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AIM: To evaluate health- and vision-related quality of life (HR- and VR-QoL) and perceptual visual dysfunction (PVD) in adolescents with hydrocephalus surgically treated in infancy. METHODS: In total, 23 adolescents (15 males and 8 females; median age 14.9 years) with hydrocephalus and 31 controls were evaluated using validated instruments to measure HR-QoL and VR-QoL. PVDs were reported by history taking in five areas: recognition, orientation, depth, movement and simultaneous perception. RESULTS: Adolescents with hydrocephalus and the parent proxy reports showed lower mean total Paediatric Quality of Life Inventory 4.0 scores (75.8 and 63.7, respectively) compared with controls (87.6 and 91.5), p = 0.016 and p < 0.0001. Parent-reported scores were lower than self-reported scores (p = 0.001). Adolescents with myelomeningocele (n = 10) showed lower physical health scores (p = 0.001). No VR-QoL difference was found between groups. PVDs were reported in ≥1 area by 14/23 hydrocephalus participants and 2/31 controls (p < 0.0001). Associations were found in the hydrocephalus group between VR-QoL and HR-QoL (rs = 0.47, p = 0.026) and number of PVD areas (rs = -0.6, p = 0.003). CONCLUSION: Adolescents with hydrocephalus and their parents reported lower HR-QoL and more PVDs. These problems indicate the need for not only ophthalmological follow-ups but also evaluation of QoL and PVDs in individuals with infantile hydrocephalus.
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Hidrocefalia , Qualidade de Vida , Humanos , Hidrocefalia/cirurgia , Hidrocefalia/psicologia , Masculino , Feminino , Adolescente , Estudos de Casos e Controles , Lactente , Criança , Transtornos da Visão/psicologia , Transtornos da Visão/etiologiaRESUMO
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.
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Hidrocefalia de Pressão Normal , Humanos , Feminino , Masculino , Hidrocefalia de Pressão Normal/cirurgia , Hidrocefalia de Pressão Normal/diagnóstico , Idoso , Estudos Prospectivos , Idoso de 80 Anos ou mais , Resultado do Tratamento , Testes Neuropsicológicos , Pessoa de Meia-IdadeRESUMO
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 holistically probable (h-probable) iNPH fulfilling radiologic criteria according to I.G. plus highly iNPH-specific changes according to an experienced neuroradiologist. 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 h-probable iNPH. Forty participants (5.1%) had I.G. radiologic features of iNPH (70% men vs 30% women, p = 0.005). Gait disturbances were more common in participants with EI >0.3 without other radiologic iNPH features (B) (33%) compared with the reference group (A) (19%) (p = 0.006). All clinical symptoms were more common in participants with I.G. radiologic features of iNPH (C + D) than they were in the reference group (A) (p < 0.03). 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.
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Hidrocefalia de Pressão Normal , Masculino , Humanos , Feminino , Idoso de 80 Anos ou mais , Idoso , Suécia/epidemiologia , Estudos Transversais , Hidrocefalia de Pressão Normal/diagnóstico por imagem , Hidrocefalia de Pressão Normal/epidemiologia , Prevalência , MarchaRESUMO
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.
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Anormalidades Cardiovasculares , Hidrocefalia de Pressão Normal , Humanos , Hidrocefalia de Pressão Normal/diagnóstico por imagem , Hidrocefalia de Pressão Normal/cirurgia , Hidrocefalia de Pressão Normal/patologia , Estudos Retrospectivos , Resultado do Tratamento , Ventrículos Cerebrais/diagnóstico por imagem , Ventrículos Cerebrais/cirurgia , Ventrículos Cerebrais/patologia , Derivação Ventriculoperitoneal/métodos , Imageamento por Ressonância Magnética/métodos , Anormalidades Cardiovasculares/patologia , Anormalidades Cardiovasculares/cirurgiaRESUMO
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.
