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- Georgiopoulos, Charalampos, et al.
(author)
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Noninvasive assessment of glymphatic dysfunction in idiopathic normal pressure hydrocephalus with diffusion tensor imaging
- 2024
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In: Journal of Neurosurgery. - 0022-3085. ; 140:3, s. 612-620
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Journal article (peer-reviewed)abstract
- OBJECTIVE: Diffusion tensor imaging (DTI) along the perivascular space (ALPS) (DTI-ALPS)-by calculating the ALPS index, a ratio accentuating water diffusion in the perivascular space-has been proposed as a noninvasive, indirect MRI method for assessing glymphatic function. The main aim of this study was to investigate whether DTI-ALPS would reveal glymphatic dysfunction in idiopathic normal pressure hydrocephalus (iNPH) and whether the ALPS index was associated with disease severity. METHODS: Thirty iNPH patients (13 men; median age 77 years) and 27 healthy controls (10 men; median age 73 years) underwent MRI and clinical assessment with the Timed Up and Go test (TUG) and Mini-Mental State Examination (MMSE); only the patients were evaluated with the Hellström iNPH scale. MRI data were analyzed with the DTI-ALPS method and Radscale screening tool. RESULTS: iNPH patients showed significantly lower mean ALPS index scores compared with healthy controls (median [interquartile range] 1.09 [1.00-1.15] vs 1.49 [1.36-1.59], p < 0.001). Female healthy controls showed significantly higher ALPS index scores than males in both hemispheres (e.g., right hemisphere 1.62 [1.47-1.67] vs 1.33 [1.14-1.41], p = 0.001). This sex difference was not seen in iNPH patients. The authors found a moderate exponential correlation between mean ALPS index score and motor function as measured with time required to complete TUG (r = -0.644, p < 0.001), number of steps to complete TUG (r = -0.571, p < 0.001), 10-m walk time (r = -0.637, p < 0.001), and 10-m walk steps (r = -0.588, p < 0.001). The authors also found a positive linear correlation between mean ALPS index score and MMSE score (r = 0.416, p = 0.001). Simple linear regression showed a significant effect of diagnosis (B = -0.39, p < 0.001, R2 = 0.459), female sex (B = 0.232, p = 0.002, R2 = 0.157), and Evans index (B = -4.151, p < 0.001, R2 = 0.559) on ALPS index. Multiple linear regression, including diagnosis, sex, and Evans index score, showed a higher predictive value (R2 = 0.626) than analysis of each of these factors alone. CONCLUSIONS: The ALPS index, which was significantly decreased in iNPH patients, could serve as a marker of disease severity, both clinically and in terms of neuroimaging. However, it is important to consider the significant influence of biological sex and ventriculomegaly on the ALPS index, which raises the question of whether the ALPS index solely reflects glymphatic function or if it also encompasses other types of injury. Future studies are needed to address potential confounding factors and further validate the ALPS method.
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| 2. |
- Rydja, Johanna, et al.
(author)
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Evaluating the cerebrospinal fluid tap test with the Hellstrom iNPH scale for patients with idiopathic normal pressure hydrocephalus
- 2021
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In: Fluids and Barriers of the CNS. - : BioMed Central. - 2045-8118. ; 18:1
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Journal article (peer-reviewed)abstract
- Background The cerebrospinal fluid tap test (CSF TT) is used for selecting shunt surgery candidates among patients with idiopathic normal pressure hydrocephalus (iNPH). We aimed to evaluate the predictive value of the CSF TT, by using the Hellstrom iNPH scale for shunted iNPH patients with a standardized method. Methods One hundred and sixteen shunt-operated iNPH patients were retrospectively included in this study. The gait and balance domains in the iNPH scale were used as outcome measures for the CSF TT and the total iNPH scale score as the postoperative outcome. A positive response to CSF TT was defined as a change of >= 5 points in the gait domain and >= 16 points in the balance domain. Differences between CSF TT responders and non-responders, sensitivity, specificity, positive and negative predictive values, accuracy, and correlations between changes from baseline to post CSF TT and from baseline to the postoperative follow-up, were calculated. Results In the CSF TT there were 63.8% responders in the gait domain and correspondingly 44.3% in the balance domain. CSF TT responders had a significantly better postoperative outcome in the total scale score (gait P <= 0.001, balance P <= 0.012) and gait CSF TT responders improved more in gait (P <= 0.001) and balance CSF TT responders in balance (P <= 0.001). No differences between CSF TT gait or balance responders could be found in neuropsychological or urinary continence assessments postoperatively. The sensitivity and specificity of the CSF TT and the outcome of the total iNPH scale score postoperatively were 68.1% and 52.0% for gait and 47.8% and 68.0% for balance, respectively. Conclusions The CSF TT, with the Hellstrom iNPH scale as the outcome measure, has clear limitations in predicting postoperative results. The gait domain may be used to predict outcomes for gait, but the balance domain is too insensitive.
