Cerebrospinal fluid dynamics in idiopathic intracranial hypertension: a literature review and validation of contemporary findings.

BACKGROUND: Idiopathic intracranial hypertension (IIH) is a rare disease of unknown aetiology related possibly to disturbed cerebrospinal fluid (CSF) dynamics and characterised by elevated intracranial pressure (ICP) causing optic nerve atrophy if not timely treated. We studied CSF dynamics of the IIH patients based on the available literature and our well-defined cohort. METHOD: A literature review was performed from PubMed between 1980 and 2020 in compliance with the PRISMA guideline. Our study includes 59 patients with clinical, demographical, neuro-ophthalmological, radiological, outcome data, and lumbar CSF pressure measurements for suspicion of IIH; 39 patients had verified IIH while 20 patients did not according to Friedman's criteria, hence referred to as symptomatic controls. RESULTS: The literature review yielded 19 suitable studies; 452 IIH patients and 264 controls had undergone intraventricular or lumbar CSF pressure measurements. In our study, the mean CSF pressure, pulse amplitudes, power of respiratory waves (RESP), and the pressure constant (P0) were higher in IIH than symptomatic controls (p < 0.01). The mean CSF pressure was higher in IIH patients with psychiatric comorbidity than without (p < 0.05). In IIH patients without acetazolamide treatment, the RAP index and power of slow waves were also higher (p < 0.05). IIH patients with excess CSF around the optic nerves had lower relative pulse pressure coefficient (RPPC) and RESP than those without (p < 0.05). CONCLUSIONS: Our literature review revealed increased CSF pressure, resistance to CSF outflow and sagittal sinus pressure (SSP) as key findings in IIH. Our study confirmed significantly higher lumbar CSF pressure and increased CSF pressure waves and RAP index in IIH when excluding patients with acetazolamide treatment. In overall, the findings reflect decreased craniospinal compliance and potentially depleted cerebral autoregulation resulting from the increased CSF pressure in IIH. The increased slow waves in patients without acetazolamide may indicate issues in autoregulation, while increased P0 could reflect the increased SSP.

Surgical techniques for degenerative cervical spine in Finland from 1999 to 2015.

PURPOSE: The purpose of this study is to assess the trends and regional variations in the operative techniques used for degenerative or rheumatoid cervical spine disease in Finland between 1999 and 2015. METHODS: The Finnish Hospital Discharge Register (FHDR) was searched for the data on all the primary operations for degenerative cervical spine disease (DCSD) or rheumatoid atlanto-axial subluxation (rAAS). Operative codes were used to identify the patients from the FHDR and combined with diagnosis codes to verify patient inclusion. The patients were classified into three groups: anterior cervical decompression and fusion (ACDF), posterior decompression and fusion (PDF) and decompression. RESULTS: A total of 19,701 primary operations were included. The adjusted incidence of ACDF rose from 6.5 to 27.3 operations/100,000 adults. ACDF became the favoured technique in all the diagnostic groups except AAS, and by 2015, ACDF comprised 84.5% of the operations. The incidence of PDF for DCSD increased from 0.2 to 0.7/100,000 people. Solely decompressive operations declined from 13.7 to 4.0 operations/100,000 people. The regional differences in the incidence of operations were most marked in the incidence of ACDF, with overall incidences ranging from 11.2 to 37.0 operations/100,000. The distribution of the operative techniques used varied as well. CONCLUSIONS: Between 1999 and 2015, the operative techniques used for DCSD changed from prevalently decompressive to utilising ACDF in 68.8 to 91.0% of the operations, depending on the treating hospital. ACDF became the most commonly applied technique for all degenerative diagnoses except AAS.

Surgery for degenerative cervical spine disease in Finland, 1999-2015.