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Hidrocefalia , Adulto , Humanos , Hidrocefalia/diagnósticoRESUMO
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 (Aß38), Aß40, Aß42, amyloid beta 42/40 ratio (Aß42/40), soluble amyloid precursor protein alfa (sAPPα), sAPPß, 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 R2 = 0.06, p = 0.047. The Aß42/40 ratio was bimodally distributed across all samples, as well as in the subgroups of improved and unimproved patients but did not contribute to outcome prediction. The preoperative MMSE score was lower within the low Aß ratio group (median 25, IQR 23-28) compared to the high subgroup (26, 24-29) (p = 0.028). The T-Tau x Aß40/42 ratio and P-tau x Aß40/42 ratio did not contribute to shunt response prediction. The prevalence of vascular risk factors did not affect shunt response. 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.
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Doença de Alzheimer , Hidrocefalia de Pressão Normal , Humanos , Peptídeos beta-Amiloides/metabolismo , Hidrocefalia de Pressão Normal/cirurgia , Hidrocefalia de Pressão Normal/patologia , Neurogranina , Proteínas tau/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , BiomarcadoresRESUMO
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.
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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 (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. 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 (ρ= -0.49, p = 0.01) whereas the correlation between the 10MWT and voluntary walking was weak (ρ = -0.34, p = 0.01). 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.
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Introduction: In this study, we examine similarities and differences between 52 patients with idiopathic normal pressure hydrocephalus (iNPH) and 17 patients with subcortical small vessel disease (SSVD), in comparison to 28 healthy controls (HCs) by a panel of cerebrospinal fluid (CSF) biomarkers. Methods: We analyzed soluble amyloid precursor protein alpha (sAPPα) and beta (sAPPß), Aß isoforms -38, -40, and -42, neurofilament light protein (NFL), glial fibrillary acidic protein (GFAP), myelin basic protein (MBP), matrix metalloproteinases (MMP -1, -2, -3, -9, and -10), and tissue inhibitors of metalloproteinase 1 (TIMP1). Radiological signs of white matter damage were scored using the age-related white matter changes (ARWMC) scale. Results: All amyloid fragments were reduced in iNPH and SSVD (p < 0.05), although more in iNPH than in SSVD in comparison to HC. iNPH and SSVD showed comparable elevations of NFL, MBP, and GFAP (p < 0.05). MMPs were similar in all three groups except for MMP-10, which was increased in iNPH and SSVD. Patients with iNPH had larger ventricles and fewer WMCs than patients with SSVD. Conclusion: The results indicate that patients with iNPH and SSVD share common features of subcortical neuronal degeneration, demyelination, and astroglial response. The reduction in all APP-derived proteins characterizing iNPH patients is also present, indicating that SSVD encompasses similar pathophysiological phenomena as iNPH.
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BACKGROUND: The relationship between cerebrospinal fluid (CSF) biomarkers and the clinical features of idiopathic normal pressure hydrocephalus (iNPH) has been inconclusive. We aimed to evaluate CSF biomarkers reflecting Alzheimer's disease (AD)-related amyloid ß (Aß) aggregation, tau pathology, neuroinflammation and axonal degeneration in relation to the clinical features of pre- and post-shunt surgery in iNPH patients. METHODS: Mini Mental State Examination (MMSE) scores and gait velocity were evaluated pre- and postoperatively in cohorts of 65 Finnish (FIN) and 82 Swedish (SWE) iNPH patients. Lumbar CSF samples were obtained prior to shunt surgery and analysed for soluble amyloid precursor protein alpha (sAPPα) and beta (sAPPß); amyloid-ß isoforms of 42, 40 and 38 (Aß42, Aß40, Aß38); total tau (T-tau); phosphorylated tau (P-tau181); neurofilament light (NfL) and monocyte chemoattractant protein 1 (MCP1). RESULTS: Preoperative patient characteristics showed no significant differences between patients in the FIN and SWE cohorts. Patients in both cohorts had significantly improved gait velocity after shunt surgery (p < 0.0001). Low CSF T-tau and absence of apolipoprotein E ε4 predicted over 20% gait improvement postoperatively (p = 0.043 and p = 0.008). Preoperative CSF T-tau, P-tau181 and NfL correlated negatively with MMSE scores both pre- (p < 0.01) and post-surgery (p < 0.01). Furthermore, T-tau, NfL and Aß42 correlated with MMSE outcomes (p < 0.05). Low preoperative CSF P-tau181 (p = 0.001) and T-tau with NfL (p < 0.001 and p = 0.049) best predicted pre- and postoperative MMSE scores greater than or equal to 26. CONCLUSIONS: CSF biomarkers of neurodegeneration appeared to correlate with pre- and postoperative cognition, providing a window into neuropathological processes. In addition, preoperative CSF neurodegeneration biomarkers may have potential in the prediction of gait and cognitive outcomes after shunt surgery.
