Ventriculomegaly Is the First Brain Morphological Change in Prodromal Idiopathic Normal Pressure Hydrocephalus

A 77‐year‐old man was referred to our hospital because of progressive gait disturbance, frequent urination, and mild memory problems. He first developed pollakiuria at the age of 70 years. He then recognized a decrease in his walking speed at the age of 71 years and had episodes of requiring rescue during long‐distance hiking at the age of 73 and 74 years. At the time of presentation, he could keep walking for only 10 minutes. He complained of mild memory decline and misplaced objects. He underwent annual brain MRI as a part of a private health checkup from the age of 61 years, but his medical history was unremarkable aside from a history of habitual drinking.

A neurologic examination confirmed reduced facial expression, left‐predominant mild bradykinesia, and wide‐based unsteady gait with mild freezing. Brain MRI revealed typical imaging features of disproportionally enlarged subarachnoid‐space hydrocephalus (DESH), such as enlarged lateral ventricles, moderately dilated sylvian fissures, sharpened callosal angle, and mild narrowing of the sulci at high convexity and the midline¹ (Fig. 1A). ¹²³I–IMP single‐photon emission computed tomography (SPECT) revealed apparent hyperperfusion in the high‐convexity area typical of iNPH² (Fig. 1B). A ¹²³I‐ioflupane SPECT (dopamine transporter scan) revealed mildly reduced left striatal uptake (Fig. 1C); however, levodopa treatment did not improve his motor deficits. He responded to a CSF tap test (the time of the timed up‐and‐go test improved from 15.5 to 11.06 sec, the MMSE score improved from 21 to 25, and the urination frequency was reduced). One month later, he underwent ventriculoperitoneal shunt placement; thereafter, his symptoms significantly improved, and a final diagnosis of idiopathic normal pressure hydrocephalus (iNPH) was made.

FIG. 1.

(A) Longitudinal brain MRI image (T1‐weighted image) during 16 years to diagnosis of iNPH. Frequent urination, gait disturbance and cognitive decline developed 7, 6, 1 years before diagnosis respectively. DESH is only significant in latest few years. EI: Evan's index, CA: Callosal angle, DS: DESH scale score. (B) ¹²³I –IMP SPECT at time of presentation showing convexity apparent hyperperfusion (CAPPAH) sign. (C) ¹²³I‐ioflupane SPECT (dopamine transporter imaging).

His longitudinal brain MRIs from his private medical checkup revealed that enlargement of lateral ventricles was evident (Evan's index > 0.3) 13 years before the diagnosis. Approximately 5 years later (8 years before diagnosis), the posterior end of the Sylvian fissures and temporal horns had begun to dilate, and 7 and 6 years before diagnosis, frequent micturition and slowness of gait had developed. Dilation of Sylvian fissures and sharpening of the callosal angle were already prominent 5 years prior to his diagnosis, and were followed by the development of tight high convexity and focal sulcal dilation at 4 and 3 years before diagnosis, respectively, leading to complete DESH (Fig. 1A).³ Gait disturbance significantly worsened over time, and mild memory loss was noticed shortly before the first visit.

iNPH is a common neurological disorder characterized by disproportionately enlarged ventricles.⁴ However, the time course of symptoms and brain morphological changes in the preclinical phase is poorly understood. The prevalence of asymptomatic ventriculomegaly on MRI has been reported among 1% of the elderly population, and approximately one‐fourth of cases with DESH develop iNPH within 4–8 years.⁵ Although DESH is the diagnostic MRI feature of iNPH, it remains unclear how complete DESH develops before diagnosis. In the current case, the lateral ventricles started to enlarge 13 years prior to diagnosis (the preclinical stage), followed by dilatation of Sylvian fissures and sharpening of the callosal angle (beginning of the prodromal stage). Thereafter, high convexity tightness became prominent only a few years prior to the diagnosis (the early clinical stage). Our observations suggest that the prediagnostic phase of iNPH is longer than previously thought and highlight the importance of ventriculomegaly as the initial brain morphological change in the prodromal phase of iNPH. Furthemore, dilatation of Sylvian fissures and sharpening of the callosal angle may help to rule out ventriculomegaly caused by the progressive atrophy associated with aging and neurodegenerative disorders.

Author Roles

(1) Research Project: A. Conception, B. Organization, C. Execution; (2) Statistical Analysis: A. Design, B. Execution, C. Review and Critique; (3) Manuscript: A. Writing of the First Draft, B. Review and Critique.

T.T.: 1A, 1B, 1C, 2A, 2B, 2C, 3A, 3B

T.B.: 1A, 1B, 1C, 2A, 2B, 2C, 3B

K.N.: 1B, 1C, 2C, 3B.

A.T.: 1B, 1C, 2C, 3B

Disclosures

Ethical Compliance Statement

This study was approved by the institutional review board (Reference number: R2‐6), and informed consent was obtained from the patient for publication of this case report and accompanying images. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines.

Funding Sources and Conflicts of Interest

The authors declare that there are no funding sources or conflicts of interest relevant to this work.

Financial Disclosures for the Previous 12 Months

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