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Case 1: DESH misinterpreted as cortical atrophy. (a) Axial FLAIR MRI demonstrating ventriculomegaly (Evan's index of 0.35) and sulcal dilation. Lines indicate the measurements for Evan's index -the maximum width of the frontal horns of the lateral ventricles divided by the maximum diameter of the inner skull wall at that same level (>0.30 is considered ventriculomegaly). (b) Post-contrast coronal FLAIR MRI demonstrating ventriculomegaly, sulcal dilation ("atrophy") and tightening in the posterior convexity.
Source publication
Disproportionately enlarged subarachnoid-space hydrocephalus (DESH), a feature of normal pressure hydrocephalus (NPH), is often misinterpreted as cortical atrophy. We report a 67-year-old man with features of NPH but not diagnosed because radiographic findings were interpreted as cortical atrophy. Autopsy showed findings consistent with NPH and no...
Contexts in source publication
Context 1
... revealed ventriculomegaly, with an Evan's index of 0.35 (Figure 1(a)). Sulcal dilation was observed predominately on the medial frontal surface and superior parietal lobe (Figure 1(a,b)), which was interpreted as cortical atrophy. ...
Context 2
... revealed ventriculomegaly, with an Evan's index of 0.35 (Figure 1(a)). Sulcal dilation was observed predominately on the medial frontal surface and superior parietal lobe (Figure 1(a,b)), which was interpreted as cortical atrophy. Tight sulci at the convexity of the posterior parietal and occipital lobes were present (Figure 1(b)). ...
Context 3
... dilation was observed predominately on the medial frontal surface and superior parietal lobe (Figure 1(a,b)), which was interpreted as cortical atrophy. Tight sulci at the convexity of the posterior parietal and occipital lobes were present (Figure 1(b)). MRI of the spine revealed stenosis at the boundary of L4 and L5, but the spinal cord was unaffected. ...
Citations
... The potential role of a loss-of-function variant in CFAP43 (recently described in a Japanese kindred of familial iNPH and confirmed by a knocked out mouse model) in the aetiology of "sporadic" iNPH is currently uncertain (31). Post mortem studies do not go beyond case series and "definite" iNPH, pathological findings remain non-specific (32,33). There is controversy over whether pathological findings of AD, CVD, LBD and PSP, represent co-morbidity (17), wrong diagnosis (34)(35)(36) or even subtype (26). ...
This mini-review focuses on cognitive impairment in iNPH. This symptom is one of the characteristic triad of symptoms in a condition long considered to be the only treatable dementia. We present an update on recent developments in clinical, neuropsychological, neuroimaging and biomarker aspects. Significant advances in our understanding have been made, notably regarding biomarkers, but iNPH remains a difficult diagnosis. Stronger evidence for permanent surgical treatment is emerging but selection for treatment remains challenging, particularly with regards to cognitive presentations. Encouragingly, there has been increasing interest in iNPH, but more research is required to better define the underlying pathology and delineate it from overlapping conditions, in order to inform best practise for the clinician managing the cognitively impaired patient. In the meantime, we strongly encourage a multidisciplinary approach and a structured service pathway to maximise patient benefit.
... The distinction between iNPH and hydrocephalus ex vacuo caused by encephalic volume loss may be strictly challenging [14,21]. To resolve this problem and determine the shunt responsiveness in patients with suspicion of iNPH, multiple imaging studies have remarked on the importance of DESH in association with iNPH pathophysiology [10,22,23]. In a recent study by Shinoda [10]. ...
Background:
The occurrence of neurodegenerative disease in patients with normal pressure hydrocephalus (NPH) is emphasized in recent reports. Based on this common co-occurrence, some of the hydrocephalic disorders appearing in late adulthood have been hypothesized to result from initially unapparent parenchymal abnormalities of neurodegenerative origin. Among these diseases, progressive supranuclear palsy (PSP) has been specifically remarked on. We aimed to comparatively investigate the neuroimaging clues of iNPH in our PSP subjects.
Methods:
Eighteen patients with a clinical diagnosis of PSP, 44 with Parkinson's disease (PD), and 44 healthy control (HC) individuals were enrolled. The disproportionately enlarged subarachnoid space hydrocephalus (DESH) score, the Evans' index (EI), and the callosal angle (CA) were measured on the conventional magnetic resonance imaging (MRI). The comparative analyses were performed using IBM SPSS Statistics 26.
