Editing Cerebrospinal fluid (section)

==Clinical significance==
===Pressure===
{{Further|Cerebral shunt}}
'''CSF pressure''', as measured by [[lumbar puncture]], is 10–18&nbsp;[[Centimetre of water|cmH<sub>2</sub>O]] (8–15&nbsp;[[mmHg]] or 1.1–2&nbsp;[[kilopascal|kPa]]) with the patient lying on the side and 20–30 cmH<sub>2</sub>O (16–24&nbsp;mmHg or 2.1–3.2&nbsp;kPa) with the patient sitting up.<ref>{{cite web|url=http://neuropathology-web.org/chapter14/chapter14CSF.html|title=Chapter 14 – Cerebrospinal Fluid :THE NORMAL CSF|date=May 2011|publisher=Northeast Ohio Medical University|work=Neuropathology| first = Dimitri | last = Agamanolis | name-list-style = vanc |access-date=2014-12-25}}</ref> In newborns, CSF pressure ranges from 8 to 10 [[centimetre of water|cmH<sub>2</sub>O]] (4.4–7.3&nbsp;mmHg or 0.78–0.98&nbsp;kPa). Most variations are due to coughing or internal compression of [[jugular vein]]s in the neck. When lying down, the CSF pressure as estimated by lumbar puncture is similar to the [[intracranial pressure]].

[[Hydrocephalus]] is an abnormal accumulation of CSF in the ventricles of the brain.<ref name=DAVIDSONS2010B>{{cite book |editor1-first=Nicki R. |editor1-last=Colledge |editor2-first=Brian R. |editor2-last=Walker |editor3-first=Stuart H. |editor3-last=Ralston | name-list-style = vanc |title=Davidson's principles and practice of medicine |year=2010 |publisher=Churchill Livingstone/Elsevier |location=Edinburgh |isbn=978-0-7020-3084-0 |edition=21st |pages=1220–1}}</ref> Hydrocephalus can occur because of [[obstructive hydrocephalus|obstruction]] of the passage of CSF, such as from an infection, injury, mass, or [[congenital abnormality]].<ref name=DAVIDSONS2010B /><ref name=NIH2017 /> [[normal pressure hydrocephalus|Hydrocephalus without obstruction associated with normal CSF pressure]] may also occur.<ref name=DAVIDSONS2010B /> Symptoms can include [[gait dysfunction|problems with gait]] and [[Motor coordination|coordination]], [[urinary incontinence]], [[nausea]] and [[vomiting]], and progressively impaired [[cognition]].<ref name=NIH2017 /> In infants, hydrocephalus can cause an enlarged head, as the bones of the skull have not yet fused, seizures, irritability and drowsiness.<ref name=NIH2017 /> A [[CT scan]] or [[MRI scan]] may reveal enlargement of one or both lateral ventricles, or causative masses or lesions,<ref name=DAVIDSONS2010B /><ref name=NIH2017 /> and [[lumbar puncture]] may be used to demonstrate and in some circumstances relieve high intracranial pressure.<ref name=HARRISONS2015>{{cite book |last1=Kasper |first1=Dennis |last2=Fauci |first2=Anthony |last3=Hauser |first3=Stephen |last4=Longo |first4=Dan |last5=Jameson |first5=J. |last6=Loscalzo |first6=Joseph | name-list-style = vanc |title=Harrison's Principles of Internal Medicine|date=2015|publisher=McGraw-Hill Professional|isbn=978-0-07-180215-4|edition=19|pages=2606–7}}</ref> Hydrocephalus is usually treated through the insertion of a [[Cerebral shunt|shunt]], such as a [[ventriculo-peritoneal shunt]], which diverts fluid to another part of the body.<ref name=DAVIDSONS2010B /><ref name="NIH2017">{{cite web|title=Hydrocephalus Fact Sheet|url=https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Hydrocephalus-Fact-Sheet|website=www.ninds.nih.gov|publisher=National Institute of Neurological Disorders and Stroke|access-date=19 May 2017}}</ref>

[[Idiopathic intracranial hypertension]] is a condition of unknown cause characterized by a rise in CSF pressure. It is associated with headaches, [[double vision]], difficulties seeing, and a [[Papilledema|swollen optic disc]].<ref name=DAVIDSONS2010B /> It can occur in association with the use of vitamin A and [[tetracycline]] antibiotics, or without any identifiable cause at all, particularly in younger [[obese]] women.<ref name=DAVIDSONS2010B /> Management may include ceasing any known causes, a [[carbonic anhydrase inhibitor]] such as [[acetazolamide]], repeated drainage via lumbar puncture, or the insertion of a shunt such as a ventriculo-peritoneal shunt.<ref name=DAVIDSONS2010B />

