Asymptomatic Ventriculomegaly Research Articles

Epidemiology, Natural History, and Genetic Factors of Idiopathic Normal Pressure Hydrocephalus

According to a cohort study in a Japanese rural area, the prevalence of idiopathic normal pressure hydrocephalus (iNPH) in the 80s was 7.7% among the older inhabitants, despite only a small percentage of the population seeking consultation. The 16-year observation of the cohort revealed that people were in the state of asymptomatic ventriculomegaly with features of iNPH on magnetic resonance imaging or asymptomatic ventricular enlargement several years before presenting symptoms and intracranial changes of iNPH. SFMBT1 was found to be a risk gene for iNPH, and investigating these risk genes will further the study of iNPH pathophysiology.

Prevalence and development of idiopathic normal pressure hydrocephalus: A 16-year longitudinal study in Japan.

We previously investigated the preclinical state of idiopathic normal pressure hydrocephalus (iNPH): asymptomatic ventriculomegaly with features of iNPH on magnetic resonance imaging (AVIM) found in community inhabitants. The aim of the study was to determine how iNPH develops longitudinally. A previous longitudinal prospective community-based cohort study was initiated in 2000. The 271 70year-old participants were followed up in 2016 at the age of 86 years. At this time, 104 participants could be reached for clinical examinations and brain magnetic resonance imaging (MRI). iNPH in this study was diagnosed if the participant had more than one symptom in the clinical triad and disproportionately enlarged subarachnoid space hydrocephalus (DESH) on MRI, fulfilling at least an Evans index >0.3 (ventricular enlargement, VE) and a narrowing of the subarachnoid space at the high convexity (tight high convexity, THC). Asymptomatic VE (AVE) plus THC were considered AVIM. Longitudinally throughout 16 years, 11 patients with iNPH were found. The hospital consultation rate was only 9%. Five of the eight patients with AVIM (62.5%) and six of 30 with AVE (20.0%) developed iNPH. Cross-sectionally, eight patients had iNPH (8/104, 7.7% prevalence at the age of 86) in 2016. Disease development was classified into THC-preceding and VE-preceding iNPH. One VE-preceding iNPH case was considered a comorbidity of Alzheimer's dementia. Idiopathic normal pressure hydrocephalus had a high prevalence among octogenarians in the evaluated community. iNPH developed not only via AVIM but also via AVE, the latter was also frequent in the elderly.

Epidemiology of Idiopathic Normal Pressure Hydrocephalus and Hereditary Hydrocephalus

Several cohort studies in Japan have revealed that the prevalence of idiopathic normal pressure hydrocephalus(iNPH)is around 1.6% among the elderly population(≧ 50 years old). The incidence of iNPH from the Yamagata(Takahata)cohort was 1.2/ 1,000 person-years in the elderly population. Although the Japanese guidelines for iNPH clearly describe the definition of "possible iNPH with MRI support," it is still difficult to find out not only patients with iNPH but also individuals in its preclinical stage with radiological findings of asymptomatic ventriculomegaly with features of iNPH on MRI(AVIM)or asymptomatic ventricular enlargement(AVE). It is assumed that only less than 10% of patients with iNPH were referred to hospitals in Japan. Several genes associated with congenital hydrocephalus have been found, including ciliopathy-related genes that directly affect the ependymal cilia in ventricles. Loss of the copy number of SFMBT1 was found to be a risk factor for iNPH. Knowledge about risk genes and their mechanisms in congenital and familial NPH may be a clue for the further understanding of the pathophysiology of iNPH.

Ventricular size determination and management of ventriculomegaly and hydrocephalus in patients with diffuse intrinsic pontine glioma: an institutional experience.

