 years, median age 33 years) were included. Structured interviews, questionnaires, and clinical assessments for medical, social, physical, and cognitive functions were used.

Results: There was large variation among participants as regards the consequences of their spina bifida. Individuals < 46 years seemed to have more secondary conditions such as hydrocephalus, Chiari II malformation, tethered cord symptoms, and latex allergy. A higher proportion of the individuals >46 years and older was able to walk, and they had performed better in primary school and on tests of psychomotor speed and executive function.

Conclusions: This study demonstrates that adults with spina bifida have a complex set of physical, cognitive, and social needs that need to be addressed in order to improve their health issues and living conditions. The high prevalence of urinary and fecal incontinence, pain, and overweight underline that these issues need much attention during follow-up. The future generations of older adults may need more attention in many ways, since they at a younger age do have more complex medical conditions, lower physical and cognitive functions, and lower prerequisites for independent living and participation in society than those > 46 years today. This elucidates that adults with spina bifida need systematic follow-up services and social support throughout life.
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http://dx.doi.org/10.1002/brb3.1736DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7428499PMC
August 2020

Voiding conditions, renal and bowel function in a cohort of adults with spina bifida.

Neurourol Urodyn 2020 08 12;39(6):1796-1802. Epub 2020 Jun 12.

Rehab Station Stockholm, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.

Aim: To map voiding patterns, degree of continence, use of drugs for voiding disorders, kidney function and surgical interventions but also the bowel function in a near-total regional cohort of adults with spina bifida aged more than or equal to 18 years.

Methods: All individuals more than or equal to 18 years of age with spina bifida registered at a regional outpatient clinic (n = 219) were invited to participate, of which 196 persons were included. Bladder and bowel function were assessed according to questions used by the Nordic Spinal Cord Injury Registry by structured interviews and questionnaires in combination with review of patient charts including kidney function.

Results: Twenty percent of the patients voided spontaneously. Fifty-four percent used clean intermittent catherization (CIC) and of these, 14% had also undergone augmentation of the bladder and/or implantation of an artificial sphincter or sling, 23% had undergone major urological surgery, and 3% had an indwelling catheter. Seventeen percent of patients voiding spontaneously or using CIC reported total continence but as many as 36% reported daily leakage. Anticholinergics was the most common drug, used by 21% in the total cohort. About 13% of the patients had a reduced kidney function but only 1.5% had end stage renal failure. Seventy-three percent had problems emptying the bowel and 18% experienced fecal leakage weekly or even daily.

Conclusion: We found a large variation in problems with bladder and bowel function in this adult group of persons with spina bifida. A structured customized program for follow-up seems necessary to optimize their health status in these areas.
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http://dx.doi.org/10.1002/nau.24422DOI Listing
August 2020

Effect of Sit-to-Stand Exercises Combined With Protein-Rich Oral Supplementation in Older Persons: The Older Person's Exercise and Nutrition Study.

J Am Med Dir Assoc 2020 Sep 26;21(9):1229-1237. Epub 2020 May 26.

Stockholms Sjukhem R&D Unit, Stockholm, Sweden; Theme Aging, Karolinska University Hospital, Stockholm, Sweden; Department of Neurobiology, Care Science and Society, Division of Nursing, Karolinska Institutet, Stockholm, Sweden; Western Norway University of Applied Sciences, Haugesund, Norway. Electronic address:

Objectives: Nursing home (NH) residents are often undernourished and physically inactive, which contributes to sarcopenia and frailty. The Older Person's Exercise and Nutrition Study aimed to investigate the effects of sit-to-stand exercises (STS) integrated into daily care, combined with a protein-rich oral nutritional supplement (ONS), on physical function, nutritional status, body composition, health-related quality of life, and resource use.

Design: Residents in 8 NHs were randomized by NH units into an intervention group (IG) or a control group (CG) (n = 60/group). The IG was a combination of STS (4 times/day) and ONS (2 bottles/day providing 600 kcal and 36 g protein) for 12 weeks.

Setting And Participants: The participants resided in NH units (dementia and somatic care), were ≥75 years of age, and able to rise from a seated position.

Methods: The 30-second Chair Stand Test was the primary outcome. Secondary outcomes were balance, walking speed, dependence in activities of daily living, nutritional status and body composition, health-related quality of life, and resource use.

Results: Altogether, 102 residents (age 86 ± 5 years, 62% female) completed the study. No improvement in the physical function assessments was observed in the IG, whereas body weight increased significantly (2.05 ± 3.5 kg, P = .013) vs the CG. Twenty-one (of 52) participants with high adherence to the intervention (ie, at least 40% compliance to the combined intervention) increased their fat free mass (2.12 kg (0.13, 4.26 interquartile range), P = .007 vs CG). Logistic regression analyses indicated that the odds ratio for maintained/improved 30-second Chair Stand Test was 3.5 (confidence interval 1.1, 10.9, P = .034) among the participants with high adherence compared with the CG.

Conclusions/implications: Twelve-week intervention of daily STS combined with ONS in NH residents did not improve physical function, but increased body weight. Subgroup analyses indicated that high adherence to the combined intervention was associated with maintained or improved physical function and a gain of fat free mass.
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http://dx.doi.org/10.1016/j.jamda.2020.03.030DOI Listing
September 2020

The cholinergic system in subtypes of Alzheimer's disease: an in vivo longitudinal MRI study.

Alzheimers Res Ther 2020 05 6;12(1):51. Epub 2020 May 6.

