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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.

Additional file 6: Table S3. Primary antibodies forimmunoblot investigations.

Additionalfile 1: Figure S1. H-Tx rats for genetic risk identification.

Additional file 7: Table S4. Reagents forimmunofluorescence investigations.

Additionalfile 2: Figure S2. Ptpn20 expression in the tissues of mice.

Additional file 5: Table S2. Assay of real-time PCR.

Additionalfile 3: Figure S3. Immunoblotting of pNKCC1 protein expression in agedPtpn20−/− mice and H-Tx rats.

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-�� (A��) and hyperphosphorylated �� (HP��) in the biopsies predicted the neurodegenerative diseases so that there were 4 A�� positive/low Alzheimer���s disease neuropathological change (ADNC) cases, 4 A�� positive/intermediate ADNC cases, 1 A�� positive case with both low ADNC and progressive supranuclear palsy (PSP), 1 HP��/PSP and primary age-related tauopathy (PART) case, 1 A��/HP�� and low ADNC/synucleinopathy case and 1 case with A��/HP�� 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., Free Neuropathology, Vol. 3 (2022)

Additional file 4: Table S1. Copy number variations.