There is no consensus on the optimal clinical management of ventriculomegaly and hydrocephalus in patients with diffuse intrinsic pontine glioma (DIPG). To date, the impact on survival in patients with ventriculomegaly and CSF diversion for hydrocephalus in this population remains to be elucidated. Herein, the authors describe their institutional experience. Patients diagnosed with DIPG and treated with up-front radiation therapy (RT) at The Hospital for Sick Children between 2000 and 2019 were identified. Images at diagnosis and progression were used to determine the frontal/occipital horn ratio (FOR) as a method to measure ventricular size. Patients with ventriculomegaly (FOR ≥ 0.36) were stratified according to the presence of symptoms and categorized as follows: 1) asymptomatic ventriculomegaly and 2) symptomatic hydrocephalus. For patients with ventriculomegaly who did not require CSF diversion, post-RT imaging was also evaluated to assess changes in the FOR after RT. Proportional hazards analyses were used to identify clinical and treatment factors correlated with survival. The Kaplan-Meier method was used to perform survival estimates, and the log-rank method was used to identify survival differences between groups. Eighty-two patients met the inclusion criteria. At diagnosis, 28% (n = 23) of patients presented with ventriculomegaly, including 8 patients who had symptomatic hydrocephalus and underwent CSF diversion. A ventriculoperitoneal shunt was placed in the majority of patients (6/8). Fifteen asymptomatic patients were managed without CSF diversion. Six patients had resolution of ventriculomegaly after RT. Of 66 patients with imaging at the time of progression, 36 (55%) had ventriculomegaly, and 9 of them required CSF diversion. The presence of ventriculomegaly at diagnosis did not correlate with survival on univariate analysis. However, patients with symptomatic hydrocephalus at the time of progression who underwent CSF diversion had a survival advantage (p = 0.0340) when compared to patients with ventriculomegaly managed with conservative approaches. Although ventriculomegaly can be present in up to 55% of patients with DIPG, the majority of patients present with asymptomatic ventriculomegaly and do not require surgical interventions. In some cases ventriculomegaly improved after medical management with steroids and RT. CSF diversion for hydrocephalus at the time of diagnosis does not impact survival. In contrast, our results suggest a survival advantage in patients who undergo CSF diversion for hydrocephalus at the time of progression, albeit that advantage is likely to be confounded by biological and individual patient factors. Further research in this area is needed to understand the best timing and type of interventions in this population.

A multi-center, prospective study on the progression rate of asymptomatic ventriculomegaly with features of idiopathic normal pressure hydrocephalus on magnetic resonance imaging to idiopathic normal pressure hydrocephalus

IntroductionOur previous community-based study demonstrated that some individuals with AVIM [asymptomatic ventriculomegaly with features of idiopathic normal pressure hydrocephalus (iNPH) on magnetic resonance imaging (MRI)] progressed to iNPH in several years. In this hospital-based study, we investigated the progression rate from AVIM to iNPH and its possible predictors. MethodsWe conducted a prospective study of participants with AVIM from several medical institutions/hospitals in Japan. AVIM is defined as “asymptomatic ventriculomegaly with features of iNPH on MRI”; in the present study, asymptomatic was defined as “0 (no symptoms) or 1 (presence of only subjective, but not objective, symptoms) on the iNPH Grading Scale (iNPH-GS).” We also measured possible predicting factors for AVIM-to-iNPH progression, including age, sex, body weight, blood pressure, diabetes mellitus, dyslipidemia, history of mental disease/head injury/sinusitis/smoking/alcohol-intake, Evans index, and the presence of DESH (disproportionately enlarged subarachnoid-space hydrocephalus) findings on brain MRI, and analyzed these potential predictive values. ResultsIn 2012, 93 participants with AVIM were registered and enrolled in the study. Of these, 52 participants were able to be tracked for three years (until 2015). Of the 52 participants, 27 (52%) developed iNPH during the follow-up period (11 definite, 6 probable, and 10 possible iNPH), whereas 25 participants remained asymptomatic in 2015. Among the possible predictive factors examined, the baseline scores of iNPH-GS predicted the AVIM-to-iNPH progression. ConclusionsThe multicenter prospective study demonstrated that the progression rate from AVIM to iNPH was ~17% per year, and the baseline scores of iNPH-GS predicted the AVIM-to-iNPH progression.

