CSF

CSFCerebrospinal fluid: Anatomy Physiology and utility of an examination in disease states

OUTLINE

Anatomy Cerebrospinal fluid circulation Physiology Function CSF analysis Hydrocephalus pseudotumor cerebri Low CSF pressure syndrome

ANATOMY Lateral ventricle

Anterior or frontal horn Body Atrium Posterior or occipital horn Inferior or temporal horn

Interventricular foramen (foramen of Monro) Third ventricle(separating right and left

diencephalon) Cerebral aqueduct of Sylvius Fourth ventricle (between pons and

cerebellum extending as far caudal as medulla)

Foramen of Luschka Foramen of Magendie Subarachnoid space (between pia and

arachnoid) Choroid plexus Arachnoid granulation

CSF CIRCULATION Choriod plexus (lateral, third, and fourth ventricle) Lateral ventricle Foramen of Monro Third ventricle Cerebral aqueduct of Sylvius Fourth ventricle Foramen of Luschka Foramen of Magendie Subarachnoid space (between pia and arachnoid) Arachnoid granulation

Subarachnoid cistern

PHYSIOLOGY OF CSF FORMATION CSF is produced by the choroid plexus in the

lateral, third and fourth ventricles. normal adults, approximately 20 mL of CSF is

produced each hour from : uptodate 17.1

PHYSIOLOGY OF CSF FORMATION the CSF volume is 125 to 150 mL. Approximately 20 percent of the CSF is contained

in the ventricles CSF is reabsorbed in the arachnoid villi, Arachnoid villi normally allow the passage of

particles less than 7.5 µm in diameter from the CSF into the blood from : uptodate 17.1

PHYSIOLOGY OF CSF FORMATION the average intracranial volume is 1,700 mL the volume of the brain is from 1,200 to 1,400 mL, CSF volume ranges from 70 to 160 mL (mean: 104),

the spinal subarachnoid space contains 10 to 20 mL of CSF the CSF occupies somewhat less than 10 percent of the

intracranial and intraspinal spaces blood is approximately 150 mL. In addition (Meese and coworkers);

the distance between the caudate nuclei at the anterior horns gradually widens by approximately 1.0 to 1.5 cm,

the width of the third ventricle increases from 3 to 6 mm by age 60 years

from Adams and Victor’s neurology, 2009

PHYSIOLOGY OF CSF FORMATION AND FLOW

CSF pressure less than 150 mmH20. lateral recumbent position with the legs extended,

the normal CSF pressure is 60 to 200 mmH20 obese patients may have CSF pressures up to 250

mmH20 Pressures >250 mmH20 are considered to be

elevated from : uptodate 17.1

PHYSIOLOGY OF CSF FORMATION AND FLOW

The brain and spinal cord : no lymphatic channel

CSF serves to remove the waste products of cerebral

metabolism : CO2, lactate, hydrogen ions helps to preserve a stable chemical environment

for neurons and their myelinated fibers

from : uptodate 17.1

BLOOD-BRAIN BARRIER

separate the brain and the CSF from the blood prevent entry by simple diffusion of fluids,

electrolytes, and other substances from blood into the CSF or brain

5000-fold greater surface area than the blood-CSF barrier

controls the content of brain interstitial fluid anatomic basis for the blood-brain barrier

series of high-resistance, tight junctions between endothelial cells of capillaries in the CNS as well as astrocytes with processes

Lipid-soluble small molecules with a molecular mass less than 400 to 600 Da are transported readily through the blood-brain barrier

BLOOD - CSF BARRIER AND BRAIN-CSF BARRIER

Blood –CSF barrier : (tight junction) choroid plexus arachnoid membrane and endothelial cells in capillaries

Brain – CSF barrier : (gap junction) Pia mater A continuous layer of astrocytes overlies the basement

membrane of cells and CSF

WEAK POINTS IN BLOOD BRAIN BARRIER Weaknesses in the blood brain barrier

circumventricular organs high vascularization 6 major circumventricular organs a secretory function

