Panventriculomegaly with a wide foramen of Magendie and large cisterna magna

Abstract

C ertain congenital anomalies of adult-onset hydrocephalus share clinical symptoms with idiopathic normal pressure hydrocephalus (iNPH), such as long-standing overt ventriculomegaly, aqueductal stenosis, 29 and Blake's pouch cyst. 8 However, no disease-associated gene mutations have been identified, including those responsible for these congenital diseases. Moreover, although L1CAM mutations can cause aqueductal stenosis, patients carrying these mutations have clinical features different from patients with NPH. obJective The authors' goal in this paper is to provide the first clinical, radiological, and genetic studies of panventriculomegaly (PaVM) defined by a wide foramen of Magendie and large cisterna magna. methods Clinical and brain imaging data from 28 PaVM patients (including 10 patients from 5 families) were retrospectively studied. Five children were included. In adult patients, the age at onset was 56.0 ± 16.7 years. Tetraventricular dilation, aqueductal opening with flow void on T2-weighted images, and a wide foramen of Magendie and large cisterna magna (wide cerebrospinal fluid space at the fourth ventricle outlet) were essential MRI findings for PaVM diagnosis. 3D fast asymmetrical spin echo sequences were used for visualization of cistern membranes. Time-spatial labeling inversion pulse examination was performed to analyze cerebrospinal fluid movement. Copy number variations were determined using high-resolution microarray and were validated by quantitative polymerase chain reaction with breakpoint sequencing. results Adult patients showed gait disturbance, urinary dysfunction, and cognitive dysfunction. Five infant patients exhibited macrocranium. Patients were divided into 2 subcategories, those with or without downward bulging third ventricular floors and membranous structures in the prepontine cistern. Patients with bulging floors were successfully treated with endoscopic third ventriculostomy. Genetic analysis revealed a deletion in DNAH14 that encodes a dynein heavy chain protein associated with motile cilia function, and which co-segregated with patients in a family without a downward bulging third ventricular floor. coNclusioNs Panventriculomegaly with a wide foramen of Magendie and a large cisterna magna may belong to a subtype of congenital hydrocephalus with familial accumulation, younger age at onset, and symptoms of normal pressure hydrocephalus. In addition, a family with PaVM has a gene mutation associated with dysfunction of motile cilia.

Fluid Distribution Pattern in Adult-Onset Congenital, Idiopathic, and Secondary Normal-Pressure Hydrocephalus: Implications for Clinical Care

“…The other five patients exhibited enlargement of all ventricles, without a downward bulging third ventricular floor (Figures 7 – 9 ). These five patients met the diagnostic criteria for panventriculomegaly with a wide foramen of Magendie and a large cisterna magna, which was recently described by Kageyama et al ( 9 ).…”

“…Recent developments in genetic studies have facilitated detection of susceptibility genes for many late-onset genetic disorders. For example, panventriculomegaly with a wide foramen of Magendie and a large cisterna magna is associated with a DNAH14 mutation that contributes to motile cilia ( 9 ). Additionally, there were few patients with adult-onset congenital NPH.…”

“…However, we excluded the patients diagnosed with adult-onset congenital NPH from our previous volumetric analyses ( 3 – 5 ). Although case series with adult-onset congenital NPH have been reported ( 7 – 9 ), there has been no study to compare adult-onset congenital NPH with idiopathic or secondary NPH.…”

Protein tyrosine phosphatase receptor type Q in cerebrospinal fluid reflects ependymal cell dysfunction and is a potential biomarker for adult chronic hydrocephalus

“…We validated the results for the NC group and patients with iNPH (Finnish iNPH group) in the Finnish cohort. Next, we intended to clarify the role and significance of PTPRQ in acquired (secondary) normal‐pressure hydrocephalus (NPH; in which symptoms appeared subsequent to a preceding neurological injury, e.g., subarachnoid haemorrhage, meningitis) and congenital/developmental aetiologies, which present with panventriculomegaly, wide foramen of Magendie and large cisterna magna [19].…”

“…A retrospective analysis of the detailed course of clinical symptoms was performed. Evaluation items included Mini Mental State Examination (MMSE) scores [19,20] and iNPH Grading Scale (iNPHGS) scores [21].…”