Association between the Onset of Idiopathic Normal Pressure Hydrocephalus Symptoms and Reduced Default Mode Network Connectivity

Objective: The aim was to examine the association between connectivity changes in the default mode network (DMN) and the progression of idiopathic normal pressure hydrocephalus (iNPH). Methods: We retrospectively recruited cases of preclinical and clinical iNPH from 2,196 patients who had received whole-body ¹⁸F-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) scanning. We included 31 cases with asymptomatic ventriculomegaly with features of iNPH on MRI (AVIM; reported as preclinical iNPH) and 12 with iNPH. We performed a voxel-based analysis of the brain FDG-PET images of the AVIM and iNPH groups as well as for each background-matched normal control (NC) group, using Statistical Parametric Mapping 12. Volume of interest (VOI)-based analysis was also performed. We set the VOI as the region from the precuneus to the posterior cingulate cortices (PCC), and compared the mean regional standardized uptake value ratio (SUVR) between the AVIM and iNPH group FDG-PET/CT images and each corresponding NC group. Results: The voxel-based analysis showed a greater decreased FDG uptake in the PCC in the iNPH group than in the AVIM group. The VOI-based analysis revealed no significant difference in the mean SUVR of the AVIM group and the corresponding NC group, but that of the iNPH group was significantly lower than that of its corresponding NC group. Conclusions: DMN connectivity was reduced in the clinical iNPH group but not in the preclinical group. These data suggest that alterations in the functional connectivity of the DMN are related to the onset of iNPH symptoms.

Changes in cerebral glucose metabolism caused by morphologic features of prodromal idiopathic normal pressure hydrocephalus

BackgroundDecreased cerebral glucose metabolism has been reported in idiopathic normal pressure hydrocephalus (iNPH). However, the timing of appearance in the preclinical stage of iNPH remains unknown. Herein, we evaluated the changes in regional cerebral glucose metabolism with respect to the characteristic morphologic features of iNPH.MethodsWe performed a cross-sectional study in > 2000 elderly patients who received a whole body 18F-fluorodeoxyglucose-positron emission tomography/computed tomography scanning and recruited subjects with clinical and preclinical iNPH. We included 12 subjects with iNPH, 32 subjects with asymptomatic ventriculomegaly with features of iNPH on magnetic resonance imaging (AVIM), and 33 subjects with preclinical morphologic features of DESH (PMD). We previously reported that iNPH develops in the order of PMD (asymptomatic subjects with incomplete DESH), AVIM (asymptomatic subjects with DESH), and iNPH (symptomatic subjects with DESH). We measured the median regional standardized uptake value ratio (SUVR) on 18F-fluorodeoxyglucose-positron emission tomography/computed tomography images between the three groups and compared them with background-matched normal controls in the frontal lobes, temporal lobes, medial parietal lobes, striata, and thalami.ResultsIn the frontal and temporal lobes, the SUVR distributions of the PMD, AVIM, and PMD groups were significantly lower than for each NC (p < 0.05 for all). In the medial parietal lobes, the SUVR distributions were significantly higher in PMD and AVIM groups (p < 0.05 for all). In the thalami and striata, the SUVR distributions were significantly lower in the iNPH group (p < 0.05 for all).ConclusionsChanges in brain glucose metabolism in the cortices are observed in preclinical iNPH, while metabolic decline in the basal ganglia is only detected in clinical iNPH.

The Conundrum of Ventricular Dilatations Following Decompressive Craniectomy: Is Ventriculoperitoneal Shunt, The Only Panacea?

