CEREBROSPINAL FLUID -ANATOMICAL

SPACES,PHYSIOLOGY,DISORDERS.
DR.T.ABHILASH
3-7-2018
 TOPICS TO BE COVERED
• History
• Anatomy of CSF-Related Spaces and Barriers Between Blood,
CSF,and Brain
• Physiology and Constituents of CSF
• Techniques, Contraindications,and Complications of CSF
Collection Procedures
• CSF in Clinical Syndromes
• Hydrocephalus
• ICP Monitoring and Management of Raised ICP
 History

• The Edwin Smith Papyrus dates back to 1500 BC- 48 Case reports of
traumatic injuries to brain,spinal cord,peripheral nerves.Case number six is
of utmost interest with respect to CSF.

• Herophilus described the fourth ventricle,meninges, and his name is still

associated with the confluence of sinuses, the torcula Herophili.Also, the
choroid plexus appears in his scripts for the first time.

• Torack referred to Galen(AD 129–216), discovering the CSF.

• Wax cast of the ventricular system by da Vinci (probably from an ox’s
brain)

• Antonio Pacchioni precisely described the arachnoid granulations, and

he still stands for these structures eponymously(Pacchionus 1705 ).

• The first to describe the inter-ventricular foramen in a distinct and accurate

way was Alexander Monro secundus, (Monro 1783 ). Monro was a
Scottish anatomist at the University of Edinburgh.
• The connection between the third and fourth ventricle, the aqueduct, has been
described in full detail for the first time by Franciscus Sylvius after whom also
the lateral cerebral sulcus is named.

• CSF production by the choroid plexus was introduced by Willis and finally
established by von Luschka (Willis 1664 ).

• CSF absorption by the arachnoid granulations was acknowledged by the

landmark publication of Key and Retzius (Key and Retzius 1876 ).
• Heinrich Irenaeus Quincke (Quincke 1891)was the first to perform
diagnostic lumbar puncture .

• Ludwig Lichtheim who first performed quantitative CSF analyses by

determining protein and glucose in patients with tubercular meningitis
(Lichtheim 1893 ).

• William Mestrezat gave a comprehensive account of normal values in the

CSF for protein and glucose concentrations as well as pressure and cell
constitutions (Mestrezat 1911 ).

• Elvin Kabat introduced electrophoresis in clinical neurology.

 Anatomy,Cisterns,Barriers
• The anatomy of CSF spaces comprises all intracerebral ventricles, spinal and
brain subarachnoid spaces, such as cisterns and sulci, and the central canal
of the spinal cord .

• The total volume of CSF space is between 90 and 150 mL in adults,and

the spinal CSF space (subarachnoid space) makes up about 30 mL.

• These compartments of the CNS are separated by a barrier system (blood-

brain barrier (BBB) and blood-CSF barrier (BCB) which is important for
maintenance of the cerebral environment and protection of the brain from the
systemic circulation.
• The ventricular system is comprised of four interconnected
CSFfilled,ependymal-lined cavities that lie deep within the brain.

• The paired lateral ventricles communicate with the third ventricle via the Y-
shaped foramen of Monro.

• The third ventricle communicates with the fourth ventricle via the cerebral
aqueduct (of Sylvius).
•

• In turn, the fourth ventricle

communicates with the SAS via its
outlet foramina (the midline
foramen of Magendie and the two
lateral foramina of Luschka).
 Lateral ventricles

• Each lateral ventricle has a body, atrium,and three projections ("horns").

• The roof of the frontal horn is formed by the corpus callosum genu. It is
bordered laterally and inferiorly by the head of the caudate nucleus.

• The septi pellucidi is a thin, bilayered membrane that extends from the
corpus callosum genu anteriorly to the foramen of Monro posteriorly and
forms the medial borders of both frontal horns.
• The body of the lateral ventricle passes posteriorly
under the corpus callosum. Its floor is formed by the
dorsal thalamus and its medial wall is bordered by the
fornix. Laterally, it curves around the body and tail of the
caudate nucleus.

• The atrium contains the choroid plexus glomus and is

formed by the confluence of the body with the temporal
and occipital horns.
• The temporal horn extends anteroinferiorly from the atrium and is bordered on its floor
and medial wall by the hippocampus. Its roof is formed by the tail of the caudate
nucleus.

• The occipital horn is surrounded entirely by white matter fiber tracts, principally the
geniculocalcarine tract and the forceps major of the corpus callosum.

• Foramen of Monro is a Y-shaped structure with two long arms extending towards
each lateral ventricle and a short inferior common stem that connects with the roof of
the third ventricle.
 Third ventricle

• The third ventricle is a single, slit-like, midline,

vertically oriented cavity that lies between the
thalami.

• Its roof is formed by the tela choroidea, a double

layer of invaginated pia. The lamina terminalis
and anterior commissure lie along the anterior
border of the third ventricle.
• The floor of the third ventricle is formed by several critical anatomic
structures. From front to back these include the optic chiasm, hypothalamus
with the tuber cinereum and infundibular stalk, mammillary bodies, and roof
of the midbrain tegmentum.

• The third ventricle has two inferiorly located CSF-filled projections: The
slightly rounded optic recess and the more pointed infundibular recess.
• Two small recesses, the suprapineal and pineal recesses, form the posterior
borderof the third ventricle. A variably sized interthalamic adhesion (also
called the massa intermedia) lies between the lateral walls of the third
ventricle. The massa intermedia is not a true commissure.

• Cerebral aqueduct is an elongated tubular conduit that lies between the

midbrain tegmentum and the quadrigeminal plate. It connects the third
ventricle with the fourth ventricle.
 Fourth ventricle
•

• The fourth ventricle is a roughly diamond shaped cavity

that lies between the pons anteriorly and the cerebellar
vermis posteriorly.

• Its roof is covered by the anterior (superior) medullary

velum above and the inferior medullary velum below.
• The fourth ventricle has five distinctly shaped recesses.

• The posterior superior recesses are paired, thin, flat, CSF-filled pouches that
cap the cerebellar tonsils.

