Dysautonomia, Cerebellar Signs and Multisystem Atrophy
The Many Faces of Dysautonomia
Dysautonomia, which means autonomic dysfunction, is a broad term that describes any disease or malfunction of the autonomic nervous system. The signs and symptoms of autonomic dysfunction are numerous and vary widely from person to person. It is seen in multisystem atrophy, which is a variation of Parkinson's disease. It is also seen in other neurological diseases such as, Chiari malformations, Alzheimer's disease, and multiple sclerosis, as well as Ehler's-Danlos syndrome, because they all affect the autonomic nervous system.
The autonomic nervous system, which is also known as the vegetative nervous system, controls and regulates automatic functions of all the internal organs and circulatory systems of the body such as heart beat, blood pressure, respiration, temperature, sweating etc. Among other things, dysautonomia in multisystem atrophy is associated with orthostatic hypotension in which blood pressure falls too low when the patient stands upright. In contrast to multisystem atrophy, Ehlers-Danlos (EDS) is often associated with a condition called postural orthostatic tachycardia syndrome (POTS), which causes heart rate to increase when the patient stands or sits upright. The difference in the dysautonomia signs and symptoms seen in multisystem atrophy and Ehlers-Danlos may be due to Chiari 1 malformations, normal pressure hydrocephalus (NPH)and benign intracranial hypertension (BIH).
The dysautonomia, Parkinsonism and cerebellar signs seen in multisystem atrophy and other conditions may be due to an increase in cerebrospinal fluid (CSF) in the basal cisterns of the brain. As the volume of CSF increases it starts to rise in the cranial vault and affect the cisterns located at higher levels which can then impact the brain structures at those levels and in some cases causing dysautonomia. The drawing of an MRI above by Anne Olsen, which was taken from a neurology lecture shows a normal brain. The cisterns are the blue areas surrounding the brainstem and cerebellum. The lateral ventricle is the gray area in the middle of the brain. The third and fourth ventricles are black and are labeled Roman numerals III and IV. The third ventricle sits below the lateral ventricles. The fourth ventricle is the triangular shaped black area between the rear of the brainstem and the front side of the cerebellum. CSF is produced in the ventricles of the brain where it is filtered from blood. What remains after filtration is essentially water, with some sugar and other elements.
The cisterns in the drawing are blue and are expansions in the subarachnoid space, which is the pathway for CSF. A cistern is a well. The basal cisterns are wells filled with cerebrospinal fluid (CSF) that surround and protect the brainstem and base of the brain from the hard walls of the cranial vault. The CSF that fills the wells comes from and is produced in the ventricles.
After CSF leaves the ventricles it enters the basal cisterns. The cisterns are expansions in the subarachnoid space. The subarachnoid space is a tunnel for flow that travels through the protective coat of the brain. The subarachnoid space surrounds the entire brain and passes into all of its cracks and creases called fissure and sulci, as well as every space. Similar to the ventricles, excess CSF volume is sometimes seen in the subarachnoid spaces, such as the cisterns and sella turcica. The sella turcica is a protective vault located in the subfloor of the middle fossa of the cranial vault behind the eyes. The sella turcica contains the pituitary gland, which is the master gland that regulates hormones in the body. Looking at the picture above the suprasellar cistern (A) sits above the sella turcica/pituitary.
Multisystem Atrophy and Other Related Syndromes
Excess CSF volume in the cisterns is also associated with Dandy-Walker Syndrome and multisystem atrophy.
Dandy-Walker is seen in children and can start in utero (during pregnancy). It is often due to poorly developed CSF pathways that causes the CSF to become trapped in the lowest (fourth) ventricle (see IV) or in the lowest cistern. (See cisterna magna). The cause is often unknown. Dandy-Walker syndrome affects females far more frequently than males.
The brain scan below is from a patient with multisystem atrophy. The image is used with permission from the Department of Radiology at the University of Cincinnati College of Medicine. Multisystem atrophy (MSA) is a variant of Parkinson’s disease seen in adults that is associated with atrophy of the structures of the brainstem and cerebellum in the posterior fossa causing dysautonomia and cerebellum signs. The cerebellum controls posture, walking (gait), coordination and balance. It affects males far more frequently than females.
In the scan below the cerebellum is the lower rear portion of the cranial vault and appears pushed upwards and is smaller in size than usual. The gray area below it is filled with CSF. The rest of the brainstem in front of the cerebellum has three parts. The top is the midbrain. The middle is the pons and the lower portion is the medulla. The pons is the round protruding belly-like structure of the brainstem. In the image below it is flatter than usual. The midbrain above and the medulla below are also slightly smaller in size than normal and all three structures are surrounded by excess CSF volume in the cisterns. Compare the abnormal MRI to the drawing above to see the structural differences mentioned.
Because of the stuctures it affects, multisystem atrophy used to be called olivopontocerebellar atrophy. Shy-Drager is another formerly used term to describe multisystem atrophy associated with dysautonomia. Regardless of the name, multisystem atrophy is associated with atrophy of the brainstem and cerebellum and an increase in the volume of cerebrospinal fluid in the basal cisterns. The increase in CSF volume in the cisterns may be a cause of cerebellar dysfunction and dysautonomia.
