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Article ; Online: Symptoms and signs did not predict outcome after surgery: a prospective study of 143 patients with idiopathic normal pressure hydrocephalus.

Andrén, Kerstin / Wikkelsø, Carsten / Laurell, Katarina / Kollén, Lena / Hellström, Per / Tullberg, Mats

2024

Abstract: Objective: To determine the utility of symptoms, signs, comorbidities and background variables for the prediction of outcome of treatment in iNPH.: Methods: A prospective observational study of consecutively included iNPH patients, who underwent ... ...

Abstract	Objective: To determine the utility of symptoms, signs, comorbidities and background variables for the prediction of outcome of treatment in iNPH. Methods: A prospective observational study of consecutively included iNPH patients, who underwent neurological, physiotherapeutic and neuropsychological assessments before and after shunt surgery. The primary outcome measure was the total change on the iNPH scale, and patients were defined as improved postoperatively if they had improved by at least five points on that scale. Results: 143 iNPH patients were included, and 73% of those were improved after surgery. None of the examined symptoms or signs could predict which patients would improve after shunt surgery. A dominant subjective complaint of memory problems at baseline was predictive of non-improvement. The reported comorbidities, duration of symptoms and BMI were the same in improved and non-improved patients. Each of the symptom domains (gait, neuropsychology, balance, and continence) as well as the total iNPH scale score improved significantly (from median 53 to 69, p < 0.001). The proportions of patients with shuffling gait, broad-based gait, paratonic rigidity and retropulsion all decreased significantly. Discussion: This study confirms that the recorded clinical signs, symptoms, and impairments in the adopted clinical tests are characteristic findings in iNPH, based on that most of them improved after shunt surgery. However, our clinical data did not enable predictions of whether patients would respond to shunt surgery, indicating that the phenotype is unrelated to the reversibility of the iNPH state and should mainly support diagnosis. Absence of specific signs should not be used to exclude patients from treatment.
Language	English
Publishing date	2024-03-05
Publishing country	Germany
Document type	Journal Article
ZDB-ID	187050-6
ISSN	1432-1459 ; 0340-5354 ; 0012-1037 ; 0939-1517 ; 1619-800X
ISSN (online)	1432-1459
ISSN	0340-5354 ; 0012-1037 ; 0939-1517 ; 1619-800X
DOI	10.1007/s00415-024-12248-w
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Article: Physical Capacity and Activity in Patients With Idiopathic Normal Pressure Hydrocephalus.

Rydja, Johanna / Kollén, Lena / Ulander, Martin / Tullberg, Mats / Lundin, Fredrik

Frontiers in neurology

2022 Volume 13, Page(s) 845976

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 ...

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. Methods: In total, 127 patients were consecutively included and randomized to the exercise group ( Results: All patients improved at 3 months postoperatively in the 10MWT ( 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. Trial registration: clinicaltrials.gov, Id: NCT02659111.
Language	English
Publishing date	2022-03-28
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2564214-5
ISSN	1664-2295
ISSN	1664-2295
DOI	10.3389/fneur.2022.845976
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Article ; Online: The demography of idiopathic normal pressure hydrocephalus: data on 3000 consecutive, surgically treated patients and a systematic review of the literature.

Sundström, Nina / Lundin, Fredrik / Arvidsson, Lisa / Tullberg, Mats / Wikkelsø, Carsten

Journal of neurosurgery

2022 , Page(s) 1–11

Abstract: Objective: The objective of this study was to describe the demographic characteristics of patients with idiopathic normal pressure hydrocephalus (iNPH) through an analysis of 3000 consecutive, surgically treated Swedish patients and a systematic review ... ...