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| 3. |
- Rydja, Johanna, 1972-
(author)
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Gait Characteristics, Physical Activity and Subjective Outcome after Shunt Surgery in Normal Pressure Hydrocephalus
- 2024
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Doctoral thesis (other academic/artistic)abstract
- Background Idiopathic normal pressure hydrocephalus (iNPH) is a common but under-diagnosed disease among the elderly. The condition is characterised by gait disturbance, postural instability, cognitive decline and incontinence, caused by accumulated cerebrospinal fluid within the central nerve system. The treatment is a shunt insertion to divert excess fluid. Few studies have described the detailed gait in INPH, there is a lack of research about physical activity, and patient-reported outcomes after shunt surgery are sparsely described. The overall aim of this thesis was to increase the knowledge of the gait pattern, the level of physical activity, and to evaluate the effect of a physical exercise programme in iNPH. Another aim was to evaluate the patient’s self-experienced outcome after surgery. Methods and results, study I In total 127 patients were randomised to either a supervised 12-week high-intensity exercise programme or to standard care after shunt surgery. Evaluation was performed with the iNPH scale and goal attainment after the intervention and after six months. There was low compliance to the exercise programme and no differences between the groups could be detected according to the iNPH scale at any of the follow-ups. Patients with high attendance rate achieved their set goals to a higher extent than the control group at the post intervention follow-up. Methods and results, study II In total 109 patients from the population in study I, were evaluated with an actigraphy recording of physical activity variables for seven days before and three- and six months after shunt surgery. In addition, physical performance was evaluated with the 10-meter walk test, the 6-minute walk test and 30 s chair stand test. The patients walked faster with improved results on the walking tests postoperatively. Improvement in the 30 s chair stand test was interpreted as improved postural control. The physical activity intensity was not affected by surgery. The patients had very low energy expenditure and were to a large extent sedentary, before and after shunt surgery. The exercise intervention had no effect on physical activity or the physical performance tests. Methods and results, study III In total 47 patients were included to a gait analysis with an inertial sensor system. Additionally, the patients were assessed with the Timed Up and Go test and the iNPH scale, pre- and three months postoperatively and in relation with 42 older healthy individuals. The patients walked with shorter strides, decreased velocity, increased time in stance and with decreased joint angles, especially in the ankle joint. The gait pattern im-proved after shunt surgery, but outcome on all variables were still worse compared to the healthy individuals, except for step hight that was normalised. Shunt surgery had no effect on stride length variability. Methods and results, study IV In total 58 patients rated their experienced changes three months after shunt surgery. The subjective outcome was analysed in relation to objective clinical outcomes (the iNPH scale) and questionnaires regarding, sense of coherence, quality of life, anxiety and depression. Clinical outcome and the questionnaires were evaluated before and three months after shunt surgery and in relation to 42 older healthy individuals. The patients reported most frequently some degree of positive changes after surgery. The subjective outcomes in overall experience, gait and continence correlated moderately with the corresponding objective outcomes, but there were not correlations within the cognition and balance areas. Depression and quality of life improved after surgery, but the result was still lower than for healthy individuals. There was no correlation between the patients´ sense of coherence and the subjective outcome. Conclusion Shunt surgery contributes to improved walking patterns, improved physical functions, reduced signs of depression and increased quality of life, but patients with iNPH are still more affected than healthy elderly. The patients report most frequently positive changes, but not total recovery after shunt surgery. Despite improvements within several areas the physical activity level is very low, both before and after the shunt operation. A postoperative high-intensity physical training program had no additional effect, which is explained by the fact that few patients completed the program. Patients with iNPH probably need guidance to additional improvement and to increase physical activity through meaningful activities after shunt surgery. Further research is needed to evaluate interventions that address the specific iNPH impairments.
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| 4. |
- Rydja, Johanna, et al.
(author)
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Physical Capacity and Activity in Patients With Idiopathic Normal Pressure Hydrocephalus
- 2022
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In: Frontiers in Neurology. - : Frontiers Media SA. - 1664-2295. ; 13
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Journal article (peer-reviewed)abstract
- Introduction: Most patients with idiopathic normal pressure hydrocephalus (iNPH) improve gait after surgery. However, knowledge on physical capacity and activity after shunt surgery is limited. One of the aims of this study was to evaluate the effect of shunt surgery in patients with iNPH on short-distance walking, functional exercise capacity, functional strength, and variables of activity and sleep, 3 and 6 months postoperatively. Another aim was to evaluate the effect of a physical exercise program. Additionally, we studied how changes in short-distance walking were correlated with functional exercise capacity and voluntary walking.& nbsp;Methods: In total, 127 patients were consecutively included and randomized to the exercise group (n = 62) or the control group (n = 65). Participants in the exercise group underwent the supervision of a 12-week exercise program. All patients were assessed before surgery, at 3 and 6 months postoperatively with the 10-m walk test (10MWT), the 6-min walk test (6MWT), 30-s chair stand test (30sCST), and with the actigraphic recordings of activity variables measured for a total of 24 h/day for at least 3 days.& nbsp;Results: All patients improved at 3 months postoperatively in the 10MWT (p < 0.001), 6MWT (p < 0.001), and 30sCST (p < 0.001). These results were maintained after 6 months. Actigraphic recordings for voluntary walking (steps per minute) were improved and nighttime sleep (%) increased after 6 months (p = 0.01, p = 0.04). There were no significant differences between the exercise group and the control group, except for the postoperative change in the proportion of daytime sleep after 3 months, which was slightly more reduced compared to baseline in the exercise group (p = 0.04). Changes after 3 months in the 10MWT and 6MWT were moderately correlated (rho= -0.49, p = 0.01) whereas the correlation between the 10MWT and voluntary walking was weak (rho = -0.34, p = 0.01).& nbsp;Conclusion: Shunt surgery improved short-distance walking, functional exercise capacity, functional strength, and voluntary walking. An exercise program did not affect these outcomes. Short-distance walking was weakly correlated with voluntary walking, indicating improved physical capacity does not directly translate to increased physical activity. Further research should address how interventions should be tailored to promote physical activity after shunt surgery.
