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Abstract The present study aims to investigate the choroidal morphology and microvascular structure in eyes of patients with idiopathic normal pressure hydrocephalus (iNPH) compared with the eyes of healthy age-matched individuals, and to assess the choroidal structure in eyes of iNPH patients before and after shunt surgery using Optical Coherence Tomography (OCT). The primary objective was to assess the choroidal morphology in eyes of iNPH patients before and after ventriculo-peritoneal (VP) surgery compared to age and sex-matched healthy individuals. The secondary objective was to compare the choroidal morphology of iNPH patients before and after a mean of 56 days from shunt surgery. Eighteen consecutive patients diagnosed with iNPH and 18 healthy controls were prospectively recruited between November 2021 and October 2022. Spectral-domain optical coherence tomography (SD-OCT) with enhanced depth imaging (EDI) was conducted before and within 4 months after shunt surgery. Images were binarized using the ImageJ software, and the choroidal vascular index (CVI) was calculated. Sub-foveal choroidal thickness (SFCT), total choroidal area (TCA), luminal choroidal area (LCA), and stromal choroidal area (SCA) were significantly increased in iNPH patients before surgery compared to the control group (p 0.05). In conclusion, the choroid was thicker in iNPH patients before and after VP shunt compared to age-matched healthy individuals. However, there were no difference in the choroidal microstructure in the eyes of iNPH patients before and after a mean of 3 months from VP shunt surgery.

Abstract Background Idiopathic normal pressure hydrocephalus (iNPH) is a clinico-radiological syndrome of elderly individuals likely sustained by different neurodegenerative changes as copathologies. Since iNPH is a potentially reversible condition, assessing neurodegenerative pathologies in vitam through CSF biomarkers and their influence on clinical features and surgical outcome represents crucial steps. Methods We measured α-synuclein seeding activity related to Lewy body (LB) pathology by the real-time quaking-induced conversion assay (RT-QuIC) and Alzheimer disease core biomarkers (proteins total-tau, phospho-tau, and amyloid-beta) by immunoassays in the cerebrospinal fluid (CSF) of 293 iNPH patients from two independent cohorts. To compare the prevalence of LB copathology between iNPH participants and a control group representative of the general population, we searched for α-synuclein seeding activity in 89 age-matched individuals who died of Creutzfeldt-Jakob disease (CJD). Finally, in one of the iNPH cohorts, we also measured the CSF levels of neurofilament light chain protein (NfL) and evaluated the association between all CSF biomarkers, baseline clinical features, and surgery outcome at 6 months. Results Sixty (20.5%) iNPH patients showed α-synuclein seeding activity with no significant difference between cohorts. In contrast, the prevalence observed in CJD was only 6.7% (p = 0.002). Overall, 24.0% of iNPH participants showed an amyloid-positive (A+) status, indicating a brain co-pathology related to Aβ deposition. At baseline, in the Italian cohort, α-synuclein RT-QuIC positivity was associated with higher scores on axial and upper limb rigidity (p = 0.003 and p = 0.011, respectively) and lower MMSEc scores (p = 0.003). A+ patients showed lower scores on the MMSEc (p = 0.037) than A- patients. Higher NfL levels were also associated with lower scores on the MMSEc (rho = -0.213; p = 0.021). There were no significant associations between CSF biomarkers and surgical outcome at 6 months (i.e. responders defined by decrease of 1 point on the mRankin scale). Conclusions Prevalent LB- and AD-related neurodegenerative pathologies affect a significant proportion of iNPH patients and contribute to cognitive decline (both) and motor impairment (only LB pathology) but do not significantly influence the surgical outcome at 6 months. Their effect on the clinical benefit after surgery over a more extended period remains to be determined.

Abstract Background Idiopathic normal pressure hydrocephalus (iNPH) is a neurological condition with gait apraxia signs from its early manifestation. Ventriculoperitoneal shunt (VPS) is a surgical procedure available for treatment. The Cerebrospinal fluid Tap Test (CSF-TT) is a quick test used as selection criterion for VPS treatment. Its predictive capacity for VPS outcomes is still sub judice. This study is aimed to test the hypothesis that wearable motion sensors provide valid measures to manage iNPH patients with gait apraxia. Methods Forty-two participants of the Bologna PRO-Hydro observational cohort study were included in the analyses. The participants performed the Timed Up and Go (TUG) and the 18 m walking test (18mW) with inertial sensors at baseline, three days after the CSF-TT, and six months after VPS. 21 instrumental variables described gait and postural transitions from TUG and 18mW recordings. Furthermore, participants were clinically assessed with scales (clinical variables). We tested the hypothesis by analysing the concurrent validity of instrumental and clinical variables, their individual- and group-level responsiveness to VPS, and their predictive validity for VPS outcomes after CSF-TT. Results The instrumental variables showed moderate to high correlation with the clinical variables. After VPS, most clinical and instrumental variables showed statistically significant improvements that reflect a reduction of apraxic features of gait. Most instrumental variables, but only one clinical variable (i.e., Tinetti POMA), had predictive value for VPS outcomes (significant adjusted R2 in the range 0.12–0.70). Conclusions These results confirm that wearable inertial sensors may represent a valid tool to complement clinical evaluation for iNPH assessment and prognosis.