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Disfunção Cognitiva , Transtornos Neurológicos da Marcha , Hidrocefalia de Pressão Normal , Avaliação de Resultados em Cuidados de Saúde , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/líquido cefalorraquidiano , Disfunção Cognitiva/líquido cefalorraquidiano , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/fisiopatologia , Estudos de Coortes , Feminino , Transtornos Neurológicos da Marcha/líquido cefalorraquidiano , Transtornos Neurológicos da Marcha/diagnóstico , Transtornos Neurológicos da Marcha/etiologia , Transtornos Neurológicos da Marcha/fisiopatologia , Humanos , Hidrocefalia de Pressão Normal/líquido cefalorraquidiano , Hidrocefalia de Pressão Normal/complicações , Hidrocefalia de Pressão Normal/diagnóstico , Hidrocefalia de Pressão Normal/cirurgia , Masculino , Derivação VentriculoperitonealRESUMO
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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Transtornos Neurológicos da Marcha/diagnóstico , Hidrocefalia de Pressão Normal/complicações , Procedimentos Neurocirúrgicos , Avaliação de Resultados em Cuidados de Saúde , Equilíbrio Postural , Sistema de Registros , Idoso , Idoso de 80 Anos ou mais , Teste de Esforço , Feminino , Transtornos Neurológicos da Marcha/etiologia , Transtornos Neurológicos da Marcha/terapia , Humanos , Hidrocefalia de Pressão Normal/cirurgia , Masculino , Pessoa de Meia-Idade , SuéciaRESUMO
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 Linköping University Hospital in Linköping 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 long-term effect on balance and higher goal achievement indicate beneficial influences of supervised physical exercise. Trial registration clinicaltrials.gov, NCT02659111. Registered 20 January 2016, https://clinicaltrials.gov/ct2/show/NCT02659111.
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Derivações do Líquido Cefalorraquidiano , Terapia por Exercício , Objetivos , Hidrocefalia de Pressão Normal/reabilitação , Hidrocefalia de Pressão Normal/cirurgia , Reabilitação Neurológica , Idoso , Idoso de 80 Anos ou mais , Seguimentos , Humanos , Masculino , Avaliação de Resultados em Cuidados de Saúde , Método Simples-CegoRESUMO
BACKGROUND: Idiopathic normal pressure hydrocephalus (iNPH) is a reversible CNS disease characterized by disturbed cerebrospinal fluid (CSF) dynamics. Changes in the extracellular matrix (ECM) composition might be involved in the pathophysiology of iNPH. The aim of this study was to explore possible differences between lumbar and ventricular CSF concentrations of the ECM markers brevican and neurocan, matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinase-1 (TIMP-1) and their relation to clinical symptoms in iNPH patients before and after shunt surgery. METHODS: Paired lumbar and ventricular CSF was collected from 31 iNPH patients, before and four months after shunt surgery. CSF was analysed for concentrations of tryptic peptides originating from brevican and neurocan using a mass spectrometry-based panel, and for MMP-1, -2, -9, -10 and TIMP-1 using fluorescent or electrochemiluminescent immunoassays. RESULTS: Brevican and neurocan peptide levels were not influenced by CSF origin, but MMP-1, -2, -10 and TIMP-1 were increased (p ≤ 0.0005), and MMP-9 decreased (p ≤ 0.0003) in lumbar CSF compared with ventricular CSF. There was a general trend of ECM proteins to increase following shunt surgery. Ventricular TIMP-1 was inversely correlated with overall symptoms (rho = - 0.62, p < 0.0001). CSF concentrations of the majority of brevican and neurocan peptides were increased in iNPH patients with a history of cardiovascular disease (p ≤ 0.001, AUC = 0.84-0.94) compared with those without. CONCLUSION: Levels of the CNS-specific proteins brevican and neurocan did not differ between the lumbar and ventricular CSF, whereas the increase of several CNS-unspecific MMPs and TIMP-1 in lumbar CSF suggests contribution from peripheral tissues. The increase of ECM proteins in CSF following shunt surgery could indicate disturbed ECM dynamics in iNPH that are restored by restitution of CSF dynamics.