• The lateral recesses curve anterolaterally from the fourth ventricle, extending
under the brachium pontis (major cerebellar peduncle) into the lower
cerebellopontine angle cisterns.

• The lateral recesses transmit choroid plexus through the foramina of

Luschka into the adjacent subarachnoid spaces.
• The fastigium is a triangular, blind-ending, dorsal midline outpouching that points
towards the cerebellar vermis.

• The fourth ventricle gradually narrows as it courses inferiorly, forming the

obex.Near the cervicomedullary junction, the obex becomes continuous with the
central canal of the spinal cord.
 Cisterns and Subarachnoid Spaces

• The SASs lie between the pia and arachnoid. The sulci are CSF-filled spaces
between the gyral folds.

• Focalexpansions of the SASs form the brain CSF cisterns.

• These cisterns are found at the base of the brain around the brainstem, tentorial
incisura, and foramen magnum.

• All SAS cisterns communicate with each other and the ventricular system,
providing natural pathways for disease spread (e.g., meningitis, neoplasms).
• The brain cisterns are conveniently grouped into supra-, peri-,and infratentorial
cisterns which contain numerous important critical structures, such as vessels and
cranial nerves.

• Supratentorial/Peritentorial -
suprasellar,interpeduncular,perimesencephalic(ambient),quadrigeminal cisterns

• Infratentorial -prepontine,premedullary,superior cerebellar,cerebellopontine

angle,cerebellomedullary cisterns and cisterna magna
• The suprasellar cistern lies between the diaphragma sellae and the
hypothalamus. Critical contents include the infundibulum,optic chiasm,
and circle of Willis.

• The interpeduncular cistern is the posterior continuation of the suprasellar

cistern. Lying between the cerebral peduncles,it contains the oculomotor
nerves as well as the distal basilar artery and proximal segments of the
posterior cerebral arteries.

• The perimesencephalic(ambient) cisterns are thin wings of CSF that

extend posterosuperiorly from the suprasellar cistern to the quadrigeminal
cistern. They wraparound the midbrain and contain the trochlear nerves, P2
PCA segments, superior cerebellar arteries, and basal vein of
Rosenthal.
• Quadrigeminal cistern with the ambient cisterns laterally and the superior cerebellar
cistern inferiorly.

• The quadrigeminal cistern contains the pineal gland, trochlear nerves, P3 PCA
segments, proximal choroidal arteries, and vein of Galen.

• An anterior extension,the velum interpositum, lies below the fornix and above the third
ventricle. The velum interpositum contains the internal cerebral veins and medial
posterior choroidal arteries.
• Prepontine cistern lies between the
upper clivus and the "belly" of the
pons. It contains numerous
important structures including the
basilar artery, the anterior
inferior cerebellar arteries
(AICAs), and the trigeminal and
abducens nerves (CN5 and CN6).
 •
• Premedullary cistern is the inferior
continuation of the prepontine cistern.
• It lies between the lower clivus in front
and the medulla behind.
• It extends inferiorly to the foramen
magnum and contains the vertebral
arteries and branches (e.g., PICAs)
and the hypoglossal nerve (CN12).
• The cerebellopontine angle cisterns
(CPAs) lie between the
pons/cerebellum and the petrous
temporal bone.

• Their most important contents are the

trigeminal, facial, and
vestibulocochlear nerves (CN5, CN7,
and CN8). Other structures found here
include the petrosal veins and AICAs.
• The cerebellomedullary cisterns extend laterally around
the medulla and are continuous with the cisterna magna
below and the CPAs above.

• They contain the vagus,glossopharyngeal, and spinal

accessory nerves (CN9, CN10,and CN11).

• A tuft of choroid plexus exits each foramen of Luschka

into the cerebellomedullary cistern. The flocculus of the
cerebellum that projects into this cistern can appear very
prominent.
 Choroid Plexus
• Development:Shortly after closure of the neural tube, the choroid plexus begins to
appear as invaginations of mesenchymal-derived epithelial tissue that push into the
neural tube at the sites of formation of the cerebral ventricles.

• Choroid plexus in the fourth ventricle appears first followedby the lateral
ventricle, and finally the third ventricle.

• Carbonic anhydrase (required for secretion) is produced by the ninth week, and
tight junctions (required to maintain the BCSFB)are present very early on in
development, .

• Choroid plexus blood flow increases considerably between the third and fourth
postnatal week.
• The choroid plexus arises from the roofs of
the third and fourth ventricles and the wall
of each lateral ventricle.

• The anterior choroidal (from the

supraclinoid internal carotid artery) and the
lateral posterior choroidal (from the
posterior cerebral artery) arteries are the
main supply to the lateral ventricular
choroid plexus .
• The choroid plexus in the third ventricle is supplied by the paired medial
posterior choroidal arteries arising from the posterior cerebral arteries.

• The fourth ventricle choroid plexus is supplied by the posterior inferior

cerebellar artery.

• Rich venous networks join at a thickened site in the free membranous edge,
termed the glomus, and form a single large vein that continues to run anteriorly
in the free border .

• The glomus is located in the atrium of the lateral ventricles.

• The choroidal epithelium is composed of simple cuboidal cells covered in cilia and
forms fine frond-like projections, consisting of a tiny villous process composed of an
enclosing central core containing a capillary and a small amount of loose
connective tissue, with a large surface area of approximately 200 cm2 for a mass of
only 2 g.

• The main function of the choroid plexus is to secrete CSF .

• Mean CSF production in humans is 0.36 mL/min (approximately 20 mL/hr, or 500

mL/day).

• The choroid plexus has a blood supply 10 times that of the cortex and can produce
CSF at a rate up to 0.21 mL/min/g tissue, a rate higher than any other secretory
epithelium
• Subtype AQP 1 is found on the apical surface of the choroid plexus
epithelium, and AQP 4 is prevalent on astrocytes.

• AQP 1 inhibition has been proposed as a method to treat hydrocephalus by

reducing CSF production; however, AQP knockouts (mice bred without the
AQP 1 channel) have normal CSF production, suggesting other
transmembrane mechanisms of water transport exist.
• Larger molecules are transported by transcytosis, endocytosis, or specific
oligopeptide transporters.