Introduction:Ventriculomegaly and hydrocephalus (HCP) are sometimes a bewildering sequela of decompressive craniectomy (DC). The distinguishing criteria between both are less well defined. Majority of the studies quoted in the literature have defined HCP radiologically, rather than considering the clinical status of the patient. Accordingly, these patients have been treated with permanent cerebrospinal fluid (CSF) diversion procedures. We hypothesize that asymptomatic ventriculomegaly following DC should undergo aspiration with cranioplasty and be followed up regularly.Materials and Methods:All patients with post-DC who were scheduled for cranioplasty and satisfied the radiological criteria for HCP were included. These patients were categorized into two groups. Group 1 included ventriculomegaly with clinical signs attributable to HCP and Group 2 constituted ventriculomegaly but no clinical signs attributable to HCP. All patients in Group 1 underwent ventriculoperitoneal shunt followed by cranioplasty, whereas all patients in Group 2 underwent cranioplasty along with simultaneous ventriculostomy and temporary aspiration of the lateral ventricle. All patients were regularly followed as the outpatient basis.Results:There were 21 patients who developed ventriculomegaly following DC. There were 10 patients in Group 1 and 11 patients in Group 2. The average duration of follow-up was from 6 months to 2 years. Two patients in the shunt group - (group 1) had over drainage and required revision. One patient in aspiration group - (group 2) required permanent CSF diversion.Conclusions:Cranioplasty with aspiration is a viable option in selected group of patients in whom there is ventriculomegaly but no signs or symptoms attributable to HCP.

A hospital-based prospective study on the frequency of developing iNPH among those with asymptomatic ventriculomegaly with features of iNPH on MRI (AVIM)

Background: How many subjects with asymptomatic ventriculomegaly with features of iNPH on MRI (AVIM) eventually develop iNPH and what predicts that development are unclear.

Incidence of idiopathic normal pressure hydrocephalus (iNPH): A 10-year follow-up study of a rural community in Japan

BackgroundThe epidemiology and pathophysiology of iNPH remain unclear. We aimed to investigate the incidence of iNPH in elderly inhabitants of the community, and to identify how ventriculomegaly develops on brain MRIs and how symptoms develop in iNPH patients. MethodsIn 2000, 350 inhabitants, all 70-year-olds living in the community of Takahata in Japan, were asked to participate in a survey that included a questionnaire, physical examinations, cognitive screenings, and brain MRI studies. Using brain MRI as a screening, we defined having both Evans index of >0.3 and a narrow subarachnoid space and cortical sulci at high convexity (tight high convexity, THC) as suspicious findings for iNPH. Among the subjects who showed the iNPH feature on brain MRI, those who had gait disturbance and/or dementia were defined as possible iNPH. Twice during the 10years, we administered the same check-up. ResultsIn the first survey, 271 inhabitants participated. During the 10years, three new possible iNPH patients were found. The incidence of iNPH above 70years old was estimated at 1.2/1000 persons per year. The iNPH patients developed their symptoms and brain MRI findings as follows; first, only THC without ventriculomegaly was observed on their brain MRIs, next, asymptomatic ventriculomegaly with features of iNPH on brain MRIs (AVIM) was seen, and then a final expression of symptoms of iNPH was shown. ConclusionsThe estimated incidence of iNPH in a community was higher than those estimated by previous studies where they collected patients at hospitals. There were subclinical or preclinical states before the development of iNPH.

Subclinical Declines in the Verbal Fluency and Motor Regulation of Patients with AVIM (Asymptomatic Ventriculomegaly with Features of Idiopathic NPH on MRI): A Case-controlled Study

We previously reported that, on brain MRI, iNPH features were observed in approximately 1% of asymptomatic elderly community dwellers. This phenomenon is designated asymptomatic ventriculomegaly with features of iNPH on MRI (AVIM). The aim of the present study was to clarify whether a subclinical decline in the neuropsychological function is present in patients with AVIM. We examined eight subjects with AVIM, six subjects with possible iNPH and 21 elderly controls. Neuropsychological tests were used, including the mini-mental state examination (MMSE), the Hasegawa dementia scale-revised (HDS-R), the frontal assessment battery (FAB), the trail making test A&B and semantic and letter verbal fluency tests. When comparing the individuals with AVIM with the control subjects, significant differences were found in the scores achieved on the semantic verbal fluency tests and Luria's motor series (fist-edge-palm), a subtest of the FAB. The present study suggests that individuals with AVIM demonstrate a slight subclinical decline in the cognitive function and motor regulation, which may represent a prodromal stage of iNPH.