Abstract	Objective: The objective of this study was to describe the demographic characteristics of patients with idiopathic normal pressure hydrocephalus (iNPH) through an analysis of 3000 consecutive, surgically treated Swedish patients and a systematic review of the literature. Methods: Data on age, sex, comorbidities, diagnostic delay, initial symptoms, and severity of symptoms at diagnosis were extracted from the Swedish Hydrocephalus Quality Registry. In addition, a systematic PRISMA-based review of the literature published from database inception until August 2019 was performed using the PubMed, Cochrane, and Scopus databases on the basis of two concepts: normal pressure hydrocephalus and demography and their association with related terms. Of 1020 unique articles, 16 were eligible for study inclusion and were assessed for quality using the Newcastle-Ottawa Scale. Mean and weighted mean values were calculated. Results: The mean patient age at the time of surgery was 74.4 years, 79% of patients were in their 70s, and 60% of the patients were men. Almost 50% of the patients had symptoms from four main domains (i.e., balance, gait, cognition, and urinary dysfunction) at disease onset. Patients aged < 60 years (2%) reported more headaches and fewer balance problems than those aged ≥ 60. Women were more impaired in function than men at the time of diagnosis. Dementia (Mini-Mental State Examination score < 25) was found in 47% of the patients. Men had more diabetes, heart disease, hypertension, and stroke than women, and comorbidity correlated with increased impairment. The incidence of surgery for iNPH was 20%-40% of the disease incidence according to survey and operation-based studies. Conclusions: Most iNPH patients undergo surgery in their 70s. Those aged < 60 years show slightly different symptomatology and probably present with a specific disease entity, indicating that the lower age limit for iNPH should be 60 years. iNPH patients have severe impairment preceded by a long diagnostic delay. Even though the included study designs differed, the systematic review showed that the disorder has a very low treatment incidence. The importance of diagnosing and treating iNPH is further emphasized by the fact that iNPH may account for a considerable part of all cases of dementia.
Language	English
Publishing date	2022-04-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	3089-2
ISSN	1933-0693 ; 0022-3085
ISSN (online)	1933-0693
ISSN	0022-3085
DOI	10.3171/2022.2.JNS212063
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Article ; Online: Response to the Letter to the Editor regarding the article entitled 'Early shunt surgery improves survival in idiopathic normal pressure hydrocephalus'.

Andrén, Kerstin / Wikkelsø, Carsten / Hellström, Per / Tullberg, Mats / Jaraj, Daniel

European journal of neurology

2021 Volume 28, Issue 11, Page(s) e90

MeSH term(s)	Cerebrospinal Fluid Shunts ; Humans ; Hydrocephalus, Normal Pressure/surgery
Language	English
Publishing date	2021-03-22
Publishing country	England
Document type	Letter ; Comment
ZDB-ID	1280785-0
ISSN	1468-1331 ; 1351-5101 ; 1471-0552
ISSN (online)	1468-1331
ISSN	1351-5101 ; 1471-0552
DOI	10.1111/ene.14804
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Article ; Online: Early shunt surgery improves survival in idiopathic normal pressure hydrocephalus.

Andrén, Kerstin / Wikkelsø, Carsten / Hellström, Per / Tullberg, Mats / Jaraj, Daniel

European journal of neurology

2021 Volume 28, Issue 4, Page(s) 1153–1159

Abstract: Background and purpose: To examine the effect of delayed compared to early planning of shunt surgery on survival, in patients with idiopathic normal pressure hydrocephalus (iNPH), a long-term follow-up case-control study of patients exposed to a severe ... ...

Abstract	Background and purpose: To examine the effect of delayed compared to early planning of shunt surgery on survival, in patients with idiopathic normal pressure hydrocephalus (iNPH), a long-term follow-up case-control study of patients exposed to a severe delay of treatment was performed. Methods: In 2010-2011 our university hospital was affected by an administrative and economic failure that led to postponement of several elective neurosurgical procedures. This resulted in an unintentional delay of planning of treatment for a group of iNPH patients, referred to as iNPH Results: Median follow-up time was 6.0 years. Crude 4-year mortality was 39.4% in iNPH Conclusions: The present data indicate that shunt surgery is effective in iNPH and that early treatment increases survival.
MeSH term(s)	Case-Control Studies ; Humans ; Hydrocephalus, Normal Pressure/surgery ; Registries ; Treatment Outcome ; Ventriculoperitoneal Shunt
Language	English
Publishing date	2021-01-25
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1280785-0
ISSN	1468-1331 ; 1351-5101 ; 1471-0552
ISSN (online)	1468-1331
ISSN	1351-5101 ; 1471-0552
DOI	10.1111/ene.14671
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Article ; Online: The timed up and go test in idiopathic normal pressure hydrocephalus: a Nationwide Study of 1300 patients.

