5-Year health-related quality of life outcome in patients with idiopathic normal pressure hydrocephalus.

BACKGROUND: Health-related quality of life (HRQoL) is severely impaired in persons with idiopathic normal pressure hydrocephalus (iNPH). The HRQoL improves in a number of patients after the placement of a cerebrospinal fluid (CSF) shunt, but long-term follow-up of HRQoL is rare. METHODS: Extended follow-up (60 months) of a prospective cohort study involving 189 patients with iNPH who underwent shunt surgery. Preoperative variables were used to predict favorable HRQoL outcome (improvement or non-deterioration) measured by the 15D instrument 5 years after shunting. RESULTS: Out of the 189 initially enrolled study participants, 88 had completed 5-year HRQoL follow-up (46%), 64 had died (34%), and 37 (20%) failed to complete the HRQoL follow-up but were alive at the end of the study. After initial post-operative HRQoL improvement, HRQoL deteriorated so that 37/88 participants (42%) had a favorable HRQoL outcome 5 years after shunting. Multivariate binary logistic regression analysis indicated that younger age (adjusted OR 0.86, 95% CI 0.77-0.95; p < 0.005), lower body mass index (adjusted OR 0.87, 95% CI 0.77-0.98; p < 0.05) and better Mini-Mental State Examination performance (adjusted OR 1.16, 95% CI 1.01-1.32; p < 0.05) before surgery predicted favorable 5-year outcome. CONCLUSIONS: This extended follow-up showed that the self-evaluated HRQoL outcome is associated with iNPH patients' pre-operative cognitive status, overweight and age. The post-operative deterioration may reflect the natural progression of iNPH, but also derive from aging and comorbidities. It indicates a need for long-term follow-up.

Protein tyrosine phosphatase receptor type Q in cerebrospinal fluid reflects ependymal cell dysfunction and is a potential biomarker for adult chronic hydrocephalus.

BACKGROUND AND PURPOSE: Protein tyrosine phosphatase receptor type Q (PTPRQ) was extracted from the cerebrospinal fluid (CSF) of patients with probable idiopathic normal-pressure hydrocephalus (iNPH) by proteome analysis. We aimed to assess the feasibility of using CSF PTPRQ concentrations for the additional diagnostic criterion of iNPH in Japanese and Finnish populations. METHODS: We compared PTPRQ concentrations among patients with probable iNPH and neurologically healthy individuals (normal control [NC] group), patients with normal-pressure hydrocephalus (NPH) of acquired and congenital/developmental aetiologies, patients with Alzheimer's disease and patients with Parkinson's disease in a Japanese analysis cohort. A corresponding iNPH group and NC group in a Finnish cohort was used for validation. Patients in the Finnish cohort who underwent biopsy were classified into two groups based on amyloid and/or tau deposition. We measured PTPRQ expression levels in autopsied brain specimens of iNPH patients and the NC group. RESULTS: Cerebrospinal fluid PTPRQ concentrations in the patients with NPH of idiopathic, acquired and congenital/developmental aetiologies were significantly higher than those in the NC group and those with Parkinson's disease, but iNPH showed no significant differences when compared with those in the Alzheimer's disease group. For the patients with iNPH, the area under the receiver-operating characteristic curve was 0.860 in the Japanese iNPH and 0.849 in the Finnish iNPH cohorts. Immunostaining and in situ hybridization revealed PTPRQ expression in the ependymal cells and choroid plexus. It is highly possible that the elevated PTPRQ levels in the CSF are related to ependymal dysfunction from ventricular expansion. CONCLUSIONS: Cerebrospinal fluid PTPRQ levels indicated the validity of this assay for auxiliary diagnosis of adult chronic hydrocephalus.

Unfolding the outcomes of surgical treatment of lumbar spinal stenosis-a prospective 5- and 10-year follow-up study.