• CSF formation is influenced by enzyme inhibitors, the autonomic nervous system, and
choroidal blood flow.

• Steroids, acetazolamide, diuretics, low temperatures, and changes in CSF osmolality

can all reduce CSF production.

• Acute rises in intracranial pressure probably result in a reduced CSF production by

reducing choroidal blood flow
• The choroid plexus is also involved in supply and distribution of peptides and growth
factors to the brain.

• Recent studies suggest that the choroid plexus also acts to eliminate xenobiotics
(substances foreign to the body, such as antibiotics) and endogenous waste from CSF
to blood.

• There are organic anion-transporting polypeptides (OATP), organic ion transporters

(OAT), peptide transporters (PEPT2 in humans), and multidrug-resistance-associated
proteins on the apical (CSF) border of the choroid plexus epithelial cells.
 Blood-Brain Barrier (BBB)
• The concept of an anatomical barrier separating blood and CNS first
emerged from the studies of Goldmann ( 1913 ) who injected trypan blue into
the venous system and observed that staining occurred throughout the body,
whereas only the brain and CSF remained unstained.

• When he injected the dye into the CSF, the CNS tissue including the
leptomeninges was strongly stained (Goldmann 1913 ).

• The special components of the BBB include capillary walls of endothelial

cells, the basal membrane, and the perivascular layer of astrocytic end-feet.

• The BBB structures comprise a large surface area of 12–18 m2 in adult

humans for exchange of humoral and cellular factors across this barrier.
• The capillary wall consists of a monolayer of non-fenestrated endothelial cells
which form the functionally most important part of the BBB and are connected to
each other by tight junction protein complexes known as zonulae occludentes.

• The tight junctions of the BBB consist of different integral membrane proteins
including occludins, claudins, junctional adhesion molecules, and associated
cytoplasmatic proteins
• The endothelium basement membrane
with a width of about 300–500 Ǻ offers
free passage of hydrophilic molecules.

• A further element of the BBB is the

extracellular space with a width of about
200 Ǻ that is labyrinthically ramifying
between neurons, glial cells, and
capillaries that allows the unrestricted
passage of ions and substances of
colloidal size .
 The Blood-CSF Barrier (BCB)

• The BCB is formed by epithelial cells of

the choroid plexus located in the four
ventricles of the brain and the
subarachnoid epithelial structures facing
the CSF space in intracranial and spinal
areas.

• The BCB has several fenestrations (“gap

junctions”) and pinocytosis vesicles,
which form a macrofilter for proteins.
• According to Reiber, all factors contributing to increases of CSF protein
concentration can be explained by a reduced CSF flow.

• A spinal block as well as polyradiculitis or purulent meningitis will lead to a

reduced CSF flow which causes a holdup of proteins in the vascular system,
which in turn leads to an increased gradient between blood and CSF
compartments which finally will result in an increase of protein transfer across
the BCB.
 CSF PATHWAYS
• CSF is produced mainly within the lateral, third, and
fourth ventricles.

• Net bulkflowoccurs from the lateral to the third

ventricle via the foramen of Monro, on into the fourth
ventricle via the aqueduct of Sylvius, and then out of
the fourth ventricle via the midline foramen of
Magendie,and the lateral foramina of Lushka into the
cisterna magna.
• CSF moves in a pulsatile manner between compartments with each cardiac
systole and respiratory inhalation and to a lesser extent because of the
movement of the ependymal cilia.

• MR phase imaging, intraoperative ultrasound, and animal experimental work

support a dominant role of cardiac pulsation in relation to CSF flow.

• Peak CSF velocities occur within the lower fourth ventricle, followed by
the aqueduct and the foramen of Monro and implicate the movement of the
cerebellum, tonsils, and choroid plexus in the initiation of CSF flow.

• In the spinal canal, MR imaging indicates that cardiac systole initiates an

anterior and caudal spinal cord movement.
• Spinal cord movement and cord systolic expansion also produce significant
local CSF flow, which is more prominent beyond the distal cervical spine .

• In recent canine investigations and human MR studies, lumbar CSF pulse

waves consisted of spinal arterial pulsations (40%), venous pulsations in the
lumbar canal (40%), and intracranial pulsations (20%).

• Reabsorption into the systemic circulation occurs via the venous system at
the arachnoid granulations in the superior sagittal sinus, the lymphatics
across the cribriform plate, and the nerve root subarachnoid angles.
• An arachnoid villus is an
invagination of the arachnoid into a
venous area .

• They are present in the cranial

venous sinuses and have also been
described at arachnoid angles in
spinal nerve roots.

• A massive dilatation of the

subarachnoid space within a villus
produces an arachnoid, or
Pacchionian, granulation or body.
• Arachnoid granulations are usually found in humans over the age of 18 months, while
arachnoid villi have been found in younger infants and other animals.

• A recent study of 100 patients used 3D MRI techniques and demonstrated 433
arachnoid granulations in 92 patients situated in the superior sagittal (54%),
transverse (28%), and straight sinuses (18%) (95).

• Mean granulation diameters were 1.5,4.1, and 3.8 mm for superior sagittal,
transverse, and straight sinuses, respectively .
• CSF flow into the sinuses appears to be passive along a pressure gradient.

• Electron microscopy shows that cells form giant vacuoles that may
communicate with both the subarachnoid and luminal parts of the cell
simultaneously .

• The greater the pressure differential, the greater the number of vacuoles that
forms, supporting an energy independent transcellular route for fluid transport
• Lymphatics are not found within the central nervous system, although
experimental observations suggest a route to extracranial lymphatics exists.

• Ink tracers, labeled albumin, or Microfil injected into the brain of

experimental animals and human cadavers found in the perivascular
spaces, around cranial nerves, and eventually in the cervical and spinal
lymph nodes, reaching a peak after 4 to 15 hours.

• In humans, extracranial metastases from high-grade cerebral glioma are

rare (about 2%) and preferentially metastasize to cervical lymph nodes
and lung.
• The cribriform plate appears to be the central
region for extra-arachnoidal cranial CSF
clearance.

