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Home , Arachnoid trabeculae, Cerebellar tentorium, Ventricular system

Meninges and Brad Cole, MD

1.

The CNS is enclosed by three connective tissue membranes that together constitute the meninges: the pia, arachnoid, and .

(a) The innermost layer is the . It closely adheres to the and , and into every sulci and depression on the surface of the CNS. The pia is vascular and contains vessels that supply the CNS.

(b) The next layer, the arachnoid, does not follow the uneven surfaces of the brain but extends across depressions and sulci. The space between the pia and arachnoid is called the subarachnoid space. In places, the subarachnoid space is much larger and is called a cistern Examples of this include the (located posterior to the medulla, below the ), and the lumbar cistern (a large collection of CSF below L1-2 where the spinal cord terminates). Thin threads of connective tissue extend through the subarachnoid space connecting the pia to the arachnoid (called ).

The subarachnoid space is filled with cerebrospinal fluid (CSF) which coats the entire CNS (brain and spinal cord). If blood vessels in the pia mater should bleed (such as occurs when an aneurysm ruptures), they bleed into the subarachnoid space. This is called a .

• An of the meninges () results in inflammatory cells in the subarachnoid space.

It is often desirable to examine the CSF for blood or inflammatory cells (normally they are absent in the CSF). A takes advantage of the large lumbar cistern. During this procedure you withdraw CSF from the subarachnoid space by inserting a long needle between the L4-L5 vertebrae. Since the spinal cord ends at L1-2, you don’t need to worry about hitting the spinal cord.

Subarachnoid Space: Normal contents Pathologic contents CSF Blood (aneurysm rupture) Inflammatory Cells (meningitis)

CSF can also be collected from the cisterna magna. For obvious reasons of safety, this is rarely performed today.

(c) The outermost membrane, the dura mater, consists of dense connective tissue and is very strong. The dura consists of an outer periosteal layer which contains blood vessels and nerves and is attached to the inner surface of the cranium, and an inner meningeal layer which is attached to the arachnoid. The dura covers the entire brain and spinal cord all the way down to the second sacral vertebrae and helps to anchor the spinal cord to the meninges via the .

At certain areas these two layers separate to form the large venous sinuses, where the venous blood and CSF eventually drain from the intracranial cavity.

The potential space between the arachnoid and the dura is called the . After head trauma, venous blood can collect in the subdural space, due to shearing of the bridging . This is called a . The space between the dura and bone is called the . Head trauma can also result man epidural hemorrhage. This hemorrhage is more likely to be arterial from a laceration of the middle meningeal artery. Epidural hematomas are more likely to be associated with a fracture and, since the dura is attached to the skull, the blood does not cross suture margins resulting a focal wedge into the brain.

Notice below the crescent shape of a subdural hematoma (left) in contrast to the wedge shape into the brain of an epidural hematoma (right). The latter also reveals a skull fracture (red arrow):

Epidural hematomas more likely occur in younger individuals since the dura becomes more adherent to the skull with age whereas subdural hematomas are more likely in the elderly population.

The dura has two important infoldings into the brain. These serve to restrict potentially damaging movements of the brain in the skull. The large extends into the interhemispheric fissure and divides the left and right halves of the brain. Posteriorly, the falx cerebri divides into two parts that extend over the surface of the cerebellum, the . The anterior edge of the cerebellar tentorium has an opening for the brain stem. The cerebellar tentorium and the petrous portions of the temporal bones separate the supratentorial (above) and infratentorial (below) regions. These terms are generally used to refer to the cerebral hemispheres (supratentorial) from the brain stem and cerebellum (infratentorial).

• Uncal herniation: Under conditions of increased (a tumor or a hemorrhage in the brain for example), the temporal lobe may herniate through the opening of the cerebellar tentorium. The most medial portion of the temporal lobe (the uncus) will often push on the ipsilateral (Ill) resulting in a 3rd nerve palsy (a dilated pupil with the eye deviated laterally). These patients are also in a coma.

2. Cerebral Ventricles and Cerebrospinal Fluid (CSF)

(a) - The paired lateral ventricles are located in the cerebral hemispheres and consist of a central body (posterior to interventricular foramen of Monro), the atrium (or trigone, is the area of convergence of the occipital and temporal horns with the body) and the individual horns that project into three lobes of the brain: anterior (frontal) horn, posterior (occipital) horn, and the inferior (temporal) horn. The frontal horn is the largest and is bordered medially by the . The caudate nucleus bulges into the lateral aspect of the frontal horn while the tail of the caudate is found in the temporal horn. The forms the medial wall of the temporal horn.

(b) - CSF from each lateral ventricle communicates with the third ventricle via the foramen of Monro (there are two foramen of Monro and one third ventricle). The third ventricle is an important landmark, since it is surrounded by the two thalami.

(c) - CSF from the third ventricle communicates with the fourth ventricle via the . The cerebral aqueduct divides the from the tectum in the . The fourth ventricle is between the pons and medulla (anterior) and the cerebellum (posterior).