Sundström, Nina / Rydja, Johanna / Virhammar, Johan / Kollén, Lena / Lundin, Fredrik / Tullberg, Mats

Fluids and barriers of the CNS

2022 Volume 19, Issue 1, Page(s) 4

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 ...

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.
MeSH term(s)	Aged ; Aged, 80 and over ; Exercise Test ; Female ; Gait Disorders, Neurologic/diagnosis ; Gait Disorders, Neurologic/etiology ; Gait Disorders, Neurologic/therapy ; Humans ; Hydrocephalus, Normal Pressure/complications ; Hydrocephalus, Normal Pressure/surgery ; Male ; Middle Aged ; Neurosurgical Procedures ; Outcome Assessment, Health Care ; Postural Balance ; Registries ; Sweden
Language	English
Publishing date	2022-01-10
Publishing country	England
Document type	Journal Article
ZDB-ID	2595406-4
ISSN	2045-8118 ; 2045-8118
ISSN (online)	2045-8118
ISSN	2045-8118
DOI	10.1186/s12987-021-00298-5
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Article ; Online: Association between ventricular CSF biomarkers and outcome after shunt surgery in idiopathic normal pressure hydrocephalus.

Grønning, Rebecca / Jeppsson, Anna / Hellström, Per / Laurell, Katarina / Farahmand, Dan / Zetterberg, Henrik / Blennow, Kaj / Wikkelsø, Carsten / Tullberg, Mats

Fluids and barriers of the CNS

2023 Volume 20, Issue 1, Page(s) 77

Abstract: Introduction: The relationship between neurochemical changes and outcome after shunt surgery in idiopathic normal pressure hydrocephalus (iNPH), a treatable dementia and gait disorder, is unclear. We used baseline ventricular CSF to explore associations ...

Abstract	Introduction: The relationship between neurochemical changes and outcome after shunt surgery in idiopathic normal pressure hydrocephalus (iNPH), a treatable dementia and gait disorder, is unclear. We used baseline ventricular CSF to explore associations to outcome, after shunting, of biomarkers selected to reflect a range of pathophysiological processes. Methods: In 119 consecutive patients with iNPH, the iNPH scale was used before and after shunt surgery to quantify outcome. Ventricular CSF was collected perioperatively and analyzed for biomarkers of astrogliosis, axonal, amyloid and tau pathology, and synaptic dysfunction: glial fibrillary acidic protein (GFAP), chitinase-3-like protein 1 (YKL40/CHI3L1), monocyte chemoattractant protein-1 (MCP-1) neurofilament light (NfL), amyloid beta 38 (Aβ38), Aβ40, Aβ42, amyloid beta 42/40 ratio (Aβ42/40), soluble amyloid precursor protein alfa (sAPPα), sAPPβ, total tau (T-tau), phosphorylated tau (P-tau), growth-associated protein 43 (GAP43), and neurogranin. Results: The neurogranin concentration was higher in improved (68%) compared to unimproved patients (median 365 ng/L (IQR 186-544) vs 330 (205-456); p = 0.046). A linear regression model controlled for age, sex and vascular risk factors including neurogranin, T-tau, and GFAP, resulted in adjusted R Discussion: A higher preoperative ventricular CSF level of neurogranin, which is a postsynaptic marker, may signal a favorable postoperative outcome. Concentrations of a panel of ventricular CSF biomarkers explained only 6% of the variability in outcome. Evidence of amyloid or tau pathology did not affect the outcome.
MeSH term(s)	Humans ; Amyloid beta-Peptides/metabolism ; Hydrocephalus, Normal Pressure/surgery ; Hydrocephalus, Normal Pressure/pathology ; Neurogranin ; tau Proteins/metabolism ; Amyloid beta-Protein Precursor/metabolism ; Biomarkers ; Alzheimer Disease
Chemical Substances	Amyloid beta-Peptides ; Neurogranin (132654-77-4) ; tau Proteins ; Amyloid beta-Protein Precursor ; Biomarkers
Language	English
Publishing date	2023-10-25
Publishing country	England
Document type	Journal Article
ZDB-ID	2595406-4
ISSN	2045-8118 ; 2045-8118
ISSN (online)	2045-8118
ISSN	2045-8118
DOI	10.1186/s12987-023-00475-8
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Article ; Online: Prevalence of Possible Idiopathic Normal Pressure Hydrocephalus in Sweden: A Population-Based MRI Study in 791 70-Year-Old Participants