• Animal studies in rats and sheep indicate that

50% of CSF exits the skull inthis location.

• Potential anatomical connections between the

olfactory nerve and extracranial lymphatic
vessels. In schematic (A) the lymphatics are
connected directly with the CSF space.
• Possible anatomical routes for spinal CSF reabsorption include flow out as
the nerve root sheaths merge with the perineurium at the arachnoid angle,
spinal arachnoid granulations, or direct movement across the dura into the
epidural space to be absorbed by blind-ending spinal lymphatic vessels.
 CSF CONSTITUENTS
• Cerebrospinal fluid is clear and colorless with a density of 1.003 to 1.008
g/cm3 .

• There is, on average, 140 mL of CSF, divided between the ventricular system
(35 mL, or 25%), the spinal canal (30–70 mL, or 20–50%), and the cranial
subarachnoid space (35–75 mL, or 25–55%).

• In young children, the total amount of CSF is smaller, around 70 mL.

• Normal cerebrospinal fluid is a thin, colorless, sparkling, crystal clear fluid

that does not coagulate.
 APPEARANCE

• To determine that the cerebrospinal fluid is clear and colorless, at least 1.0 ml
of fluid in a clear glass tube is required, and subtle changes in color or clarity
can be more readily detected in larger volumes of 5 ml or more.

• The tube of cerebrospinal fluid should be compared with an equal quantity of

water in an identical tube, by looking down the long axis of the tube against a
white sheet of paper preferably in the sunlight
 Turbidity or lack of clarity can be graded as follows:
• 0 = crystal clear fluid;
• 1 + = faintly cloudy,smoky, hazy with slight (barely visible) turbidity;
• 2+ = turbidity clearly present,but newsprint can be easily read through the
tube;
• 3+ = newsprint not easily read through the tube;
• 4+ = newsprint cannot be seen through the tube.
• Turbidity may be caused by as few as 400 blood cells per cublic millimeter ,
microorganisms, contrast media, or subdural fat aspirated during lumbar
puncture.

• Larger clots, suggesting protein levels of over 100 mg/dl, may be evident at
room temperature, while smaller clots or pellicles become evident after
standing in a refrigerator.

• Xanthochromia is the yellow discoloration indicating the presence of bilirubin

in the cerebrospinal fluid (CSF).

• CSF xanthochromia is present in all patients up to 2 weeks postSAH

and is still present in 70% of patients at 3 weeks.
• Spectrophotometry of CSF in the visible region is, in general, considered more
sensitive than visual examination, with peaks at 415 and ∼440–460 nm
indicating the presence of hemoglobin (Hb) and bilirubin, respectively.

• Xanthochromia is due to blood pigments or high protien levels(>150mg/dl) in csf

or severe bilirubinemia or csf contamination with iodine skin disinfectant.

• Bilirubin
• From lysed erythrocytes present in cerebrospinal fluid for over 12 hours after
subarachnoid hemorrhage
• From plasma due to increased levels of direct (conjugated) bilirubin (over 5-
10 mg/dl) in the presence of a normal blood-brain barrier, or due to
increased levels of indirect (unconjugated) bilirubin in the presence of an
excessively permeable blood-brain barrier (as is the case following stroke, or
in neonates with an immature blood-brain barrier).

• Bilirubin is yellow and is first detected in the CSF 10 hours after

subarachnoid bleeding. Its concentration is maximal at 2 days and may
persist for up to a month.

• Other causes for coloration of CSF include an elevated systemic bilirubin

from liver disease; a brownish or gray coloration in the presence of CNS
melanoma; and a greenish tinge related to leukemic meningeal infiltration.
• The Pandy test, which was often performed at the bedside, utilized 1.0 ml of
a saturated, filtered aqueous solution of phenol in a small glass test tube to
which one drop of cerebrospinal fluid was added.

• Clouding of the solution (which could be graded on a scale of one to

four)occurred with an increased total protein above about 100 mg/dl or an
increased amount of globulin in a cerebrospinal fluid with normal or nearly
normal total protein content.

• In normal adult CSF, there are 0-5lymphocytes or mononuclear cells per

mm3, and no polys (PMN s) or RBCs. In the absence ofRBCs, 5-10 WBCs
per mm3 is suspicious, and > 10 WBCs per mm3 is definitely abnormal.

• Differentiating true leukocytosis from traumatic tapIn non-anemic patients,

there should be 1-2 WBCs for every 1000 RBCs .
• In the presence of anemia or peripheral leukocytosis, use Fishman's formula

Estimating true total CSF protein content with a traumatic tap

If the hemogram and peripheral protein are normal, then have the cell count and protein
content run on the same tube, and the correction is subtract 1 mg per 100 ml of protein
for every 1000 RBC per mm3
• CSF has a lower concentration of protein, glucose, potassium, and higher
concentration of chloride than plasma.

• Beta 2 transferrin is the desialated isoform of the iron-binding glycoprotein

transferrin and is only found in CSF, perilymph, and ocular fluids.

• When tested with a paired serum sample, the presence of beta 2 transferrin
in a persistent watery discharge can be used to confirm CSF leakage.
 CSF PROTIEN
• The majority of CSF protein is derived from the serum, and the CSF/serum
albumin ratio is approximately 1:200. This ratio implies that the entry rate of
protein from the serum to the CSF is approximately 200 times less than its
exit rate.

• When a significant amount of blood is present in the CSF (e.g., subarachnoid

hemorrhage), a correction for the total protein concentration should be
calculated. The presence of 1000 RBCs in the CSF results in the increase of
protein by 1mg/dL.

• A spinal-subarachnoid block can cause Froin's syndrome and is usually the

result of a spinal cord tumor and can cause very significant elevations in CSF
protein (greater than 1000mg/dL).[
Certain proteins arise within the intrathecal compartment.
• Immunoglobulins produced by CNS lymphocytes,
• Transthyretin (produced by choroid plexus),
• various structural proteins found in brain tissue (including glial fibrillary
acidic, tau, and myelin basic proteins).

• Immunoglobulins compose a substantial fraction of normal CSF (5% to

12%).