(d) Subarachnoid Space - CSF exits the fourth ventricle via two Lateral foramen of Luschka and via a single Middle foramen of Magendie. The outlet of these foramen is initially into the cisterna magna. Once CSF exits the fourth ventricle, it is now in the subarachnoid space and out of the ventricular system. The CSF in the subarachnoid space coats the brain and spinal cord and eventually empties into the (the venous sinus over the interhemispheric fissure), via specialized structures in the wall of the sinus called arachnoid villi. The arachnoid villi are small evaginations of the arachnoid which protrude through the meningeal layer of the dura into the superior sagittal sinus. Several of these villi together are called arachnoid granulations. The CSF is able to pass through the arachnoid villi because the hydrostatic pressure is higher in the subarachnoid space than in the venous sinuses. The superior sagittal sinus eventually drains into the internal jugular where both the venous blood and CSF exit the intracranial cavity.

The in the spinal cord is a continuation of the ventricular system. It is, however, essentially an embryologic remnant that has no functional significance.

3. Function of the CSF

The CSF is produced by the , which is located in the lateral ventricles, third ventricle, and the fourth ventricle. The composition of CSF is similar to that of blood with several important exceptions. Normally there are no red blood cells or white blood cells in the CSF. The CSF glucose is about 2/3 that in the blood, while CSF protein is only 0.5% that of blood.

The brain and spinal cord are protected not only by the skull and vertebral canal, but also by the meninges and CSF. The specific weight of nervous tissue is only slightly greater than that of water, which means that the brain and spinal cord almost float in the CSF. This buoyancy reduces the weight of the nervous tissue and results in less traction on vessels and nerves connected to the CNS. The CSF and meninges also minimize the impact of external forces on the brain and spinal cord by serving as a cushion between the CNS and bone.

Review of CSF circulation (label the drawing on the previous page): Lateral Ventricles (2) → Interventricular foramen of Monro (2) → Third Ventricle → Cerebral aqueduct → Fourth Ventricle → Foramen of Luschka (2) and Foramen of Magendie→ Cisterna Magna/Subarachnoid Space → Arachnoid Villi → Superior Sagittal Sinus → Cerebral Venous System → Internal

The CSF also filters out potentially toxic substances from the brain (such as potassium ions during periods of intense neuronal activity) and keeping a relatively constant composition for the neurons. Recently the glymphatic system was identified as a perivascular pathway where CSF flows through brain tissue to filter out potential toxins. Most importantly, amyloid beta, which accumulates in Alzheimer’s , is filtered out by this system.

4.

The total volume of CSF in the ventricular system and the subarachnoid space is about 150 ml in an adult. The choroid plexus produces about 500 ml of CSF every day. Thus, the total amount of CSF is renewed several times every day. If there is a blockage of CSF flow, the ventricles may expand resulting in hydrocephalus. For example, if the cerebral aqueduct becomes occluded, the third ventricle and the lateral ventricles will dilate since the CSF produced in these ventricles cannot drain into the subarachnoid space. The fourth ventricle, however, will not change in size since its flow is not impeded. In infants and children this results in an increased head circumference if the sutures have not yet closed. In adults, this results in increased intracranial pressure and can result in herniation of the brain through the if not treated.

Hydrocephalus is divided into three main types:

(a) Non-communicating Hydrocephalus - the CSF of some part of the ventricular system does not “communicate” with another part of the ventricular system or with the subarachnoid space CSF. Anything compressing the interventricular foramen of Monro, cerebral aqueduct, or the outlets from the fourth ventricle could all produce this type of hydrocephalus. A lumbar puncture should not be performed in this type of hydrocephalus since this lowers the pressure in the lumbar cistern and creates a pressure gradient between the ventricular CSF (which is already increased in this type of hydrocephalus) and the subarachnoid CSF. can result.

(b) Communicating Hydrocephalus - the CSF of the ventricular system and subarachnoid space “communicate”. The blockage is usually in the arachnoid granulations. An old subarachnoid hemorrhage or meningitis, for example, can result in scarring and closure of the arachnoid villi. If needed, lumbar puncture can be safely performed in this type of hydrocephalus.

(c) Hydrocephalus ex-vacuo - As the brain atrophies, particularly in neurodegenerative conditions such as Alzheimer’s disease, the ventricles appear larger. This is simply due to a loss of the normal brain tissue around the ventricles. This is diagnosed by identifying both central and peripheral atrophy of the brain by MRI or CT scan. “Central” refers to brain tissue around the ventricular system, “peripheral” refers to the .