1. Posterior Pituitary or Median Eminence a neuroendocrine transducer in the CNS into

blood borne signals 2. Area Postrema

at the wall of the 4th ventricle in the junction with the spinal canal

the vomiting center : emetic substances (apomorphine and digitalis glycosides

neurophysin, oxytocin, and vasopressin

WEAK POINTS IN BLOOD BRAIN BARRIER 3. Organum Vasculosum of the

Lamina luteinizing hormone releasing factor

(LHRH) and somatostatin, which inhibits the release of somatotropin (growth hormone)

4. Sub-commissural Organ beneath the posterior commissure at

the junction of the third ventricle and the cerebral aqueduct

the function is unknown 5. Pineal Gland

pinealocytes produces the hormone melatonin

under the influence of light deprivation

6. Subfornical Organ between the interventricular foramina may regulate body fluids

COMPOSITION OF CSF Color :

Clear and colorless Turbid appearance:

RBC > 400 cell/ml WBC > 200 cell/ml

Grossly bloody appearance : RBC ≥ 6,000 cell/ml

RBC lysis in CSF : oxyhemoglobin (pink) early and later to bilirubin (yellow)

known as xanthochromia. Appear 2-4 hours after RBCs have entered the

subarachnoid space, (90 % in 12 hrs.) persists for 2-4 weeks

Xanthochromia can also occur protein ≥ 150 mg/dL systemic hyperbilirubinemia (serum bilirubin >10 to 15

mg/dL) traumatic LP with more than 100,000 red blood cells/mlFrom uptodate 17.1

COMPOSITION OF CSF Traumatic tap

No xanthochromia (at least six hours after the onset of headache) 1 WBC : 500-1500 RBC A more accurate method

Predicted CSF WBC count/microL = CSF RBC count x (peripheral blood WBCcount ÷ peripheral blood RBC count)

If : A CSF WBC count > 10 times the predicted value had a

48 % positive predictive value for bacterial meningitis A CSF WBC count < 10 times the predicted value had a

99% negative predictive value for meningitis.

From uptodate 17.1

COMPOSITION OF CSF WBC :

acellular, although up to 5 WBCs and 5 RBCs are considered normal in adults

More than 3 polymorphonuclear leukocytes (PMNs)/ml are abnormal in adults

PMN predominated in Early (within 12-24 hrs onset) 2/3 of viral meningitis cases Bacterial meningitis

Lymphoctye predominated in Viral meningitis (Rare) early phase of bacterial meningitis

Eosinophilia parasitic infestations Mycobacterium tuberculosis Mycoplasma pneumoniae Rickettsia rickettsii some fungi non-infectious conditions (lymphomas, leukemias of various

types , subarachnoid hemorrhage, and obstructive hydrocephalus)

COMPOSITION OF CSF Protein :

Normal range 23-38 mg/dl Mild elevation in DM False elevation :

Subarachnoid hemorrhage or traumatic tap Correction : protein 1mg/dl : RBC 1,000 cell/dl

Elevation in : Infection Non infection CSF flow obstruction

elevations may persist for weeks or months following recovery from meningitis and have little utility in assessing cure or the response to therapy

COMPOSITION OF CSF Glucose

Capillaries to CSF : Facilitated transport and simple diffusion CSF to capillaries : transport across capillaries and arachnoid villi cells lining the ventricular cavities and

subarachnoid spaces several hours for the serum glucose to

equilibrate with the CSF glucose CSF-to-serum glucose ratio is approximately 0.6 glucose concentration : ventricular CSF > CSF in the lumbar : 6 - 18

mg/dL

COMPOSITION OF CSF low CSF glucose concentrations Infections :

Bacterial meningitis (esp. < 18 mg/dl) Mycobacterial meningitis Fungal meningitis Recovery phase : improvement

Glucose > cell count or protein

Non infections : Malignant processes infiltrating the meninges Subarachnoid hemorrhage CNS sarcoidosis

Normal CSF glucose concentrations Viral CNS infection (except : mumps, enteroviruses,

lymphocyticchoriomeningitis (LCM), herpes simplex, and herpes zoster viruses)

High CSF glucose concentrations Hyperglycemia (CSF glucose levels rarely exceed 300

mg/dL even in patients with severe hyperglycemia)