BACKGROUND: The incidence of surgery for degenerative cervical spine disease (DCSD) has risen by almost 150% in the USA in the last three decades and stabilized at slightly over 70 operations/100,000 people. There has been significant regional variation in the operation incidences. We aim to assess the diagnosis-based, age-adjusted trends in the operation incidences and the regional variation in Finland between 1999 and 2015. METHODS: Data from the Finnish Hospital Discharge Register (FHDR), the Cause of Death Register, and the registers of the Social Insurance Institution were combined to analyze all the primary operations for DCSD or rheumatoid atlanto-axial subluxation (rAAS). Combinations of the operative and the diagnosis codes were used to classify the patients into five diagnostic groups. RESULTS: A total of 19,701 primary operations were included. The age-adjusted operation incidence rose from 21.0 to 36.5/100,000 people between 1999 and 2013 and plateaued thereafter. The incidence of surgery for radiculopathy increased from 13.1 to 23.3 operations/100,000 people, and the incidence of surgery for DCM increased from 5.8 to 7.0 operations/100,000 people. The rise was especially pronounced in surgery for foraminal stenosis, which increased from 5.3 to 12.4 operations/100,000 people. Of the five diagnostic groups, only operations for rAAS declined. Operations increased especially in the 40- to 65-year-old age group. The overall operation incidences varied from 18.3 to 43.1 operations/100,000 people between the university hospitals. CONCLUSIONS: The age-adjusted incidence of surgery for DCSD has risen in Finland by 76%, but the rise has plateaued. Surgery for radiculopathy, especially for foraminal stenosis, increased more steeply than surgery for degenerative medullopathy, with vast regional differences in the operation incidences.

Acute hormonal findings after aneurysmal subarachnoid hemorrhage - report from a single center.

PURPOSE: The aim was to assess anterior pituitary hormone levels during the acute phase of aneurysmal subarachnoid hemorrhage (aSAH) and analyze the possible association with the clinical condition and outcome. MATERIAL AND METHODS: Forty patients with aSAH whose aneurysm was secured by endovascular coiling were enrolled. Basal secretions of cortisol, testosterone, luteinizing hormone (LH), prolactin (PRL), and sex hormone binding globulin (SHBG) levels were measured up to 14 days after the incident. RESULTS: The main finding was that hypocortisolism was rare whereas testosterone deficiency was common in male patients. Furthermore, various other hormone deviations were frequent and there was wide interindividual variability. We found no association between delayed cerebral ischemia (DCI), outcome of the patients or aneurysm location, and hormone abnormalities, while both Hunt & Hess and Fisher grade were associated with low PRL levels. Hunt & Hess 5 was associated with low PRL concentration when compared to grades 1 (OR = 4.81, 95% CI 1.15-20.14, p = 0.03), 3 (OR 7.73, 95% CI 1.33-45.01, p = 0.02), and 4 (OR = 6.86 95% CI 1.28-26.83, p = 0.02). Fisher grade 4 was associated with low PRL concentration when compared to grades 3 (OR 3.37, 95% CI 1.06-10.73, p = 0.03) and 2 (OR 9.71, 95% CI 1.22-77.10, p = 0.04). CONCLUSION: Deviations from normal and huge interindividual differences are common in hormone levels during the acute phase of aSAH. Routine assessment of anterior pituitary function in the acute phase of aSAH is not warranted. During the follow-up in the outpatient clinic, hormone concentrations were not measured, which would have brought a more long-term perspective into our findings.

Prospective flutemetamol positron emission tomography and histopathology in normal pressure hydrocephalus.

UNLABELLED: BACKGOUND/OBJECTIVE: To determine the level of association between uptake of the amyloid positron emission tomography (PET) imaging agent [(18)F]flutemetamol and the level of amyloid-ß measured by immunohistochemical and histochemical staining in a frontal cortical region biopsy site. METHODS: Seventeen patients with probable normal pressure hydrocephalus (NPH) underwent prospective [(18)F]flutemetamol PET and subsequent frontal cortical brain biopsy during ventriculoperitoneal shunting. Tissue amyloid-ß was evaluated using the monoclonal antibody 4G8, thioflavin S and Bielschowsky silver stain. RESULTS: Four of the 17 patients (23.5%) had amyloid-ß pathology based on the overall pathology read and also showed increased [(18)F]flutemetamol uptake. [(18)F]Flutemetamol standardized uptake values from the biopsy site were significantly associated with biopsy specimen amyloid-ß levels (Pearson's r = 0.67; p = 0.006). There was also good correlation between the biopsy specimen amyloid-ß level and uptake of [(18)F]flutemetamol in the region contralateral to the biopsy site (r = 0.67; p = 0.006), as well as with composite cortical [(18)F]flutemetamol uptake (r = 0.65; p = 0.008). The blinded visual read showed a high level of agreement between all readers (κ = 0.88). Two of 3 readers were in full agreement on all images; 1 reader disagreed on 1 of the 17 NPH cases. Blinded visual assessments of PET images by 1 reader were associated with 100% sensitivity to the overall pathology read, and assessments by the 2 others were associated with 75% sensitivity (overall sensitivity by majority read was 75%); specificity of all readers was 100%. CONCLUSIONS: [(18)F]Flutemetamol detects brain amyloid-ß in vivo and shows promise as a valuable tool to study and possibly facilitate diagnosis of Alzheimer's disease both in patients with suspected NPH and among the wider population.

