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Cerebrospinal Fluid and Hydrocephalus: Physiology, Diagnosis, and Treatment Andreas K

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Cerebrospinal Fluid and Hydrocephalus: Physiology, Diagnosis, and Treatment Andreas K The physiology of CSF is a complex topic, and treatment for hydrocephalus typically depends on its cause. Artwork courtesy of Julie Gilbert Pollard. Impatiens by the Creek (detail). Watercolor on paper, 12" × 12". Cerebrospinal Fluid and Hydrocephalus: Physiology, Diagnosis, and Treatment Andreas K. Filis, MD, Kamran Aghayev, MD, and Frank D. Vrionis, MD, PhD Background: Cerebrospinal fluid (CSF) is found around and inside the brain and vertebral column. CSF plays a crucial role in the protection and homeostasis of neural tissue. Methods: Key points on the physiology of CSF as well as the diagnostic and treatment options for hydrocephalus are discussed. Results: Understanding the fundamentals of the production, absorption, dynamics, and pathophysiology of CSF is crucial for addressing hydrocephalus. Shunts and endoscopic third ventriculostomy have changed the therapeutic landscape of hydrocephalus. Conclusions: The treatment of hydrocephalus in adults and children represents a large part of everyday practice for the neurologist, both in benign cases and cancer-related diagnoses. Cerebrospinal Fluid in the ventricles), whereas the total volume of CSF is 50 mL Production in newborns. The daily amount of CSF secreted is 500 mL, Approximately 70% of cerebrospinal fluid (CSF) is meaning that CSF is renewed 3 times every 24 hours. produced by the choroid plexus of the lateral ven- tricles and the tela choroidea of the third and fourth Function ventricles.1 There is also extrachoroidal secretion of Spector et al3 studied the multiple functions of CSF, CSF by the epithelium of the ependyma and by the noting that CSF serves as a cushion for the brain and capillaries via the blood–brain barrier. Choroid plex- provides buoyancy. The average adult brain alone us can develop as early as the 41st day in the embryo.2 weighs more than 1000 g, but this force is effectively In general, the volume of CSF in an adult is approxi- 10 to 15 times less with CSF. Because molecules are cir- mately 150 mL (125 mL in the subarachnoid space, 25 mL culated through the blood–brain and blood–CSF barri- ers, the neural tissue is nourished and toxic products of From the Department of Neuro-Oncology, H. Lee Moffitt Cancer metabolism are carried away. Center & Research Institute, and University of South Florida Morsani College of Medicine, Tampa, Florida. Absorption and Circulation Dr Filis is now affiliated with the Department of Neurosurgery, The CSF circulates from the lateral ventricles through Imland Klinik, Rendsburg, Germany. Dr Vrionis is now affiliated with the Marcus Neuroscience Institute, Boca Raton Regional Hos- the interventricular foramina to the third ventricle pital and the Charles E. Schmidt College of Medicine, Florida Atlan- and then via the cerebral aqueduct into the fourth tic University, Boca Raton, Florida. ventricle. From there, via the 2 lateral apertures and Received January 5, 2016; accepted August 26, 2016. median aperture, it enters the subarachnoid space Address correspondence to Andreas K. Filis, MD, Imland Klinik, Lilienstrasse 20-28, 24768 Rendsburg, Germany. E-mail: and is distributed into the cerebral hemispheres and [email protected] around the spinal cord. The spinal cord has a thin 6 Cancer Control January 2017, Vol. 24, No. 1 central canal that also contains CSF and contributes to the sinus. Similarly, the blood–brain barrier separates the distribution of CSF within the vertebral column. the brain tissue from the surrounding blood vessels. The sites of CSF absorption are mainly the arach- Both barriers selectively allow the passage of different noid villi in the superior sagittal sinus. The arach- molecules. noid villi are protrusions of the arachnoid layer into the sinus and are lined with epithelium.4 The villi are Hydrocephalus thought to function as valves. Classification Additional sites of CSF absorption include the spi- Hydrocephalus is defined as the accumulation of an nal arachnoid villi close to the epidural spinal veins and abnormal quantity of CSF in the ventricles. However, the meningeal sheaths of the spinal and cranial nerves. this description is oversimplified because hydroceph- Lymphatics located proximal to arteries and nerves are alus is multifactorial. In textbooks of neurosurgery, also part of the mechanism of CSF absorption. numerous classification schemes can be found.8,9 Gen- erally, hydrocephalus falls into the obstructive or com- Composition municating group. The CSF is a clear, colorless liquid. In an average adult External hydrocephalus is considered to be a lying down, the opening pressure of CSF as measured separate entity. The condition refers to abnormal col- via