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CSF

Cerebrospinal 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 Subarachnoid cistern 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

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 m 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 Victors 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 RBC 6,000 cell/ml 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 protein 150 mg/dL systemic hyperbilirubinemia (serum bilirubin >10 to 15 mg/dL) traumatic LP with more than 100,000 red blood cells/ml

Grossly bloody appearance :

RBC lysis in CSF :

Xanthochromia can also occur


From 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 Viral meningitis (Rare) early phase of bacterial meningitis

Lymphoctye predominated in

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) Hyperglycemia (CSF glucose levels rarely exceed 300 mg/dL even in patients with severe hyperglycemia)

High CSF glucose concentrations

COMPOSITION OF CSF
Lactate Higher sensitivity and specificity > the ratio of CSF-toblood 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 ischemicanoxic states acute hepatic failure hypertensive encephalopathy Hypercarbia Reye hepatocerebral syndrome

Generalized brain swelling :


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 choroid plexus tumor

Increases CSF production

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 ganglionicfrontal 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 visible

the "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 Vomiting

50 % of cases

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 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)

CSF analysis

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 - Hypacusia - Nausea

- Tinnitus - Photophobia

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

THE END