Parkinsonism and cerebrospinal fluid disorders

Youn, Jinyoung; Todisco, Massimiliano; Zappia, Mario; Pacchetti, Claudio; Fasano, Alfonso

doi:10.1016/j.jns.2021.120019

Cited by 9 publications

(18 citation statements)

References 119 publications

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“…Altogether, these neurological signs define a predominant parkinsonian phenotype of iNPH, which the LB pathology might at least partially sustain. Indeed, parkinsonian features, including short and symmetrical steps, freezing of gait, start hesitation, magnetic gait, bradykinesia, and rigidity, belong to the clinical spectrum of iNPH [ 33 ]. Of note, none of the patients included in our study fulfilled the criteria for a clinical diagnosis of probable or clinically established PD, PDD, or DLB.…”

Section: Discussionmentioning

confidence: 99%

In vivo assessment of Lewy body and beta-amyloid copathologies in idiopathic normal pressure hydrocephalus: prevalence and associations with clinical features and surgery outcome

Giannini

Baiardi

Dellavalle

et al. 2022

Fluids Barriers CNS

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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.

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Section: Discussionmentioning

confidence: 99%

In vivo assessment of Lewy body and beta-amyloid copathologies in idiopathic normal pressure hydrocephalus: prevalence and associations with clinical features and surgery outcome

Giannini

Baiardi

Dellavalle

et al. 2022

Fluids Barriers CNS

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“…Interestingly, L-dopa was tested in the majority of patients, both positive and negative, in keeping with the notion that subtle appendicular parkinsonian signs can be seen in iNPH. 9 Notably, the response to tap test was comparable between groups although the base of support did not improve and step length was significantly shorter in positive versus, negative patients. In addition, while shunt surgery was considered beneficial in RT-QuIC positive patients, their gait parameters were only marginally and not significantly improved compared to baseline.…”

Section: Discussionmentioning

confidence: 87%

“…From a clinical standpoint, αSyn RT‐QuIC positive iNPH patients were largely indistinguishable from negative patients, with the exception of a more frequent response to L‐dopa and wider gait base at baseline. Interestingly, L‐dopa was tested in the majority of patients, both positive and negative, in keeping with the notion that subtle appendicular parkinsonian signs can be seen in iNPH 9 . Notably, the response to tap test was comparable between groups although the base of support did not improve and step length was significantly shorter in positive versus, negative patients.…”

Section: Discussionmentioning

confidence: 88%

“…This study sheds light on the link between iNPH and PD pathology, which was found in a relatively small proportion of cases. In fact, parkinsonian clinical features and neuroimaging evidence of nigrostriatal involvement are commonly reported, thus raising the possibility that these more often represent the effect rather than the cause of iNPH 9,11 . In keeping with this notion, it has been recently reported that the nigrostriatal involvement (as measured with dopamine transporter SPECT) is partially reversed by shunt surgery, thus suggesting that the dopaminergic pathway sustains a stretch injury exerted by ventriculomegaly rather than a neurodegenerative process 11,12 …”

Section: Discussionmentioning

confidence: 99%

“…The pathophysiology of iNPH is still unclear and particularly debated is the overlap between iNPH and neurodegeneration, as many autopsy cases have revealed co‐morbid Alzheimer disease (AD) pathology 8 . In addition, not only have parkinsonian features been frequently reported in iNPH patients (reviewed in 9 ), but a progressive ventricular enlargement has also been described in PD patients 10 . Recent studies using dopamine transporter imaging have identified a striatal dopaminergic deficit in more than 60% of iNPH patients that is partially reversed by shunt surgery 11,12 .…”

Section: Introductionmentioning

confidence: 99%

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Alpha‐Synuclein RT‐QuIC in Idiopathic Normal Pressure Hydrocephalus

Fasano

Martínez-Valbuena

Azevedo

et al. 2022

Annals of Neurology

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This study quantified the occurrence of an underlying synucleinopathy in 50 patients with idiopathic normal pressure hydrocephalus by means of real-time quaking-induced conversion, a highly sensitive and specific technique capable of detecting and amplifying misfolded aggregated forms of α-synuclein in the cerebrospinal fluid. Seven patients were positive and they did not differ from negative cases, except for a more frequent L-dopa responsiveness and gait characterized by a wider base. The two groups did not differ in terms of response rate to tap test or shunt surgery, although step length and gait velocity improved by a lesser extent in positive cases.

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Clinical Features of Idiopathic Normal Pressure Hydrocephalus: Critical Review of Objective Findings

Bluett¹,

Ash

Farheen

et al. 2022

Movement Disord Clin Pract

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Background Idiopathic normal pressure hydrocephalus (iNPH) is characterized by the classic clinical triad of gait, cognitive, and urinary dysfunction, albeit incomplete in a relevant proportion of patients. The clinical findings and evolution of these symptoms have been variably defined in the literature. Objectives To evaluate how the phenomenology has been defined, assessed, and reported, we performed a critical review of the existing literature discussing the phenomenology of iNPH. The review also identified the instrumental tests most frequently used and the evolution of clinical and radiologic findings. Methods The review was divided into 3 sections based on gait, cognitive, and urinary dysfunction. Each section performed a literature search using the terms “idiopathic normal pressure hydrocephalus” (iNPH), with additional search terms used by each section separately. The number of articles screened, duplicates, those meeting the inclusion criteria, and the number of articles excluded were recorded. Findings were subsequently tallied and analyzed. Results A total of 1716 articles with the aforementioned search criteria were identified by the 3 groups. A total of 81 full‐text articles were reviewed after the elimination of duplicates, articles that did not discuss phenomenological findings or instrumental testing of participants with iNPH prior to surgery, and articles with fewer than 10 participants. Conclusions “Wide‐based gait” was the most common gait dysfunction identified. Cognitive testing varied significantly across articles, and ultimately a specific cognitive profile was not identified. Urodynamic testing found detrusor overactivity and “overactive bladder” as the most common symptom of urinary dysfunction.

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Parkinsonism and cerebrospinal fluid disorders

Cited by 9 publications

References 119 publications

In vivo assessment of Lewy body and beta-amyloid copathologies in idiopathic normal pressure hydrocephalus: prevalence and associations with clinical features and surgery outcome

In vivo assessment of Lewy body and beta-amyloid copathologies in idiopathic normal pressure hydrocephalus: prevalence and associations with clinical features and surgery outcome

Alpha‐Synuclein RT‐QuIC in Idiopathic Normal Pressure Hydrocephalus

Clinical Features of Idiopathic Normal Pressure Hydrocephalus: Critical Review of Objective Findings

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