Division of Clinical Geriatrics, Centre for Alzheimer Research, Department of Neurobiology, Care Sciences, and Society, Karolinska Institutet, NEO, Floor 7th, Blickagången 16, 141 52, Huddinge, Stockholm, Sweden.

Background: The heterogeneity within Alzheimer's disease (AD) seriously challenges the development of disease-modifying treatments. We investigated volume of the basal forebrain, hippocampus, and precuneus in atrophy subtypes of AD and explored the relevance of subtype stratification in a small clinical trial on encapsulated cell biodelivery (ECB) of nerve growth factor (NGF) to the basal forebrain.

Methods: Structural MRI data was collected for 90 amyloid-positive patients and 69 amyloid-negative healthy controls at baseline, 6-, 12-, and 24-month follow-up. The effect of the NGF treatment was investigated in 10 biopsy-verified AD patients with structural MRI data at baseline and at 6- or 12-month follow-up. Patients were classified as typical, limbic-predominant, hippocampal-sparing, or minimal atrophy AD, using a validated visual assessment method. Volumetric analyses were performed using a region-of-interest approach.

Results: All AD subtypes showed reduced basal forebrain volume as compared with the healthy controls. The limbic-predominant subtype showed the fastest basal forebrain atrophy rate, whereas the minimal atrophy subtype did not show any significant volume decline over time. Atrophy rates of the hippocampus and precuneus also differed across subtypes. Our preliminary data from the small NGF cohort suggest that the NGF treatment seemed to slow the rate of atrophy in the precuneus and hippocampus in some hippocampal-sparing AD patients and in one typical AD patient.

Conclusions: The cholinergic system is differentially affected in distinct atrophy subtypes of AD. Larger studies in the future should confirm that this differential involvement of the cholinergic system may contribute to subtype-specific response to cholinergic treatment. Our preliminary findings suggest that future clinical trials should target specific subtypes of AD, or at least report treatment effects stratified by subtype.

Trial Registration: ClinicalTrials.gov identifier: NCT01163825. Registered 14 July 2010.
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http://dx.doi.org/10.1186/s13195-020-00620-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7203806PMC
May 2020

The Stockholm Spinal Cord Uro Study: 2. Urinary tract infections in a regional prevalence group: frequency, symptoms and treatment strategies.

Scand J Urol 2020 Apr 9;54(2):155-161. Epub 2020 Mar 9.

Department NVS, Division of Clinical Geriatrics, Karolinska Institute, Stockholm, Sweden.

To examine symptomatic urinary tract infections (UTI) in a regional prevalence group of patients with traumatic spinal cord injury (SCI), to assess risk factors for recurring infections and to identify a high-risk sub-population for frequently recurring and severe febrile UTIs. Four hundred and twelve patients who attended a yearly check-up at the Spinalis SCI clinic were included. A regional programme for neurogenic bladder dysfunction was applied, including S-creatinine and S-cystatin-C, urine culture, residual urine, ultrasound of kidneys, urodynamic studies and a questionnaire regarding complications during the preceding year. Descriptive statistics and regression analysis were used to estimate risk factors. Nearly half of all patients reported ≥1 UTI during the preceding year with a mean number of 3.6. Persons who use normal voiding had the lowest frequency, while those with catheter-assisted voiding reported the highest numbers. A sub-group of patients had more frequent and severe UTIs. They were characterized by a cervical or thoracic neurological level lesion and a more severe injury and the presence of SCI-related complications such as spasticity, neuropathic pain and autonomic dysreflexia. The most common signs and symptoms of UTI were smelly and cloudy urine, feelings of malaise and increased spasticity. Risk profiles for recurring and severe UTIs were catheter-assisted voiding, cervical or thoracic levels and more complete neurological lesions and the co-existence of other SCI-related complications. There is a need for an increased understanding of the special symptoms of UTI in this patient group and a strategy to avoid unspecific antibiotic treatment.
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http://dx.doi.org/10.1080/21681805.2020.1734078DOI Listing
April 2020

The Stockholm Spinal Cord Uro Study: 1. Basic characteristics and problem inventory.

Scand J Urol 2019 Dec 21;53(6):403-410. Epub 2019 Oct 21.

Department NVS Division of Clinical Geriatrics, Karolinska Institutet, Solna, Sweden.

To assess urinary tract function and complications in a regional prevalence group of patients with traumatic spinal cord injury (SCI), and to estimate risk factors for recurring complications. A total of 412 patients who attended a yearly check-up at the Spinalis SCI clinic were included. A regional follow-up programme for neurogenic bladder dysfunction was applied, including S-creatinine and S-cystatin-C, urine culture, residual urine, ultrasound of kidneys, urodynamic studies, and a questionnaire regarding complications during the preceding year. Descriptive statistics and logistic regression were used to estimate risk factors. All patients completed blood tests and the questionnaire. A urine culture was completed by 96%, ultrasound by 88%, residual urine by 75%, urodynamics by 51%, and all parts of the study by 47%. One quarter of patients displayed pathological findings regarding kidney function. Urodynamics verified neurogenic overactive bladder in a majority, and a high proportion with intravesical filling pressures above 40 cm HO, a commonly used cut-off level for kidney safety. Subjectively, 47% of patients reported complications during the past year with urinary tract infection (UTI) as the most common one. Other complications were rare. With the aid of a regular follow-up programme, SCI patients can achieve a relatively stable situation regarding urinary tract function. UTI is the most common complication. Indicators of renal complications are frequent but not clearly related to the number of UTIs, nor to intravesical filling pressures. Main risk factors for complications are cervical levels and more complete neurological lesions.
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http://dx.doi.org/10.1080/21681805.2019.1673812DOI Listing
December 2019

Long-term use of noble metal alloy coated urinary catheters reduces recurrent CAUTI and decreases proinflammatory markers.

