Physiology of the CSF Circulation
The CSF is produced mainly by the choroid plexus in the lateral ventricles. The choroid plexus consists of connective tissue core lined by epithelium in villous folds within the brain ventricles.
The CSF is produced by carbonic anhydrase dependent active transport system which can be blocked by carbonic anhydrase inhibitors e.g. acetazolamide. A smaller amount of the CSF is produced through diffusion from the cerebral tissue which acts as brain lymph. The total amount of CSF in the adult is approximately 150ml, while in infants it is 50ml.
The CSF circulates through a pair of lateral ventricles that connect to the midline third ventricle through foramen of Monro. The third ventricle connects with the fourth ventricle through the aqueduct of Sylvius where the CSF circulates through two foramina of Luschka and one foramen of Magendie.
Absorption of the CSF occurs through the arachnoid villi, which drains into the systemic venous channels in the sagittal venous sinus. Arachnoid villi are protruded cells from subarachnoid space into the sinuses to allow passive absorption of CSF into the sinuses according to the pressure gradient.
Classification of Hydrocephalus
- Communicating hydrocephalus: the increased intracranial pressure is due to deficient absorption or increased production of the CSF in the subarachnoid space. There is no anatomical obstruction in the normal CSF circulation.
- Non-communicating (obstructive) hydrocephalus: the increased intracranial pressure is due to anatomical obstruction of the CSF flow inside the ventricular system.
- Normal pressure hydrocephalus occurs mainly in adults where the ventricles are enlarged but with no increase in the intracranial pressure.
Pathology of Hydrocephalus
Obstructive hydrocephalus: anatomical obstruction to the CSF flow will lead to elevated pressure and subsequent dilatation of the ventricle proximal to the obstruction. The obstruction can be at the level of the fourth ventricle, foramen of Monro or Aqueduct of Sylvius.
Excessive CSF production: CSF production exceeds the rate of absorption which may be due to CSF secreting choroid plexus papilloma. The CSF pressure increases with dilatation of the ventricular system with no anatomical obstruction.
Impaired CSF absorption: impaired absorption can occur due to inflammation of the arachnoid villi or elevated pressure in the venous sinuses.
Increased CSF pressure will lead to enlargement of the head in infants before fusion of the skull sutures. Further pressure on the brain parenchyma will lead to compression of the brain tissue with edema, ischemia and disruption of the ependymal lining of the ventricles.
Eventually, this will lead to atrophy of the white matter with flattening of brain gyri and sulci, demyelination and axonal degeneration. The pathology is more dramatic in adults after fusion of the skull sutures and with acute hydrocephalus with a rapid increase in the intracranial pressure.
Etiology of Hydrocephalus
Neural tube defects and CNS malformations
- Chiari II malformation associated with myelomeningocele and encephalocele. The brain stem and cerebellum is displaced caudally leading to obstruction of the CSF flow into the spinal canal.
- Dandy-Walker malformation is characterized by a large cyst in the posterior fossa with mal-development of the cerebellum. The CSF flow is obstructed by atresia of the foramina of Luschka and foramen of Magendie.
- Bickers-Adams syndrome is an X-linked disease with congenital stenosis of the aqueduct and mental retardation associated with adduction flexion of the thumb.
Intrauterine infection: Rubella, syphilis, toxoplasma, Zika virus and the cytomegalo virus all are responsible for congenital hydrocephalus. The inflammation and subsequent fibrosis and calcification can lead to obstruction of the CSF flow or decrease its absorption.
Aqueduct stenosis: responsible for isolated hydrocephalus due to congenital narrowing or intrauterine infection or sometimes maternal antidepressants use during pregnancy.
Choroid plexus papilloma can cause increased CSF production and communicating type hydrocephalus.
- Subarachnoid hemorrhage: Bleeding in the ventricles or the subarachnoid space leads to impaired CSF absorption and obstruction of the CSF flow. It can cause communicating and obstructive hydrocephalus in both adults and premature infants.
- Infections: e.g. meningitis and encephalitis can lead to impaired CSF absorption or obstruction of the flow with fibrosis and anatomical distortion.
- Tumors: e.g. ependymomas, pineal body tumors and posterior fossa tumors can lead to obstructive hydrocephalus.
Clinical Picture of Hydrocephalus
For infants with hydrocephalus, the first symptom is usually an enlarged head with failure to thrive and developmental delays. Older children will have different complaints similar to adults with persistent headache, nausea, vomiting, neck pain, blurring of vision, diplopia, gait disturbance and focal neurological lesions related to the etiology of increased intracranial pressure. Enlargement of the third ventricle can lead to precocious puberty and short stature.
In adults, the complaints are usually headache, nausea, vomiting, vision abnormalities, behavioral changes and sometimes confusion and disturbed conscious level in acute cases.
Manifestations of increased intracranial pressure in infants will include enlarged head circumferences in serial measurements, prominent scalp veins and bulging anterior fontanelle. Frontal bossing is the abnormal contour of the skull with prominent forehead in hydrocephalus, as well as abnormal percussion note can be noted over the spread skull sutures.
Enlarged head with bossing of the forehead make the sclera visible above the iris which is known as the sun set. The upward gaze is also impaired due to increased pressure on the brain stem. Focal neurological signs include spasticity of the lower limbs. Eye examination for diplopia and ophthalmoplegia from a stretch of the abducent or oculomotor nerve. Papilledema will be more evident in adults than children.
