Colpocephaly in adults

Abstract

Colpocephaly is a congenital abnormality in the ventricular system of the brain. The radiological diagnosis is usually made in the perinatal period and later presages intellectual disability. Adult cases of newly diagnosed colpocephaly have only rarely been reported. We have studied an adult with massive colpocephaly who is an otherwise functional woman. The diagnosis should be considered in patients with ventriculomegaly disproportionately affecting the occipital horns and must be differentiated from the more common form of adult ventriculomegaly—idiopathic normal pressure hydrocephalus (NPH).

Background

We report a striking case of colpocephaly in an otherwise functional adult. This case is of major clinical importance because it confirms that colpocephaly has a broader clinical spectrum than previously recognised. With today's disseminated use of CT and MRI, it is likely that adults with colpocephaly are encountered in clinical practice, but go misdiagnosed as normal pressure hydrocephalus (NPH). Patients with colpocephaly may also have motor and cognitive disturbances, potentiating a misdiagnosis. Knowing the respective clinical and radiological findings can aid clinicians in differentiating between the two.¹

Case presentation

A 60-year-old woman presented to the emergency room for evaluation after a series of falls. Questioning revealed lifelong gait instability. She suffered a major mechanical fall 1 month prior to presentation, resulting in minor head trauma. Since then, she reported daily headaches, worsening gait instability and increasing frequency of falls. Her medical history was significant for poor vision, and lifelong clumsiness which were said to be sequelae from congenital toxoplasmosis. Growing up, she had a reading learning disability; however, she graduated from high school with average grades, married in her 20s and had one child. She worked in a factory and most recently as a home health aide. At the time of presentation, she was disabled from blindness and lived alone, but admitted to difficulty doing housework.

She was alert, appropriately oriented and had normal language function. Mental status review showed a flattened affect and deficits in recent memory. She had bilateral vitreous opacities and cataracts. Her right pupil was unreactive, while the left pupil was only sluggishly reactive. Vision was minimally present on the left. She had normal strength, sensation and appendicular coordination. Alternating movements were slow and reflexes decreased symmetrically. Gait was wide-based and unsteady.

Investigations

Serum sodium content was 116 mmol/l. Work up was consistent with the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Non-contrast CT of the head showed massive dilation of the lateral and third ventricles. The fourth ventricle was relatively normal with no evidence of obstruction. Multiple punctate calcific densities were scattered within the brain parenchyma, consistent with congenital toxoplasmosis (figure 1). Non-contrast brain MRI revealed massive symmetrical dilation of the posterior lateral and the third ventricles, thin parieto-occipital white matter and partial agenesis of the corpus callosum. Multiple thin crescentic subdural haematomas—deemed to be subacute—were noted on fluid-attenuated inversion recovery MRI (figure 2).

Figure 1.

CT scan demonstrating ventriculomegaly and punctate calcifications within the parenchyma, consistent with the given history of congenital toxoplasmosis.

Figure 2.

Non-contrast brain MRI in the (A) axial plane showing massive dilation of the occipital horns and of the third ventricle and (B) sagittal plane, again showing massive ventriculomegaly, as well as agenesis of the corpus callosum.

Differential diagnosis

She was diagnosed with congenital colpocephaly because of the radiological findings of (1) non-obstructive ventriculomegaly (2) disproportionate dilation of the occipital horns compared to the frontal horns and (3) partial agenesis of the corpus callosum. Brain calcifications and ventriculomegaly, combined with a history of congenital blindness, were all consistent with the history of congenital toxoplasmosis. The recently decompensated gait was attributed to SIADH, which likely developed as a result of traumatic brain injury suffered in a recent fall.

Outcome and follow-up

Hyponatraemia improved with conservative management and she was discharged to a rehabilitation facility for continued gait training. On follow-up at 6 months, the patient lived in a nursing home. Her gait had improved, but she required assistance with the activities of daily living because of debilitating blindness.

Discussion

Colpocephaly is a widely recognised paediatric diagnosis, with only two other adult cases described in medical literature.^{2 3} It is a congenital form of ventriculomegaly that was first described by Benda in 1941.⁴ The original patient was a 3-year-old boy with intellectual disability, paralysis and seizures—many of the clinical features now commonly associated with the disorder. He died at the age of 10. Autopsy revealed enlarged lateral ventricles, thin and undifferentiated occipital lobes, absent corpus callosum, macrogyria and microgyria.