COMPOSITION OF CSF Lactate Higher sensitivity and specificity > the ratio of

CSF-to-blood glucose Cytology

useful for the diagnosis of malignancy involving the CNS

at least 10 to 15 mL of fluid

FUNCTION OF CSF Transports hormones and removes metabolic waste

products Cushions and floats brain

Brain weight 1500 gm in air Brain weight 48 gm in CSF

Sensitive to changes in increase ICP Normal pressure (lateral decubitus): 6 to 13 mmHg (90-

180 mm H2O) Minimal changes in ICP : arterial pulse (shifts of CSF from

skull into subarachnoid space) Major changes in ICP : the brain shrinking (slowly)

Responses to increased ICP Bradycardia and hypertension : ICP > 40-50 mmHg Respiration slows and becomes irregular :brainstem

respiratory centers are compressed) Papilledema : compression of retinal vein Brain herniations From rapid review neuroscience, 2007

CO2 AND INTRACRANIAL PRESSURE

Inhalation or retention of CO2 effect Increase blood PCO2 Decrease pH in CSF

INTRACRANIAL PRESSURE

A. the three components of the intracranial contents: the incompressible brain tissue (shaded) the vascular system (white channel) the CSF (light blue)

B. With ventricular obstruction C. With obstruction at or near the points of outlet of the CSF D. With obstruction of the venous outflow

INCREASE INTRACRANIAL PRESSURE Physiologic consideration Monro Kellei doctrine

CAUSES OF RAISED ICP A cerebral or extracerebral mass :

brain tumor massive infarction with edema extensive traumatic contusion parenchymal, subdural, or extradural hematoma Abscess

Generalized brain swelling : ischemic–anoxic states acute hepatic failure hypertensive encephalopathy Hypercarbia Reye hepatocerebral syndrome

increase in venous pressure cerebral venous sinus thrombosis heart failure obstruction of the superior mediastinal or jugular

veins

CAUSES OF RAISED ICP Obstruction to the flow or absorption of CSF hydrocephalus results :

obstruction is within the ventricles or in the subarachnoid space at the base of the brain

ventricles remain normal in size or enlarge only Slightly If the block is confined to the absorptive sites adjacent

to the cerebral convexities and superior sagittal sinus because the pressure over the convexities

approximates the pressure within the lateral ventricles Process that expands the volume of CSF

meningitis, subarachnoid hemorrhage Increases CSF production

choroid plexus tumor

CLINICAL MANIFESTATION OF RAISED ICP

Manifestation Headache Nausea and vomiting Drowsiness Ocular palsies Papilledema After several days or longer

papilledema may result in periodic visual obscurations If papilledema is protracted, optic atrophy and blindness may

follow

Normal mental alertness with ICP < 25 to 40 mm Hg loss of consciousness : ICP exceeds 40 to 50 mmHg

decreased cerebral blood flow

OBSTRUCTIVE (TENSION) HYDROCEPHALUS

Hydrocephalus (water brain) Tension hydrocephalus (ventricular enlargement caused by

increased intraventricular pressure) hydrocephalus ex vacuo ( ventricular enlargement caused by

cerebral atrophy) Colpocephaly (ventricular enlargement because of failure of

development of the brain) communicating and noncommunicating (obstructive)

hydrocephalus Communicating hydrocephalus : the observations that dye injected

into a lateral ventricle would diffuse readily downward into the lumbar subarachnoid space and that air injected into the lumbar subarachnoid space would pass into the ventricular system

But the obstruction is virtually never complete. obstruction to the flow of CSF at

ventricular pathway or aqueduct of Sylvius (most common) The medullary foramina of exit (Luschka and Magendie) the basal or convexity subarachnoid spaces

NEUROPATHOLOGIC EFFECTS OF HYDROCEPHALUS

Maximal expansion in frontal horn of lateral ventricle Impairment of frontal lobe functions Impairment of basal ganglionic–frontal motor

activity All forms of hydrocephalus

The central white matter compression Unaffected site

the cortical gray matter Thalami basal ganglia brainstem structures

Myelinated fibers and axons are injured and astrocytic gliosis and loss of oligodendrocytes in affected areas

ACUTE HYDROCEPHALUS Increased CSF production

Papillomas of choroid plexus subarachnoid hemorrhage cerebral hemorrhage or brain abscess that

rupture into the ventricles Decreased CSF absorbtion rapidly expand the volume of CSF produce

the most dramatic forms of acute hydrocephalus

generalized dilatation of the ventricular system and basal cisterns (possibly because of increased CSF volume)