The cause of the excess CSF volume in the cisterns of adults with multisystem atrophy is currently attributed to degeneration and a decrease in the size of the different parts of the brainstem, which is called atrophy. The different parts of the brainstem it affects are the olives (located in the medulla), the pons and the cerebellum of the brainstem.
Ventricle Versus Cistern Causes of Parkinson's
An increase in CSF volume in the ventricles in children is called hydrocephalus. Hydrocephalus causes the ventricles and head to enlarge. One of the primary causes of hydrocephalus in children is stenosis (narrow) of the cerebral aqueduct which connects the third and fourth ventricle. Hydrocephalus also causes an increase in pressure inside the cranial vault called intracranial pressure.
In contrast to hydrocephalus in children, normal pressure hydrocephalus (NPH) is seen in aging adults. NPH causes the ventricles to enlarge the same as hydrocephalus in children. The difference is that intracranial pressure remains normal or only slightly elevated. NPH has been associated with Alzheimer’s, primary Parkinson’s, and Huntington’s disease. It may also play a role in multiple sclerosis.
As I discuss in my book, the difference in intracranial pressure in hydrocephalus in children compared to NPH in adults is probably due to the different degrees of compliance of the skull, which is its ability to expand. A child’s skull is much more compliant due to the open state of its special joints called sutures. The sutures of the cranial vault, however, eventually close with age, which decreases compliance. Consequently, since the skull can't expand in adults, CSF pressure remains low or normal. Consequently, because the skull can't expand the brain gets compressed.
Primary Parkinson’s disease is associated with degeneration and dysfunction (malfunction) of the nigrostriatal pathways. The nigrostriatal pathways include the substantia nigra and basal ganglia. For reasons that are unknown, primary Parkinson’s affects the substantia nigra of the nigrostriatal pathways. The cause of the degeneration is unknown. One possible cause is the location of the substantia nigra in the midbrain.
The midbrain is situated at the top of the brainstem. It connects to the hypothalamus of the brain above and to the pons of the brainstem below. The midbrain is surrounded by the suprasellar (A) and quadrigeminal (B) cisterns in the drawing above. Its location makes it susceptible to compression from blocked CSF outflow and an increase in CSF volume in the cisterns that surround it. Therefore, an increase in volume of CSF in the suprasellar and quadrigeminal cisterns could compress the midbrain and affect the substantia nigra. The midbrain also contains the cerebral aqueduct which connects the third and fourth ventricles as mentioned above.
In addition to its impact on the midbrain, the suprasellar cistern also sits above and dips down into a portion of the sella turcica. The sella turcica houses the pituitary gland. It looks like a small sack hanging down from the bottom of the brain. An increase in CSF volume in the suprasellar cistern can thus affect the pituitary gland as well.
Severe compression of the midbrain causes a characteristic appearance on brain scans called a hummingbird sign because the pons looks like the breast of the bird and the midbrain looks like the head and beak. The hummingbird sign is associated with multisystem atrophy.
In contrast to classic primary Parkinon's, which affects the substantia nigra primarily, olivoponcerebellar atrophy and Shy-Drager types of multisystem atrophy are associated with dysfunction of the cerebellum and the autonomic nervous system causing dysautonomia. In this regard, the midbrain is connected to the the hypothalamus of the brain above it.
Among other things, the hypothalamus produces releasing factors that stimulate the pituitary gland, which regulates the hormones of the endocrine system. It can also cause dysautonomia as it plays an important role in the autonomic nervous system, daily cycles, sleep, voluntary urination, sweating and temperature regulation among other things. Interestingly, many MS patients have heat intolerance. The hypothalamus is surrounded by the ambient cistern.
Currently neurologists prefer to breakdown multisystem atrophy into three categories depending on the predominant signs and symptoms. Patients with more Parkinsonism type signs and symptoms are labeled MSA-P category. Patients with predominantly cerebellar signs are referred to as MSA-C and those with predominantly autonomic signs or dysautonomia MSA-A.
CSF Volume - The Cause
The point to be made here is that an increase in CSF volume in any of the the cisterns can compress the different parts of the brainstem and cause dysautonomia, Parkinsonism and cerebellar signs and symptoms just the same as an increase CSF volume in the ventricles.
The cause of the increase in CSF volume may be due to poor flow between the brain and spinal cord. In this regard, the upper cervical spine is a critical choke point for blood and CSF flow between the cranial vault and spinal canal. Inherited design problems and acquired misalignments due to injuries and aging of the upper cervical spine can affect the normal ebb and flow of blood and CSF between the cranial vault and spinal canal. Below the upper cervical spine, degeneration of the lower spine called spondylosis, and stenosis of the spinal canal can, likewise, affect the flow of CSF and its volume in the ventricles and basal cisterns of the brain. Abnormal curvatures of the spine, called scoliosis and kyphosis can also affect blood and CSF flow in the spinal canal and cranial vault.
In either case, stenosis affects the contents of the spinal canal, which includes the spinal cord and its blood and CSF circulatory systems. Moreover, the spinal canal is connected to the cranial vault and brain by the foramen magnum. Therefore, blood and CSF flow in the spinal canal can affect blood and CSF flow in the cranial vault. Blockage of CSF flow between the brain and cord can cause CSF volume to increase in the cisterns. The increase in CSF volume in the cisterns may be the cause of dysautonomia, cerebellar and Parkinsonism signs and symptoms seen in multisystem atrophy, as well as many other neurodegenerative conditions.
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