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Proteínas da Matriz Extracelular/líquido cefalorraquidiano , Hidrocefalia de Pressão Normal/líquido cefalorraquidiano , Hidrocefalia de Pressão Normal/cirurgia , Punção Espinal/métodos , Derivação Ventriculoperitoneal/métodos , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/líquido cefalorraquidiano , Estudos de Coortes , Feminino , Humanos , Masculino , Punção Espinal/tendências , Derivação Ventriculoperitoneal/tendênciasRESUMO
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 iNPHDelayed (n = 33, waiting time for shunt surgery 6-24 months). These were compared to patients treated within 3 months, iNPHEarly (n = 69). Primary outcome was mortality. Dates and underlying causes of death were provided by the Cause of Death Registry. Survival was analysed by Kaplan-Meier plots and a Cox proportional hazard model adjusted for potential confounders. RESULTS: Median follow-up time was 6.0 years. Crude 4-year mortality was 39.4% in iNPHDelayed compared to 10.1% in iNPHEarly (p = 0.001). The adjusted hazard ratio in iNPHDelayed was 2.57; 95% confidence interval 1.13-5.83, p = 0.024. Causes of death were equally distributed between the groups except for death due to malignancy which was not seen in iNPHDelayed but in 4/16 cases in iNPHEarly (p = 0.044). CONCLUSIONS: The present data indicate that shunt surgery is effective in iNPH and that early treatment increases survival.
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Hidrocefalia de Pressão Normal , Estudos de Casos e Controles , Humanos , Hidrocefalia de Pressão Normal/cirurgia , Sistema de Registros , Resultado do Tratamento , Derivação VentriculoperitonealRESUMO
BACKGROUND: Altered levels of two extracellular matrix (ECM) proteoglycans, brevican and neurocan, have been found in brain injury models; however, their proteolytic processing in traumatic brain injury (TBI) remains unexplored. A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) is a possible contributor to ECM remodelling following TBI. The aims of this study were to evaluate proteolytic brevican/neurocan patterns and ADAMTS-like activity in cerebrospinal fluid (CSF) in the context of TBI. MATERIALS AND METHODS: Forty-two acute TBI patients and 37 idiopathic normal pressure hydrocephalus (iNPH) patients were included in the analysis of tryptic brevican and neurocan peptides in CSF using parallel reaction monitoring mass spectrometry. Twenty-nine TBI and 36 iNPH patients were analysed for ADAMTS-like activity in CSF using a quenched fluorescent substrate. RESULTS: The majority of CSF concentrations of brevican peptides significantly decreased in TBI patients compared with the iNPH group (p ≤ 0.002), while ADAMTS-like activity increased (p < 0.0001). Two C-terminal brevican peptides strongly correlated with unfavourable outcome of TBI patients (rho = 0.85-0.93, p ≤ 0.001). CONCLUSIONS: The decreased CSF concentrations of brevican peptides in TBI are associated with their increased degradation by ADAMTS enzymes. Furthermore, the N- and C-terminal parts of brevican are differentially regulated following TBI and may serve as outcome markers.