CONGENITAL OR INFANTILE HYDROCEPHALUS Types

1.intraventricular matrix hemorrhages in premature infants

2. fetal and neonatal infections 3. type II Chiari malformation 4. aqueductal atresia and stenosis 5. the Dandy-Walker syndrome

Clinical manifestation the head usually enlarges rapidly and soon

surpasses the ninetyseventh percentile The anterior and posterior fontanels are tense

even when the patient is in the upright position. The infant is fretful, feeds poorly, and may vomit

frequently

CONGENITAL OR INFANTILE HYDROCEPHALUS Late manifestation

the upper eyelids are retracted the eyes tend to turn down there is paralysis of upward gaze the sclerae above the irises are visiblethe "setting-sun sign"

NORMAL PRESSURE HYDROCEPHALUS Definition :

A stage is reached where the CSF pressure reaches a high normal level of 150 to 200 mm H2O while the patient still manifests the cerebral effects of the hydrocephalic state

compression of the choroid plexuses and absorption increases in proportion to CSF pressure

Formation of CSF = CSF absorption

NORMAL PRESSURE HYDROCEPHALUS Clinical triad

a slowly progressive gait disorder (earliest feature) (unsteadiness and impairment of balance)

impairment of mental function broadly speaking, "frontal" in character embody mainly apathy dullness in thinking and actions slight inattention.

sphincteric incontinence (late presentation) Urgency and frequency incontinence

No Babinski signs and no papilledema

NORMAL PRESSURE HYDROCEPHALUS Etiology

Sequelae of subarachnoid hemorrhage from ruptured aneurysm or head trauma

resolved acute meningitis or a chronic meningitis (tubercular, syphilitic, or other)

Paget disease of the base of the skull mucopolysaccharidosis of the meninges Achondroplasia Unknown

NORMAL PRESSURE HYDROCEPHALUS Diagnosis

difficult to differentiate from the periventricular white matter change that is ubiquitous in the elderly

Difficult to selected the patients for ventriculoatrial or ventriculoperitoneal shunt

CT or MRI finding : lateral ventricular span at the level of the anterior horns was

in excess of 50 mm (~ 18 mm on the usual CT film) disproportionate enlargement of the ventricular system in

comparison to the degree of cortical atrophy (CT or MRI) degree of transependymal egress of water surrounding the

ventricles (MRI) Lumbar puncture

Most cases CSF pressure > 155mmH2O Drainage of large amounts of CSF (20 to 30 mL or more) by

lumbar puncture Clinical improvement in stance and gait for a few days (high

predictive value for success of shunting)

NORMAL PRESSURE HYDROCEPHALUS Treatment

ventricular shunt tubing with one-way valves (ventriculoatrial shunt) or (ventriculoperitoneal shunt)

a complete or nearly complete restoration of mental function and gait after several weeks or months (after shunting)

Overdrainage causes headaches (chronic or orthostatic headache) small subdural collections of fluid (CSF and

proteinaceous fluid derived from blood products) Complication of shunting

Subdural hygroma or hematoma Valve and catheter infection Ventriculitis Occasionally bacteremia

IDIOPATHIC INTRACRANIAL HYPERTENSION Headache and papilledema : suspicion of

hydrocephalus or tumor Synonym : otitic hydrocephalus or pseudotumor

cerebri Clinical feature :

headaches that are diffuse, worse at night, and often wake them from sleep in the early hours of the morning.

Sudden movements, such as coughing, aggravate headache

Headaches may be present for several months before a diagnosis is made

Transient loss of vision (transient obscuration) enlarged blind spot papilledema false localizing sign of CN VI palsy

IDIOPATHIC INTRACRANIAL HYPERTENSION

diagnosis Clinical criteria ( headache, papilledema, visual loss) ruling out other causes of increased intracranial

pressure All patients require a CT or MRI scan to look for

hydrocephalus and mass lesions lumbar puncture is needed

the CSF include normal or low protein, normal glucose, no cells,

elevated CSF pressure

IDIOPATHIC INTRACRANIAL HYPERTENSION

Goals of treatment : the alleviation of symptoms (usually headache) the preservation of vision