Disability and pain after anterior cervical decompression and fusion: A group-based trajectory analysis.

OBJECTIVES: This study aimed to identify the clusters of patients with different developmental trajectories of pain and disability after anterior cervical decompression and fusion (ACDF). METHODS: Group-based trajectory analysis among 318 patients undergoing the ACDF. RESULTS: Three developmental trajectories of disability were identified: "Steadily good functioning," "Improved functioning," and "Steadily poor functioning." Three developmental trajectories of neck pain were identified: "Worsened pain," "Pain relief," and "Steadily severe pain." Two developmental trajectories of arm pain were identified: "Decreased arm pain" and "Severe arm pain with only short-term relief." No associations were found between sex, preoperative pain duration, or body weight and probability to be classified into a particular disability trajectory group. Female sex (relative risk ratio (RRR) 1.78) and longer history of preoperative pain (RRR 2.31-2.68) increased the probability to be classified into a group with steadily severe neck pain. Longer history of preoperative pain increased the probability to be classified into group with severe arm pain with only short-term pain relief (RRR 2.68). CONCLUSION: After the ACDF, dissimilar developmental trajectories of pain and disability were identified between the patient clusters. While sex, preoperative pain duration, and body weight were not associated with differences in improvement in disability level, female sex and longer duration of preoperative pain were correlated with more severe neck and arm pain after surgery.

Risk Variants Associated With Normal Pressure Hydrocephalus: Genome-Wide Association Study in the FinnGen Cohort.

BACKGROUND AND OBJECTIVES: Large-scale genome-wide studies of chronic hydrocephalus have been lacking. We conducted a genome-wide association study (GWAS) in normal pressure hydrocephalus (NPH). METHODS: We used a case-control study design implementing FinnGen data containing 473,691 Finns with genotypes and nationwide health records. Patients with NPH were selected based on ICD-10 G91.2 diagnosis. To select patients with idiopathic NPH (iNPH) for sensitivity analysis, we excluded patients with a potentially known etiology of the condition using an algorithm on their disease history. The controls were the remaining non-hydrocephalic participants. For a replication analysis, the NPH cohort from UK Biobank (UKBB) was used. RESULTS: We included 1,522 patients with NPH (mean age 72.2 years, 53% women) and 451,091 controls (mean age 60.5 years, 44% women). In the GWAS comparing patients with NPH with the controls, we identified 6 gene regions significantly (p < 5.0e-8) associated with NPH that replicated in a meta-analysis with UKBB (NPH n = 173). The top loci near the following genes were rs7962263, SLCO1A2 (odds ratio [OR] 0.71, 95% CI 0.65-0.78, p = 1.0e-14); rs798495, AMZ1/GNA12 (OR 1.29, 95% CI 1.20-1.39, p = 2.9e-12); rs10828247, MLLT10 (OR 0.77, 95% CI 0.71-0.83, p = 1.5e-11); rs561699566 and rs371919113, CDCA2 (OR 0.76, 95% CI 0.70-0.82, p = 1.5e-11); rs56023709, C16orf95 (OR 1.24, 95% CI 1.16-1.33, p = 3.0e-9); and rs62434144, PLEKHG1 (OR 1.23, 95% CI 1.14-1.32, p = 1.4e-8). In the sensitivity analysis comparing only patients with iNPH (n = 1,055) with the controls (n = 451,091), 4 top loci near the following genes remained significant: rs7962263, SLCO1A2 (OR 0.70, 95% CI 0.63-0.78, p = 2.1e-11); rs10828247, MLLT10 (OR 0.74, 95% CI 0.62-0.82, p = 4.6e-10); rs798511, AMZ1/GNA12 (OR 1.28, 95% CI 1.17-1.39, p = 1.7e-8); and rs56023709, C16orf95 (OR 1.28, 95% CI 1.17-1.39, p = 1.7e-8). DISCUSSION: We identified 6 loci significantly associated with NPH in the thus far largest GWAS in chronic hydrocephalus. The genes near the top loci have previously been associated with blood-brain barrier and blood-CSF barrier function and with increased lateral brain ventricle volume. The effect sizes and allele frequencies remained similar in NPH and iNPH cohorts, indicating the identified loci are risk determinants for iNPH and likely not explained by associations with other etiologies. However, the exact role of these loci is still unknown, warranting further studies.