INPH (Idiopathic normal pressure hydrocephalus) and AVIM (asymptomatic ventriculomegaly with features of iNPH on MRI)

We investigated if there are individuals at a preclinical stage of idiopathic normal pressure hydrocephalus (iNPH) in a general population. All the residents aged 61 years and 70-72 years in the two communities of Japan (n=1142) were requested to take brain MRI examination. 790 residents (69.2%) participated in this study. Among them, 51 individuals (6.46%) had the enlarged ventricles (Evans index of >0.3), 12 (1.52%) of which showed the iNPH features on MRI. Of the 12 individuals, 8 were asymptomatic, while 4 had gait disturbance and/or dementia (possible iNPH). During a follow-up period of 4-8 years, two of the 8 asymptomatic subjects developed dementia and/or gait disturbance. The prevalence of possible iNPH was 0.51% (4/790) among Japanese elderly (>61 years of age). Asymptomatic ventriculomegaly with the iNPH features on MRI (AVIM) may represent a preclinical stage of iNPH. To identify a possible genetic change of AVIM and possible iNPH, we performed a genome-wide screening for copy number variations (CNV), and found that a segmental copy number loss of the SFMBT1 gene may be a genetic risk for the disease.

Asymptomatic ventriculomegaly with features of idiopathic normal pressure hydrocephalus on MRI (AVIM) in the elderly: A prospective study in a Japanese population

We investigated if there are individuals at a preclinical stage of idiopathic normal pressure hydrocephalus (iNPH) in a general population. All the residents (n=1142) aged 61 years (n=306, men/women=156/150) and 70–72 years (n=836, men/women=356/480) in the two communities of Japan were requested to take brain MRI examination. The “iNPH features on MRI” were defined as an Evans index of >0.3 and a narrowing of the subarachnoid space and cortical sulci at the high convexity of the cerebrum. “Possible iNPH” was defined as the presence of one or more symptoms of iNPH, together with such MRI features. 790 (69.2%) of the 1142 residents participated in this study. Among them, 51 individuals (men/women=35/16) (6.46%) had the enlarged ventricles (Evans index of >0.3), 12 (men/women=7/5) (1.52%) of which showed the iNPH features on MRI. Of the 12 individuals, 8 (men/women=4/4) (1.01%) were asymptomatic, while 4 (men/woman=3/1) (0.51%) had gait disturbance and/or dementia (possible iNPH). During a follow-up period of 4–8 years, two of the 8 asymptomatic subjects developed dementia and/or gait disturbance with worsening of ventriculomegaly on brain MRI in one case. The prevalence of possible iNPH was 0.51% (4/790) among Japanese elderly (>61 years of age). Asymptomatic ventriculomegaly with the iNPH features on MRI (AVIM) may represent a preclinical stage of iNPH.

Occult Hydrocephalus in Children with Cerebral Palsy

Many children with cerebral palsy have chronic ventriculomegaly as a consequence of perinatal intraventricular hemorrhage or periventricular leukomalacia, without symptoms of hydrocephalus. Children with cerebral palsy who are treated with intrathecal baclofen have a higher rate of cerebrospinal fluid (CSF) leaks along the baclofen catheter than do adults treated with intrathecal baclofen. We postulated that the cause of the increased frequency of CSF leaks was increased CSF pressure, that is, occult hydrocephalus. Lumbar punctures were performed in 24 children with cerebral palsy and asymptomatic ventriculomegaly. Their median age was 4.7 years. Mild or moderate ventriculomegaly was present in 23 children and severe ventriculomegaly was present in 1 child. Opening pressures were abnormally high in 23 (96%) of 24 children and ranged from 22 to 41 cm H2O (mean, 27.3 cm H2O). Opening pressures did not correlate with the extent of ventriculomegaly. Children with cerebral palsy and ventriculomegaly seem to have a high incidence of increased CSF pressure, and thus, of occult hydrocephalus. The increased pressure is probably a significant cause of the increased frequency of CSF leaks for these children during intrathecal baclofen therapy. The long-term risks of untreated increased CSF pressures in this patient population are not known but are cause for concern. Treatment with CSF shunts offers the potential of improved development, which was reported anecdotally in some children who were treated with ventriculoperitoneal shunts after their pressure was found to be increased. Prospective multicenter studies of this problem are needed.