Differentiating comorbidities and predicting prognosis in idiopathic normal pressure hydrocephalus using cerebrospinal fluid biomarkers: a review

Idiopathic normal pressure hydrocephalus (iNPH) is a condition resulting from impaired cerebrospinal fluid (CSF) absorption and excretion characterized by a triad of symptoms comprising dementia, gait disturbance (impaired trunk balance), and urinary incontinence. CSF biomarkers not only assist in diagnosis but are also important for analyzing the pathology and understanding appropriate treatment indications. As the neuropathological findings characteristic of iNPH have yet to be defined, there remains no method to diagnose iNPH with 100% sensitivity and specificity. Neurotoxic proteins are assumed to be involved in the neurological symptoms of iNPH, particularly the appearance of cognitive impairment. The symptoms of iNPH can be reversed by improving CSF turnover through shunting. However, early diagnosis is essential as once neurodegeneration has progressed, pathological changes become irreversible and symptom improvement is minimal, even after shunting. Combining a variety of diagnostic methods may lead to a more definitive diagnosis and accurate prediction of the prognosis following shunt treatment. Identifying comorbidities in iNPH using CSF biomarkers does not contraindicate shunting-based intervention, but does limit the improvement in symptoms it yields, and provides vital information for predicting post-treatment prognosi

Shunt Intervention for Possible Idiopathic Normal Pressure Hydrocephalus Improves Patient Outcomes: A Nationwide Hospital-Based Survey in Japan

Background and Purpose: This study aimed to investigate the efficacy of cerebrospinal fluid shunt intervention for idiopathic normal pressure hydrocephalus (iNPH) using data from a nationwide epidemiological survey in Japan.Methods: We conducted a cross-sectional study using data from a nationwide epidemiological survey performed in Japan. Propensity score matching was used to select 874 patients from 1,423 patients aged ≥60 years, who were diagnosed with iNPH based on clinical guidelines following a hospital visit in 2012. Patients who experienced an improvement of at least 1 modified Rankin Scale (mRS) grade after the intervention were classified as “improved,” while the remaining patients were classified as “non-improved.” In the shunt intervention (n = 437) and non-shunt intervention (n = 437) groups, the differences in mRS grade improvement were analyzed using the Mann-Whitney U-test. Finally, we examined subjects in the shunt intervention group (n = 974) to compare the outcomes and complications of ventriculoperitoneal (VP) shunt (n = 417) with lumboperitoneal (LP) shunt (n = 540).Results: We examined subjects with iNPH to compare the non-shunt intervention group to the shunt intervention group following adjustment for age and mRS grade at baseline by propensity score matching (0.31–0.901). The mRS grade (mean [SD]) was found to improve with non-shunt intervention (2.46 [0.88]) and shunt intervention (1.93 [0.93]) (p < 0.001) in iNPH patients. The mRS outcome score and complications comparison between the VP and LP shunt groups did not show significant difference.Conclusions: In this study, analysis of the efficacy of shunts for possible iNPH conducted in Japan indicated a significant improvement in the mRS grade between baseline and outcome within 1 year, regardless of the surgical technique, and shunt intervention was found to be effective

Table_1_Shunt Intervention for Possible Idiopathic Normal Pressure Hydrocephalus Improves Patient Outcomes: A Nationwide Hospital-Based Survey in Japan.DOCX

<p>Background and Purpose: This study aimed to investigate the efficacy of cerebrospinal fluid shunt intervention for idiopathic normal pressure hydrocephalus (iNPH) using data from a nationwide epidemiological survey in Japan.</p><p>Methods: We conducted a cross-sectional study using data from a nationwide epidemiological survey performed in Japan. Propensity score matching was used to select 874 patients from 1,423 patients aged ≥60 years, who were diagnosed with iNPH based on clinical guidelines following a hospital visit in 2012. Patients who experienced an improvement of at least 1 modified Rankin Scale (mRS) grade after the intervention were classified as “improved,” while the remaining patients were classified as “non-improved.” In the shunt intervention (n = 437) and non-shunt intervention (n = 437) groups, the differences in mRS grade improvement were analyzed using the Mann-Whitney U-test. Finally, we examined subjects in the shunt intervention group (n = 974) to compare the outcomes and complications of ventriculoperitoneal (VP) shunt (n = 417) with lumboperitoneal (LP) shunt (n = 540).</p><p>Results: We examined subjects with iNPH to compare the non-shunt intervention group to the shunt intervention group following adjustment for age and mRS grade at baseline by propensity score matching (0.31–0.901). The mRS grade (mean [SD]) was found to improve with non-shunt intervention (2.46 [0.88]) and shunt intervention (1.93 [0.93]) (p < 0.001) in iNPH patients. The mRS outcome score and complications comparison between the VP and LP shunt groups did not show significant difference.</p><p>Conclusions: In this study, analysis of the efficacy of shunts for possible iNPH conducted in Japan indicated a significant improvement in the mRS grade between baseline and outcome within 1 year, regardless of the surgical technique, and shunt intervention was found to be effective.</p

Guidelines for Management of Idiopathic Normal Pressure Hydrocephalus (Third Edition): Endorsed by the Japanese Society of Normal Pressure Hydrocephalus.

Among the various disorders that manifest with gait disturbance, cognitive impairment, and urinary incontinence in the elderly population, idiopathic normal pressure hydrocephalus (iNPH) is becoming of great importance. The first edition of these guidelines for management of iNPH was published in 2004, and the second edition in 2012, to provide a series of timely, evidence-based recommendations related to iNPH. Since the last edition, clinical awareness of iNPH has risen dramatically, and clinical and basic research efforts on iNPH have increased significantly. This third edition of the guidelines was made to share these ideas with the international community and to promote international research on iNPH. The revision of the guidelines was undertaken by a multidisciplinary expert working group of the Japanese Society of Normal Pressure Hydrocephalus in conjunction with the Japanese Ministry of Health, Labour and Welfare research project. This revision proposes a new classification for NPH. The category of iNPH is clearly distinguished from NPH with congenital/developmental and acquired etiologies. Additionally, the essential role of disproportionately enlarged subarachnoid-space hydrocephalus (DESH) in the imaging diagnosis and decision for further management of iNPH is discussed in this edition. We created an algorithm for diagnosis and decision for shunt management. Diagnosis by biomarkers that distinguish prognosis has been also initiated. Therefore, diagnosis and treatment of iNPH have entered a new phase. We hope that this third edition of the guidelines will help patients, their families, and healthcare professionals involved in treating iNPH