Constantinescu, Clara / Wikkelsø, Carsten / Westman, Eric / Ziegelitz, Doerthe / Jaraj, Daniel / Rydén, Lina / Skoog, Ingmar / Tullberg, Mats

Neurology

2023 Volume 102, Issue 2, Page(s) e208037

Abstract: Background and objectives: Very divergent prevalence rates for idiopathic normal pressure hydrocephalus (iNPH) are reported, probably due to differences in study sample selection and diagnostic criteria. This MRI-based study aimed to determine the ... ...

Abstract	Background and objectives: Very divergent prevalence rates for idiopathic normal pressure hydrocephalus (iNPH) are reported, probably due to differences in study sample selection and diagnostic criteria. This MRI-based study aimed to determine the prevalence of iNPH and iNPH-specific radiologic changes and their association with clinical symptoms in a large, 70-year-old population-based cohort (Gothenburg H70). Methods: In this cross-sectional study, disturbances in gait and balance, cognition, and urinary continence were assessed using clinical examination and self-report. MRI was evaluated for iNPH-specific imaging markers. iNPH was diagnosed according to International Guidelines (I.G.). Based on radiologic findings, participants were allocated to 1 of 4 groups: (A) Evans index (EI) ≤0.3 (reference), (B) EI >0.3 without other iNPH-typical radiologic findings, (C) radiologically probable iNPH according to I.G., and (D) radiologically Results: The Gothenburg H70 Studies include 791 individuals (377 men, 414 women) born in 1944 who underwent brain MRI. The prevalence of iNPH was 1.5% (2.1% for men, 0.96% for women) according to I.G. Ninety participants (11%) had EI >0.3 without other iNPH-typical radiologic findings, 29 (3.7%) fulfilled the I.G. radiologic probable iNPH criteria alone, and 11 (1.4%) were classified as radiologically Discussion: The iNPH prevalence of 1.5% among 70-year-olds, which is considerably higher than earlier reported in this age group, suggests that iNPH may be more common than previously assumed. This is supported by the 5.1% total prevalence of imaging signs of iNPH. Ventriculomegaly without other iNPH-typical radiologic findings may be an early sign of developing iNPH in some patients.
MeSH term(s)	Male ; Humans ; Female ; Aged, 80 and over ; Aged ; Sweden/epidemiology ; Cross-Sectional Studies ; Hydrocephalus, Normal Pressure/diagnostic imaging ; Hydrocephalus, Normal Pressure/epidemiology ; Prevalence ; Gait
Language	English
Publishing date	2023-12-22
Publishing country	United States
Document type	Journal Article
ZDB-ID	207147-2
ISSN	1526-632X ; 0028-3878
ISSN (online)	1526-632X
ISSN	0028-3878
DOI	10.1212/WNL.0000000000208037
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Article ; Online: Classification of Chronic Hydrocephalus in Adults: A Systematic Review and Analysis.

Tullberg, Mats / Toma, Ahmed K / Yamada, Shigeki / Laurell, Katarina / Miyajima, Masakazu / Watkins, Laurence D / Wikkelsø, Carsten

World neurosurgery

2023 Volume 183, Page(s) 113–122

Abstract: Background: Chronic hydrocephalus in adults (CHiA) includes all nonacute forms of hydrocephalus occurring in adulthood. It covers a spectrum of disorders. Some of these have relatively agreed on definitions, while others are less well characterized. The ...