Ther Adv Urol 2019 Jan-Dec;11:1756287219854915. Epub 2019 Jun 18.

Bactiguard AB, Tullinge, Stockholm, Sweden.

Background: The objective of this study was to investigate a case of a permanently (suprapubic) catheterized woman with neurogenic bladder dysfunction. The patient had suffered from recurrent catheter-associated urinary tract infections (CAUTIs) since 2009, despite several prevention approaches and attempts. In 2013, the patient's catheter was substituted for the BIP Foley Catheter, coated with a noble metal alloy (NMA) of gold, silver, and palladium.

Method: This is a retrospective-prospective clinical case study covering 4 years history for the control catheters and up to 2.5 years for the anti-infective BIP Foley Catheter. CAUTI incidences, symptoms, antibiotics, catheter performance, and comfort were evaluated. Levels of proinflammatory cytokines were measured pre- and post-substitution to BIP Foley Catheter in urine of the case and of four other permanently catheterized patients. In addition, the levels of noble metals were assessed in urine of the case subject during use of the BIP Foley Catheter.

Results: While using control catheters, the patient experienced symptomatic CAUTIs requiring antibiotics almost every month for 4 years. After 1 month with the BIP Foley Catheter, the symptoms disappeared, and the patient remained free of symptomatic CAUTIs and antibiotic treatment for the following 2.5 years, despite bacteriuria. The patient was satisfied with the comfort during insertion, use, and removal of the BIP Foley Catheter. Urinary levels of the proinflammatory cytokines interleukin (IL)-6, IL-8, and tumor necrosis factor alpha (TNFα) decreased towards normal levels post catheter type substitution. Traces of noble metals detected in a few urine samples were ⩽4% of the permitted daily exposure. The levels of the noble metals gold, silver, and palladium remaining on the BIP Foley Catheter after use were the same as for unused catheters.

Conclusion: Long-term use of a NMA-coated catheter was associated with cessation of frequent CAUTIs. The catheter was experienced as comfortable and inflammatory markers were reduced with time. The coating was stable, with no significant metal release into urine and is therefore safe for patient use.
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http://dx.doi.org/10.1177/1756287219854915DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6585253PMC
June 2019

Risk assessment during preventive home visits among older people.

J Multidiscip Healthc 2018 24;11:609-620. Epub 2018 Oct 24.

Department of Neurobiology, Care Sciences and Society, Division of Nursing, Karolinska Institutet, Stockholm, Sweden,

Background: Preventive home visits (PHV) may contribute to identify risks and needs in older people, and thereby delay the onset of functional decline and illness, otherwise often followed by home care or admission to hospital or nursing homes. There is a need to increase knowledge about which factors are associated with different risk areas among older people, so that the PHV questionnaire focuses on relevant tests and questions to make the PHV more specific and have a clear focus and purpose.

Objective: The objective of this study was to examine associations between five kinds of risks: risk of falls, malnutrition, polypharmacy, cognitive impairment, and risk of developing illness and factors related to lifestyle, health, and medical diagnoses among older people living at home.

Methods: A cross-sectional study design was applied. PHV were conducted by nurses among 77-year-old people in an urban municipality and among ≥75-year-old people in a rural municipality. A questionnaire including tests and a risk assessment score for developing illness was used. Descriptive and inferential statistics including regression models were analyzed.

Results: The total sample included 166 persons. Poor perceived health was associated with increased risk of developing illness and risk of fall, malnutrition, and polypharmacy. Lifestyle and health factors such as lack of social support, sleep problems, and feeling depressed were associated with risk of developing illness. Risk of falls, malnutrition, polypharmacy, and cognitive impairment were also associated with increased risk of developing illness. None of the independent factors related to lifestyle, health, or medical diagnosis were associated with risk of cognitive impairment.

Conclusion: Poor perceived health was associated with health-related risks in older persons living at home. Preventive health programs need to focus on social and lifestyle factors and self-reported health assessment to identify older people at risk of developing illnesses.
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http://dx.doi.org/10.2147/JMDH.S176646DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6205137PMC
October 2018

A study protocol of Older Person's Exercise and Nutrition Study (OPEN) - a sit-to-stand activity combined with oral protein supplement - effects on physical function and independence: a cluster randomized clinical trial.

BMC Geriatr 2018 06 7;18(1):138. Epub 2018 Jun 7.

Stockholms Sjukhem R&D unit, Stockholm, Sweden.

Background: Poor nutrition and age per see add to the development of sarcopenia, i.e. loss of muscle mass and strength, which contributes to increased risk of impaired activities of daily living (ADL) and reduced independence. Protein deficiency plays an important role in the development of sarcopenia. In order to increase the muscle mass protein intake should be combined with physical exercise. A daily physical activity, the sit-to-stand exercise, has been proven to decrease older persons' dependence in ADL. Our study aims to evaluate the effects of the sit-to-stand exercise in combination with a protein-rich nutritional supplement, on physical function and independence in frail nursing home residents. The resident's perceptions and experiences of the intervention and the staff's experiences of supporting the resident to complete the intervention will also be explored.

