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Written by
Fiona Lim
Medically Reviewed by
Dr. Danielle Desroche

Your brain and spinal cord are surrounded and protected from injury by a clear, colorless liquid called cerebrospinal fluid (CSF). CSF is produced by specialized cells in the brain and washes through the central nervous system several times each day, delivering nutrients and removing waste products. Normally, CSF contains very little protein and very few white blood cells. In a condition called albuminocytologic dissociation (ACD), though, the CSF contains more protein than expected, while the number of white blood cells remains normal. In this article we’ll talk about what ACD is, how it relates to autoimmunity, and what it means if you are found to have elevated levels of protein in your CSF.

What Is Cerebrospinal Fluid (CSF)?

The central nervous system (CNS) is made up of the brain and the spinal cord, which connect at the base of the skull. Wrapped around and enclosing the CNS are three layers of protective tissue called meninges. Cerebrospinal fluid is found in the space between the two inner meninges, known as the subarachnoid space. (Source, Source)

Cerebrospinal fluid is produced by the choroid plexus, highly vascularized tissue in the ventricles of the brain, and circulates through the CNS on a regular path. Adults generally have about 150 ml of CSF washing through the CNS delivering nutrients, removing waste products, and adding an extra layer of protection for delicate brain tissue. CSF is also continually reabsorbed into the body, so to maintain CSF volume the choroid plexus produces 400 ml to 600 ml of CSF per day. In effect, the brain has its own circulatory system. (Source, Source)

What Causes Elevated Protein in CSF?

In addition to CSF, the choroid plexus also produces minute amounts of protein, and it is also possible for a very small amount of protein to diffuse into the CNS from the blood. Normally, though, there is very little protein in CSF. (Source, Source, Source)

Elevated levels of protein in the CSF may be caused by easily diagnosed conditions such as inflammation of the meninges, known as meningitis. With bacterial meningitis, for example, the body’s immune response causes increased numbers of white blood cells (WBCs) in the CSF, plus increased protein levels due to leakage in the blood–brain barrier. (Source)

But when protein levels are increased and the number of WBCs remains normal, this is called albuminocytologic dissociation (ACD) — that is, the increase in protein is dissociated, or disconnected, from any increase in WBCs.

Albuminocytologic dissociation is thought to occur in diseases, such as Guillain-Barré syndrome (GBS) and multiple sclerosis (MS), that alter the blood–brain barrier, increase protein production, or obstruct the flow of cerebrospinal fluid. (Source, Source, Source)

Elevated Protein Is Not the Same as ACD

The measurement of protein in CSF may be reported as total protein, spinal fluid (TPSF) or CSF total protein (CSF-TP). A diagnosis of ACD requires a CSF-TP that is significantly above normal, although we don’t yet know exactly what the limits of “normal” are.

Research suggests older people tend to have more protein in their CSF as a normal part of aging. For more than a century the upper limit to the normal range has been set at 45 mg/dl (milligrams per deciliter) regardless of age, but it is now thought the upper limit for adults 50 and over should be at least 60 mg/dl. Research into other possible variables in normal CSF-TP — such as gender and body mass index — continues. (Source, Source, Source)

How Is Albuminocytologic Dissociation Diagnosed?

Albuminocytologic dissociation is diagnosed by taking a sample of CSF and testing it for its protein content. A sample of CSF can be obtained through a lumbar puncture, or spinal tap. In this procedure, a needle is used to draw a small amount of CSF from around the spinal cord, which can then be analyzed for any abnormalities. (Source)

Albuminocytologic dissociation is not a diagnosis in itself. Your health care provider may want to check your CSF for elevated protein if you have neurological symptoms that are suggestive of an autoimmune disorder such as GBS or MS. These might include:

  • sensation of “pins and needles” or prickling in extremities (fingers, toes, ankles and/or wrists)
  • weakness in the legs and lower body
  • difficulty with coordination or unsteadiness
  • difficulty walking or climbing stairs
  • difficulty with facial movements, such as speaking, chewing or swallowing
  • double vision or inability to move eyes
  • difficulty with bladder control or bowel function
  • difficulty breathing
  • digestion issues
  • fatigue

(Source, Source, Source)

What Causes Albuminocytologic Dissociation?

