Neurosurgeon

The candidates for this study were patients with suspected iNPH. After obtaining written informed consent, the eligible patients were pre-registered and received lumbar puncture. The inclusion criteria were (1) age between 60 and 85 years, (2) presence of one or more symptom(s) of the triad (gait disturbance, cognitive impairment, and urinary symptoms), which were measurable on the iNPH Grading Scale (iNPHGS) [14 (link)], (3) MRI features of iNPH, i.e., both ventriculomegaly of Evans' index > 0.3 and tight high-convexity and medial subarachnoid spaces on coronal T1-weighted MRI (Figure 1) [10 (link)], (4) absence of known disorders causing ventriculomegaly, and (5) normal cerebrospinal fluid (CSF) content (protein ≤ 50 mg/dl and cell count ≤ 3 μm³) and pressure (≤ 20 cmH₂O). Exclusion criteria were (1) presence of musculoskeletal, cardiopulmonary, renal, hepatic, or mental disorders that would make it difficult to evaluate changes of symptoms, (2) obstacles to one-year follow-up, and (3) hemorrhagic diathesis or anticoagulant medication. For the evaluation of the MRIs, Evans' index, size of the Sylvian fissures rated according to the protocol of Kitagaki et al. [10 (link)], presence or absence of focal dilatation of the cerebral sulci, and white-matter changes according to scale of Fazekas et al. [15 (link)], were assessed on each site and recorded.
The candidates were pre-registered before CSF examination via a web-based case report system. MRI was reviewed by each site in the pre-registration phase, and the final eligibility of the subjects was judged by the central MRI review committee, which consist of neurosurgeons, neurologists, and a neuroradiologist. The central MRI review committee excluded those whose MRI did not fulfil the inclusion criteria. After the confirmation of normal CSF content and pressure, the investigator was notified of registration via the web system. Tap test was carried out in all subjects with 30 ml CSF removal via lumbar puncture. CT cisternography was carried out 1 week after the tap test with iohexol (Omnipaque^®: 180 mg/ml) 30 mg/kg. Cerebral blood flow was measured using ¹²³I-Iodoamphetamine and single photon emission computed tomography at baseline. However, the results of these measures were not considered for the eligibility.

Patients were periodically followed up at the 3rd month and 6th month postoperatively and yearly thereafter. Follow-up evaluations of seizure and tumor recurrence or progression, as well as neurological statuses, were performed by neurosurgeons at the clinic and/or by telephone interview in each patient. Favorable seizure outcomes with Engel classification were defined as Engel class I, and unfavorable seizure outcomes were Engel class II-IV at the last follow-up evaluation.

All patients underwent an individualized preoperative evaluation, including detailed medical history and physical examination, seizure semiology, video electroencephalogram (EEG) and brain magnetic resonance imaging (MRI). The lesion size was represented by the mean tumor diameter of T1-weighted MRI scans. The video EEG monitoring was performed in all patients for at least 16 h, and the concordant EEG findings of interictal epileptiform discharges and ictal seizure rhythms were defined as epileptiform discharge sources localized in the same tumor-invading brain hemisphere.
After detailed preoperative evaluations by neurologists, neurosurgeons, neuroradiologists and electrophysiologists, surgical plans were made. The aim of the operation was to remove the tumor and relevant epileptogenic zone (EZ). The EZ was determined by the findings of the detailed preoperative evaluation and/or intraoperative electrocorticography (ECoG). Intraoperatively, neurological electrophysiological monitoring and neuronavigation were also performed for safe tumor resection. In particular, according to the resection extent of brain tissue (determined by operative records and postoperative MRI), extensive tumor resection was defined as resection of both tumor and peritumoral cortex (or hippocampus), while simple tumor resection was those with simply resection of the tumor.

The 30-day survival rate and 90-day consciousness rate were chosen as the primary outcomes. Mortality data were obtained from medical records or by telephone contact with primary care physicians or family members. Consciousness was determined based on the National Institutes of Health Stroke Scale (NIHSS) (item 1a: value 0, 1, or 2 for consciousness, value 3 for unconsciousness), which was obtained from a clinic visit at 90-day follow-up or by telephone contact by two trained neurosurgeons blinded to research data.