Results:
We found that dilated Sylvian fissures score (p = 0.016) and focal sulcal dilatation score (p = 0.037) were higher in the PSP group in comparison to HC whereas the CA score was higher in PSP subjects in comparison to both PD patients and HC (p = 0.000). Remarkably, the DESH score was also found to be higher in the PSP group in comparison to the age-matched HC group (p = 0.024).
Conclusions:
We found that the NPH-like MRI features were more common in PSP subjects in comparison to PD subjects and age-matched HC. These results may provide critical contributions to the literature regarding the overlap between PSP and NPH.
... The enlarged intra-and extraventricular CSF spaces and compression of the cortex in patients with iNPH and DESH may be misinterpreted as atrophy and has been termed "pseudoatrophy." 20 In this study, we showed that these findings are, at least in part, reversed after CSF diversion. Of note, neither DESH nor HCTS was required for inclusion in this study, nor is it required for a diagnosis of iNPH and shunt placement, but HCTS was present in all except 2 patients. ...
Background and purpose:
While changes in ventricular and extraventricular CSF spaces have been studied following shunt placement in patients with idiopathic normal pressure hydrocephalus, regional changes in cortical volumes have not. These changes are important to better inform disease pathophysiology and evaluation for copathology. The purpose of this work is to investigate changes in ventricular and cortical volumes in patients with idiopathic normal pressure hydrocephalus following ventriculoperitoneal shunt placement.
Materials and methods:
This is a retrospective cohort study of patients with idiopathic normal pressure hydrocephalus who underwent 3D T1-weighted MR imaging before and after ventriculoperitoneal shunt placement. Images were analyzed using tensor-based morphometry with symmetric normalization to determine the percentage change in ventricular and regional cortical volumes. Ventricular volume changes were assessed using the Wilcoxon signed rank test, and cortical volume changes, using a linear mixed-effects model (P < .05).
Results:
The study included 22 patients (5 women/17 men; mean age, 73 [SD, 6] years). Ventricular volume decreased after shunt placement with a mean change of -15.4% (P < .001). Measured cortical volume across all participants and cortical ROIs showed a mean percentage increase of 1.4% (P < .001). ROIs near the vertex showed the greatest percentage increase in volume after shunt placement, with smaller decreases in volume in the medial temporal lobes.
Conclusions:
Overall, cortical volumes mildly increased after shunt placement in patients with idiopathic normal pressure hydrocephalus with the greatest increases in regions near the vertex, indicating postshunt decompression of the cortex and sulci. Ventricular volumes showed an expected decrease after shunt placement.
... However, such neuropathological confirmation of "definite" iNPH is rarely achieved. 13 AD is the most common pathology found in about 30%-40% of patients with iNPH at autopsy, 14,15 brain biopsies obtained during shunt surgeries, and amyloid positron emission tomography (PET) scans. 16 This finding has also been attributed to unrelated aging processes because this frequency is also seen in autopsy studies of adults without dementia who were older than 75 years and in amyloid PET studies of the general population. ...
... 66,68,69 Wholebrain volumetry may be required as a minimal standard in future patients to assess whether changes in the brain parenchyma reflect true atrophy or the pseudoatrophy of DESH. 13 Dedicated imaging techniques, such as sagittal FIESTA-C (fast imaging employing steady-state acquisition-C), would be useful to better detect aqueductal stenosis in patients with longstanding overt ventriculomegaly in adults. 32 Further distinction between pure and comorbid forms of NPH may also benefit from additional imaging techniques, such as 18 F fluorodeoxyglucose, amyloid and tau PET, and dopamine transporter single-photon emission computed tomography. ...
... However, such neuropathological confirmation of "definite" iNPH is rarely achieved. 13 AD is the most common pathology found in about 30%-40% of patients with iNPH at autopsy, 14,15 brain biopsies obtained during shunt surgeries, and amyloid positron emission tomography (PET) scans. 16 This finding has also been attributed to unrelated aging processes because this frequency is also seen in autopsy studies of adults without dementia who were older than 75 years and in amyloid PET studies of the general population. ...
