Association between shunt-responsive idiopathic normal pressure hydrocephalus and alcohol

Hickman, Thu-Trang T.; Shuman, Matthew E.; Johnson, Tatyana A.; Yang, Felix; Rice, Rebecca R.; Rice, Isaac M.; Chung, Esther H.; Wiemann, Robert; Tinl, Megan; Iracheta, Christine; Chen, Grace; Flynn, Patricia M.; Mondello, Mary Beth; Thompson, Jillian; Meadows, Mary–Ellen; Carroll, Rona S.; Yang, Hong; Xing, Hongyan; Pilgrim, David; Chiocca, E. Antonio; Dunn, Ian F.; Golby, Alexandra J.; Johnson, Mark D.

doi:10.3171/2016.6.jns16496

Cited by 12 publications

(15 citation statements)

References 36 publications

(62 reference statements)

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“…Alcohol consumption was recently suggested to be a potential risk factor for iNPH in two studies [14,67]. Our results don't back up this finding, but it must be noted that our questionnaire represents only the time close to the diagnosis and not their alcohol consumption earlier in life.…”

Section: Alcohol Sleep Apnea Sfmbt1 and Apoe ε4contrasting

confidence: 72%

Diabetes is associated with familial idiopathic normal pressure hydrocephalus: a case–control comparison with family members

Räsänen

Huovinen

Korhonen

et al. 2020

Fluids Barriers CNS

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Background The pathophysiological basis of idiopathic normal pressure hydrocephalus (iNPH) is still unclear. Previous studies have shown a familial aggregation and a potential heritability when it comes to iNPH. Our aim was to conduct a novel case-controlled comparison between familial iNPH (fNPH) patients and their elderly relatives, involving multiple different families. Methods Questionnaires and phone interviews were used for collecting the data and categorising the iNPH patients into the familial (fNPH) and the sporadic groups. Identical questionnaires were sent to the relatives of the potential fNPH patients. Venous blood samples were collected for genetic studies. The disease histories of the probable fNPH patients (n = 60) were compared with their ≥ 60-year-old relatives with no iNPH (n = 49). A modified Charlson Comorbidity Index (CCI) was used to measure the overall disease burden. Fisher’s exact test (two-tailed), the Mann–Whitney U test (two-tailed) and a multivariate binary logistic regression analysis were used to perform the statistical analyses. Results Diabetes (32% vs. 14%, p = 0.043), arterial hypertension (65.0% vs. 43%, p = 0.033), cardiac insufficiency (16% vs. 2%, p = 0.020) and depressive symptoms (32% vs. 8%, p = 0.004) were overrepresented among the probable fNPH patients compared to their non-iNPH relatives. In the age-adjusted multivariate logistic regression analysis, diabetes remained independently associated with fNPH (OR = 3.8, 95% CI 1.1–12.9, p = 0.030). Conclusions Diabetes is associated with fNPH and a possible risk factor for fNPH. Diabetes could contribute to the pathogenesis of iNPH/fNPH, which motivates to further prospective and gene-environmental studies to decipher the disease modelling of iNPH/fNPH.

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Section: Alcohol Sleep Apnea Sfmbt1 and Apoe ε4contrasting

confidence: 72%

Diabetes is associated with familial idiopathic normal pressure hydrocephalus: a case–control comparison with family members

Räsänen

Huovinen

Korhonen

et al. 2020

Fluids Barriers CNS

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“…Furthermore, oral intake of ethanol was reported to decrease the beating frequency of motile cilia on the ependymal cells of lateral and third ventricles in a rat model [ 61 ]. Recently, two case-control studies provided evidence indicating that alcohol consumption showed a higher frequency in iNPH patients compared with an age-matched general population [ 62 , 63 ]. Therefore, alcohol consumption is a potential risk factor for developing iNPH due to motile cilia dysfunction on the ependymal cells.…”

Section: Introductionmentioning

confidence: 99%

Exploring mechanisms of ventricular enlargement in idiopathic normal pressure hydrocephalus: a role of cerebrospinal fluid dynamics and motile cilia