There are several proposed mechanisms for how excessive amounts of protein may find their way into the CSF. They include:

  • inflammation causing proteins to be produced in the subarachnoid space (the space between the two inner meninges, where the CSF is found)
  • inflammation of the meninges (meningitis) allowing proteins in the bloodstream to pass through the blood–brain barrier, which would normally keep them out
  • damage to peripheral nerves allowing proteins in the bloodstream to pass through the blood–nerve barrier that is normally maintained at the ends of the nerves
  • pressure on the spinal cord (spinal compression) causing CSF to collect in isolated pockets
  • injury or disease disrupting the normal flow of CSF

(Source, Source, Source, Source)

Albuminocytologic Dissociation and Autoimmunity

Some causes of ACD, such as peripheral nerve damage, may be related to autoimmune diseases such as Guillain-Barré syndrome (GBS) and multiple sclerosis (MS). This makes ACD itself a symptom of these diseases.

Guillain-Barré Syndrome

Guillain-Barré syndrome is a rare autoimmune disorder in which the immune system attacks nerves. It often begins with weakness and tingling that can spread throughout the body and, in severe cases, may cause paralysis. GBS affects approximately 1 in 100,000 people, and in the United States around 3,000 to 6,000 people develop the condition annually. (Source)

GBS was once thought to be a single disorder, but it comes in several different forms.

  • Acute inflammatory demyelinating polyradiculoneuropathy (AIDP) is characterized by muscle weakness that begins in the lower parts of the body and then spreads upward, damaging the myelin coating around neurons and interfering with nerve signals. It is the most common form of GBS in North America and Europe.
  • Miller Fisher syndrome (MFS) is characterized by paralysis that begins in the eyes and may progress to unsteady gait, difficulty with muscle coordination and balance, absence of tendon reflexes, and in some cases, respiratory failure. It is more common in Asia, and many patients with MFS have an antibody unique to the disorder.
  • Acute motor axonal neuropathy (AMAN) and acute motor-sensory axonal neuropathy (AMSAN) are characterized by weakness of distal muscles (in the hands, feet, lower arms or lower legs), reflexes, and sensory issues. These conditions are more common in Asia and Central and South America.

(Source, Source, Source)

Multiple Sclerosis

Multiple Sclerosis (MS) is an autoimmune disease that affects the central nervous system. The immune system attacks the protective layer covering nerve fibers, which interferes with communication between the brain and the rest of the body. This can eventually lead to the permanent damage of nerves. Presently, MS affects 2.8 million people worldwide. (Source, Source)

As with GBS, there are different types of MS.

  • Clinically isolated syndrome is a first episode of MS-like symptoms that does not result in a diagnosis of MS. This first episode may or may not progress to MS, although progression is more likely if specific kinds of lesions are seen on an MRI of the brain.
  • Relapsing remitting MS (RRMS) is the most common type. It is characterized by periods of noticeable symptoms, called relapses or exacerbations, alternating with periods of lesser or absent symptoms, called remissions. Over time the relapses may become more severe and may cause disability that is not relieved by remission.
  • Secondary progressive MS (SPMS) occurs when the relapse/remission pattern of  RRMS progresses to a worsening of symptoms without periods of remission.
  • Primary progressive MS (PPMS) occurs when symptoms of neurological dysfunction are steady from the very beginning, without any initial period of relapses and remissions.

(Source)

What Does It Mean if I Have ACD?

Finding that you have increased protein in the CSF without increased WBCs does not mean you have an autoimmune disorder such as GBS or MS, but it does mean more investigation is needed.

In addition to evaluating your neurological symptoms, your health care provider may suggest additional diagnostics.

  • Magnetic resonance imaging (MRI) is used to look for lesions in the brain that are characteristic of MS.
  • Electromyography looks at whether muscle tissue is responding appropriately to signals sent by the nervous system.
  • Nerve conduction studies look at how quickly electrical signals move through nerves.

(Source, Source)

The Bottom Line on Albuminocytologic Dissociation

The cerebrospinal fluid (CSF) that circulates around the brain and spinal cord normally contains very small amounts of protein. A healthy immune response to some easily diagnosed diseases such as meningitis may cause increased amounts of protein in the CSF, but this happens along with increased numbers of white blood cells (WBCs).

Abnormal levels of protein in the CSF without an attendant increase in WBCs is called albuminocytologic dissociation (ACD), because there is a dissociation between the amount of protein and the number of WBCs. This dissociation may occur naturally in relation to aging, gender, or body mass index, but it is also sometimes seen with autoimmune disorders that affect the nervous system, such as Guillain-Barré syndrome (GBS) and multiple sclerosis (MS).

Albuminocytologic dissociation is not a diagnosis in itself, but is considered along with certain neurological symptoms and other diagnostic testing to reach a diagnosis.

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