Endoscopic third ventriculostomy for adults with hydrocephalus: creating a prognostic model for success: protocol for a retrospective multicentre study (Nordic ETV).

INTRODUCTION: Endoscopic third ventriculostomy (ETV) is becoming an increasingly widespread treatment for hydrocephalus, but research is primarily based on paediatric populations. In 2009, Kulkarni et al created the ETV Success score to predict the outcome of ETV in children. The purpose of this study is to create a prognostic model to predict the success of ETV for adult patients with hydrocephalus. The ability to predict who will benefit from an ETV will allow better primary patient selection both for ETV and shunting. This would reduce additional second procedures due to primary treatment failure. A success score specific for adults could also be used as a communication tool to provide better information and guidance to patients. METHODS AND ANALYSIS: The study will adhere to the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis reporting guidelines and conducted as a retrospective chart review of all patients≥18 years of age treated with ETV at the participating centres between 1 January 2010 and 31 December 2018. Data collection is conducted locally in a standardised database. Univariate analysis will be used to identify several strong predictors to be included in a multivariate logistic regression model. The model will be validated using K-fold cross validation. Discrimination will be assessed using area under the receiver operating characteristic curve (AUROC) and calibration with calibration belt plots. ETHICS AND DISSEMINATION: The study is approved by appropriate ethics or patient safety boards in all participating countries. TRIAL REGISTRATION NUMBER: NCT04773938; Pre-results.

Occurrence, Risk Factors, and Time Trends for Late Reoperations due to Degenerative Cervical Spine Disease: A Finnish National Register Study of 19 377 Patients Operated on Between 1999 and 2015.

BACKGROUND: Surgery for degenerative cervical spine disease has escalated since the 1990s. Fusion has become the mainstay of surgery despite concerns regarding adjacent segment degeneration. The patient-specific trends in reoperations have not been studied previously. OBJECTIVE: To analyze the occurrence, risk factors, and trends in reoperations in a long-term follow-up of all the patients operated for degenerative cervical spine disease in Finland between 1999 and 2015. METHODS: The patients were retrospectively identified from the Hospital Discharge Registry. Reoperations were traced individually; only reoperations occurring >365 d after the primary operation were included. Time trends in reoperations and the risk factors were analyzed by regression analysis. RESULTS: Of the 19 377 identified patients, 9.2% underwent a late reoperation at a median of 3.6 yr after the primary operation. The annual risk of reoperation was 2.4% at 2 yr, 6.6% at 5 yr, 11.1% at 10 yr, and 14.2% at 15 yr. Seventy-five percent of the late reoperations occurred within 6.5 yr of the primary operation. Foraminal stenosis, the anterior cervical decompression and fusion (ACDF) technique, male gender, weak opiate use, and young age were the most important risk factors for reoperation. There was no increase in the risk of reoperations over the follow-up period. CONCLUSION: The risk of reoperation was stable between 1999 and 2015. The reoperation risk was highest during the first 6 postoperative years and then declined. Patients with foraminal stenosis had the highest risk of reoperation, especially when ACDF was performed.

Copy number loss in SFMBT1 is common among Finnish and Norwegian patients with iNPH.

OBJECTIVE: To evaluate the role of the copy number loss in SFMBT1 in a Caucasian population. METHODS: Five hundred sixty-seven Finnish and 377 Norwegian patients with idiopathic normal pressure hydrocephalus (iNPH) were genotyped and compared with 508 Finnish elderly, neurologically healthy controls. The copy number loss in intron 2 of SFMBT1 was determined using quantitative PCR. RESULTS: The copy number loss in intron 2 of SFMBT1 was detected in 10% of Finnish (odds ratio [OR] = 1.9, p = 0.0078) and in 21% of Norwegian (OR = 4.7, p < 0.0001) patients with iNPH compared with 5.4% in Finnish controls. No copy number gains in SFMBT1 were detected in patients with iNPH or healthy controls. The carrier status did not provide any prognostic value for the effect of shunt surgery in either population. Moreover, no difference was detected in the prevalence of hypertension or T2DM between SFMBT1 copy number loss carriers and noncarriers. CONCLUSIONS: This is the largest and the first multinational study reporting the increased prevalence of the copy number loss in intron 2 of SFMBT1 among patients with iNPH, providing further evidence of its role in iNPH. The pathogenic role still remains unclear, requiring further study.