Yamada

Ishikawa

Nozaki

2021

Fluids Barriers CNS

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Idiopathic normal pressure hydrocephalus (iNPH) is considered an age-dependent chronic communicating hydrocephalus associated with cerebrospinal fluid (CSF) malabsorption; however, the aetiology of ventricular enlargement in iNPH has not yet been elucidated. There is accumulating evidence that support the hypothesis that various alterations in CSF dynamics contribute to ventricle dilatation in iNPH. This review focuses on CSF dynamics associated with ventriculomegaly and summarises the current literature based on three potential aetiology factors: genetic, environmental and hydrodynamic. The majority of gene mutations that cause communicating hydrocephalus were associated with an abnormal structure or dysfunction of motile cilia on the ventricular ependymal cells. Aging, alcohol consumption, sleep apnoea, diabetes and hypertension are candidates for the risk of developing iNPH, although there is no prospective cohort study to investigate the risk factors for iNPH. Alcohol intake may be associated with the dysfunction of ependymal cilia and sustained high CSF sugar concentration due to uncontrolled diabetes increases the fluid viscosity which in turn increases the shear stress on the ventricular wall surface. Sleep apnoea, diabetes and hypertension are known to be associated with the impairment of CSF and interstitial fluid exchange. Oscillatory shear stress to the ventricle wall surfaces is considerably increased by reciprocating bidirectional CSF movements in iNPH. Increased oscillatory shear stress impedes normal cilia beating, leading to motile cilia shedding from the ependymal cells. At the lack of ciliary protection, the ventricular wall is directly exposed to increased oscillatory shear stress. Additionally, increased oscillatory shear stress may be involved in activating the flow-mediated dilation signalling of the ventricular wall. In conclusion, as the CSF stroke volume at the cerebral aqueduct increases, the oscillatory shear stress increases, promoting motor cilia shedding and loss of ependymal cell coverage. These are considered to be the leading causes of ventricular enlargement in iNPH.

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“…The hydrocephalus, gait dysfunction, incontinence, and dementia that characterize iNPH usually appear after the age of 60, with most iNPH patients being asymptomatic and behaviorally normal prior to disease onset ( 1 , 2 ). We recently reported that loss-of-function deletions in CWH43 are enriched among patients with sporadic iNPH and cause an iNPH-like syndrome in genetically engineered mice ( 7 ).…”

Section: Discussionmentioning

confidence: 99%

“…Unlike the congenital hydrocephalus and developmental abnormalities that are frequently seen with L1CAM mutations, iNPH manifests late in life in previously asymptomatic individuals ( 2 – 6 ). Hydrocephalus and gait abnormalities are detectable in CWH43 mutant mice during early adulthood.…”

Section: Discussionmentioning

confidence: 99%

Increased plasmin-mediated proteolysis of L1CAM in a mouse model of idiopathic normal pressure hydrocephalus

Yang

Luiselli

et al. 2021

Proc. Natl. Acad. Sci. U.S.A.

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Idiopathic normal pressure hydrocephalus (iNPH) is a common neurological disorder that is characterized by enlarged cerebral ventricles, gait difficulty, incontinence, and dementia. iNPH usually develops after the sixth decade of life in previously asymptomatic individuals. We recently reported that loss-of-function deletions in CWH43 lead to the development of iNPH in a subgroup of patients, but how this occurs is poorly understood. Here, we show that deletions in CWH43 decrease expression of the cell adhesion molecule, L1CAM, in the brains of CWH43 mutant mice and in human HeLa cells harboring a CWH43 deletion. Loss-of-function mutations in L1CAM are a common cause of severe neurodevelopmental defects that include congenital X-linked hydrocephalus. Mechanistically, we find that CWH43 deletion leads to decreased N-glycosylation of L1CAM, decreased association of L1CAM with cell membrane lipid microdomains, increased L1CAM cleavage by plasmin, and increased shedding of cleaved L1CAM in the cerebrospinal fluid. CWH43 deletion also decreased L1CAM nuclear translocation, suggesting decreased L1CAM intracellular signaling. Importantly, the increase in L1CAM cleavage occurred primarily in the ventricular and subventricular zones where brain CWH43 is most highly expressed. Thus, CWH43 deletions may contribute to adult-onset iNPH by selectively downregulating L1CAM in the ventricular and subventricular zone.

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Association between shunt-responsive idiopathic normal pressure hydrocephalus and alcohol

Cited by 12 publications

References 36 publications

Diabetes is associated with familial idiopathic normal pressure hydrocephalus: a case–control comparison with family members

Diabetes is associated with familial idiopathic normal pressure hydrocephalus: a case–control comparison with family members

Exploring mechanisms of ventricular enlargement in idiopathic normal pressure hydrocephalus: a role of cerebrospinal fluid dynamics and motile cilia

Increased plasmin-mediated proteolysis of L1CAM in a mouse model of idiopathic normal pressure hydrocephalus

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