Colpocephaly can result from a wide range of congenital insults. Chromosomal abnormalities, maternal toxin exposure, anoxic encephalopathy and intrauterine infection, such as toxoplasmosis, have been described as potential causes. Just before the fifth month of life, the fetus undergoes a stage of relative hydrocephalus that is normally abolished by the migration of glial cells and growth of the surrounding white matter and corpus callosum.^{5 6} Any intrauterine insult that interferes with this maturation process can theoretically cause the retained fetal ventricular configuration that defines colpocephaly.

Radiologically, colpocephaly is characterised by disproportionate dilation of the occipital horns and is commonly associated with full or partial agenesis of the corpus callosum.⁷ In fact, both previously published adult cases were associated with complete agenesis of the corpus callosum, while our patient had partial agenesis of the corpus callosum. Other radiological associations include microcephaly, myelocele, macrogyria, microgyria, schizencephaly, lissencephaly, pachygyria, cerebellar atrophy and optic nerve atrophy.⁸

In contrast, idiopathic NPH is an adult onset form of progressive ventriculomegaly. It was originally described as causing the clinical triad of disabling dementia, gait disturbance and urinary incontinence.⁹ The diagnosis of “probable” NPH is made by demonstrating at least two of the three features in the clinical triad, a normal cerebrospinal fluid pressure at lumbar puncture and the presence of non-obstructive dilation of the ventricular system that is disproportionate to the level of brain atrophy^{10 11} (table 1). Early in the course, there may be transependymal flow in the periventricular white matter or dilation of the temporal horns. With disease progression, the lateral ventricles are affected, culminating in ballooning of the frontal horns. Quantitative measures include the Evans index, callosal angle, aqueductal flow rate, apparent diffusion coefficient and intracranial compliance index.^12–15

Table 1.

Diagnostic criteria for idiopathic NPH based on Japanese Guidelines from 2008

Possible NPH	1. Symptoms develop at the age of 60 or older 2. Two of three symptoms from clinical triad (dementia, gait disturbance and urinary incontinence) 3. Ventricular dilation with Evans index greater than 0.3 4. Normal CSF pressure and profile 5. Neurological symptoms cannot be explained by another diagnosis 6. No preceding disease causing ventricular dilation, including subarachnoid haemorrhage, meningitis, head injury, congenital hydrocephalus and aqueductal stenosis
Probable NPH	1. Meets requirements for ‘possible idiopathic NPH’ 2. Meets one of the following: (a) improvement of symptoms after CSF tap test, (b) improvement of CSF after CSF drainage test, (c) abnormality in cerebral fluid outflow resistance measurement and intracranial pressure monitoring
Definite NPH	Improvement of symptoms after a CSF shunting procedure

NPH, normal pressure hydrocephalus; CSF, cerebrospinal fluid.

Colpocephaly can also be assessed quantitatively. The posterior to anterior ratio (P/A ratio) was originally described by Noorani, Bodensteiner and Barnes as a measure of occipital horn enlargement. To calculate, the maximal width of the occipital horn is divided by the maximal width of the anterior horn of the lateral ventricle (figure 3). Disproportionate enlargement of the occipital horns was defined as a P/A ratio ≥3, and was found positive in 7 of the 14 patients in the original cohort. In the remaining cases, diagnosis of colpocephaly was based on the recognition of the characteristic configuration of the lateral ventricles. In the right clinical setting, a P/A ratio ≥3 is highly specific for colpocephaly and may be used as a diagnostic tool to distinguish colpocephaly from NPH. Because of the low sensitivity, one must also take into account the history and physical examination findings.

Figure 3.

The posterior to anterior (P/A) ratio is calculated by taking the maximal width of the posterior horn and dividing by the maximal width of the anterior horn of the lateral ventricle. A ratio ≥3 is specific for colpocephaly.

When encountering ventriculomegaly in an adult, one must distinguish between the different forms of obstructive and non-obstructive ventriculomegaly. We propose that colpocephaly be considered in the differential for adults with non-obstructive ventriculomegaly. When secondary causes have been ruled out, distinguishing between colpocephaly and NPH can be done through a careful history, physical examination and evaluation of the radiological characteristics. Doing so can prevent the iatrogenic risk associated with surgical shunting.¹⁶

Learning points.

• Colpocephaly is a form of congenital ventriculomegaly, characterised by non-obstructive ventriculomegaly, disproportionate dilation of the occipital horns and often associated with partial or full agenesis of the corpus callosum.

• Clinically, colpocephaly is associated with motor abnormalities, intellectual disability, vision problems and seizures.

• When encountered radiologically, colpocephaly must be distinguished from normal pressure hydrocephalus (NPH).

• The posterior to anterior ratio ratio may aid in distinguishing colpocephaly from NPH.