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| 5. |
- Rydja, Johanna, et al.
(author)
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Physical exercise and goal attainment after shunt surgery in idiopathic normal pressure hydrocephalus: a randomised clinical trial
- 2021
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In: Fluids and Barriers of the CNS. - : Springer Science and Business Media LLC. - 2045-8118. ; 18:1
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Journal article (peer-reviewed)abstract
- Background: Rehabilitation in iNPH is suggested to be an important factor to improve patients'functions but there are lack of clinical trials evaluating the effect of rehabilitation interventions after shunt surgery in iNPH. The objective of this study was to evaluate the effect of a physical exercise programme and goal attainment for patients with idiopathic normal pressure hydrocephalus (iNPH) after surgery compared to a control group. Methods: This was a dual centre randomised controlled trial with assessor blinding, intention-to-treat (ITT) and per protocol (PP) analysis. Individuals diagnosed with iNPH scheduled to undergo shunt surgery at the Linkoping University Hospital in Linkoping and Sahlgrenska University Hospital in Gothenburg, Sweden were consecutively eligible for inclusion. Inclusion was conducted between January 2016 and June 2018. The patients were randomised 1:1 using sequentially numbered sealed envelopes to receive either written exercise information (control group) or written information and an additional supervised high-intensity, functional exercise programme (HIFE) executed twice weekly over 12 weeks (exercise group). Preoperatively, the patients set individual goals. The primary outcome was change from baseline in the total iNPH scale score at the post-intervention follow-up. Secondary outcomes were goal attainment, and change in the separate scores of gait, balance, neuropsychology and continence and in the total score after 6 months. Results: In total, 127 participants were randomised to the exercise group (n = 62) and to the control group (n=65). In the ITT population (exercise group, n =50; control group, n=59), there were no between-group differences in the primary outcome, but the attrition rate in the exercise group was high. The exercise group improved more than the control group in the balance domain scores after 6 months. Post-intervention, the PP exercise population achieved their set goals to a greater extent than the controls. Conclusions: An additional effect of the 12-week HIFE-programme on the overall improvement according to the iNPH-scale after shunt surgery in iNPH was not shown. This could be due to high attrition rate. However, the longterm effect on balance and higher goal achievement indicate beneficial influences of supervised physical exercise.
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| 6. |
- Sundström, Nina, et al.
(author)
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The timed up and go test in idiopathic normal pressure hydrocephalus : a Nationwide Study of 1300 patients
- 2022
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In: Fluids and Barriers of the CNS. - London, United Kingdom : BioMed Central. - 2045-8118. ; 19:1
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Journal article (peer-reviewed)abstract
- Background: The aim of this study was to describe the outcome measure timed up and go (TUG) in a large, nationwide cohort of patients with idiopathic normal pressure hydrocephalus (iNPH) pre- and post-operatively. Furthermore, to compare the TUG test to the 10-m walk test (10MWT), the iNPH scale, the modified Rankin scale (mRS) and the Mini Mental State Examination (MMSE), which are commonly applied in clinical assessment of iNPH.Methods: Patients with iNPH (n = 1300), registered in the Swedish Hydrocephalus Quality Registry (SHQR), were included. All data were retrieved from the SHQR except the 10MWT, which was collected from patient medical records. Clinical scales were examined pre- and 3 months post-operatively. Data were dichotomised by sex, age, and preoperative TUG time.Results: Preoperative TUG values were 19.0 [14.0–26.0] s (median [IQR]) and 23 [18–30] steps. Post-operatively, significant improvements to 14.0 [11.0–20.0] s and 19 [15–25] steps were seen. TUG time and steps were higher in women compared to men (p < 0.001) but there was no sex difference in improvement rate. Worse preoperative TUG and younger age favoured improvement. TUG was highly correlated to the 10MWT, but correlations of post-operative changes were only low to moderate between all scales (r = 0.22–0.61).Conclusions: This study establishes the distribution of TUG in iNPH patients and shows that the test captures important clinical features that improve after surgery independent of sex and in all age groups, confirming the clinical value of the TUG test. TUG performance is associated with performance on the 10MWT pre- and post-operatively. However, the weak correlations in post-operative change to the 10MWT and other established outcome measures indicate an additional value of TUG when assessing the effects of shunt surgery.
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