===CSF leak===
{{main|Cerebrospinal fluid leak}}
CSF can leak from the [[dura mater|dura]] as a result of different causes such as physical trauma or a lumbar puncture, or from [[idiopathy|no known cause]] when it is termed a [[spontaneous cerebrospinal fluid leak]].<ref name=DAVIDSONS2010 /> It is usually associated with [[intracranial hypotension]]: low CSF pressure.<ref name=HARRISONS2015 /> It can cause headaches, made worse by standing, moving and coughing,<ref name=HARRISONS2015 /> as the low CSF pressure causes the brain to "sag" downwards and put pressure on its lower structures.<ref name=HARRISONS2015 /> If a leak is identified, a [[beta-2 transferrin]] test of the leaking fluid, when positive, is highly specific and sensitive for the detection for CSF leakage.<ref name=DAVIDSONS2010>{{cite book |editor1-first=Nicki R. |editor1-last=Colledge |editor2-first=Brian R. |editor2-last=Walker |editor3-first=Stuart H. |editor3-last=Ralston | name-list-style = vanc |title=Davidson's principles and practice of medicine |year=2010 |publisher=Churchill Livingstone/Elsevier |location=Edinburgh |isbn=978-0-7020-3084-0 |edition=21st |pages=1147–8}}</ref> [[Medical imaging]] such as CT scans and MRI scans can be used to investigate for a presumed CSF leak when no obvious leak is found but low CSF pressure is identified.<ref name="PALDINO2003">{{cite journal | vauthors = Rosen CL | title = Meningiomas: the role of preoperative angiography and embolization | journal = Neurosurgical Focus | volume = 15 | issue = 4 | pages = 1 p following ECP4 | date = October 2003 | pmid = 15376362 | doi = 10.3171/foc.2003.15.6.8 | doi-access = free }}</ref> [[Caffeine]], given either orally or [[intravenous]]ly, often offers symptomatic relief.<ref name=PALDINO2003 /> Treatment of an identified leak may include injection of a person's blood into the epidural space (an [[epidural blood patch]]), [[spinal surgery]], or [[fibrin glue]].<ref name=PALDINO2003 />

===Lumbar puncture===
[[Image:4 vials of human cerebrospinal fluid.jpg|thumb|Vials containing human cerebrospinal fluid]]
{{Main|Lumbar puncture}}
CSF can be tested for the diagnosis of a variety of [[neurological disease]]s, usually obtained by a procedure called lumbar puncture.<ref name=AMP2003>{{cite journal | vauthors = Seehusen DA, Reeves MM, Fomin DA | title = Cerebrospinal fluid analysis | journal = American Family Physician | volume = 68 | issue = 6 | pages = 1103–8 | date = September 2003 | pmid = 14524396 | url = http://www.aafp.org/afp/20030915/1103.html | access-date = 2009-03-05 | archive-date = 2008-05-15 | archive-url = https://web.archive.org/web/20080515204056/http://www.aafp.org/afp/20030915/1103.html | url-status = dead }}</ref> Lumbar puncture is carried out under sterile conditions by inserting a needle into the subarachnoid space, usually between the third and fourth [[lumbar vertebrae]]. CSF is extracted through the needle, and tested.<ref name=DAVIDSONS2010 /> About one third of people experience a headache after lumbar puncture,<ref name=DAVIDSONS2010 /> and pain or discomfort at the needle entry site is common. Rarer complications may include bruising, [[meningitis]] or ongoing post lumbar-puncture leakage of CSF.<ref name=WRIGHT2012/>