PURPOSE: In this prospective study, we aim to determine surgical outcomes in patients with lumbar spinal stenosis (LSS) 10 years after surgery. METHODS: The study population consisted of 96 LSS patients who underwent decompressive surgery, 72 of whom participated in the 10-year follow-up. The patients completed a questionnaire preoperatively and 3 months, 5 years, and 10 years postoperatively. Outcome measures were satisfaction with the surgical outcomes, the Oswestry Disability Index (ODI), the visual analog scale (VAS), the numeric rating scale (NRS-11), and walking ability quantified in meters. Postoperative improvements at 5 and 10 years were analyzed using linear mixed models. Furthermore, comparisons between postoperative time points were made for clinical courses of pain, disability, and walking ability. RESULTS: At the 10-year follow-up, 68% of the patients were satisfied with the surgical outcomes. All the measured outcomes showed statistically significant improvement from baseline to the 5- and 10-year follow-up. The mean VAS score was 9.8 mm higher at the 5-year follow-up and 7.8 mm at the 10-year follow-up compared to the 3-month follow-up point. Similarly, the mean ODI was 4.8% higher at the 10-year follow-up compared to the 3-month follow-up point. CONCLUSION: This study reports the clinical course of pain, disability, and walking distance after LSS surgery with the 10-year follow-up. Based on our study results, patients with LSS could expect to have positive effects of their back surgery up to 10 years. However, minor worsening in pain and disability may occur and one-fourth of the patients may need a reoperation during the 10-year follow-up period.

The Kuopio idiopathic normal pressure hydrocephalus protocol: initial outcome of 175 patients.

BACKGROUND: The Kuopio University Hospital (KUH) idiopathic normal pressure hydrocephalus (iNPH) cerebrospinal fluid (CSF) shunting protocol is described together with the initial outcomes of 175 patients with probable iNPH treated according to this protocol from a defined population. Our secondary aim was to display the variety of differential diagnoses referred to the KUH iNPH outpatient clinic from 2010 until 2017. METHODS: Patients were divided into four groups according to the prognostic tests: tap test (positive or negative) and infusion test (positive or negative). The short-term outcome was compared between groups. The 3-month outcome following shunt surgery was assessed by measuring gait speed improvement, using a 12-point iNPH grading scale (iNPHGS) and the 15D instrument. RESULTS: From 341 patients suspected of iNPH, 88 patients were excluded from further research mostly due to deviation from the protocol's gait assessment guidelines. Hence 253 patients with suspected iNPH were included in the study, 177/253 (70%) of whom were treated with a CSF shunt. A favorable clinical outcome following surgery was observed in 79-93% of patients depending on the prognostic group. A moderate association (Cramer's V = 0.32) was found between the gait speed improvement rate and the prognostic group (X2, p = 0.003). Patients with a positive tap test had the highest gait speed improvement rate (75%). In addition, an improvement in walking speed was observed in 4/11 patients who had both a negative tap test and a negative infusion test. Other outcome measures did not differ between the prognostic groups. Conditions other than iNPH were found in 25% of the patients referred to iNPH outpatient clinic, with the most prevalent being Alzheimer's disease. CONCLUSIONS: Our results emphasize the importance of a systematic diagnostic and prognostic workup especially in cases with an atypical presentation of iNPH. Additional diagnostic testing may be required, but should not delay adequate care. Active surgical treatment is recommended in patients with a high clinical probability of iNPH. Other neurological conditions contributed to most of the non iNPH diagnoses.

Frontotemporal dementia as a comorbidity to idiopathic normal pressure hydrocephalus (iNPH): a short review of literature and an unusual case.

Behavioural variant frontotemporal dementia (bvFTD) and idiopathic normal pressure hydrocephalus (iNPH) are neurodegenerative diseases that can present with similar symptoms. These include decline in executive functions, psychomotor slowness, and behavioural and personality changes. Ventricular enlargement is a key radiological finding in iNPH that may also be present in bvFTD caused by the C9ORF72 expansion mutation. Due to this, bvFTD has been hypothesized as a potential comorbidity to iNPH but bvFTD patients have never been identified in studies focusing in clinical comorbidities with iNPH. Here we describe a patient with the C9ORF72 expansion-associated bvFTD who also showed enlarged ventricles on brain imaging. The main clinical symptoms were severe gait disturbances and psychiatric problems with mild cognitive decline. Cerebrospinal fluid removal increased the patient's walking speed, so a ventriculoperitoneal shunt was placed. After insertion of the shunt, there was a significant improvement in walking speed as well as mild improvement in cognitive function but not in neuropsychiatric symptoms relating to bvFTD. Comorbid iNPH should be considered in bvFTD patients who have enlarged ventricles and severely impaired gait.

