Among the various disorders that manifest with gait disturbance, cognitive impairment, and urinary incontinence in the elderly population, idiopathic normal pressure hydrocephalus (iNPH) is becoming of great importance. The first edition of these guidelines for management of iNPH was published in 2004, and the second edition in 2012, to provide a series of timely, evidence-based recommendations related to iNPH. Since the last edition, clinical awareness of iNPH has risen dramatically, and clinical and basic research efforts on iNPH have increased significantly. This third edition of the guidelines was made to share these ideas with the international community and to promote international research on iNPH. The revision of the guidelines was undertaken by a multidisciplinary expert working group of the Japanese Society of Normal Pressure Hydrocephalus in conjunction with the Japanese Ministry of Health, Labour and Welfare research project. This revision proposes a new classification for NPH. The category of iNPH is clearly distinguished from NPH with congenital/developmental and acquired etiologies. Additionally, the essential role of disproportionately enlarged subarachnoid-space hydrocephalus (DESH) in the imaging diagnosis and decision for further management of iNPH is discussed in this edition. We created an algorithm for diagnosis and decision for shunt management. Diagnosis by biomarkers that distinguish prognosis has been also initiated. Therefore, diagnosis and treatment of iNPH have entered a new phase. We hope that this third edition of the guidelines will help patients, their families, and healthcare professionals involved in treating iNPH.

BACKGROUND AND PURPOSE: Despite the remarkable progress of 3D graphics technology, the Evans index has been the most popular index for ventricular enlargement. We investigated a novel reliable index for the MR imaging features specified in idiopathic normal pressure hydrocephalus, rather than the Evans index. MATERIALS AND METHODS: The patients with suspected idiopathic normal pressure hydrocephalus on the basis of the ventriculomegaly and a triad of symptoms underwent the CSF tap test. CSF volumes were extracted from a T2-weighted 3D spin-echo sequence named “sampling perfection with application-optimized contrasts by using different flip angle evolutions (SPACE)” on 3T MR imaging and were quantified semiautomatically. Subarachnoid spaces were divided as follows: upper and lower parts and 4 compartments of frontal convexity, parietal convexity, Sylvian fissure and basal cistern, and posterior fossa. The maximum length of 3 axial directions in the bilateral ventricles and their frontal horns was measured. The “z-Evans Index” was defined as the maximum z-axial length of the frontal horns to the maximum cranial z-axial length. These parameters were evaluated for the predictive accuracy for the tap-positive groups compared with the tap-negative groups and age-adjusted odds ratios at the optimal thresholds. RESULTS: In this study, 24 patients with tap-positive idiopathic normal pressure hydrocephalus, 25 patients without response to the tap test, and 23 age-matched controls were included. The frontal horns of the bilateral ventricles were expanded, with the most excessive expansion being toward the z-direction. The CSF volume of the parietal convexity had the highest area under the receiver operating characteristic curve (0.768), the z-Evans Index was the second (0.758), and the upper-to-lower subarachnoid space ratio index was the third (0.723), to discriminate the tap-test response. CONCLUSIONS: The CSF volume of the parietal convexity of <38 mL, upper-to-lower subarachnoid space ratio of 0.42 were newly proposed useful indices for the idiopathic normal pressure hydrocephalus diagnosis, an alternative to the Evans Index.

To elucidate the prognostic role of ¹³¹I radioactive iodine therapy (RIT), we conducted a retrospective cohort study analyzing the clinical factors that affect survival of postoperative patients with differentiated thyroid carcinoma (DTC). Methods: We included 198 DTC patients with extrathyroidal extension who received total or near-total thyroidectomy and then RIT in our hospital from January 1997 to June 2009: patients with lymph node metastases only (n = 47), lung metastases without bone metastases (n = 105), or bone metastases and other distant metastases (lung, liver, brain, and skin) (n = 46). Hemithyroidectomy or subtotal thyroidectomy had been performed before total or near-total thyroidectomy in 59 patients. Disease-specific survival after initial RIT was statistically evaluated using relevant clinical parameters, including age at initial RIT, pathology, sex, therapeutic history before initial RIT, pre- and posttherapeutic serum thyroglobulin (“prethyroglobulin” and “postthyroglobulin,” respectively) at initial RIT, thyroglobulin under thyroid-stimulating hormone stimulation at initial RIT (“peak thyroglobulin”), grade of uptake at scintigraphy, extent of metastasis, and number of total RITs. Results: During follow-up after initial RIT (average, 5.37 y), 24 patients died from DTC (11 male patients and 13 female). The most common reasons for death were respiratory failure due to lung metastases (n = 11) and uncontrollable brain metastases (n = 6). Univariate analysis showed that disease-specific survival was related to the following factors: extent of metastasis, age at initial RIT (<45 y), prethyroglobulin (<125 ng/mL), peak thyroglobulin (<1,000 ng/mL), and interval from total thyroidectomy to initial RIT (<180 d). A past history of hemithyroidectomy or subtotal thyroidectomy was not related to disease-specific survival. Multivariate analysis showed 3 factors to be independent prognostic factors—grade of ¹³¹I uptake at whole-body scintigraphy, extent of metastasis, and interval to RIT (P ≤ 0.001, 0.010, and 0.005, respectively)—and also showed that risk of death in patients with an interval over 180 d was 4.22 times higher than in those with an interval within 180 d. Kaplan–Meier analysis revealed that a shorter interval (180, 365, or 1,000 d) had prognostic value even in the subgroups 45 y or older, with lung metastases, and with bone metastases or more. Conclusion: The present study suggests that delaying initial RIT until more than 180 d after total thyroidectomy may result in poor survival for DTC patients.