IntroductionThe aim of this study was to compare clinical and functional performances of idiopathic normal pressure hydrocephalus (INPH) patients with and without parkinsonism at the initial evaluation, 72 h after the cerebrospinal fluid tap test (CSF TT), and 6 months after ventriculoperitoneal shunt (VPS) surgery.Materials and methodsThis is an observational prospective study on patients with INPH who underwent VPS. Patients were classified into INPH with parkinsonism (INPH-P+) and without parkinsonism (INPH-P−). We used the time up and go (TUG) test, Tinetti Performance-Oriented Mobility Assessment (POMA) test, INPH grading scale (INHPGS), and modified Rankin scale (mRS) at baseline, 72 h after CSF TT, and 6 months after VPS surgery.ResultsA total of 64 patients with probable INPH were included, 12 patients with INPH-P+ and 52 controls with INPH-P−. Patients with INPH showed significant improvement in all clinical and neurological parameters after VPS including TUG, Tinetti POMA, INPHGS, and mRS (p < 0.001) with the exception of mRS where there was no significant change 72 h after CSF TT compared to baseline for patients with INPH (p = 0.182). Patients with INPH-P+ performed significantly worse than patients with INPH-P− on Tinetti POMA and mRS at baseline, at 72 h post-CSF TT, and at 6 months post-VPS with INPHGS being worst at 72 h post-CSF TT. There was no difference between patients with INPH-P+ and patients with INPH-P− for TUG at baseline (p = 0.270), at 72 h post-CSF TT (p = 0.487), and at 6 months post-VPS (p = 0.182). Patients with INPH-P+ did not show any change in any of the parameters at 72 h post-CSF TT compared to baseline; however, there was a trend toward improvement on TUG (p = 0.058), Tinetti gait (p = 0.062), and Tinetti total (p = 0.067). INPH-P+ significantly improved in all parameters 6 months post-VPS compared to baseline except for mRS (p = 0.124). Patients with INPH-P− significantly improved in all parameters at 72 h post-CSF TT and at 6 months post-VPS compared to baseline, respectively, except on mRS 72 h after CSF TT (p = 0.299).ConclusionPatients with INPH and parkinsonism overall do worse than patients without parkinsonism. An unsatisfying response to the CSF tap test in INPH patients with parkinsonism should not be used as an exclusion criterion from VPS surgery since patients with and without parkinsonism showed significant improvement post-VPS.

In 1965, Prof. Salomón Hakim described, for the first time, a condition characterized by normal pressure hydrocephalus and gait alterations. During the following decades, definitions such as “Frontal Gait”, “Bruns’ Ataxia” and “Gait Apraxia” have been frequently used in pertinent literature in the attempt to best define this peculiar motor disturbance. More recently, gait analysis has further shed light on the typical spatiotemporal gait alterations that characterize this neurological condition, but a clear and shared definition of this motor condition is still lacking. In this historical review, we described the origins of the terms “Gait Apraxia”, “Frontal Gait” and “Bruns’ Ataxia”, starting with the first works of Carl Maria Finkelburg, Fritsch and Hitzig and Steinthal during the second half of the 19th century and ending with Hakim’s studies and his formal definition of idiopathic normal pressure hydrocephalus (iNPH). In the second part of the review, we analyze how and why these definitions of gait have been associated with Hakim’s disease in the literature from 1965 to the present day. The definition of “Gait and Postural Transition Apraxia” is then proposed, but fundamental questions about the nature and mechanisms underlying this condition remain unanswered.

Abstract Background Gait disturbances are typical of persons with idiopathic normal pressure hydrocephalus (iNPH) without signs distinctive from other neurodegenerative and vascular conditions. Cerebrospinal fluid tap-test (CSF-TT) is expected to improve the motor performance of iNPH patients and is a prognostic indicator in their surgical management. This observational prospective study aims to determine which spatio-temporal gait parameter(s), measured during instrumented motor tests, and clinical scale(s) may provide a relevant contribution in the evaluation of motor performance pre vs. post CSF-TT on iNPH patients with and without important vascular encephalopathy. Methods Seventy-six patients (20 with an associated vascular encephalopathy) were assessed before, and 24 and 72 h after the CSF-TT by a timed up and go test (TUG) and an 18 m walking test (18 mW) instrumented using inertial sensors. Tinetti Gait, Tinetti Balance, Gait Status Scale, and Grading Scale were fulfilled before and 72 h after the CSF-TT. Stride length, cadence and total time were selected as the outcome measures. Statistical models with mixed effects were implemented to determine the relevant contribution to response variables of each quantitative gait parameter and clinical scales. Results and conclusion From baseline to 72 h post CSF-TT patients improved significantly by increasing cadence in 18 mW and TUG (on average of 1.7 and 2.4 strides/min respectively) and stride length in 18 mW (on average of 3.1 cm). A significant reduction of gait apraxia was reflected by modifications in double support duration and in coordination index. Tinetti Gait, Tinetti Balance and Gait Status Scale were able to explain part of the variability of response variables not covered by instrumental data, especially in TUG. Grading Scale revealed the highest affinity with TUG total time and cadence when considering clinical scales alone. Patients with iNPH and an associated vascular encephalopathy showed worst performances compared to pure iNPH but without statistical significance. Gait improvement following CSF-TT was comparable in the two groups. Overall these results suggest that, in order to augment CSF-TT accuracy, is key to assess the gait pattern by analyzing the main spatio-temporal parameters and set post evaluation at 72 h. Trial registration Approved by ethics committee: CE 14131 23/02/2015.