Methods: The study is a two-arm cluster-randomized controlled trial which will be performed in nursing homes at two municipalities in Sweden. We will recruit 120 residents, age 75 or older and able to stand up from a seated position. Residents (n = 60) randomized to the intervention group will perform the sit-to-stand exercise at four occasions daily and will be offered a protein-rich oral supplement, twice a day. The intervention period will last for 12 weeks and measures of physical function, nutritional status, quality of life and health economy will be performed at baseline and at 12-weeks follow-up. The primary outcome will be the number of chair rises performed in 30 s. The control group will receive standard care. Data will be analysed by intention-to-treat analysis and with mixed effect models. During the last part of the intervention period individual interviews with the residents, on the topic of feasibility with the OPEN concept will be held. Likewise, focus-group-interviews with staff will be performed.

Discussion: The residents' physical and mental health could be expected to improve. Even the work situation for staff could be positively affected. One innovative feature of the OPEN study is the simple intervention consisting of a basic daily activity that can be performed by several nursing home residents with the support of existing staff and available resources.

Trial Registration: ClinicalTrials.gov Identifier: NCT02702037.
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http://dx.doi.org/10.1186/s12877-018-0824-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6000965PMC
June 2018

Assessment of voice, speech and communication changes associated with cervical spinal cord injury.

Int J Lang Commun Disord 2018 07 24;53(4):761-775. Epub 2018 Feb 24.

Department of Clinical Sciences, Intervention, and Technology (CLINTEC)/Division of Speech and Language Pathology, Karolinska Institutet, Stockholm, Sweden.

Background: Respiratory muscle impairment following cervical spinal cord injury (CSCI) may lead to reduced voice function, although the individual variation is large. Voice problems in this population may not always receive attention since individuals with CSCI face other, more acute and life-threatening issues that need/receive attention. Currently there is no consensus on the tasks suitable to identify the specific voice impairments and functional voice changes experienced by individuals with CSCI.

Aims: To examine which voice/speech tasks identify the specific voice and communication changes associated with CSCI, habitual and maximum speech performance of a group with CSCI was compared with that of a healthy control group (CG), and the findings were related to respiratory function and to self-reported voice problems.

Methods & Procedures: Respiratory, aerodynamic, acoustic and self-reported voice data from 19 individuals (nine women and 10 men, aged 23-59 years, heights = 153-192 cm) with CSCI (levels C3-C7) were compared with data from a CG consisting of 19 carefully matched non-injured people (nine women and 10 men, aged 19-59 years, heights = 152-187 cm).

Outcomes & Results: Despite considerable variability of performance, highly significant differences between the group with CSCI and the CG were found in maximum phonation time, maximum duration of breath phrases, maximum sound pressure level and maximum voice area in voice-range profiles (all p = .000). Subglottal pressure was lower and phonatory stability was reduced in some of the individuals with CSCI, but differences between the groups were not statistically significant. Six of 19 had voice handicap index (VHI) scores above 20 (the cut-off for voice disorder). Individuals with a vital capacity below 50% of the expected for an equivalent reference individual performed significantly worse than participants with more normal vital capacity. Completeness and level of injury seemed to impact vocal function in some individuals.

Conclusions & Implications: A combination of maximum performance speech tasks, respiratory tasks and self-reported information on voice problems help to identify individuals with reduced voice function following CSCI. Early identification of individuals with voice changes post-CSCI, and introducing appropriate rehabilitation strategies, may help to minimize development of maladaptive voice behaviours such as vocal strain, which can lead to further impairments and limitations to communication participation.
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http://dx.doi.org/10.1111/1460-6984.12380DOI Listing
July 2018

Prescription Changes During Geriatric Care Episodes: A Trend Analysis Conducted in Sweden.

Drugs Aging 2018 03;35(3):243-248

Karolinska Institutet, Stockholm, Sweden.

Background: The number of drugs prescribed for old people has been rising in recent decades. With increasing age and multiple medications, the risk of complications and drug prescription complexity increases. Multiple changes to prescriptions could be a factor that improves treatment quality.

Objectives: Our objective was to investigate trends in drug prescriptions and factors that contribute to prescription changes. Specific objectives were to find out whether high numbers of prescription changes are significantly correlated with age, sex, comorbidity, length of care episode, and number of drugs.

Methods: Data were extracted from geriatric clinic records in Stockholm in 2005, 2010, and 2015. Indicators for good drug therapy were used to assess the effects of prescription changes on quality, using an index of inappropriate drug use (IDU). Data were analyzed with Student's t-test, PR test, Wilcoxon's rank sum test, and linear regression.

Results: Patients had more comorbidities and used more drugs but had shorter hospital stays and significantly fewer prescription changes in 2015 than in 2005. Length of care episode was significantly associated with prevalence of prescription changes. Our model showed that, for each day by which the length of care episode decreased, the number of prescription changes decreased by 8%. The number of prescription changes was negatively correlated to the IDU index score.

Conclusions: The study showed that more prescription changes were associated with longer care episodes and improved drug prescribing quality as per the IDU index. Given prescription changes are regarded as a quality factor in geriatric care, quality may have decreased along with the length of care episodes between 2005 and 2015.
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http://dx.doi.org/10.1007/s40266-017-0509-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5884893PMC
March 2018

Incidence, aetiology and injury characteristics of traumatic spinal cord injury in Stockholm, Sweden: A prospective, population-based update.

J Rehabil Med 2017 May;49(5):431-436

, Neurobiology, Care Sciences and Society, Karolinska Institutet, 14183 Huddinge, Stockholm, Sweden.

Objectives: To update the incidence rate, aetiology and injury characteristics of acutely-injured adults with traumatic spinal cord injury in Stockholm, Sweden, using international standards of reporting.