Health-related quality-of-life outcome in patients with idiopathic normal-pressure hydrocephalus - a 1-year follow-up study.

BACKGROUND AND PURPOSE: This prospective study explored the factors affecting the health-related quality-of-life (HRQoL) outcome in patients with idiopathic normal-pressure hydrocephalus (iNPH) 1 year after the installation of the cerebrospinal fluid shunt. METHODS: The HRQoL outcome was evaluated using a 15D instrument, in which the minimum clinically significant change/difference has been estimated to be ±0.015. The follow-up data (15D, Mini-Mental State Examination, Beck Depression Inventory, iNPH Grading Scale), frontal cortical biopsy, Charlson Age Comorbidity Index and body mass index of 145 patients diagnosed with iNPH by clinical and radiological examination were analyzed. RESULTS: At 1-year follow-up, 63 (43%) patients had experienced a clinically significant improvement in HRQoL. Multivariate binary logistic regression analysis indicated that the absence of amyloid-ß and hyperphosphorylated tau pathology in the frontal cortical biopsy (53% vs. 33%; absolute risk difference, 20%; adjusted odds ratio, 2.27; 95% confidence interval, 1.07-4.84; P < 0.05) and lower body mass index (adjusted odds ratio, 0.90, 95% confidence interval, 0.82-0.98; P < 0.05) predicted favorable HRQoL outcome 1 year after the shunting. CONCLUSIONS: Less than half of the patients with iNPH experienced clinically significant favorable HRQoL outcome, partly explained by the patient's characteristics and comorbidities. The HRQoL approach reveals aspects that are important for the patient's well-being, but may also improve the quality of the outcome assessment of cerebrospinal fluid shunting. Study results may help clinicians to estimate which patients will benefit shunt surgery.

Health-related quality of life in patients with idiopathic normal pressure hydrocephalus.

BACKGROUND AND PURPOSE: Factors affecting health-related quality of life (HRQoL) were explored in patients with idiopathic normal pressure hydrocephalus (iNPH). METHODS: Using the 15D instrument HRQoL was evaluated in 132 patients diagnosed with iNPH by clinical and neuroradiological examinations. The severity of iNPH symptoms was measured with the iNPH grading scale (iNPHGS), depressive symptoms with the Beck Depression Inventory (BDI-21) and cognitive impairment with the Mini-Mental State Examination. RESULTS: The mean (SD) 15D score (on a 0-1 scale) of patients with iNPH was significantly lower than that of an age- and gender-matched sample of the general population [0.718 (0.103) vs. 0.870 (0.106); P < 0.001]. The mean 15D score was lower in iNPH patients with moderate or severe depressive symptoms than in patients without depressive symptoms (P = 0.003). According to stepwise multiple linear regression analysis, a higher total iNPHGS score (b = -0.62, P < 0.001) and a higher BDI-21 total score (ß = -0.201, P = 0.025) predicted a lower 15D score; in combination, these explained 51% of the variance in the 15D score (R(2)  = 0.506, P < 0.001). CONCLUSIONS: Idiopathic normal pressure hydrocephalus impairs patients' HRQoL on multiple dimensions, similarly to other chronic diseases. Potentially treatable depressive symptoms contribute greatly to the HRQoL impairment of iNPH patients, but only if they are moderate or severe. The 15D portrayed HRQoL dimensions affected by iNPH in a similar way to broader assessment batteries and thus is a potentially useful tool for treatment evaluation and cost-utility analysis.

Positron emission tomography with [18F]flutemetamol and [11C]PiB for in vivo detection of cerebral cortical amyloid in normal pressure hydrocephalus patients.

