The Lateral Ventricles and Neurodegenerative Diseases

The lateral ventricles are the largest of the four ventricles. The ventricles are chambers in the core of the brain and brainstem that are filled with a watery substance called cerebrospinal fluid (CSF). The ventricles are the red structures in the picture below. In contrast to the third and fourth ventricles, the lateral ventricles separate into two compartments during embryonic development of the primitive neural tube. A thin membranous wall, called the septum pellucidum, separates them.

Enlargement of the lateral ventricles, called ventriculomegaly, is associated with mental disorders due to neurodegenerative diseases, such as normal pressure hydrocephalus, Alzheimer’s disease, dementia, schizophrenia, and bipolar disorder, as well as movement disorders such as Parkinson’s disease, Parkinson's plus variants and Huntington’s diseaseThe cause of ventriculomegaly is often unknown.

One cause of ventriculomegaly can be due to atrophy of structures that surround the lateral ventricles. A decrease in the size of the surrounding periventricular structures allows the ventricles to expand and fill in the space. Another cause of ventriculomegaly is from blockage of venous blood or CSF flow that increases CSF volume in the ventricles. Still another cause is from mechanical compression and shear stresses that result in damage and atrophy of nearby structures that surround the ventricles. Some of the suspected causes of the compression and shear stresses are blockage of venous blood and CSF flow, venous back pressure, abnormal pressure waves and pounding type waves, called water hammers. Among other things, the structures that surround the lateral ventricles are important to controlled meaningful movements, motivation, mood and memories. Dysfunction can result in loss of cognition and memory, as well as behavioral and movement disorders. 

Periventricular Lobes and Nuclei

Each lateral ventricle is divided into a main central portion called the atrium or body, and three extensions, called the anterior, posterior and inferior horns. The body and horns of the ventricles are located adjacent to the inside border of all of the lobes of the brain including the frontal, parietal, temporal and occipital lobes. The area surrounding the ventricles is called the periventricular area. The periventricular areas contain important command and control centers, called nuclei, that are related to the limbic system of the brain. The limbic system is important to mental health, long-term memories and meaningful controlled movements. The limbic system will be covered separately on this site. Ventriculomegaly causes compression and shear stresses that strain these nuclei.

The bodies of the two lateral ventricles are located within the parietal lobes. The parietal lobes are located above the level of the ears toward the rear of the brain. The anterior horns are located in the frontal lobes behind the forehead. The posterior horns are located in the occipital lobe in the back of the skull. The inferior horns are located in the temporal lobes, which are located by the ears below the top of the ear lobe. The parietal lobes are located above the temporal and occipital lobes.

The sketch below is the inside of the right half of the brain with the head facing to the left. The corpus callosum can be seen in the center of the brain. The corpus callosum is a communication link between the left and right hemispheres of the brain that forms the roof of the lateral ventricles. The medial walls and part of the floor of the lateral ventricles are formed by the fornix and hippocampus. The hippocampus is part of the temporal lobe and is important to long-term memories. The fornix is a communication bridge that links the hippocampus to other nuclei of the limbic system.

The floor of the lateral ventricles is formed by the front portion of the body of the fornix, which is located over the roof of the third ventricle. Technically, the floor of the lateral ventricles is also formed by other structures such as the upper and outer surface of the thalamus, the stria terminalis, and the caudate nucleus of the basal ganglia discussed elsewhere on this site. The floor also contains a hole called the interventricular foramen of Monroe that connects the lateral ventricles to the third ventricle below, which is located inside the two halves of the thalamus. Absence, stenosis (narrowing) or blockage of the foramen of Monroe between the lateral and third ventricles can cause hydrocephalus and ventriculomegaly. 

In light of the picture at the top of the page, it is important to note that the basal ganglia and thalamus of the diencepahlon lie between the anterior and inferior horns of the lateral ventricles. The anterior and inferior horns are located above and below them and to their sides. The third ventricle is in the middle and separates the left and right halves of the thalamus as mentioned previously. This makes the basal ganglia, and thalamic and other nuclei located between the lateral and third ventricles more susceptible to getting squeezed by excess CSF volume in the ventricles. Dysfunction (malfunction) of the basal ganglia is associated with Parkinson's and Huntington's disease. Thalamic malfunction is discussed elsewhere on this site.

The third ventricle, which is seen between the anterior (upper) and lower (inferior) horns of the lateral ventricles in the picture at the top of the page, drains into the cerebral aqueduct which connects it to the fourth ventricle. The fourth ventricle is the lowest ventricle and is also seen in the same picture, below the inferior horn of the lateral ventricle. Blockage or sluggish outflow from the fourth ventricle can affect CSF volume in the third and lateral ventricles above it. Chronic blockage can lead to ventriculomegaly.

The Choroid Plexus and CSF

The lateral ventricles are filled with CSF produced by the choroid plexus. The choroid plexus contains clusters of small capillary sized blood vessels covered by a layer of cells called the ependyma. The choroid plexuses are found throughout the ventricles except in the anterior and posterior horns and the cerebral aqueduct that links the third and fourth ventricle. The choroid plexus of the lateral ventricle starts in the inferior horn and continues through the opening in its floor (foramen of Monroe) into the third ventricle where it attaches to the roof. The telea choroidea is a double layer of pia mater that attaches the choroid plexus to adjacent brain structures on the roofs of the ventricles.

