What Are All of These Tests For? The Neurologist’s Diagnostic Toolkit

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The Neuro Exam is the most indispensable tool in the neurologist tool kit and is nearly universally employed for assessing the health of a patient’s nervous system and making a determination of what further tests to perform.  There are many different ways to perform a neuro exam and they can take anywhere from two minutes to nearly an hour to perform, depending on the symptoms presented. In each case however, the strategy is essentially the same.  The doctor works his/her way through the wiring diagram of the nervous system to determine which circuits are working properly and which are not.  In some cases, the symptoms will be very obvious and clear, such as paralysis on one side of the body.  In other cases, the person may be asked to answer different kinds of questions and perform different tasks to determine what kinds of mental or physical tasks they are having trouble doing.  In many cases, a doctor will be able to make a preliminary diagnosis after a neuro exam, or at least rule out many possibilities and determine what tests need to be done next.   Most importantly, the neuro exam will narrow down the possible causes of the person’s symptoms and inform which test(s) should be performed to make a more definitive diagnosis.

Magnetic resonance imaging, or MRI, is the most broadly useful neurological diagnostic tool.  An MRI machine essentially uses a large electromagnet to create a magnetic field which aligns water molecules in the body. The electromagnetic field is rapidly turned on and off in cycles. When the field is turned on, the water molecules align.  When it is turned off, the water molecules relax back to a random orientation.  Bombarding the body with radio frequency waves while all of the water molecules are aligned causes the hydrogen atoms in the water molecules to vibrate or resonate at a radio frequency which the machine can detect.  So, in essence, an MRI machine is a water detector.  Gadolinium causes water molecules to move a bit faster and can be injected into the blood stream of a person to increase the contrast in an MRI image. While many different tissues in the body have the same density to X-rays, they often contain very different amounts of water.  Therefore, while an X-ray machine can show very little structural detail in the brain, an MRI can reveal a great deal.  Most notably, white matter areas which consist primarily of electrically insulated (myelinated) axons, contain much lower amounts of water than gray matter areas consisting primarily of neuronal cell bodies and unmyelinated processes.  The cerebrospinal fluid in the ventricles has an even higher concentration of water and the walls of major blood vessels have significantly less water than either other brain tissue or the blood within the vessels.  The differences in water content of these different tissues mean that white matter bundles, ventricles and large blood vessels can be readily distinguished in MRI images.

From the structural details visible in MRI images, doctors can diagnose a range of conditions such as Multiple Sclerosis (MS), stroke, and brain cancer.  A modification of the MRI reading parameters allows MRI machines to detect differences in the magnetic properties and resonating frequencies of hemoglobin (the oxygen carrying molecule in red blood cells) with and without a bound oxygen molecule.  Since more oxygen rich blood flow is directed to areas of the brain that are more active, the blood oxygen level detection (or BOLD) signal in any region of the brain correlates strongly with the level of neuronal activity. Functional MRI (fMRI) images basically show which areas of the brain are most active at any given time and are receiving higher amounts of oxygenated blood.  FMRIs can identify whether a part of the brain is being activated when a person is performing a particular mental task and therefore can determine which areas of the brain may not be working correctly.   However, fMRIs are currently used primarily for research and there is not yet enough information about differences in regional brain activity associated with various disease conditions for these kinds of images to be used as routine diagnostic tests.

MRIs allow doctors to see a lot of structural detail in the brain or spinal cord, but they are not magical or all seeing.  In particular, MRIs cannot reveal the kind of low level diffuse damage associated with mild concussion or the early stages of neurodegenerative diseases.  MRIs also cannot distinguish between living tissue and dead or dying cells until the cells have actually started to break down. After a stroke, major head trauma, or spinal cord injury, MRIs can only reveal the site of the tissue damage and the current area of cell death and break down (necrosis).  They cannot reveal how much more tissue will die and degenerate over the next couple of days.  Essentially, MRI images taken immediately after a stroke or trauma can only define the best case scenario.  Furthermore, since no two brains are exactly alike, it can be difficult to determine whether small differences between the brain that is being imaged and a “typical” brain are due to a disease process or simply individual variation. Likewise, a single MRI cannot distinguish between a recent injury, which could be responsible for the patient’s current symptoms, and an old injury which the person has already recovered from. Ideally, the current image should be compared to an earlier MRI. This approach of repeated MRI imaging is used to identify evidence of new lesions or enlarging lesions in patients with multiple sclerosis.

There are many different ways of taking an MRI image in order to enhance detection of different kinds of features.  These different MRI settings are comparable to different lenses, filters, and lights that a professional photographer can use to make certain features of a model, or his/her clothing, stand out.  It is therefore important for the doctor to have some idea of what he/she is looking for before ordering an MRI.

MRIs have the advantage of not exposing the patient to any damaging radiation.  There are no known health risks associated with exposure to the magnetic field or radiofrequencies of an MRI machine.  The gadolinium contrast agent is generally well tolerated.  The only exception to this is that individuals with poor kidney function or kidney failure cannot effectively clear the contrast agent and may need to have dialysis after an MRI using gadolinium contrast agent.  Most people experience no sensation at all during an MRI.  However, MRI machines do tend to feel a bit claustrophobic (like being placed in a large garbage can) and they can be quite noisy.  Furthermore, the person having the MRI must stay perfectly still during the imaging.  A few people may also experience very small muscle twitches or tingling sensations from the magnetic fields.  All of these unpleasant aspects of the MRI experience are inherent to the way the machine must be designed in order to work. Newer model MRI machine models therefore are only slightly less noisy, claustrophobic and slow than older models.  Wearing ear plugs or listening to music on headphones can make the experience more pleasant and most MRI facilities will offer the person being scanned a choice of music and sometimes different projected images to make him/her feel more comfortable.