BACKGROUND AND PURPOSE: This study determined the correlation between uptake of the amyloid positron emission tomography (PET) imaging agent [(18) F]flutemetamol and amyloid-ß measured by immunohistochemical and histochemical staining in a frontal cortical biopsy. METHODS: Fifteen patients with possible normal pressure hydrocephalus (NPH) and previous brain biopsy obtained during intracranial pressure monitoring underwent [18F]flutemetamol PET. Seven of these patients also underwent [11C] Pittsburgh compound B (PiB) PET. [18F]Flutemetamol and [11C]PiB uptake was quantified using standardized uptake value ratio (SUVR) with the cerebellar cortex as a reference region. Tissue amyloid-ß was evaluated using the monoclonal antibody 4G8, Thioflavin-S and Bielschowsky silver stain. RESULTS: [18F]Flutemetamol and [11C]PiB SUVRs correlated with biopsy specimen amyloid-ß levels contralateral (r = 0.86, P < 0.0001; r = 0.96, P = 0.0008) and ipsilateral (r = 0.82, P = 0.0002; r = 0.87, P = 0.01) to the biopsy site. Association between cortical composite [(18) F]flutemetamol SUVRs and [11C]PiB SUVRs was highly significant (r = 0.97, P = 0.0003). CONCLUSIONS: [18F]Flutemetamol detects brain amyloid-ß in vivo with moderate to high sensitivity and high specificity. This agent, therefore, represents a valuable new tool to study and verify the presence of amyloid-ß pathology, both in patients with possible NPH and among the wider population.

Preoperative predictors for good postoperative satisfaction and functional outcome in lumbar spinal stenosis surgery--a prospective observational study with a two-year follow-up.

BACKGROUND AND AIMS: Lumbar spinal stenosis (LSS) is the most frequent indication for back surgery in adults aged over 65 years, but about one-third of operated patients have less than good/excellent results from the operation. Awareness of outcome predictors and their predictive values may help clinicians in their assessment of the prognosis of patients when considering surgical treatment. Our aim was to study the preoperative predictors in LSS for a good postoperative outcome (satisfaction with surgery and functional improvement) with a two-year follow-up. MATERIAL AND METHODS: LSS patients (n = 102) completed a questionnaire preoperatively and on two-year follow-up. Preoperative patient-related predictors, self-rated health, comorbidities and preoperative treatment were assessed. Satisfaction with the surgical outcome was assessed with a seven-category scale; satisfaction was determined to be good if the patient response was "condition has considerably improved" or "totally cured". Other responses ("condition has slightly improved" or worse) represented poorer satisfaction. A good functional outcome was determined as >30% relative improvement compared to the presurgery score in the Oswestry Disability Index (ODI). RESULTS: The predictors for good satisfaction were age < 75 years at operation (OR 4.03; 95% CI 1.35-12.02; p = 0.012) and no previous lumbar operation (OR 3.65; 95% CI 1.13-11.79; p = 0.031). Predictors for a good improvement in the ODI score were regular preoperative analgesic use < 12 months (OR 3.40; 95% CI 1.21-9.53; p = 0.020), non-smoking (OR 3.47; 95% CI 1.09-11.03; p = 0.035) and good (above average) self-rated health (OR 3.27; 95% CI 1.06-10.12; p = 0.039). CONCLUSIONS: In LSS, regular analgesic treatment preoperatively for 12 months or less, self-rated health above average and non-smoking predicted a good postoperative functional improvement. An age under 75 years and no previous lumbar operation predicted good post-operative satisfaction with the surgery.

CSF biomarkers for Alzheimer disease correlate with cortical brain biopsy findings.