... 66,68,69 Wholebrain volumetry may be required as a minimal standard in future patients to assess whether changes in the brain parenchyma reflect true atrophy or the pseudoatrophy of DESH. 13 Dedicated imaging techniques, such as sagittal FIESTA-C (fast imaging employing steady-state acquisition-C), would be useful to better detect aqueductal stenosis in patients with longstanding overt ventriculomegaly in adults. 32 Further distinction between pure and comorbid forms of NPH may also benefit from additional imaging techniques, such as 18 F fluorodeoxyglucose, amyloid and tau PET, and dopamine transporter single-photon emission computed tomography. ...
Idiopathic normal pressure hydrocephalus is considered common but remains underinvestigated. There are no uniformly accepted diagnostic criteria and therapeutic guidelines. We summarize the accumulated evidence regarding the definition, pathophysiology, diagnosis, and treatment of idiopathic normal pressure hydrocephalus, highlighting the many gaps and controversies, including diagnostic challenges, the frequent association with neurodegeneration and vascular disease, and the many unknowns regarding patient selection and outcome predictors. A roadmap to fill these gaps and solve the controversies around this condition is also proposed. More evidence is required with respect to diagnostic criteria, the value of ancillary testing, prospective population-based studies and novel trial designs. Furthermore, a need exists to develop new advanced options in shunt technology. © 2020 International Parkinson and Movement Disorder Society.
Neuroimaging is increasingly being included in clinical trials of Huntington’s disease (HD) for a wide range of purposes from participant selection and safety monitoring, through to demonstration of disease modification. Selection of the appropriate modality and associated analysis tools requires careful consideration. On behalf of the EHDN Imaging Working Group, we present current opinion on the utility and future prospects for inclusion of neuroimaging in HD trials. Covering the key imaging modalities of structural-, functional- and diffusion- MRI, perfusion imaging, positron emission tomography, magnetic resonance spectroscopy, and magnetoencephalography, we address how neuroimaging can be used in HD trials to: 1) Aid patient selection, enrichment, stratification, and safety monitoring; 2) Demonstrate biodistribution, target engagement, and pharmacodynamics; 3) Provide evidence for disease modification; and 4) Understand brain re-organization following therapy. We also present the challenges of translating research methodology into clinical trial settings, including equipment requirements and cost, standardization of acquisition and analysis, patient burden and invasiveness, and interpretation of results. We conclude, that with appropriate consideration of modality, study design and analysis, imaging has huge potential to facilitate effective clinical trials in HD.
Background
Disproportionately enlarged subarachnoid-space hydrocephalus (DESH) is a key feature for Hakim disease (idiopathic normal pressure hydrocephalus: iNPH), but subjectively evaluated. To develop automatic quantitative assessment of DESH with automatic segmentation using combined deep learning models.
Methods
This study included 180 participants (42 Hakim patients, 138 healthy volunteers; 78 males, 102 females). Overall, 159 three-dimensional (3D) T1-weighted and 180 T2-weighted MRIs were included. As a semantic segmentation, 3D MRIs were automatically segmented in the total ventricles, total subarachnoid space (SAS), high-convexity SAS, and Sylvian fissure and basal cistern on the 3D U-Net model. As an image classification, DESH, ventricular dilatation (VD), tightened sulci in the high convexities (THC), and Sylvian fissure dilatation (SFD) were automatically assessed on the multimodal convolutional neural network (CNN) model. For both deep learning models, 110 T1- and 130 T2-weighted MRIs were used for training, 30 T1- and 30 T2-weighted MRIs for internal validation, and the remaining 19 T1- and 20 T2-weighted MRIs for external validation. Dice score was calculated as (overlapping area) × 2/total area.
Results
Automatic region extraction from 3D T1- and T2-weighted MRI was accurate for the total ventricles (mean Dice scores: 0.85 and 0.83), Sylvian fissure and basal cistern (0.70 and 0.69), and high-convexity SAS (0.68 and 0.60), respectively. Automatic determination of DESH, VD, THC, and SFD from the segmented regions on the multimodal CNN model was sufficiently reliable; all of the mean softmax probability scores were exceeded by 0.95. All of the areas under the receiver-operating characteristic curves of the DESH, Venthi, and Sylhi indexes calculated by the segmented regions for detecting DESH were exceeded by 0.97.