Abstract	Background: Chronic hydrocephalus in adults (CHiA) includes all nonacute forms of hydrocephalus occurring in adulthood. It covers a spectrum of disorders. Some of these have relatively agreed on definitions, while others are less well characterized. The existing medical classification systems lack adequate structure and are neither clinically oriented nor easy to use, which severely hampers research and clinical care efforts. Methods: A systematic literature review and data analysis were performed, focusing on the terms "adult hydrocephalus" and "classification," using the PubMed, Scopus, and Cochrane Library databases. Data on terminology, definitions, patient demographics, symptom duration, and clinical presentations were extracted, analyzed, and compiled. A Delphi process was followed to define CHiA disorders. Results: A total of 33 studies collectively used 48 terms to define various CHiA disorders. Different terms were used to describe similar conditions. CHiA disorders were found to be clustered into 7 distinctive clinical entities based on the clinical characteristics. Conclusions: An evidence-based new clinical classification for CHiA is suggested. Our review identified gaps in knowledge and areas for further research.
MeSH term(s)	Adult ; Humans ; Hydrocephalus/diagnosis
Language	English
Publishing date	2023-12-22
Publishing country	United States
Document type	Systematic Review ; Journal Article ; Review
ZDB-ID	2534351-8
ISSN	1878-8769 ; 1878-8750
ISSN (online)	1878-8769
ISSN	1878-8750
DOI	10.1016/j.wneu.2023.12.094
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Article ; Online: Evaluation of a Fully Automated Method for Ventricular Volume Segmentation Before and After Shunt Surgery in Idiopathic Normal Pressure Hydrocephalus.

Ziegelitz, Doerthe / Hellström, Per / Björkman-Burtscher, Isabella M / Agerskov, Simon / Stevens-Jones, Oskar / Farahmand, Dan / Tullberg, Mats

World neurosurgery

2023 Volume 181, Page(s) e303–e311

Abstract: Background: Determination of the ventricle size in idiopathic normal pressure hydrocephalus (iNPH) is essential for diagnosis and follow-up of shunt results. Fully automated segmentation methods are anticipated to optimize the accuracy and time ... ...

Abstract	Background: Determination of the ventricle size in idiopathic normal pressure hydrocephalus (iNPH) is essential for diagnosis and follow-up of shunt results. Fully automated segmentation methods are anticipated to optimize the accuracy and time efficiency of ventricular volume measurements. We evaluated the accuracy of preoperative and postoperative ventricular volume measurements in iNPH by a magnetic resonance imaging (MRI)-based licensed software for fully automated quantitative assessment. Methods: Forty-eight patients diagnosed with iNPH were retrospectively analyzed. All patients received a ventriculoperitoneal shunt and had symptom grading and routine MRI preoperatively and 3-6 months postoperatively. Ventricular volumes, generated by fully automated T1-weighted imaging volume sequence segmentation, were compared with semiautomatic measurements and routine radiologic reports. The relation of postoperative ventricular size change to clinical response was evaluated. Results: Fully automated segmentation was achieved in 95% of the MRIs, but showed various rates of 8 minor segmentation errors. The correlation between both segmentation methods was very strong (r >0.9) and the agreement very good using Bland-Altman analyses. The ventricular volumes differed significantly between semiautomated and fully automated segmentations and between preoperative and postoperative MRI. The fully automated method systematically overestimated the ventricles by a median 15 mL preoperatively and 14 mL postoperatively; hence, the magnitudes of volume changes were equivalent. Routine radiologic reports of ventricular size changes were inaccurate in 51% and lacked association with treatment response. Objectively measured ventricular volume changes correlated moderately with postoperative clinical improvement. Conclusions: A fully automated volumetric method permits reliable evaluation of preoperative ventriculomegaly and postoperative ventricular volume change in idiopathic normal pressure hydrocephalus.
MeSH term(s)	Humans ; Hydrocephalus, Normal Pressure/diagnostic imaging ; Hydrocephalus, Normal Pressure/surgery ; Hydrocephalus, Normal Pressure/pathology ; Retrospective Studies ; Treatment Outcome ; Cerebral Ventricles/diagnostic imaging ; Cerebral Ventricles/surgery ; Cerebral Ventricles/pathology ; Ventriculoperitoneal Shunt/methods ; Magnetic Resonance Imaging/methods ; Cardiovascular Abnormalities/pathology ; Cardiovascular Abnormalities/surgery
Language	English
Publishing date	2023-10-13
Publishing country	United States
Document type	Journal Article
ZDB-ID	2534351-8
ISSN	1878-8769 ; 1878-8750
ISSN (online)	1878-8769
ISSN	1878-8750
DOI	10.1016/j.wneu.2023.10.045
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