OBJECTIVE: To assess the relationship between Alzheimer disease (AD)-related pathologic changes in frontal cortical brain biopsy and AD biomarkers in ventricular vs lumbar CSF, and to evaluate the relationships of AD biomarkers in CSF and cortical biopsy with the final clinical diagnosis of AD. METHODS: In 182 patients with presumed normal pressure hydrocephalus (152 with known APOE carrier status), Aß plaques and tau in the cortical brain biopsies were correlated with the ventricular and lumbar CSF Aß42, total tau, and p-tau levels measured by ELISA. In a median follow-up of 2.0 years, 51 patients developed AD dementia. RESULTS: The patients with Aß plaques in the cortical biopsy had lower (p = 0.009) CSF Aß42 levels than those with no Aß plaques. The patients with tau in the cortical biopsy had lower (p = 0.014) Aß42 but higher (p = 0.015) p-tau 181 in CSF as compared to those with no tau in the cortical biopsy. The patients with amyloid + tau + biopsies had the lowest Aß42 and highest tau and p-tau 181 levels in CSF. The Aß42 levels were lower and the tau and p-tau 181 higher in the ventricular vs corresponding lumbar CSF samples. In multivariate analysis, the presence of cortical Aß was independently predicted by the APOE ε4 carrier status and age but not by CSF Aß42 or tau levels. CONCLUSIONS: Amyloid plaques and hyperphosphorylated tau in cortical brain biopsies are reflected by low CSF Aß42 and high CSF tau and p-tau levels, respectively.

Post-mortem findings in 10 patients with presumed normal-pressure hydrocephalus and review of the literature.

AIMS: Neuropathological features of idiopathic normal-pressure hydrocephalus (iNPH) are poorly characterized. Brain biopsy during life may help in the differential diagnosis of dementia, but post-mortem validation of biopsy findings is scarce. Here we review and report brain biopsy and post-mortem neuropathological findings in patients with presumed NPH. METHODS: We evaluated 10 patients initially investigated by intraventricular pressure monitoring and a frontal cortical biopsy for histological and immunohistochemical assessment as a diagnostic procedure for presumed NPH. RESULTS: Out of the 10 patients, eight were shunted and seven benefited. Until death, six had developed severe and two mild cognitive impairment. One was cognitively unimpaired, and one was mentally retarded. Three subjects displayed amyloid-ß (Aß) aggregates in their frontal cortical biopsy obtained at the initial procedure. One of these patients developed Alzheimer's disease during a follow-up time of nearly 10 years. One patient with cognitive impairment and NPH suffered from corticobasal degeneration. In six patients various vascular lesions were seen at the final neuropathological investigation. Five of them were cognitively impaired, and in four vascular lesions were seen sufficient in extent to be considered as causative regarding their symptoms. CONCLUSIONS: The frequent finding of vascular pathology in NPH is intriguing, suggesting that vascular alterations might be causative of cognitive impairment in a notable number of patients with NPH and dementia. Brain biopsy can be used to detect Aß aggregates, but neuropathological characteristics of iNPH as a distinct disease still need to be discovered.

Indigenous healers' explanations of low back pain and its relief.

UNLABELLED: Significant number of Finns consults annually indigenous healers for their low back pain (LBP). Bone setting is the most vital traditional Finnish mobilization treatment of LBP. In the present study we have clarified healers' believes on the pathophysiology of back pain and observed them at work to clarify the effectiveness of treatment by medical check-up and by interviewing the patients who also compared the benefits of this method with their previous other treatments such as drugs, exercise and physiotherapy. STUDY DESIGN: Two of the oldest bone setters participated in the study. In the patient follow-up they treated 35 consecutive chronic LBP subjects. A medical check-up of the patients was done before and after their treatments. After 7 months mean follow-up time patients replied by using questionnaires and evaluated the effectiveness of the method. RESULTS: The indigenous bone setters told that they followed the hundreds of years old tradition. The healers explained that the back pain was due to difference in the leg lengths and this was reflected in the pelvic and spinal asymmetry as well as increased muscle tension. After the sessions the subjects reported relaxation and clear immediate pain alleviation. The patients reported in the follow-up questionnaires benefits from their LBP treatment in 28 cases out of 29 who replied after the treatment. According to physician's evaluation 27 patients (from 35 or 77%) got excellent or good result in their chronic LBP. There was no change in one case, and none got worse. Bone setting received in patients' reports better evaluation than drug treatment and physical therapy.

Disc herniation-related back pain impairs feed-forward control of paraspinal muscles.