Testing often includes observing the colour of the fluid, measuring CSF pressure, and counting and identifying [[white blood cell|white]] and [[red blood cell]]s within the fluid; measuring protein and glucose levels; and [[Microbiological culture|culturing]] the fluid.<ref name=DAVIDSONS2010 /><ref name="AMP2003" /> The presence of red blood cells and [[xanthochromia]] may indicate [[subarachnoid hemorrhage]]; whereas [[central nervous system]] infections such as [[meningitis]], may be indicated by elevated white blood cell levels.<ref name=AMP2003/> A CSF culture may yield the [[microorganism]] that has caused the infection,<ref name="DAVIDSONS2010"/> or [[Polymerase chain reaction|PCR]] may be used to identify a viral cause.<ref name="AMP2003" /> Investigations to the total type and nature of proteins reveal point to specific diseases, including [[multiple sclerosis]], [[paraneoplastic syndrome]]s, [[systemic lupus erythematosus]], [[neurosarcoidosis]], [[cerebral angiitis]];<ref name="WRIGHT2012" /> and specific [[antibodies]] such as [[aquaporin-4]] may be tested for to assist in the diagnosis of [[autoimmune]] conditions.<ref name=WRIGHT2012/> A lumbar puncture that drains CSF may also be used as part of treatment for some conditions, including [[idiopathic intracranial hypertension]] and [[normal pressure hydrocephalus]].<ref name=WRIGHT2012/>

Lumbar puncture can also be performed to measure the [[intracranial pressure]], which might be increased in certain types of [[hydrocephalus]]. However, a lumbar puncture should never be performed if increased intracranial pressure is suspected due to certain situations such as a tumour, because it can lead to fatal [[brain herniation]].<ref name=DAVIDSONS2010 />

===Anesthesia and chemotherapy===
{{See also|Blood–cerebrospinal fluid barrier}}
Some [[anesthetic]]s and [[chemotherapy]] drugs are injected [[intrathecal]]ly into the subarachnoid space, where they spread around CSF, meaning substances that cannot cross the [[blood–brain barrier]] can still be active throughout the central nervous system.<ref name=HOCKING2004/><ref>{{cite web|title=Intrathecal Chemotherapy for Cancer Treatment {{!}} CTCA|url=http://www.cancercenter.com/treatments/intrathecal-chemotherapy/|website=CancerCenter.com|access-date=22 May 2017|archive-date=1 January 2018|archive-url=https://web.archive.org/web/20180101135319/https://www.cancercenter.com/treatments/intrathecal-chemotherapy/|url-status=dead}}</ref>  [[Baricity]] refers to the density of a substance compared to the density of human cerebrospinal fluid and is used in [[regional anesthesia]] to determine the manner in which a particular drug will spread in the [[intrathecal]] space.<ref name="HOCKING2004">{{cite journal | vauthors = Hocking G, Wildsmith JA | title = Intrathecal drug spread | journal = British Journal of Anaesthesia | volume = 93 | issue = 4 | pages = 568–78 | date = October 2004 | pmid = 15220175 | doi = 10.1093/bja/aeh204 | doi-access = free }}</ref>

===Liquorpheresis===

Liquorpheresis is the process of filtering the CSF in order to clear it from endogen or exogen pathogens. It can be achieved by means of fully implantable or extracorporeal devices, though the technique remains experimental today.<ref>{{Cite book |last=Menendez-Gonzalez |first=Manuel |title=Liquorpheresis: Cerebrospinal Fluid Filtration to Treat CNS Conditions |publisher=Springer Cham |year=2023 |isbn=978-3-031-43481-5 |edition=First |location=London |publication-date=November 2023 |pages=1–67 |language=English}}</ref>
===CSF drug delivery===
CSF drug delivery refers to a number of methods designed to administer therapeutic agents directly into the CSF, bypassing the BBB to achieve higher drug concentrations in the CNS. This technique is particularly beneficial for treating neurological disorders such as brain tumors, infections, and neurodegenerative diseases. Intrathecal injection, where drugs are injected directly into the CSF via the lumbar region, and intracerebroventricular injection, targeting the brain's ventricles, are common approaches. These methods ensure that drugs can reach the CNS more effectively than systemic administration, potentially improving therapeutic outcomes and reducing systemic side effects. Advances in this field are driven by ongoing research into novel delivery systems and drug formulations, enhancing the precision and efficacy of treatments.
Intrathecal pseudodelivery refers to a particular drug delivery method where the therapeutic agent is introduced into a reservoir connected to the intrathecal space, rather than being released into the CSF and distributed throughout the CNS. In this approach, the drug interacts with its target within the reservoir, allowing for changing the composition of the CSF without systemic release. This method can be advantageous for maximizing efficacy and minimizing systemic side effects. 
<ref>{{Cite journal |last1=Sun |first1=Wujin |last2=Gu |first2=Zhen |date=2016-03-03 |title=ATP-Responsive Drug Delivery Systems |journal=Expert Opinion on Drug Delivery |language=en |volume=13 |issue=3 |pages=311–314 |doi=10.1517/17425247.2016.1140147 |issn=1742-5247 |pmc=4998835 |pmid=26745457}}</ref>