Conclusion
Using 3D U-Net and a multimodal CNN, DESH was automatically detected with automatically segmented regions from 3D MRIs. Our developed diagnostic support tool can improve the precision of Hakim disease (iNPH) diagnosis.
Aims: There are very few detailed post-mortem studies on idiopathic normal-pressure hydrocephalus (iNPH) and there is a lack of proper neuropathological criteria for iNPH. This study aims to update the knowledge on the neuropathology of iNPH and to develop the neuropathological diagnostic criteria of iNPH. Methods: We evaluated the clinical lifelines and post-mortem findings of 29 patients with possible NPH. Pre-mortem cortical brain biopsies were taken from all patients during an intracranial pressure measurement or a cerebrospinal fluid (CSF) shunt surgery. Results: The mean age at the time of the biopsy was 70±8 SD years and 74±7 SD years at the time of death. At the time of death, 11/29 patients (38%) displayed normal cognition or mild cognitive impairment (MCI), 9/29 (31%) moderate dementia and 9/29 (31%) severe dementia. Two of the demented patients had only scarce neuropathological findings indicating a probable hydrocephalic origin for the dementia. Amyloid-β (Aβ) and hyperphosphorylated τ (HPτ) in the biopsies predicted the neurodegenerative diseases so that there were 4 Aβ positive/low Alzheimer's disease neuropathological change (ADNC) cases, 4 Aβ positive/intermediate ADNC cases, 1 Aβ positive case with both low ADNC and progressive supranuclear palsy (PSP), 1 HPτ/PSP and primary age-related tauopathy (PART) case, 1 Aβ/HPτ and low ADNC/synucleinopathy case and 1 case with Aβ/HPτ and high ADNC. The most common cause of death was due to cardiovascular diseases (10/29, 34%), followed by cerebrovascular diseases or subdural hematoma (SDH) (8/29, 28%). Three patients died of a postoperative intracerebral hematoma (ICH). Vascular lesions were common (19/29, 65%). Conclusions: We update the suggested neuropathological diagnostic criteria of iNPH, which emphasize the rigorous exclusion of all other known possible neuropathological causes of dementia. Despite the first 2 probable cases reported here, the issue of "hydrocephalic dementia" as an independent entity still requires further confirmation. Extensive sampling (with fresh frozen tissue including meninges) with age-matched neurologically healthy controls is highly encouraged.
Background:
Focally enlarged sulci (FES) are areas of proposed extraventricular fluid entrapment that may occur within idiopathic normal pressure hydrocephalus (iNPH) with radiographic evidence of disproportionately enlarged subarachnoid-space hydrocephalus (DESH), and should be differentiated from atrophy.
Purpose:
To evaluate for change in FES size and pituitary height after shunt placement in iNPH.
Study type:
Retrospective.
Subjects:
A total of 125 iNPH patients who underwent shunt surgery and 40 age-matched controls.
Field strength/sequence:
1.5 T and 3 T. Axial T2w FLAIR, 3D T1w MPRAGE, 2D sagittal T1w.
Assessment:
FES were measured in three dimensions and volume was estimated by assuming an ellipsoid shape. Pituitary gland height was measured in the mid third of the gland in iNPH patients and controls.
Statistical tests:
Wilcoxon signed-rank test for comparisons between MRI measurements; Wilcoxon rank sum test for comparison of cases/controls. Significance level was P < 0.05.
Results:
Fifty percent of the patients had FES. FES volume significantly decreased between the pre and first postshunt MRI by a median of 303 mm3 or 30.0%. Pituitary gland size significantly increased by 0.48 mm or 14.4%. FES decreased significantly by 190 mm3 or 23.1% and pituitary gland size increased significantly by 0.25 mm or 6% between the first and last postshunt MRI.
Data conclusion:
Decrease in size of FES after shunt placement provides further evidence that these regions are due to disordered cerebrospinal fluid (CSF) dynamics and should not be misinterpreted as atrophy. A relatively smaller pituitary gland in iNPH patients that normalizes after shunt is a less-well recognized feature of altered CSF dynamics.
Evidence level:
3 TECHNICAL EFFICACY: Stage 2.