Study Design: Prospective, (regional) population-based observation.

Subjects: Forty-nine consecutively enrolled individuals.

Methods: A surveillance system of newly-injured adults with traumatic spinal cord injury was implemented for an 18-month period. The International Spinal Cord Injury Core Data Set was used to collect data on those who survived the first 7 days post-injury.

Results: After an 18-month period, 49 incident cases were registered, of whom 45 were included in this study. The crude incidence rate was 19.0 per million, consisting mainly of men (60%), and the mean age of the cohort was 55 years (median 58). Causes of injury were almost exclusively limited to falls and transport-related events, accounting for 58% and 40% of cases, respectively. The incidence has remained stable when compared with the previous study; however, significant differences exist for injury aetiology (p = 0.004) and impairment level (p = 0.01) in that more fall- and transport-related spinal cord injury occurred, and a larger proportion of persons was left with resultant tetraplegia, in the current study, compared with more sport-related injuries and those left with paraplegia in the previous study.

Conclusion: The incidence rate appeared to remain stable in Stockholm, Sweden. However, significant changes in injury aetiology and impairment-level post injury were found, compared with the previous study. There remains a need for developing fall-related prevention strategies in rehabilitation settings as well as in population-based programmes.
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http://dx.doi.org/10.2340/16501977-2224DOI Listing
May 2017

Falls and fear of falling predict future falls and related injuries in ambulatory individuals with spinal cord injury: a longitudinal observational study.

J Physiother 2017 04 28;63(2):108-113. Epub 2017 Feb 28.

Department of Neurobiology, Care Sciences and Society, Division of Physiotherapy, Karolinska Institutet, Stockholm, Sweden; Department of Research, Sunnaas Rehabilitation Hospital, Nesodden, Norway.

Questions: What is the 1-year incidence of falls and injurious falls in a representative cohort of community-dwelling ambulatory individuals with chronic spinal cord injury? What are the predictors of recurrent falls (more than two/year) and injurious falls in this population?

Design: One-year longitudinal observational multi-centre study.

Participants: A representative sample of 68 (of 73 included) community-dwelling ambulatory individuals with traumatic SCI attending regular follow-up programs at rehabilitation centres.

Outcome Measures: Primary outcome measures were incidence and predictors of recurrent falls (more than two/year) and injurious falls reported every 2 weeks for 1year.

Results: A total of 48% of participants reported recurrent falls. Of the 272 reported falls, 41% were injurious. Serious injuries were experienced by 4% of participants, all of whom were women. Multivariate logistic regression analysis showed that recurrent falls in the previous year (OR=111, 95% CI=8.6 to 1425), fear of falling (OR=6.1, 95% CI=1.43 to 26) and longer time taken to walk 10m (OR=1.3, 95% CI=1.0 to 1.7) were predictors of recurrent falls. Fear of falling (OR=4.3, 95% CI=1.3 to 14) and recurrent falls in the previous year (OR=4.2, 95% CI=1.2 to 14) were predictors of injurious falls.

Conclusion: Ambulatory individuals have a high risk of falling and of fall-related injuries. Fall history, fear of falling and walking speed could predict recurrent falls and injurious falls. Further studies with larger samples are needed to validate these findings. [Jørgensen V, Butler Forslund E, Opheim A, Franzén E, Wahman K, Hultling C, Seiger Å, Ståhle A, Stanghelle JK, Roaldsen KS (2017) Falls and fear of falling predict future falls and related injuries in ambulatory individuals with spinal cord injury: a longitudinal observational study. Journal of Physiotherapy 63: 108-113].
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http://dx.doi.org/10.1016/j.jphys.2016.11.010DOI Listing
April 2017

Health team for the elderly: a feasibility study for preventive home visits.

Prim Health Care Res Dev 2017 05 20;18(3):242-252. Epub 2017 Feb 20.

2Department of Nursing,Western Norway University of Applied Sciences,Haugesund,Norway.

The aim was to describe the development, utilization and feasibility of a model of preventive home visits, in an urban and a rural municipality in Norway.

Background: Older people >65 years will rise significantly in coming years. Increased age is associated with risk of disability, illness and need for public health services. Preventive home visits is assumed to help older people to maintain their functional level longer, delaying disease and thus delaying the need for health care.

Method: Descriptive explorative design describing the development, utilization and feasibility of preventive home visits in two different settings. All 77-year-old persons living at home in an urban municipality and all 75 years and older in a rural municipality were invited to participate. A questionnaire including a substantial number of tests concerning; fall, nutrition, polypharmacy and cognitive impairment was used by Health Team Nurses as base for a risk assessment. Pilot studies were conducted to validate the questionnaire including an inter-rater reliability study of the risk assessment tool. A multiprofessional team, Health Team for the Elderly met each week to evaluate risk assessments and make recommendations to be sent to each respective general practitioner. Data were analysed using descriptive and inferential statistics. In total, 167 persons (109 from the urban municipality and 58 from the rural municipality) participated, corresponding to 60% of the approached individuals. The mean time for the visits was 108 minutes (SD 20). Missing data were identified for; Do you feel safe in your municipality (17.5%) and Are you looking forward to ageing (11.4%). In total, 36 persons (21.7%) were identified with increased risk for developing illness. We suggest that a structured model of preventive home visits and collaboration between highly specialized health care professionals are important factors for reliable health promoting risk assessments of elderly home dwellers.
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http://dx.doi.org/10.1017/S1463423617000019DOI Listing
May 2017

High incidence of falls and fall-related injuries in wheelchair users with spinal cord injury: A prospective study of risk indicators.

