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.

Traumatic cervical spinal cord injury: Comparison of two different blood pressure targets on neurological recovery.

BACKGROUND: Controversy exists whether blood pressure augmentation therapy benefits patients suffering from spinal cord injury (SCI). This retrospective comparative study was designed to assess the impact of two different mean arterial pressure (MAP) targets (85-90 mmHg vs. 65-85 mmHg) on neurological recovery after traumatic cervical SCI. METHODS: Fifty-one adult patients with traumatic cervical SCI were retrospectively divided into two groups according to their intensive care unit (ICU) MAP targets: 85-90 mmHg (higher MAP group, n = 32) and 65-85 mmHg (lower MAP group, n = 19). Invasive MAP measurements were stored as 2-min median values for 3-7 days. The severity of SCI (AIS grade and neurological level) was evaluated upon ICU stay and during rehabilitation. Neurological recovery was correlated with individual mean MAP values and with the proportion of MAP values ≥85 mmHg upon the first 3 days (3d-MAP%≥85 ). RESULTS: The initial AIS grades were A 29.4%, B 17.6%, C 31.4%, and D 21.6%. AIS grade improved in 24 patients (47.1%). During ICU care, 82.0% and 36.8% of the measured MAP values reached ≥85 mmHg in the higher and the lower MAP groups, respectively (p < .001). The medians of individual mean MAP values were different between the groups (90.2 mmHg vs. 81.4 mmHg, p < .001). Similarly, 3d-MAP%≥85 was higher in the higher MAP group (85.6% vs. 50.0%, p < .001). However, neurological recovery was not different between the groups, nor did it correlate with individual mean MAP values or 3d-MAP%≥85 . CONCLUSION: The currently recommended MAP target of 85-90 mmHg was not associated with improved outcomes compared to a lower target in patients with traumatic cervical SCI in this cohort.

Stability of infundibular dilatations: a single center follow-up study and systematic review of the literature.

PURPOSE: Although infundibular dilatations (IDs) have been thought to be benign anatomical variants, case reports suggest that they can grow and rupture. The aim of this study was to determine whether IDs have a tendency to grow or rupture. METHODS: The study population was collected from the Tampere University Hospital (TAUH) Aneurysm Database. The presence of IDs was screened from the medical records and imaging studies of 356 intracranial aneurysm patients left to follow-up from 2005 to 2020. The imaging studies were reviewed to confirm the IDs, and their clinical course. Finally, we performed a systematic review of published cases of ID leading to aneurysmatic rupture from PubMed. RESULTS: We found 97 typical IDs in 83 patients and 9 preaneurysmal lesions resembling ID in 9 patients. Out of the typical cone-shaped IDs, none grew or ruptured in a total follow-up of 409 patient-years. One preaneurysmal lesion ruptured during a follow-up: this lesion had components of both infundibular dilatation and aneurysm at the beginning of follow-up. In the systematic literature search, we found 20 cases of aneurysmatic SAHs originating from an ID. Of those, only 7 had imaging available prerupture. All 7 IDs were typically cone-shaped, but a branching vessel originating from the apex of ID was only seen in 4/7. CONCLUSION: Typical infundibular dilatations seem to be benign anatomical variants that are stable and, thus, do not need prophylactic treatment or imaging follow-up. Likely, the SAHs reported from IDs were actually caused by misdiagnosed preaneurysmal lesions.