Hydrocephalus in which there is no actual increase in the CSF opening pressure but the ventricular size are enlarged is more common in adults over 60 with a clinical presentation of dementia, gait disturbances and urinary incontinence.
Normal Pressure Hydrocephalus
This condition may be idiopathic with no identifiable cause and maybe secondary to subarachnoid hemorrhage, viral meningitis or chronic inflammation and fibrosis, leading to impaired absorption of the CSF which accumulates inside the ventricles causing pressure and stretch on the periventricular white matter.
Gait disturbances are characterized by being slow and short. The patient’s legs are stuck to the ground externally rotated with little elevation and little forward progress. Falls are common and slow movement is evident. The gait usually improves dramatically after shunting or lowering the CSF pressure in these patients.
- Urinary symptoms in the form of urgency and incontinence.
- Dementia, depression and apathy are prominent early in the course of NPH. Cognitive impairment, psychomotor retardation and diminished attention span are all characteristics of NPH due to cortical ischemia. In late stages, patients may exhibit frontal release signs e.g. grasping reflex and suckling reflex.
Differential diagnosis of NPH
Alzheimer disease: presents with dementia but motor involvement and gait abnormality are late in the course of the disease.
Vascular dementia: dementia and focal neurological lesions but with a history of vascular disease and previous stroke. Upper motor neuron lesions can be seen with vascular dementia, while behavioral changes and urinary incontinence is more common with NPH.
Parkinson’s disease: presents with gait abnormality and sometimes depression with chronic illness, but cognitive impairment is not common with Parkinson’s disease as with NPH.
Imaging in Hydrocephalus
Ultrasonography is an excellent imaging for antenatal assessment of neural tube defects and for congenital anomalies. Measurement of the ventricular size can be achieved safely to detect any enlargement. Ultrasound can be used in early infancy to assess for ventricular enlargement.
CT & MRI are used in older children and adults to assess the brain anatomy and CSF flow. An MRI can detect small lesions in the brain, especially in the CSF physiologic pathway.
Diffusion tensor imaging (DTI) is used to assess the changes in the periventricular white matter due to elevated CSF pressure.
Lumbar puncture and assessment of the opening pressure can be diagnostic in some cases, but are contraindicated before brain imaging to exclude any space occupying lesion and avoid herniation of the brain stem during the procedure. CSF analysis can help in patients with infectious origin. Lumbar puncture and drainage of 50 ml of CSF with the improvement of gait and cognitive function within 60 minutes is considered a good predictive test for efficacy of shunting in cases with normal pressure hydrocephalus.
Radiologic findings of hydrocephalus: it is important to know what you should look for in imaging to detect cases early and avoid late presentation and complications. Dilatation of the temporal and frontal horns of the lateral ventricles, elevation of the corpus callosum, stretching of the septum pellucidum with interstitial edema and compression of the brain sulci are all signs of increased CSF pressure.
Treatment of Hydrocephalus
Medical therapy with furosemide and acetazolamide is sometimes used to lower the CSF production and pressure. It is a temporary solution before surgery.
External ventricular drain (EVD) or endoscopic third ventriculostomy (ETV) can be performed urgently to lower high CSF pressure in acute hydrocephalus. Ventriculostomy can be life-saving in some patients with the acute rapid rise of the intracranial pressure.
EDV allows CSF drainage via a catheter inserted through the skull with a collecting device, while ETV opens a hole in the third ventricular floor endoscopically to allow CSF drainage into the subarachnoid space. Endoscopic third ventriculostomy may be combined with choroid plexus cauterization for a better outcome. ETV is contraindicated in the case of communicating hydrocephalus and has no beneficial outcome.
CSF is allowed to drain from the ventricles into the systemic circulation, or the peritoneal cavity where it is easily absorbed to bypass the site of obstruction or the increased CSF secretion. A catheter is placed in the frontal horn of one of the lateral ventricles and connected to a one way valve that opens upon elevation of the pressure inside the ventricle. The valve is connected to a catheter that drains into the peritoneal space (ventriculoperitoneal shunt) which is the most common, right heart atrium (ventriculoatrial) or pleural space (ventriculopleural).
Lumpoperitoneal shunt can be used in communicating hydrocephalus by connecting the spinal canal with the peritoneal space, but it will not be effective in the case of obstructive hydrocephalus.
Complications of surgical intervention
- Over-drainage of CSF after shunting with constant headaches and sometimes subdural hemorrhage are frequent complications following shunting.
- Intracranial infection following surgery or years after. Subclinical infection may lead to fibrosis and shunt malfunctioning. Infection following surgery or malfunctioning shunt requires removal and replacement after resolution of the infection.
- Malfunctioning shunt: the patient will present with worsening symptoms of increased intracranial pressure, i.e. headaches, nausea, vomiting and papilledema. Shunt tapping will demonstrate diminished flow, while the CSF pressure will remain elevated. Treatment is usually shunt replacement.
- Seizures are common in children with shunt placement due to subarachnoid hemorrhage, infection or trauma. Seizures can affect the cognitive outcome in affected patients.
- Abdominal injury, visceral perforation or injury during shunt placement.