J Rehabil Med 2017 Jan;49(2):144-151

Department of Neurobiology, Care Sciences and Society , Division of physiotherapy, 141 83 Huddinge, Sweden.

Objective: To identify risk indicators for, and incidence of, recurrent falls and fall-related injuries in wheelchair users with traumatic spinal cord injury.

Design: Prospective multi-centre study.

Subjects: One hundred and forty-nine wheelchair users with spinal cord injury attending follow-up in Sweden and Norway.

Methods: Inclusion criteria: wheelchair users ≥ 18 years old with traumatic spinal cord injury ≥ 1 year post-injury.

Exclusion Criteria: individuals with motor complete injuries above C5. Falls were prospectively reported by text message every second week for one year and were followed-up by telephone interviews. Outcomes were: fall incidence, risk indicators for recurrent (> 2) falls and fall-related injuries. Independent variables were: demographic data, quality of life, risk willingness, functional independence, and exercise habits.

Results: Of the total sample (n = 149), 96 (64%) participants fell, 45 (32%) fell recurrently, 50 (34%) were injured, and 7 (5%) severely injured. Multivariate logistic regression analysis showed that reporting recurrent falls the previous year increased the odds ratio (OR) of recurrent falls (OR 10.2, p < 0.001). Higher quality of life reduced the OR of fall-related injuries (OR 0.86, p = 0.037).

Conclusion: Previous recurrent falls was a strong predictor of future falls. The incidence of falls, recurrent falls and fall-related injuries was high. Hence, prevention of falls and fall-related injuries is important.
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http://dx.doi.org/10.2340/16501977-2177DOI Listing
January 2017

Factors Associated With Recurrent Falls in Individuals With Traumatic Spinal Cord Injury: A Multicenter Study.

Arch Phys Med Rehabil 2016 11 27;97(11):1908-1916. Epub 2016 May 27.

Department of Neurobiology, Karolinska Institutet, Care Sciences and Society, Division of Physiotherapy, Stockholm, Sweden; Rehab Station Stockholm/Spinalis Research and Development Unit, Stockholm, Sweden.

Objective: To identify factors associated with recurrent falls in individuals with traumatic spinal cord injury (SCI).

Design: Cross-sectional multicenter study.

Setting: Two specialized rehabilitation centers.

Participants: Included: individuals with traumatic SCI ≥1 year postinjury who were aged ≥18 years. Excluded: individuals with motor complete injuries above C5 or below L5. The study sample comprised participants (N=224; 151 wheelchair users, 73 ambulatory; 77% men; mean age ± SD, 50±15y; median time since injury, 15y [range, 1-56y]) who were consecutively recruited at regular follow-up.

Interventions: Not applicable.

Main Outcome Measure: Primary outcome was factors associated with recurrent falls (defined as low frequent [0-2] or recurrent [>2]) the previous year. Independent variables were demographic data, wheelchair user or ambulatory, work, health-related quality of life, risk willingness, alcohol consumption, ability to get up from the ground, and exercise habits.

Results: Fifty percent reported recurrent falls. In the final multiple logistic regression model, ambulation (odds ratio [OR]=2.67; 95% confidence interval [CI], 1.33-5.37), ability to get up from the ground (OR=2.22; 95% CI, 1.21-4.10), and regular exercise (OR=1.86; 95% CI, 1.05-3.31) were associated with recurrent falls (P≤.05), and with increasing age the OR decreased (OR=.97; 95% CI, .95-.99).

Conclusions: Individuals with SCI should be considered at risk of recurrent falls, and thereby at risk of fall-related injuries. Fall prevention programs should be focused on ambulatory, younger, and more active individuals who had the highest risks for recurrent falls.
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http://dx.doi.org/10.1016/j.apmr.2016.04.024DOI Listing
November 2016

Fetal CD103+ IL-17-Producing Group 3 Innate Lymphoid Cells Represent the Dominant Lymphocyte Subset in Human Amniotic Fluid.

J Immunol 2016 10 2;197(8):3069-3075. Epub 2016 Sep 2.

Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, 141 86 Stockholm, Sweden;

Amniotic fluid (AF) surrounds the growing fetus, and cells derived from AF are commonly used for diagnosis of genetic diseases. Intra-amniotic infections are strongly linked to preterm birth, which is the leading cause of perinatal mortality worldwide. Surprisingly little is known, however, about mature hematopoietic cells in AF, which could potentially be involved in immune responses during pregnancy. In this study, we show that the dominating population of viable CD45 cells in AF is represented by a subset of fetal CD103 group 3 innate lymphoid cells (ILCs) producing high levels of IL-17 and TNF. Fetal CD103 ILC3s could also be detected at high frequency in second-trimester mucosal tissues (e.g., the intestine and lung). Taken together, our data indicate that CD103 ILC3s accumulate with gestation in the fetal intestine and subsequently egress to the AF. The dominance of ILC3s producing IL-17 and TNF in AF suggests that they could be involved in controlling intra-amniotic infections and inflammation and as such could be important players in regulating subsequent premature birth.
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http://dx.doi.org/10.4049/jimmunol.1502204DOI Listing
October 2016

Targeted delivery of nerve growth factor to the cholinergic basal forebrain of Alzheimer's disease patients: application of a second-generation encapsulated cell biodelivery device.

Alzheimers Res Ther 2016 07 7;8(1):30. Epub 2016 Jul 7.

Department of Clinical Neuroscience, Karolinska Institutet, 171 77, Stockholm, Sweden.