•
• Contamination of the CSF with blood may significantly elevate the IgG index
and the IgG synthesis rate.

• Within the gamma region, three patterns of bands may be observed

including one clone (monoclonal), many clones (polyclonal), and a few bands
(three to five bands, or oligoclonal bands).

• Each band represents a homogeneous protein that is secreted by a single

clone of plasma cells.

• Oligoclonal bands (OCBs) are present in the CSF when three to five bands
are seen on gel electrophoresis. More than one OCB rarely occurs in normal
CSF.
• A serum sample should also be obtained simultaneously with the acquisition
of the CSF to determine whether the OCBs are unique to the CSF.

• Oligoclonal bands are present in 83% to 94% of patients with multiple

sclerosis, 100% of patients with subacute sclerosing panencephalitis, 25% to
50% of patients with other inflammatory CNS disorders (CNS lupus,
neurosarcoidosis, cysticercosis, Behçet's disease, and viral, fungal, and
bacterial infections), as well as most with some brain tumors and Guillain-
Barré syndrome.

• Because OCBs are present in such varied conditions, their presence offers
little to a specific diagnosis.
 Patterns of OCBs
Type 1: No OCB in CSF or serum (normal pattern).

Type 2 : OCB restricted to CSF, absent in serum.

Indicates low‐level ITS. Typical pattern in MS.

Type 3 : Identical OCB in both serum and CSF with

extra bands in CSF. Pattern seen during systemic
synthesis associated with intrathecal synthesis. Seen in
MS.

Type 4 : OCBs in CSF mirror those in serum. Indicates

a systemic IgG synthesis and passive transfer of OCB
from blood to CSF, without any local synthesis.

Type 5 : Ladder‐type identical OCB in both serum and

CSF typically associated with monoclonal IgG proteins.
Peripheral IgG synthesis without local synthesis.
 CSF Lactate
• Because the concentration of CSF lactate is dependent on CNS
glycolysis,the measurement of this agent may be helpful in the diagnosis of
bacterial meningitis. This concentration of lactate increases proportionally to
the number of inflammatory cells in the CSF.

• A lactate concentration of 4.2mmol/L accurately predicted 24 out of 25

cases of bacterial meningitis, whereas no patients with presumed viral
meningitis had a lactate level that exceeded this value.

• Increased lactate may also result from a cerebral hemorrhage, malignant

hypertension, hepatic encephalopathy, diabetes mellitus, and hypoglycemic
coma.
• The measurement of CSF glutamine can be a helpful test in diagnosing
patients with confusion in the setting of hepatic encephalopathy.

• Decreased lumbar CSF levels of HVA(Dopamine) and 5-HIAA(serotonin)

have been reported in patients with parkinsonism and Alzheimer's disease.

• Decreased HVA levels have also been documented in the ventricular CSF of
patients with dystonia, cerebral palsy, multiple sclerosis, and posthypoxic
states.

• Normal HVA levels are present in the lumbar CSF of patients with
schizophrenia, decreased 5-HIAA concentrations are present in depressed
subjects.
• The detection of other CSF markers may be useful for the diagnosis of
primary or metastatic malignancies including astroprotein (glioblastoma),
carcinoembryonic antigen (carcinomas), β-2-microglobin (lymphoblastic
leukemia and lymphoma), α-fetoprotein (germ cell tumors), chorionic
gonadotropin (choriocarcinoma and testicular tumors), and ferritin
(carcinomas).

• An elevated lactate dehydrogenase (LDH) may occur in bacterial meningitis.

• Elevated levels of CSF creatinine kinase-BB are also present in a wide

variety of conditions that cause parenchymal damage.
• Adenosine deaminase (ADA) elevations can occur in tuberculous meningitis.

• Though some authors have found that increased ADA levels are sensitive for
tuberculous meningitis, it appears ADA has limited utility in the diagnosis in
HIV infected individuals due to a high false positive rate in this patient
population.
LUMBAR PUNCTURE
• Manometric tests, such as the abdominal compression test, Queckenstedt
test, are only valid if the lumbar puncture is performed with a spinal needle
that is 20 gauge or larger.

• Firm manual compression applied for at least 10 seconds to the patient's

abdomen by an assistant should increase the cerebrospinal fluid pressure as
recorded in the manometer by 5-15 cm over the resting level.

• This response is most helpful in determining that the needle is in the

subarachnoid space.
• The Queckenstedt test consists of 10 seconds of manual compression of
the patient's jugular veins bilaterally (pressure must be sufficient to compress
the veins but not so firm as to compress the carotid arteries).

• There should be a rapid rise of the cerebrospinal fluid pressure to 10-30 cm

above baseline.

• Manual compression of the jugular vein on only one side (the Tobey-Ayer
test) should produce only a slight change in cerebrospinal fluid pressure
unless there is obstruction of one of the lateral venous sinuses, such as by
sinus thrombophlebitis.
Access to the anterior frontal horn is possible at
Kocher's point (3 cm posterior
to the normal hairline and 2.5 cm lateral to the
midline),

the trigone of the lateral ventricle at Keen's

point (2.5 cm above and 2.5 cm behind the
helix of the outer ear or pinna), and

the posterior lateral ventricle through a

posterior parietal trephine (8 cm above the inion
and 2.5 to 3 cm lateral to the midline).
 Indications
General indications for spinal puncture
Diagnostic
• CSF examination
• CSF pressure measurement
• Instillation of radiological contrast media
Therapeutic
• Reduction of CSF pressure
• Instillation of drugs and contrast media
• Spinal anaesthesia
LP is also required as a therapeutic or diagnostic maneuver in the following
situations :

• Spinal anesthesia

• Intrathecal administration of chemotherapy

• Intrathecal administration of antibiotics

• Injection of contrast media for myelography or for cisternography

 Contraindications
Although there are no absolute contraindications to performing the procedure,
caution should be used in patients with:

• Possible raised intracranial pressure due to mass lesion

• Thrombocytopenia or other bleeding diathesis (including ongoing

anticoagulant therapy)

• Suspected spinal epidural abscess

• Spinal block
 Complications
• Post-LP headache

• Infection

• Bleeding

• Cerebral herniation

• Minor neurologic symptoms such as radicular pain or numbness

• Late onset of epidermoid tumors of the thecal sac

• Unilateral or Bilateral lateral rectus palsy

• Back pain
 Post LP Headache
• Headache, which occurs in 10 to 30 percent of patients following lumbar
puncture, is one of the most common complications of the procedure.

