Longstanding overt ventriculomegaly diagnosed in adolescents, not adults: a pediatric case report

Longstanding overt ventriculomegaly in adults (LOVA) is a new form of progressive hydrocephalus characterized by onset in early childhood and gradual progression into adulthood. Patients with LOVA are usually asymptomatic in childhood. The diagnosis of LOVA in adolescence has not been reported. A patient with macrocephaly and mild ventriculomegaly from infancy developed headache exacerbation and cognitive dysfunction at the age of 11 years. Brain magnetic resonance imaging showed mild tri-ventriculomegaly with no radiological aggravation compared to imaging at the age of 8 years. No papilledema was observed. Drainage of 15 ml of spinal fluid via a lumbar puncture relieved the headache and cognitive dysfunction. Based on repeated improvements in cognitive function and headaches after spinal fluid drainage, we diagnosed the patient with LOVA with symptom onset in early adolescence. A ventriculoperitoneal shunt was placed, and the headaches disappeared completely. The full-scale intellectual quotient, verbal comprehension, and working memory improved significantly. LOVA may manifest as early as adolescence. The clinical presentation, age, clinical, radiological features, and management vary, and a spinal tap exam is useful for diagnosing LOVA, even in children. The spinal tap exam may be indicated in children with longstanding ventriculomegaly and deteriorating neurological symptoms to diagnose this “treatable intellectual disability.”


Introduction
Normal pressure hydrocephalus (NPH) is very rare in childhood. A group of chronic hydrocephalus that begins in infancy and manifests in adulthood after a long and slow clinical course leads to early onset NPH. It is known as longstanding overt ventriculomegaly in adults (LOVA) [1]. Recent reports emphasize wide variations in the age of symptom onset, clinical and radiological features, and management in patients with LOVA [2]. However, only a few reports describe adolescent-onset cases. We report an adolescent case of LOVA treated at the age of 11 years. To the best of our knowledge, this is the youngest age reported for the diagnosis of LOVA. The patient was successfully treated with a ventriculoperitoneal (VP) shunt.

Case report
An 11-year-old male patient with macrocephaly from birth, mild ventriculomegaly, and mild psychomotor developmental delay was referred to our neurology division due to worsening headaches since childhood and cognitive dysfunction. His head circumference was above the 97th percentile (Fig. 1). On examination, the patient was alert and oriented but showed marked apathy and executive dysfunction. Fundoscopy showed no papilledema. Brain magnetic resonance imaging showed mild tri-ventriculomegaly (Evans index, 0.36), which did not change over three years (Fig. 2).

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Laboratory findings and electroencephalogram were normal. Thorough neuropsychological tests were performed before lumbar puncture (LP), including the Wechsler Intelligence  shows mild enlargement of the lateral ventricles and third ventricle, but no progression over 3 years. Sagittal MRI at age 11 shows no expanded or destroyed sella turcica and no obvious stenosis of aqueductal stenosis (SCWT, Fig. 3). The WISC-IV revealed predominantly low scores on the Verbal Comprehension Index and Processing Speed Index. Although MMSE and FAB were normal, the patient was mute for more than 1 min during the SCWT and finished the test without reading a single letter. LP under sedation showed high opening cerebrospinal fluid (CSF) pressure (45 cm H 2 O) with normal cell counts, protein levels, and cytology. The headache and apathy improved immediately after the removal of 15 ml of spinal fluid. We suspected progressive hydrocephalus. When the neuropsychological examination was repeated after the LP, the time required for the SCWT improved (Table 1). Communicating hydrocephalus was identified using 111In-diethylenetriaminepentaacetic acid cisternography.
We confirmed the improvements in cognitive functions before and after CSF drainage three times at 2-3-month intervals. No increase in the opening CSF pressure occurred at the second and third spinal taps. After placement of a VP shunt, the headaches disappeared and the WISC-IV and SCWT improved (Table 1). One year after VP shunt placement, the headaches did not recur. The patient is cooperative and enthusiastic about school activities, but mild to moderate intellectual disability remains.

Discussion
Longstanding ventriculomegaly without obvious symptoms of elevated intracranial pressure (ICP) is common in children. It is difficult to determine whether it is due to the brain structure or hydrocephalus because even modern imaging alone cannot distinguish between both entities. In fact, a c b Con gru ou s con dition bla ck Con gru ou s con dition color Color-Word con dit ion Fig. 3 Stroop Color and Word Test (SCWT) from our institution (written in kanji-Japanese characters). In the SCWT, patients are required to read three different tables as fast as possible. Two of them represent the "congruous condition" in which participants are required to read names of colors printed in black ink or color ink (  [2]. The pathophysiology of LOVA involves full or partial obstruction of CSF flow through the aqueduct of Sylvius before closure of the cranial sutures during infancy, followed by the creation of new CSF dynamics and a compensatory phase. This is why they are asymptomatic during childhood. The only symptom during childhood is an enlarged head circumference to compensate for the hydrocephalus. Later, during adulthood, the symptomatic phase of LOVA begins due to the failure of the compensatory phase [1,5].
In patients with LOVA, frontal lobe dysfunction is prominent [5]. In our case, apathy was the main symptom. The patient exhibited no MMSE or FAB abnormalities, but the SCWT revealed frontal lobe dysfunction. The SCWT is widely used to assess attention, processing speed, cognitive flexibility, and working memory [6]. The SCWT, which can be administered to participants who know letters and colors, is simple and appropriate for adolescents. Cognitive dysfunction in LOVA significantly improves after CSF bypass if the surgery is performed early. Delayed treatment is less likely to be effective [7]. Therefore, patients with longstanding ventriculomegaly should undergo neuropsychological testing as early as possible, especially if cognitive dysfunction is suspected.
Preoperative prediction of prognosis after surgery for LOVA remains under investigation [8]. The tap test, as in the case of NPH, is most widely used to predict the response to shunt surgery [9]. It is easy to perform and cost-effective. The amount of CSF removed (at least 30 mL in a typical adult) should be sufficient to improve CSF dynamics and symptoms [10]. In our patient, more than half of the standard adult volume was routinely drained and used as a tap test. The patient's symptoms improved when at least 15 mL of CSF was drained, and we considered this CSF volume reasonable for a child. Drainage was performed in a short time with no complications. The tap test should be considered before invasive testing in children with suspected chronic hydrocephalus.
Treatment of LOVA is either endoscopic third ventriculostomy or a VP shunt. Current evidence indicates that both treatments have similar success rates, with endoscopic third ventriculostomy having fewer complications [11], but salvage VP shunts may commonly occur with endoscopic third ventriculostomy [12].
The strength of this report is the reproducibility of improvements in cognitive function confirmed by repeated neuropsychological testing before and after the tap tests. Although the evidence for the tap test in children has not been established, this case report supports its efficacy. Opening CSF pressure may reflect abnormal intracranial pressure during sleep due to sedation or the position of the testing.

Conclusion
LOVA may manifest as early as adolescence. While patients with LOVA exhibit wide variations in presentation, age, clinical and radiological features, and management, the tap test is useful for diagnosis, even in children. The tap test may be indicated in children with longstanding ventriculomegaly and neurological symptoms to diagnose this "treatable intellectual disability."