Background: Targeted delivery of nerve growth factor (NGF) has emerged as a potential therapy for Alzheimer's disease (AD) due to its regenerative effects on basal forebrain cholinergic neurons. This hypothesis has been tested in patients with AD using encapsulated cell biodelivery of NGF (NGF-ECB) in a first-in-human study. We report our results from a third-dose cohort of patients receiving second-generation NGF-ECB implants with improved NGF secretion.

Methods: Four patients with mild to moderate AD were recruited to participate in an open-label, phase Ib dose escalation study with a 6-month duration. Each patient underwent stereotactic implant surgery with four NGF-ECB implants targeted at the cholinergic basal forebrain. The NGF secretion of the second-generation implants was improved by using the Sleeping Beauty transposon gene expression technology and an improved three-dimensional internal scaffolding, resulting in production of about 10 ng NGF/device/day.

Results: All patients underwent successful implant procedures without complications, and all patients completed the study, including implant removal after 6 months. Upon removal, 13 of 16 implants released NGF, 8 implants released NGF at the same rate or higher than before the implant procedure, and 3 implants failed to release detectable amounts of NGF. Of 16 adverse events, none was NGF-, or implant-related. Changes from baseline values of cholinergic markers in cerebrospinal fluid (CSF) correlated with cortical nicotinic receptor expression and Mini Mental State Examination score. Levels of neurofilament light chain (NFL) protein increased in CSF after NGF-ECB implant, while glial fibrillary acidic protein (GFAP) remained stable.

Conclusions: The data derived from this patient cohort demonstrate the safety and tolerability of sustained NGF release by a second-generation NGF-ECB implant to the basal forebrain, with uneventful surgical implant and removal of NGF-ECB implants in a new dosing cohort of four patients with AD.

Trial Registration: ClinicalTrials.gov identifier: NCT01163825 . Registered on 14 Jul 2010.
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http://dx.doi.org/10.1186/s13195-016-0195-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4936020PMC
July 2016

Changes in CSF cholinergic biomarkers in response to cell therapy with NGF in patients with Alzheimer's disease.

Alzheimers Dement 2015 Nov 9;11(11):1316-28. Epub 2015 Feb 9.

Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; Department of Geriatrics, Karolinska University Hospital, Stockholm, Sweden. Electronic address:

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-β, 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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http://dx.doi.org/10.1016/j.jalz.2014.11.008DOI Listing
November 2015

Brain changes in Alzheimer's disease patients with implanted encapsulated cells releasing nerve growth factor.

J Alzheimers Dis 2015 ;43(3):1059-72

Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden Department of Geriatrics, Karolinska University Hospital, Stockholm, Sweden.

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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http://dx.doi.org/10.3233/JAD-141068DOI Listing
August 2015

Neuroprotective effects of human spinal cord-derived neural precursor cells after transplantation to the injured spinal cord.

Exp Neurol 2014 Mar 8;253:138-45. Epub 2014 Jan 8.

Division of Neurodegeneration, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Geriatric Clinic Res Lab., Novum, S-14186 Stockholm, Sweden; Stockholms Sjukhem Foundation, Mariebergsgatan 22, S-11235 Stockholm, Sweden. Electronic address:

To validate human neural precursor cells (NPCs) as potential donor cells for transplantation therapy after spinal cord injury (SCI), we investigated the effect of NPCs, transplanted as neurospheres, in two different rat SCI models. Human spinal cord-derived NPCs (SC-NPCs) transplanted 9 days after spinal contusion injury enhanced hindlimb recovery, assessed by the BBB locomotor test. In spinal compression injuries, SC-NPCs transplanted immediately or after 1 week, but not 7 weeks after injury, significantly improved hindlimb recovery compared to controls. We could not detect signs of mechanical allodynia in transplanted rats. Four months after transplantation, we found more human cells in the host spinal cord than were transplanted, irrespective of the time of transplantation. There was no focal tumor growth. In all groups the vast majority of NPCs differentiated into astrocytes. Importantly, the number of surviving rat spinal cord neurons was highest in groups transplanted acutely and subacutely, which also showed the best hindlimb function. This suggests that transplanted SC-NPCs improve the functional outcome by a neuroprotective effect. We conclude that SC-NPCs reliably enhance the functional outcome after SCI if transplanted acutely or subacutely, without causing allodynia. This therapeutic effect is mainly the consequence of a neuroprotective effect of the SC-NPCs.
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http://dx.doi.org/10.1016/j.expneurol.2013.12.022DOI Listing
March 2014

Hip fractures in persons with stroke.

Stroke Res Treat 2013 4;2013:954279. Epub 2013 Apr 4.

Departments of Geriatrics and Neurology, Örebro University Hospital, 701 85 Örebro, Sweden ; NVS Department, Karolinska Institutet, 171 77 Stockholm, Sweden.

Background. Our aim was to determine the incidence of hip fractures within two years after stroke, to identify associated factors, to evaluate which test instruments that best could identify people at risk, and to describe the circumstances that prevailed when they sustained their hip fractures. Method. A total of 377 persons with first-ever stroke were followed up for a 24-month period. Stroke severity, cognition, and associated medical conditions were registered. The following test instruments were used: National Institutes of Health Stroke Scale, Mini-Mental State Examination, Berg Balance Scale, Timed Up & Go, and Stops Walking When Talking. Result. Sixteen of the persons fractured their hip within the study period, which corresponds to an incidence of 32 hip fractures per 1000 person-years. Persons with fractures more often had impaired vision and cognitive impairment and more had had previous fractures. Of the investigated test instruments, Timed Up & Go was the best test to predict fractures. Conclusion. The incidence of hip fractures in persons with stroke was high in this study. Persons with previous fractures, and visual and cognitive defects are at the greatest risk. Certain test instruments could be used in order to find people at risk, which should be targeted for fall preventive measures.
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http://dx.doi.org/10.1155/2013/954279DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3649805PMC
May 2013

Targeted delivery of nerve growth factor via encapsulated cell biodelivery in Alzheimer disease: a technology platform for restorative neurosurgery.