• Post-lumbar puncture headache (PLPHA; also known as post-dural puncture

headache) is caused by leakage of cerebrospinal fluid from the dura with
resultant traction on pain-sensitive structures.

• In 1891 Quincke introduced the lumbar puncture (LP) , and in 1898 Bier
suffered from and was the first to report PLPHA. He proposed that
ongoing leakage of cerebrospinal fluid (CSF) through the dural puncture site
was the cause of the headache.
• Of note, cerebral venous thrombosis must also be considered as a possible
cause of persisting headache following LP, since LP can rarely precipitate a
cerebral venous thrombosis.

• However, unlike PLPHA, the headache related to cerebral venous

thrombosis does not typically change with posture, and the severity
usually increases in the acute phase of illness.

• Patients with PLPHA characteristically present with frontal or occipital

headache within 6 to 72 hours of the procedure that is exacerbated in an
upright position and improved in the supine position.

• Associated symptoms may include nausea, vomiting, dizziness, tinnitus, neck

stiffness, and visual changes. Without treatment, the headache typically
lasts 2 to 15 days.
• Despite recommendations for bed rest following LP, this remedy has not
been shown to significantly decrease the risk of PLPHA .

• Since PLPHA is typically mild and resolves spontaneously, conservative

therapy for the first 24 hours is generally recommended.

• Such conservative therapy includes bed rest and a brief course of oral
analgesics that do not degrade platelet function, including opioids. Hydration
and abdominal binders are not necessary.

• For patients with moderate to severe prolonged headache refractory to

conservative measures, we suggest epidural blood patch as the next step.
CSF IN CLINICAL SYNDROMES
 HYDROCEHALUS
• External hydrocephalus was described by Hippocrates, but the first
recognized description of ventricular dilatation was that of Vesalius in about
1550 A.D.

• Surgical management of hydrocephalus was recommended by Galen.

• In 1956,Holter developed the first of many valved shunts, which have

become the mainstay of surgical management.

• By definition, hydrocephalus refers to abnormal accumulation of fluid in the

within the ventricular system.
• Two main functional subdivisions of hydrocephalus (HCP)
1. obstructive (AKA non-communicating): block proximal to the arachnoid
granulations (AG).

On CT or MRI: enlargement of ventricles proximal to block (e.g.

obstruction of aqueduct of Sylvius --lateral and 3rd ventricular
enlargement out of proportion to the 4th ventricle, sometimes referred to
as triventricular hydrocephalus)

2. communicating (AKA non-obstructive): CSF circulation blocked at level

of AG
Conditions that are not actually hydrocephalus "pseudohydrocephalus"
• A. hydrocephalus ex vacuo: enlargement of the ventricles due to loss of
cerebral tissue (cerebral atrophy), usually as a function of normal aging, but
accelerated or accentuated by certain disease processes (e.g. Alzheimer's
disease, Creutzfeldt..Jak.ob disease, traumatic brain injury).

• B. otitic hydrocephalus: obsolete term used to describe the increased

intracranial pressure seen in patients with otitis media

• C. external hydrocephalus: seen in infancy, enlarged subarachnoid space

with increasing OFCs and normal or mildly dilated ventricles .
• D. hydranencephaly: a post-neurulation defect . Total or near-total
absence of the cerebrum most commonly due to bilateral ICA infarcts. It is
critical to differentiate this from severe ("maximal") hydrocephalus (HCP)
since shunting for true HCP may produce some reexpansion of the cortical
mantle.
 EXTERNAL HYDROCEPHALUS (AKA BENIGN EXTERNAL
HYDROCEPHALUS)

• Enlarged subarachnoid spaces

over the frontal poles in the first
year of life ventricles are normal or
minimally enlarged.
• may be distinguished from subdural
hematoma by the "cortical vein
sign".
• usually resolves spontaneously by
2 years of age.
Arrested hydrocephalus satisfies the following criteria in the absence of a CSF
shunt:
• 1. near normal ventricular size
• 2. normal head growth curve
• 3. continued psychomotor development
 ENTRAPPED FOURTH VENTRICLE
• 4th ventricle that neither communicates with the 3rd ventricle (through
sylvian aqueduct) nor with the basal cisterns (through foramina of Luschka or
Magendie).

• Usually seen with chronic shunting of the lateral ventricles, especially with
post-infectious hydrocephalus (fungal, in particular) or in those with repeated
shunt infections.
• Presentation may include:
• 1. headache
• 2. lower cranial nerve palsies: swallowing difficulties
• 3. pressure on the floor of the 4th ventricle may compress the facial colliculus
leading to facial diplegia and bilateral abducens palsy
• 4. ataxia
• 5. reduced level of consciousness
• 6. nausea/vomiting
• 7. may also be an incidental finding.

• Treatment : Shunt insertion from below the tonsils under direct vision.
 CT/MRI CRITERIA OF HYDROCEPHALUS
• A.the size of both temporal horns
(TH) is >= 2 mm in width and the
sylvian & interhemispheric fissures
and cerebral sulci are not visible.
OR
• B. both TH are >=2 mm, and the
ratio FH/ID > 0.5 (where FH is the
largest width of the frontal horns,
and ID is the internal diameter from
inner-table to inner-table at this
level)
• 1.ballooning of frontal horns of lateral ventricles ("Mickey Mouse" ventricles)
and/or 3rd ventricle (the 3rd ventricle should normally be slit-like)

• 2. periventricular low density on CT, or peri ventricular high intensity signal on

T2WI on MRI suggesting transependymal absorption of CSF.