lumbar puncture is approximately 10 to 20 cm lections of CSF over the hemispheres and is a form of H2O; in a sitting individual, this pressure ranges from communicating hydrocephalus. It can be caused by in- 20 to 30 cm H2O; in children and newborns, the range fection, trauma, or prior surgery. is lower. Multiple pathologies cause obstruction at differ- In general, the CSF of an adult has fewer than ent levels. At the interventricular foramina, a colloid 5 white blood cells, a plasma glucose level of 60% to cyst or astrocytoma may cause obstruction. At the lev- 80%, and a protein level of 20 to 40 mg/100 mL, although el of the third ventricle, craniopharyngioma or optical significant differences can be observed depending on thalamic glioma may account for obstruction. Pineal where the collection of CSF was obtained. The protein cysts and solid tumors can also obstruct the cerebral level will be higher if the collection is obtained via lum- aqueduct. Gliomas, plexus papillomas, ependymo- bar puncture than if obtained via a ventricular tap. mas, and medulloblastomas are examples of possible In clinical practice, it is useful to have a method disease entities for occlusion at the level of the fourth for distinguishing between CSF and other fluids, espe- ventricle. cially in questionable cases of CSF leak. The ratio of Some causes for nonobstructive (communicating) β-2 transferrin protein in the fluid to the serum has hydrocephalus include infections that cause adhesions been proven to deliver accurate results.5 (eg, meningitis), hemorrhage following stroke, intrace- rebral bleeding, the leptomeningeal spread of cancer, Dynamics of Circulation or sinus thrombosis. A detailed description of the dynamics of CSF is be- In the fields of pediatrics and neonatology, it is yond the scope of this paper. Marmarou et al6 have important to mention the posthemorrhagic hydro- pioneered research in this field. Briefly, 3 components cephalus of prematurity related to bleeding in the are important for the dynamics of CSF, namely the subependymal germinal matrix.10,11 This condition (1) formation, (2) storage, and (3) absorption of CSF. affects premature neonates and manifests in the first In general, the formation of CSF is considered to be weeks of life. The germinal matrix is fragile, and fluc- constant under normal circumstances. The storage of tuations in cerebral blood flow can lead to subepen- CSF is proportional to the compliance of the ventricles. dymal bleeding with or without rupture to the ven- The reabsorption is proportional to the pressure gradi- tricle. Blood in the ventricle can cause obstruction of ent between CSF and the sagittal sinus and inversely the CSF pathways and subsequent posthemorrhagic proportional to flow resistance. Volumetrically, the hydrocephalus.10,11 production of CSF is equal to the storage added to ab- Chiari malformation — particularly type 2 — is as- sorption.7 Based on the equation of Marmarou et al6 for sociated with hydrocephalus, and these patients will intracerebral pressure, an increase in the production of require shunting. CSF or outflow resistance at the level of the arachnoid Normal pressure hydrocephalus can be clinically villi or at the dural sinus can lead to higher intracere- diagnosed using the Hakim triad of urinary incon- bral pressure. tinence, memory loss, and gait unsteadiness. In such cases, CSF pressure is generally below 20 cm H2O. Blood–Brain Barrier and Blood–Cerebrospinal This type of hydrocephalus can be common in older Fluid Barrier individuals, although it is not exclusive to this patient The blood–CSF barrier consists of tight junctions at population. According to a Norwegian study, the prev- the epithelial cells of the choroid villi that project into alence rates in Norway ranged from 3.3 per 100,000 January 2017, Vol. 24, No. 1 Cancer Control 7 persons aged 50 to 59 years, 49.3 per 100,000 persons drocephalus but with variable outcomes.17,18 In the field aged 60 to 69 years, to 181.7 per 100,000 persons aged of pediatric neurosurgery, endoscopic third ventricu- 70 to 79 years.12 lostomy has been used in cases of shunt failure, post- Pseudotumor cerebri syndrome (PTCS) is an en- hemorrhagic hydrocephalus, and Chiari malforma- tity that includes idiopathic intracranial hypertension tions. It has also been combined with choroid plexus and secondary PTCS (when a cause is discerned). The cauterization.19 pathogenesis of PTCS is relatively unknown, although theories have been proposed and have included ve- Conclusions nous thrombosis, increased resistance to CSF outflow, The physiology of cerebrospinal fluid is a complex top- altered vitamin A metabolism, and obesity, among oth- ic still undergoing rigorous research. Circulatory ab- ers.13 Regardless of its pathogenesis, ventriculomegaly normalities of cerebrospinal fluid are common and of- is not present in cases of PTCS,
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