Treatment No RCT Natural history of untreated IIH is unknown Avoided tetracycline derivatives

LOW CSF PRESSURE SYNDROME Pathophysiology

Traction on pain-sensitive intracranial and meningeal structures, particularly sensory nerves and bridging vein

Secondary vasodilation of the cerebral vessels to compensate for the low CSF pressure

Because jugular venous compression (vanodilation)

Epidemiology The estimated annual incidence is 5 per 100,000 The peak incidence is around age 40, but

children and elderly are also affected Women are affected more frequently than men,

with a female to male ratio of 2:1

LOW CSF PRESSURE SYNDROME

Clinical manifestation Headache :

sudden or gradual onset Intense, throbbing, and dull pain Mild to severe form Diffuse or focal location Relieved with recumbency (within minutes) Not relieved with analgesics Exacerbating factors : upright posture, head

movement, coughing, straining, sneezing, jugular venous

compression, and high altitude

LOW CSF PRESSURE SYNDROME

Clinical manifestation Associated symptoms

Neck pain or stiffness Nausea 50 % of cases Vomiting

Other symptoms Change in hearing (eg, hyperacusis, echoing, or tinnitus) Anorexia Vertigo Dizziness Diaphoresis Blurred vision Diplopia Transient visual obscurations Photophobia Unsteadiness or staggering gait Hiccups Dysgeusia

LOW CSF PRESSURE SYNDROME

Examination Normal finding

CSF analysis Opening pressure : 0- 70 mmH2O clear and colorless Moderate lymphocytic pleocytosis (up to 50 cells/mm3) (a reactive phenomenon secondary to hydrostatic

pressure changes) the presence of red blood cells Elevated protein (commonly up to 100 mg/dL) (disruption of normal hydrostatic and oncotic pressure across the venous sinus and arachnoid villi) cytology and microbiology is always normal CSF glucose is normal (never low)

LOW CSF PRESSURE SYNDROME Imaging (MRI finding) > 20% of cases : normal finding Prominent abnormal features on brain MRI include the

following: Diffuse meningeal enhancement (DME) (secondary to vascular

dilatation) Subdural hematomas or hygromas, presumably from rupture of

the bridging veins as the CSF volume decreases "Sagging" of the brain, with cerebellar tonsillar herniation and

descent of the brain stem mimicking a Chiari I malformation Engorgement of cerebral venous sinuses Pituitary enlargement flattening of the optic chiasm, and

increased anteroposterior diameter of the brainstem Decrease in the size of cisterns and ventricles

SEEPS (for Subdural fluid collections, Enhancement of the pachymeninges, Engorgement of the venous structures, Pituitary enlargement, and Sagging of the brain)

LOW CSF PRESSURE SYNDROME Imaging ( CT finding)

Usually normal Subdural fluid collections increased tentorial enhancement Slit- shaped ventricles Tight basal cisterns scant CSF over the cortex

LOW CSF PRESSURE SYNDROME Diagnosis criteria A. Diffuse and/or dull headache that worsens within 15

minutes after sitting or standing, with at least one of the following (and fulfilling criterion D):       -  Neck stiffness -  Tinnitus       -  Hypacusia -  Photophobia       -  Nausea

B. At least one of the following:       -  Evidence of low CSF pressure on MRI (eg, pachymeningeal

enhancement)       -  Evidence of CSF leakage on conventional myelography, CT

myelography, or cisternography       -  CSF opening pressure <60 mmH2O in sitting position

C. No history of dural puncture or other cause of CSF fistula

D. Headache resolves within 72 hours after epidural blood patching

LOW CSF PRESSURE SYNDROME

Treatment No RCT Epidural blood patch (history of CSF leakage post

lumbar puncture) infusion of 10 to 20 cc of autologous blood into the

epidural space Non-specific treatment

Bed rest Oral or intravenous hydration High oral caffeine intake (200 to 300 mg of caffeine,

given two to three times daily) High oral salt intake

Epidural fibrin glue Continuous epidural infusion (saline or dextran) Surgical repair

LOW CSF PRESSURE SYNDROME Prognosis

Spontaneously improvement : within 2 weeks Rare cases :within years

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