J Neurosurg 2012 Aug 1;117(2):340-7. Epub 2012 Jun 1.

Department of Neurosurgery, University Hospital, Stockholm, Sweden.

Object: The authors describe the first clinical trial with encapsulated cell biodelivery (ECB) implants that deliver nerve growth factor (NGF) to the cholinergic basal forebrain with the intention of halting the degeneration of cholinergic neurons and the associated cognitive decline in patients with Alzheimer disease (AD). The NsG0202 implant (NsGene A/S) consists of an NGF-producing, genetically engineered human cell line encapsulated behind a semipermeable hollow fiber membrane that allows the influx of nutrients and the efflux of NGF. The centimeter-long capsule is attached to an inert polymer tether that is used to guide the capsule to the target via stereotactic techniques and is anchored to the skull at the bur hole.

Methods: Six patients with mild to moderate AD were included in this Phase Ib open-label safety study and were divided into 2 dose cohorts. The first cohort of 3 patients received single implants targeting the basal nucleus of Meynert (Ch4 region) bilaterally (2 implants per patient), and after a safety evaluation, a second cohort of 3 patients received bilateral implants (a total of 4 implants per patient) targeting both the Ch4 region and the vertical limb of the diagonal band of Broca (Ch2 region). Stereotactic implantation of the devices was successfully accomplished in all patients. Despite extensive brain atrophy, all targets could be reached without traversing sulci, the insula, or lateral ventricles.

Results: Postoperative CT scans allowed visualization of the barium-impregnated tethers, and fusion of the scans with stereotactic MR images scan was used to verify the intended positions of the implants. Follow-up MRI at 3 and 12 months postimplantation showed no evidence of inflammation or device displacement. At 12 months, implants were successfully retrieved, and low but persistent NGF secretion was detected in half of the patients.

Conclusions: With refinement, the ECB technology is positioned to become an important therapeutic platform in restorative neurosurgery and, in combination with other therapeutic factors, may be relevant for the treatment of a variety of neurological disorders. Clinical trial registration no.: NCT01163825.
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http://dx.doi.org/10.3171/2012.2.JNS11714DOI Listing
August 2012

Encapsulated cell biodelivery of nerve growth factor to the Basal forebrain in patients with Alzheimer's disease.

Dement Geriatr Cogn Disord 2012 22;33(1):18-28. Epub 2012 Feb 22.

Departments of Neurobiology, Caring Sciences and Society, Karolinska Institutet, Stockholm, Sweden. maria.eriksdotter.jonhagen @ ki.se

Background/aims: 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.

Methods: This was an open-label, 12-month study in 6 AD patients. Patients were implanted stereotactically with EC-NGF biodelivery devices targeting the basal forebrain. Patients were monitored with respect to safety, tolerability, disease progression and implant functionality.

Results: All patients were implanted successfully with bilateral single or double implants without complications or signs of toxicity. No adverse events were related to NGF or the device. All patients completed the study, including removal of implants at 12 months. Positive findings in cognition, EEG and nicotinic receptor binding in 2 of 6 patients were detected.

Conclusions: This study demonstrates that surgical implantation and removal of EC-NGF biodelivery to the basal forebrain in AD patients is safe, well tolerated and feasible.
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http://dx.doi.org/10.1159/000336051DOI Listing
July 2012

Forced Runx1 expression in human neural stem/progenitor cells transplanted to the rat dorsal root ganglion cavity results in extensive axonal growth specifically from spinal cord-derived neurospheres.

Stem Cells Dev 2011 Nov 13;20(11):1847-57. Epub 2011 Apr 13.

Department of Neuroscience, Neuroanatomy, Uppsala University Biomedical Center, Uppsala, Sweden.

Cell replacement therapy holds great promise for treating a wide range of human disorders. However, ensuring the predictable differentiation of transplanted stem cells, eliminating their risk of tumor formation, and generating fully functional cells after transplantation remain major challenges in regenerative medicine. Here, we explore the potential of human neural stem/progenitor cells isolated from the embryonic forebrain (hfNSPCs) or the spinal cord (hscNSPCs) to differentiate to projection neurons when transplanted into the dorsal root ganglion cavity of adult recipient rats. To stimulate axonal growth, we transfected hfNSPC- and hscNSPC-derived neurospheres, prior to their transplantation, with a Tet-Off Runx1-overexpressing plasmid to maintain Runx1 expression in vivo after transplantation. Although pronounced cell differentiation was found in the Runx1-expressing transplants from both cell sources, we observed extensive, long-distance growth of axons exclusively from hscNSPC-derived transplants. These axons ultimately reached the dorsal root transitional zone, the boundary separating peripheral and central nervous systems. Our data show that hscNSPCs have the potential to differentiate to projection neurons with long-distance axonal outgrowth and that Runx1 overexpression is a useful approach to induce such outgrowth in specific sources of NSPCs.
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http://dx.doi.org/10.1089/scd.2010.0555DOI Listing
November 2011