STUDY DESIGN: A comparative study of lumbar paraspinal muscle reflexes during sudden upper limb loading in healthy control subjects and patients with sciatica. OBJECTIVES: To assess reflex activation of paraspinal muscles during sudden upper limb loading. SUMMARY OF BACKGROUND DATA: Sudden upper limb loading and upper limb voluntary movements cause reflex activation of trunk muscles. A short latency response of approximately 50 msec of lumbar muscles has been observed before, but the reflexes have not been studied in patients with sciatica. METHODS: The paraspinal muscle responses for upper limb loading during unexpected and expected conditions were measured by surface EMG from 20 patients selected for an operation as a result of disc herniation-related chronic low back pain and 15 back-healthy controls. Pain, disability, and depression scores were recorded. RESULTS: Short latency response of paraspinal muscles for unexpected upper limb loading was similar in healthy controls and patients with sciatica in supported standing. During normal standing anticipation shortened the lumbar reflex latency in healthy controls but not among the patients. CONCLUSIONS: The results provide evidence for impaired feed-forward control of lumbar muscles in patients with sciatica.

Back and hip extensor activities during trunk flexion/extension: effects of low back pain and rehabilitation.

OBJECTIVE: To compare lumbar paraspinal, gluteus maximus, and biceps femoris muscle function during sagittal trunk flexion and extension in patients with chronic low back pain and healthy control subjects, and to assess the influence of rehabilitation in the back pain patients. DESIGN: A cross-sectional study comparing chronic low back pain patients and healthy controls, and a prospective follow-up in back pain patients during rehabilitation. SETTING: Physical medicine and rehabilitation clinic. SUBJECTS: Nineteen women with chronic low back pain, and 19 women without pain (controls). INTERVENTION: Five-week active outpatient rehabilitation (1 hour three times a week) guided by a physiotherapist, followed by 5-week self-motivated exercise at home. OUTCOME MEASURES: Subjects performed sagittal trunk flexion and extension while surface electromyogram was bilaterally recorded of paraspinal (L1-L2 level), gluteus maximus, and biceps femoris muscles. The muscle activity was assessed from the average electromyogram and the relative muscle activation onsets and their duration were calculated. RESULTS: During early flexion, lumbar paraspinal and biceps femoris were activated simultaneously before gluteus maximus. At the end of flexion and during extension all investigated muscles were activated and relaxed in order. Lumbar paraspinal and biceps femoris muscles were activated in a similar order in low back pain patients and healthy controls during flexion and extension. However, the duration of gluteus maximus activity was shorter in the back pain patients than in controls during the trunk flexion (p<.05), and it ended earlier during extension. Active rehabilitation did not change the muscle activities of lumbar paraspinal and biceps femoris in the back pain patients, but in the measurements after rehabilitation the onset of gluteus maximus activity occurred later in flexion and earlier in extension. CONCLUSIONS: The activity of the gluteus maximus muscle during the flexion-extension cycle was reduced in patients with chronic low back pain. The gluteal muscles should be taken into consideration in the rehabilitation of these patients.

Effects of ramipril on the hormone concentrations in serum of hypertensive patients.

The effects of the angiotensin-converting enzyme inhibitor ramipril on thirteen endocrinological tests were evaluated. These tests comprised serum follitropin, lutropin, prolactin, thyrotropin, free thyroxine, total thyroxine, free triiodothyronine, parathyrin, cortisol, testosterone, sex hormone binding globulin, androstenedione and dehydroepiandrosterone sulphate. Eleven hypertensive outpatients, 9 men and 2 women, treated at the department of internal medicine in Turku University Central Hospital, received 5 mg of ramipril once a day for the study period of four weeks. The above mentioned endocrinological tests were performed before and at the end of the ramipril treatment. Ramipril decreased the value of free thyroxine statistically significantly, p = 0.011, from the mean value of 17.1 pmol/l to the mean value of 16.0 pmol/l when measured with Amerlex-MAB* free thyroxine kit. The mean within-subject difference was -1.10 pmol/l with a 95% confidence interval of -1.87 - -0.33 pmol/l. With the AutoDELFIA free thyroxine kit and with the reference method dialysis+RIA no effect was detected. Other endocrinological tests examined were not affected by ramipril. Since the decreasing effect of ramipril on free thyroxine was detected only with Amerlex-MAB* but neither with AutoDELFIA nor with dialysis+RIA, the effect was concluded to be analytical. The underlying mechanism and the component ultimately interfering with the analysis is unknown.