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Lesões Encefálicas Traumáticas , Brevicam/líquido cefalorraquidiano , Neurocam , Lesões Encefálicas Traumáticas/líquido cefalorraquidiano , Proteoglicanas de Sulfatos de Condroitina , Humanos , Lectinas Tipo C , Proteínas do Tecido Nervoso , Neurocam/líquido cefalorraquidianoRESUMO
Matrix metalloproteinases (MMPs) are extracellular enzymes involved in the degradation of extracellular matrix (ECM) proteins. Increased expression of MMPs have been described in traumatic brain injury (TBI) and may contribute to additional tissue injury and blood-brain barrier damage. The objectives of this study were to determine longitudinal changes in cerebrospinal fluid (CSF) concentrations of MMPs after acute TBI and in relation to clinical outcomes, with patients with idiopathic normal pressure hydrocephalus (iNPH) serving as a contrast group. The study included 33 TBI patients with ventricular CSF serially sampled, and 38 iNPH patients in the contrast group. Magnetic bead-based immunoassays were utilized to measure the concentrations of eight MMPs in ventricular human CSF. CSF concentrations of MMP-1, MMP-3 and MMP-10 were increased in TBI patients (at baseline) compared with the iNPH group (p < 0.001), while MMP-2, MMP-9 and MMP-12 did not differ between the groups. MMP-1, MMP-3 and MMP-10 concentrations decreased with time after trauma (p = 0.001-0.04). Increased concentrations of MMP-2 and MMP-10 in CSF at baseline were associated with an unfavourable TBI outcome (p = 0.002-0.02). Observed variable pattern of changes in MMP concentrations indicates that specific MMPs serve different roles in the pathophysiology following TBI, and are in turn associated with clinical outcomes.
Assuntos
Biomarcadores/líquido cefalorraquidiano , Lesões Encefálicas Traumáticas/diagnóstico , Metaloproteinases da Matriz/líquido cefalorraquidiano , Adulto , Idoso , Lesões Encefálicas Traumáticas/líquido cefalorraquidiano , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos ProspectivosRESUMO
INTRODUCTION: Core symptomatology in idiopathic normal pressure hydrocephalus (iNPH) points at dysfunction in the mesencephalon and pons indicating pathological changes in these regions, but only a few studies have addressed the issue. The aim of this study was to investigate diffusion (ADC) and perfusion patterns pre- and postoperatively in these areas in iNPH. METHODS: Twenty iNPH patients and 15 healthy controls were included. Patients underwent a clinical examination and brain MRI pre- and 3-6 months postoperatively. The MRI-scan included diffusion and dynamic susceptibility contrast perfusion weighted sequences. Regions of interest in the mesencephalon and pons were drawn on a FLAIR sequence and co-registered to ADC maps and perfusion data. RESULTS: There were no significant differences in pre or postoperative ADC compared to the control group, however postoperative ADC increased by 10% (p = 0.026) in the mesencephalon and 6% (p = 0.016) in the pons in all patients and also in the subgroup of shunt responders by 11% (p = 0.021) and 4% (p = 0.020), respectively. Preoperative relative cerebral blood flow (rCBF) was similar in iNPH patients and controls. Postoperatively, rCBF increased in shunt responders by 6% (p = 0.02) in the mesencephalon and 11% (p = 0.004) in the pons. This increase correlated with the degree of clinical improvement (rs = 0.80, p = 0.031 and rs = 0.66, p = 0.021, respectively). CONCLUSION: The postoperative increase in ADC and the correlation between postoperative increase in rCBF and clinical improvement in the mesencephalon and pons shown in this study point at an involvement of these areas in the core pathophysiology and its reversibility in iNPH.