The ependyma of the choroid plexus is comprised of cube shaped cells with tight junctions that serve as an extra-fine filter. This filtration system is part of what is called the brain-blood-CSF barrier, which mostly keeps things out so as to maintain a steady chemical state in the brain. It also serves as a transport system for chemicals such as peptides, neurotransmitters and hormones that contol processes in the brain and body, as well as a waste removal system.

Cerebrospinal fluid (CSF) is drawn from the plentiful supply of the dense network of capillaries in the choroid plexus by salt that is secreted from the overlying cube shaped skin-like epithelial cells of the ependyma and into the ventricles. The end product of the secretion and filtration process is called cerebrospinal fluid, which is mostly water with a few other ingredients mixed in. Upright posture also increases CSF production due to an increase in its pressure gradient. Researchers have shown that under certain circumstances, such as changes in pressure or chemical gradients CSF can be absorbed and flow backwards from the ventricles into the capillaries of the choroid plexus.

The choroid plexuses of the lateral ventricles get their blood supply from the anterior and posterior choroidal arteries. The anterior choroidal arteries are branches of the middle cerebral artery which stems from the internal carotid artery that branches off the common carotid artery that travels up the front side of the neck. The posterior choroidal arteries are branches of the posterior cerebral artery that travels up the back of the neck through tunnels in the cervical spine.

The smaller size of the choroidal branches that supply the choroid plexus makes them more susceptible to stroke. They may also degenerate with aging and eventually fail to produce enough CSF to maintain flow and properly support the brain, but that's a separate topic. Increased venous pressure in the cavernous and suboccipital cavernous sinuses can also affect blood flow to the brain. The choroidal arteries are at the tail end of the supply routes and the most likely to suffer consequences of a decrease in supply. Again, that's another topic. The choroidal veins drain into the cerebral veins that surround the lateral ventricles.

Causes of Ventriculomegaly

Abnormal cranial hydrodynamics (fluid mechanics) in the brain can affect periventricular blood vessels, lobes and nuclei resulting in ventriculomegaly and brain atrophy. The periventricular lobes and nuclei are part of the limbic system. Among other things, enlargement of the lateral ventricles can affect periventricular limbic lobes and nuclei related to long-term memories, mental health and controlled meaningful movement

There are several causes of atrophy including cardiovascular degeneration. Another possible cause is obstruction of CSF and venous blood flow in the brain, as mentioned above. Aside from a variety of blockages that can occur inside the cranial vault, one of the most likely places for blockages to occur is outside the vault in the upper cervical spine.

The upper cervical spine connects the cranial vault to the spinal canal. Structural problems in the design, alignment and function of the base of the cranium and the craniocervical junction can block venous blood and CSF flow resulting in hydrocephalic conditions in the brain. Likewise, upper cervical strains, also called misalignments, can obstruct venous blood and CSF flow between the cranial vault and spinal canal. Inherited and acquired malformations and misalignments of the cranial vault and upper cervical spine may play a role in dementia, mental health and movement disorders associated with neurodegenerative diseases.

In cases of hydrocephalus and ventriculomegaly, neurosurgeons use tubes with valves called shunts, and poke holes, called fenestrations into tissues of the brain to open or bypass obstructions to CSF flow. Correction of misalignments of the upper cervical spine may also help to improve blood and CSF flow in the cranial vault and spinal canal, as will other types of physiotherapy and correction that address problems in the lower spine. These topics will be covered separately as this site develops. 

Refererences:

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2.    AJNR Am J Neuroradiol 19:813–819, May 1998 MR Differential Diagnosis of Normal-Pressure Hydrocephalus and Alzheimer Disease: Significance of Perihippocampal Fissures, Andrei I. Holodny, Robert Waxman, Ajax E. George, et al.

3.    Progressive lateral ventricular enlargement as a clue to Alzheimer’s disease, Sunku H, Gupta A, Eric Holroy, et. al, Am J Psychiatry. 2005 Dec; 162(12):2233-45.

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7.    AJNR 1983 May-Jun;4(3):699-702. Aging, dementia, and brain atrophy: a longitudinal computed tomographic study. Gado M, Hughs CP, Danziger W, et al.

8.    Eur J Neruol. 2009 April; 16(4); 475-481 Asymmetrical lateral ventricular enlargement in Parkinson’s disease, Mechelle M. Lewis, Ph.D., Andrew B. Smith B.S, Martin Styner Ph.D., et. al.

9.    Mov Disord. 2011 Feb 1;26(2):297-301. doi: 10.1002/mds.23443. Ventricular enlargement and mild cognitive impairment in early Parkinson's disease, Dalaker TO, Zivadinov R, Ramasamy DP, et al.

10.  The Lancet, vol 359, Issue 9322, pg 2040, page 2040, 8 June 2002, Onset and progression of pathologic atrophy in Huntington disease: a longitudinal MR imaging study. Hobbs NZ, Barnes J, Frost C, Henley SM, Wild EJ, MacDonald K, Barker RA, et. al.

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INDEX OF PAGES Alzheimer's Disease
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CCSVI
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Cerebrospinal Fluid
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The Fourth Ventricle
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Multiple Sclerosis
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Multiple Sclerosis Treatment
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Normal Pressure Hydrocephalus
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Parkinson's Disease
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