• 3. used alone, the ratio FH/ID

< 40%- Normal , 40-50 % - borderline ,>50% - hydrocephalus

• 4. Evans ratio(or index): ratio ofFH to maximal biparietal diameter (BPD)

measured in the same CT slice: > 0.3 suggests hydrocephalus

• 5. sagittal MRI may show thinning and/or upward bowing of the corpus
callosum
 Etiologies
Congenital Acquired :
Chiari Type 2 malformation and/or infectious (MCC communicating HCP),
myelomeningocele (MM), post-hemorrhagic (2nd MCC communicating
Chiari Type 1 malformation, HCP),
primary aqueductal stenosis, secondary to masses,
post-op: 20% of pediatric patients develop
secondary aqueductal gliosis due to
permanent hydrocephalus (requiring shunt)
intrauterine infection or germinal matrix
following p-fossa tumor removal. May be
hemorrhage ,
delayed up to 1 yr,
Dandy Walker malformation: atresia of neurosarcoidosis
foramina ofLuschka & Magendie constitutional ventriculomegaly
X-linked inherited disorder: rare associated with spinal tumors.
 NPH
• Normal pressure hydrocephalus (NPH), AKA Hakim-Adams syndrome, first
described in 1965, is clinically important because it may cause treatable
symptoms.

• As originally described, the hydrocephalus of NPH was considered to be

idiopathic.

• However, in some cases a predisposing condition ("secondary NPH") may be

identified:
post-SAH,post-traumatic,post-meningitis,following posterior fossa surgery,
tumors, including carcinomatous meningitis,also seen in 15% of patients with
Alzheimer's disease (AD),deficiency of the arachnoid granulations
aqueductal stenosis may be an overlooked cause
• Ventriculomegaly with normal CSF pressure, altered CSF dynamics

• IMAGING

• Enlarged lateral & 3rd ventricles, 4th ventricle relatively normal

• Ventricular enlargement out of proportion to cortical sulcal enlargement

• Disproportionately enlarged subarachnoid space hydrocephalus (DESH)

(particularly sylvian fissures and basal cisterns) with effacement of
subarachnoid space over convexity
• Evans index (ratio of widest diameter of frontal horns to widest diameter of
brain on same axial slice) ≥ 0.3

• Callosal angle (angle between lateral ventricles on coronal image) ≤ 90°

• ± aqueductal flow void

• Periventricular high signal transependymal CSF flow

 LUMBAR PUNCTURE {LP)- "TAP TEST"
• In NPH the average OP is 15 ± 4.5 cm H20 (11 ± 3.3 mm Hg).

• Based on expert opinion, an upper limit of 24 cm H20 (17 .6mm Hg) is

suggested for the definition of NPH.

• Patients with an initial OP > 10 cm H20 have a higher response rate to

shunting.

• Tap test: The tap test has not undergone rigorous prospective evaluation. A
positive response to withdrawal of 40-50 ml of CSF has a PPV in the range of
73-100%, but sensitivity is low (26-61%).
• Send CSF for routine labs
 AMBULATORY LUMBAR DRAINAGE(ALD)
• A lumbar subarachnoid drain is placed with Tuohy needle, connected through a drip
chamber to a closed drainage system. The drip chamber is placed at the level of the
patient's ear when recumbent, or at the level of the shoulder when sitting or
ambulating.

• A properly functioning drain should put out 300 ml of CSF per day.

• If symptoms of nerve root irritation develop during the drainage, the catheter should be
withdrawn several millimeters.

• Daily surveillance CSF cell counts and cultures should be performed (NB: a
pleocytosis of 100 cells/mm3 is expected just with the presence of the drain).'

• A 5 day trial is recommended (mean time to improvement : 3 days).

• VP shunt is the procedure of choice.

• The most likely symptom to improve with shunting is incontinence, then gait
disturbance, and lastly dementia.

Black et al. gave the following markers for good candidates for improvement
with shunting:
• clinical: presence of the classic triad. Also 77% of patients with gait
disturbance as the primary symptom improved with shunting.
• LP: OP > 100 mm H20
• continuous CSF pressure recording: pressure > 180 mm H2O or frequent
Lundberg B waves
• CT or MRI: large ventricles with flattened sulci (little atrophy)
• Response is better when symptoms have been present for a shorter time.
IIH
 Treatment
• A low-sodium weight reduction program is recommended for all obese
patients with IIH and appears to alleviate symptoms and signs in many but
not all patients .

• Medical treatment for IIH typically starts with carbonic anhydrase inhibitors.
Loop diuretics may be used as an adjunct. Corticosteroids are not
recommended for most patients with IIH.

• In adult patients, start with 500 mg twice per day and advance the dose as
required and tolerated by the patient.
• Although doses of up to 2 to 4 g per day can be administered, many patients
develop dose limiting side effects at higher levels.

• In young children, the recommended starting dose is 25 mg/kg per day with a
maximum dose of 100 mg/kg or 2 g per day.

• Medication side effects of acetazolamide include digital and oral

paresthesias, anorexia, malaise, metallic taste, fatigue, nausea, vomiting,
electrolyte changes, mild metabolic acidosis, and kidney stones.Monitoring of
electrolytes is suggested during acetazolamide treatment.

• Pregnancy, particularly the first 20 weeks, is often considered a relative

contraindication to the use of acetazolamide, which is classified by the FDA
as category C for pregnancy risk
• Furosemide (20 to 40 mg per day for adults and 1 to 2 mg/kg per day in
children) may be a useful adjunctive therapy to acetazolamide in IIH .

• Topiramate is an antiseizure drug that inhibits carbonic anhydrase activity. Its

efficacy in the treatment of migraine headaches and its association with
weight loss are features that make it an attractive potential therapeutic option
in IIH.

• Iron supplementation in IIH patients with iron deficiency anemia appeared to

be efficacious in a case series of six patients
• The two main surgical procedures in IIH are optic nerve sheath fenestration
and CSF shunting procedures.
Potential indications for surgical therapy include :
• Worsening visual field defect despite medical therapy.

• Presence of visual acuity loss attributed to papilledema (ie, not due to serous
detachment, macular edema, hemorrhage, or choroidal folds).

• Intractable headache.

• Anticipated hypotension (blood pressure treatment, renal dialysis).