Normal Hydrocephalus Atrophy (ex vacuo)

5. Blood-Brain Barrier (BBB)

In the 1800s it was discovered that dye injected into bloodstream stains all of the organs in the body except for the brain. This is due to the BBB which separates the brain from the blood. The

site of the barrier is at the interface between the blood and the brain and is made of three main components:

• The endothelial cells that form the wall of brain capillaries, with associated tight- junctions. This is the most important part of the BBB (a frequent board question) • The basement membrane of these endothelial cells • foot processes which cover the capillaries

Notice below that lipid-soluble molecules penetrate the BBB much easier: Cross BBB freely Require active transport H2O Glucose + - O2 H and HCO3 CO2 Amino Acids Lipid soluble molecules (steroid hormones, etc.)

The BBB has numerous clinical applications. For example: • In pharmacology, it is important to consider what medications are able to cross the BBB and which ones cannot. • A number of neurologic conditions result in disruption of the BBB. These range from mass effect lesions such as brain tumors but also autoimmune conditions such as where a “leaky” BBB results in immunologic attack on the • In our neuroradiology lectures, we will discuss contrast agents that are given with CT and MRI scans. Normally, these agents do not cross the BBB. If, however, a condition results in disruption of the BBB, contrast then is able to “leak” into the brain which results in distinctive imaging findings.

6. Circumventricular Organs

The circumferential organs are areas of specialized tissue located in the midline ventricular system that lack a BBB. At the circumventricular organs, hormones and large peptides can be exchanged between the blood, the brain, and the CSF. There are seven such sites:

• : located along the caudal wall of the 4th ventricle in the medulla. This is the sometimes called the “vomiting center” because it detects toxins such as the chemotherapeutic medication cisplatin • • • Subfornical gland • Organum vasculosum of the lamina terminalis: involved in osmotic sensing • Median eminence • Neurohypophysis

7. Meningitis

Meningitis is an infectious process that involves the meninges and cerebrospinal fluid. Patients present with a severe headache and fever, which typically progresses over hours. Patients have pain with neck flexion which stretches the meninges. There are occasionally other symptoms which may provide a clue as to the specific organism such as a petechial skin rash in meningococcal . Making a rapid diagnosis by CSF analysis is critical since there are many forms of meningitis which are treatable. Untreated, bacterial meningitis is rapidly fatal. Viral meningitis is generally benign and patients typically have a good recovery. Fungal meningitis results in a chronic meningitis which usually presents more slowly and requires long- term treatment.

Most likely cause of bacterial meningitis by age:

• Birth to 3 months Gram-negative bacilli (especially E. Coli), group B streptococcus, Listeria

• 3 months —7 years H. influenza*, N. meningitides, S. pneumonia

• 7 years — adult S. pneumonia, N. meningitides, Listeria

8. Encephalitis

Encephalitis is due to invasion of the brain parenchyma itself by the organism, almost always viral. Patients with encephalitis also present with headache and fever, but also have symptoms suggestive of cortical involvement, such as: seizures, lethargy to coma, aphasia, and sometimes focal weakness if the motor cortex is involved.

Herpes Simplex Encephalitis (HSE) is the most important specific organism to consider in a patient presenting with an encephalitis, since it is treatable. HSE can present at any age. The most common symptoms are: rapidly progressive headache, fever, seizures, personality changes, encephalopathy, and aphasia if language areas are involved. CSF analysis is important in making the diagnosis of HSE (see the below). In addition, of the brain reveals edema in the temporal lobe, often in both temporal lobes. Rapid diagnosis is critical since untreated HSE results in death in at least 2/3rds of patients.

CSF data in various pathological conditions:

Etiology WBC’s RBC’s Glucose Protein Other

Bacterial meningitis ↑↑↑ 0 ↓↓ ↑↑ Culture positive

Viral meningitis ↑ 0 normal ↑

Herpes Simplex normal or ↑ ↑ ↑ PCR positive Encephalitis ↓**

normal or Subarachnoid hemorrhage ↑* ↑↑↑ ↑ Xanthochromia ↓**

Fungal meningitis ↑ 0 ↑↑ Culture positive ↓↓

• White blood cells (WBC’s) – normally, there should be less than 5 cells per microliter in the CSF. In bacterial meningitis, there are often more than 500. In viral meningitis, the count typically is between 50 and 300. WBC elevation in cases of subarachnoid hemorrhage is proportional to the increase in RBC’s.*

• Red blood cells (RBC’s) – necrosis and hemorrhage in the brain in HSE can result in an increased RBC count.

• Glucose – normal levels are 50-75 mg/dl. Notice that in most causes of viral meningitis, the glucose is normal. Glucose may be low in severe SAH and HSE since the inflammation can disrupt active transport of glucose into the CSF

• Protein – normal levels are between 15-45 mg/dl.

• Xanthochromia – during a lumbar puncture, a “traumatic tap” frequently can result in an elevated RBC count. If several tubes of CSF are collected, the number of RBC’s decreases with each tube in a traumatic tap. Checking for xanthochromia is important in distinguishing between subarachnoid hemorrhage and a traumatic tap. When the lab spins down the CSF in a tube, if the blood has been present for some time, some of the RBC’s lyse, releasing bilirubin. In a traumatic tap, there is no xanthochromia.