Assuntos
Encéfalo/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética , Hidrocefalia de Pressão Normal/patologia , Mesencéfalo/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Circulação Cerebrovascular/fisiologia , Feminino , Humanos , Hidrocefalia de Pressão Normal/diagnóstico por imagem , Hidrocefalia de Pressão Normal/cirurgia , Masculino , Pessoa de Meia-Idade , Ponte/fisiopatologia , Período Pós-OperatórioRESUMO
OBJECTIVE: To describe survival and causes of death in 979 treated iNPH patients from the Swedish Hydrocephalus Quality Registry (SHQR), and to examine the influence of comorbidities, symptom severity and postoperative outcome. METHODS: All 979 patients operated for iNPH 2004-2011 and registered in the SHQR were included. A matched control group of 4890 persons from the general population was selected by Statistics Sweden. Data from the Swedish Cause of Death Registry was obtained for patients and controls. RESULTS: At a median 5.9 (IQR 4.2-8.1) year follow-up, 37% of the iNPH patients and 23% of the controls had died. Mortality was increased in iNPH patients by a hazard ratio of 1.81, 95% CI 1.61-2.04, p < 0.001. More pronounced symptoms in the preoperative ordinal gait scale and the Mini-mental State Examination were the most important independent predictors of mortality along with the prevalence of heart disease. Patients who improved in both the gait scale and in the modified Rankin Scale postoperatively (n = 144) had a similar survival as the general population (p = 0.391). Deaths due to cerebrovascular disease or dementia were more common in iNPH patients, while more controls died because of neoplasms or disorders of the circulatory system. CONCLUSIONS: Mortality in operated iNPH patients is 1.8 times increased compared to the general population, a lower figure than previously reported. The survival of iNPH patients who improve in gait and functional independence is similar to that of the general population, indicating that shunt surgery for iNPH, besides improving symptoms and signs, can normalize survival.
Assuntos
Derivações do Líquido Cefalorraquidiano/mortalidade , Hidrocefalia de Pressão Normal/mortalidade , Hidrocefalia de Pressão Normal/cirurgia , Idoso , Comorbidade , Feminino , Humanos , Masculino , Fatores de Risco , Suécia/epidemiologiaRESUMO
OBJECTIVE: To examine the differential diagnostic significance of cerebrospinal fluid (CSF) biomarkers reflecting Alzheimer's disease-related amyloid ß (Aß) production and aggregation, cortical neuronal damage, tau pathology, damage to long myelinated axons and astrocyte activation, which hypothetically separates patients with idiopathic normal pressure hydrocephalus (iNPH) from patients with other neurodegenerative disorders. METHODS: The study included lumbar CSF samples from 82 patients with iNPH, 75 with vascular dementia, 70 with Parkinson's disease, 34 with multiple system atrophy, 34 with progressive supranuclear palsy, 15 with corticobasal degeneration, 50 with Alzheimer's disease, 19 with frontotemporal lobar degeneration and 54 healthy individuals (HIs). We analysed soluble amyloid precursor protein alpha (sAPPα) and beta (sAPPß), Aß species (Aß38, Aß40 and Aß42), total tau (T-tau), phosphorylated tau, neurofilament light and monocyte chemoattractant protein 1 (MCP-1). RESULTS: Patients with iNPH had lower concentrations of tau and APP-derived proteins in combination with elevated MCP-1 compared with HI and the non-iNPH disorders. T-tau, Aß40 and MCP-1 together yielded an area under the curve of 0.86, differentiating iNPH from the other disorders. A prediction algorithm consisting of T-tau, Aß40 and MCP-1 was designed as a diagnostic tool using CSF biomarkers. CONCLUSIONS: The combination of the CSF biomarkers T-tau, Aß40 and MCP-1 separates iNPH from cognitive and movement disorders with good diagnostic sensitivity and specificity. This may have important implications for diagnosis and clinical research on disease mechanisms for iNPH.