• Patients unable to participate in follow-up examinations (eg, noncompliance,

impaired cognition, itinerant lifestyle).
 IIHYPOTENSION
• The syndrome of spontaneous intracranial hypotension is characterized by
the following in the absence of antecedent trauma or LP (or epidural injection
):
1. orthostatic headache: dramatically worse when upright, improved in
recumbency
2. low CSF pressure
3. diffuse pachymeningeal enhancement (cerebral and/or spinal) on MRI

• In most cases, the underlying etiology is thought to be a spontaneous CSF

leak froma spinal meningeal diverticulum or dural tear.

• Cerebrospinal fluid (CSF) pressure <7 cm H2O.

Brain MRI Findings:

• A. diffuse pachymeningeal enhancement (cerebral and/or spinal) is common

• B. brain descent with low lying cerebellar tonsils
• C. reversible pituitary enlargement with a convex superior margin41
• D. subdural hematomas (in 20%) and nonhemorrhagic subdural fluid
collections (in 23%) in one series of 40 patients with SIH.
• E. small ventricles and cisterns may be seen.
• Spinal MRI: may show evidence of CSF leak. If there is focal spine pain, the
leak will often be near this location
• Radioisotope cisternography: abnormal in 90%. Revealed the site of CSF
leak in 40%.
Quantitative signs
• mamillopontine distance <5.5 mm
• pontomesencephalic angle <50˚
• callosal angle, also known, as lateral ventricle angle <90˚: angle
between medial wall of the frontal horns on coronal plane
• Treatment includes:
• 1. bed rest
• 2. analgesics
• 3. hydration
• 4. caffeine
• 5. epidural blood patch (EBP) for appropriate cases.
• Subdural fluid collections occasionally require intervention (usually drainage
of the subdural and blood patching of the spinal leak, if identified).
• Complete resolution of H/A was achieved in 70% (usually in days to weeks),
and was higher in patients receiving EBP, and was lower with multiple sites of
CSF leak.
ICP MONITORING
Lundberg A waves
(or plateau waves) represent
prolonged periods of profoundly
high ICP.

Lundberg B waves are of shorter

duration, lower amplitude
elevations in ICP
that indicate that intracranial
compliance reserves are simply
compromised.
• The main negative consequence of elevated ICP is reduced cerebral blood
flow (CBF) and secondary hypoxic-ischemic injury due to poor flow.

• Cerebral perfusion pressure (CPP) is calculated as mean arterial pressure

(MAP) – ICP.

• CPP along with cerebral blood volume determines CBF;

normally,autoregulation of the cerebral vasculature maintains CBF at a
constant level between a CPP of approximately 50 and 100 mm Hg.

• Although the optimal CPP for a given patient may vary, in general, CPP
optimization should be greater than 60 (to avert ischemia) and below 110 mm
Hg (to avoid breakthrough hyperperfusion and cerebral edema).
• Depressed level of consciousness, blurred vision,confusion, disorientation,
nausea, vomiting, diplopia, and sixth cranial nerve palsy (false localizing
sign) may be seen, especially if the rise in ICP is acute rather than chronic.

• The Cushing triad, a well-known phenomenon of hypertension and

bradycardia in the setting of critically elevated ICP, is more commonly
seen with the late phase of intracranial hypertension such as near brain
dead/herniation syndrome rather than in the beginning of an acute injury.
• Patients should generally meet three criteria prior to placement of an ICP
monitor:

• (1)brain imaging reveals a space-occupying lesion and severe cerebral

edema suggesting that the patient is at risk for high ICP;

• (2) the patient has a depressed level of consciousness ( Glasgow Coma

Scale (GCS) score of 8 or higher would meet the criteria); and

• (3) the prognosis is such that aggressive ICU treatment is indicated.

• The external ventricular drainage (EVD) catheter is believed to be the gold
standard; it consists of a catheter that is placed through a burr hole into the
ventricle and connected to a pressure transducer set at ear level.

• It allows for both ICP monitoring and therapeutic CSF drainage.

• General Measures for ICP control
• Elevation of the head to at least 30 degrees
• Acetaminophen and cooling blankets are the first line of therapy and should
be instituted when temperature is sustained over 101°F (38.3°C).
• For patients at risk for raised ICP, it is reasonable to administer prophylaxis
with an intravenous anticonvulsant.
• Patients with high ICP states should be kept euvolemic with isotonic saline.
Hypotonic solution in any form (eg, 0.45% saline, D5W, or enteral water)
must be avoided.

• Steroids are effective only for reducing the volume of mass lesions related to
abscess or neoplasm, and the mechanism is based on its effect on
vasogenic edema.

• Agitation must be avoided because it can aggravate ICP elevation.The

preferred regimen is the combination of a short-acting opioid such as fentanyl
(1 to 3 ug/kg per houror remifentanil (0.03 to 0.25 u g/kg per minute) to
provide analgesia and propofol (0.3 to 3 mg/kg per hour) because of its
extremely short half-life.
• Appropriate vasopressors to raise blood pressure and CPP include
phenylephrine (2 to 10 ug/kg per minute), dopamine (5 to 30u g/kg per
minute), or norepinephrine (0.01 to 0.6 ug/kgper minute).

• Useful agents to lower blood pressure and CPP include labetalol (5 to 150
mg per hour) and nicardipine (5 to 15 mg per hour); nitroprusside should be
avoided because of its dilating effects on all cerebral vasculature, which may
exacerbate the ICP.

• If CPP is optimized, the patient is sedated, and ICP remains elevated,

osmotherapy should be initiated.
• Mannitol, given in a 20% solution at a dose of 0.25 to 1.5 g/kg, Hypertonic
saline (2 to 5 mL/kg of 7.5% saline or 0.5 to 2.0 mL/kg of 23.4% saline over
30 minutes) is an alternative to mannitol.
 References

• Uptodate
• Goetz Textbook of Neurology
• NeuroICU Book
• Osborn Diagnostic Imaging Brain
• Greenberg Handbook of Neurosurgery
• Cerebrospinal Fluid Disorders
• CSF in Clinical Neurology
• Cerebrospinal Fluid
• Ganong Textbook of Physiology