Background— Genetic factors have an important role in the pathogenesis of intracranial aneurysm (IA). The results of previous studies have suggested several loci. Methods and Results— From 29 IA families with ≥3 individuals affected by IA, we used nonparametric (model-free) methods for linkage analyses, using GENEHUNTER and Merlin software. Genome-wide linkage analyses revealed 3 regions on chromosomes 17cen (maximum nonparametric logarithm of the odds score [MNS] = 3.00, nominal P =0.001), 19q13 (MNS=2.15, nominal P =0.020), and Xp22 (MNS=2.16, nominal P =0.019). We tested 4 candidate genes in these regions: the microfibril-associated protein 4 gene ( MFAP4 ) and the promoter polymorphism of the inducible nitric oxide synthase gene ( NOS2A ) on chromosome 17cen, the epsilon genotypes of the apolipoprotein E gene ( APOE ) on chromosome 19q13, and the angiotensin I converting enzyme 2 gene ( ACE2 ) on chromosome Xp22. Associations of their polymorphisms with IA were evaluated by a case-control study (100 cases: 29 probands from IA families and 71 unrelated subjects with IAs, 100 unrelated control subjects [unaffected members with IAs and absence of family history of IAs]). However, the case-control study showed that none of the polymorphisms of the examined genes had associations with IA. Conclusions— A genome-wide scan in 29 Japanese families with a high degree of familial clustering revealed 1 suggestive linkage region on chromosome 17cen and 2 potentially interesting regions on chromosomes 19q13 and Xp22. These regions were consistent with previous findings in various populations.

BACKGROUND AND PURPOSE: CSF volumes in the basal cistern and Sylvian fissure are increased in both idiopathic normal pressure hydrocephalus and Alzheimer disease, though the differences in these volumes in idiopathic normal pressure hydrocephalus and Alzheimer disease have not been well-described. Using CSF segmentation and volume quantification, we compared the distribution of CSF in idiopathic normal pressure hydrocephalus and Alzheimer disease. MATERIALS AND METHODS: CSF volumes were extracted from T2-weighted 3D spin-echo sequences on 3T MR imaging and quantified semi-automatically. We compared the volumes and ratios of the ventricles and subarachnoid spaces after classification in 30 patients diagnosed with idiopathic normal pressure hydrocephalus, 10 with concurrent idiopathic normal pressure hydrocephalus and Alzheimer disease, 18 with Alzheimer disease, and 26 control subjects 60 years of age or older. RESULTS: Brain to ventricle ratios at the anterior and posterior commissure levels and 3D volumetric convexity cistern to ventricle ratios were useful indices for the differential diagnosis of idiopathic normal pressure hydrocephalus or idiopathic normal pressure hydrocephalus with Alzheimer disease from Alzheimer disease, similar to the z-Evans index and callosal angle. The most distinctive characteristics of the CSF distribution in idiopathic normal pressure hydrocephalus were small convexity subarachnoid spaces and the large volume of the basal cistern and Sylvian fissure. The distribution of the subarachnoid spaces in the idiopathic normal pressure hydrocephalus with Alzheimer disease group was the most deformed among these 3 groups, though the mean ventricular volume of the idiopathic normal pressure hydrocephalus with Alzheimer disease group was intermediate between that of the idiopathic normal pressure hydrocephalus and Alzheimer disease groups. CONCLUSIONS: The z-axial expansion of the lateral ventricle and compression of the brain just above the ventricle were the common findings in the parameters for differentiating idiopathic normal pressure hydrocephalus from Alzheimer disease.

Background and Purpose— The present study aimed to identify risk factors for mortality due to subarachnoid hemorrhage (SAH) using a comprehensive questionnaire from the Japan Collaborative Cohort (JACC) Study, a Japan-wide population-based prospective study. Methods— A total of 109 293 individuals (45 551 men and 63 742 women, aged 40 to 79 years) free of stroke at entry participated in the JACC Study between 1988 and 1990. Participants were followed up annually until they died or moved away from the surveyed community, or until the end of 1999. A diagnosis of death from SAH was based on the International Classification of Diseases , 10th revision (ICD-10). The age-adjusted univariate and multivariate hazard ratios (HR) and 95% confidence intervals (CI) of various factors were calculated in sex-stratified and sex-specific analyses using the Cox proportional hazards regression model. Results— A total of 244 individuals (88 men and 156 women) died from SAH during the follow-up of 1 086 963 person-years. Our univariate analyses confirmed that preference for salty foods and history of blood transfusion, as well as hypertension, family history of stroke, cigarette smoking, heavy alcohol consumption, and low BMI, had statistically significant associations with mortality due to SAH. Multivariable analyses revealed that history of blood transfusion was an independent significant risk factor (HR=4.2 [95%CI, 2.1 to 8.5]) for men, while preference for salty foods or heavy drinking were not. Conclusions— History of blood transfusion was found to be an independent risk. The association between SAH and blood transfusion warranted further study.