The major limitation of MRI imaging is that the electromagnet strongly attracts iron and therefore the person having the MRI taken cannot have any iron metal inside of them or attached to them.  This includes: braces, steal pins or plates, surgical staples, many kinds of metal shrapnel, some pace makers, cochlear implants, insulin pumps etc.  The part of the body containing the metal cannot simply be kept outside of the scanner. The electromagnet is strong enough to pull a wheelchair from across the room and it will try and pull the metallic iron out of the person’s body.  Hardware made of titanium, gold or mercury dental fillings, or objects made of any other kind of metal which is not attracted to a magnet, are OK. The iron atoms in your body are not affected because they are present only as individual iron atoms bound to larger proteins rather than as metallic iron.

Computer aided tomography, or CAT scan (also called computed tomography or CT scan), is essentially a detailed X-ray. For a CAT scan, the patient lies on a moving table while an X-ray source and detector moves around him/her.  CAT scanning machines are not generally as noisy or claustrophobic as an MRI machine, and the images are produced more quickly. However, the person still must keep perfectly motionless for several minutes while the image is being taken.  The X-ray detector in a CAT scan machine takes many very short exposure snapshots of the area being studied and then the computer puts all of the images together to create a series of slice images of the brain.  A tracer containing iodine injected into the blood stream can enhance the visibility of blood vessels.

CAT scans are most commonly used to identify and visualize problems with blood vessels, especially the three dimensional structures of cerebral aneurysms which may require repair.  Although CAT scans do not provide as much structural detail of the brain as an MRI, CAT scan are sometimes used as the primary brain imaging tool for patients who have iron-containing metal pins, plates or pacemakers which cannot be removed and which prevent the person from entering an MRI machine.

The iodine based contrast agent used in CT scans can cause a temporary warm sensation or even burning sensation around the injection site and, like the contrast agent used for some MRI scans, individuals with poor kidney function may require dialysis after the scans are completed.

The major limitation of CT/CAT scans is that they expose the person to much higher dose of radiation than an ordinary X-ray.  A CAT scan can expose the person to as much as 100-400 times the radiation as a single chest X-ray.  Although the health risk associated with this level of radiation exposure is still small, CT scans are generally only ordered when the benefits of the information that they provide are believed to outweigh any risks.    

Conventional X-rays are of little use for imaging brain structures.  Different types of brain tissue and spinal cord tissue look pretty much the same in X-ray images because X-rays can pass as easily through gray matter as white matter. However, X-rays are very useful for detecting fractures in the bones of the skull or vertebrae, slipped discs that are pinching nerves, or major bleeding under the skull resulting from a concussion.  For individuals with skull or back injuries, X-rays are faster and cheaper than other diagnostic tools and expose patients to far lower levels of radiation than CT scans.   In general, a brain bleed that would be too small to detect in an X-ray would also be too small to treat with anything other than bed rest. Therefore, conventional X-rays (rather than CAT scans) are usually ordered for evaluating suspected concussions.

Positron emission tomography, or PET scans, are similar to CAT scans in that the imaging system detects energetic particles (radiation) and uses a computer to create a picture based on the intensity of radiation detected at different places.  Unlike an X-ray or CAT scan however, the radiation in a PET scan is not passed through the person to create an image.  Instead, a small amount of a radioactively tagged chemical is injected into the blood stream and the PET scan shows where the chemical becomes concentrated the body.  The most common radioactively tagged molecule used is a chemical which is similar to glucose, but harder for cells to break down.  Hot spots of radiation detected by a PET scan using this kind of tracer indicate areas of high metabolic activity.  These hot spots can reveal tumors that are too small for an MRI to detect and assess the growth properties of tumors that cannot be biopsied.  PET scans can also sometimes help pinpoint the starting point of an epileptic seizure. PET scans using different kinds of tracers are also used for research to identify the causes of different diseases and to help identify difficult to diagnose conditions.  PET scans are often used in combination with CT scans for neurological diagnoses, as this allows the location of the hot spots to be pinpointed relative to major brain structure.

The main concern with a PET scan is the radiation exposure.  Although the radiation levels used in a PET scan are low, each PET scan exposes the patient to a radiation dosage comparable to that of a chest X-ray. Therefore, doctors try and limit the number of PET scans that are performed on any individual patient.   

Electroencephalograms, or EEGs, are recordings of electrical activity in the brain that are taken on the surface of the scalp.  Many small sticky pads with electrically conducting gel are placed at specific positions on the head and recordings of the differences between electrical potential on different parts of the head are compared and analyzed.  Individual neurons do not produce enough of an electrical signal to be detected on the scalp, but large numbers of neurons acting together can.

EEGs are commonly used to assess the health of brain tissue after a serious injury or stroke, to determine the probability of recovery, and to distinguish between a coma (where the person is unaware of their surroundings) and a locked in state (where the person is aware but unable to respond), and to locate the starting point of epileptic seizures.  EEGs are also used to diagnose sleep disorders where different patterns of electrical activity are associated with different sleep states.  The procedure is painless but it is often time consuming and the recording array can become somewhat uncomfortable over time and restricts the person’s movements.  Someone with insomnia or other sleep problems may need to stay connected to the recording device all night, and someone with severe but infrequent seizures may need to be recorded for several hours a day for a number of days before enough information is obtained.

The main limitation of EEGs is that they cannot provide reliable information about neuronal health during the two days after a brain injury or stroke and they cannot assess the health of the brains of people in medically induced comas.  Neurons in the brain and spinal cord can go into a hibernation-like state for up to two days after an interruption of blood supply.  Brain activity measurements taken immediately after a head injury or stroke are therefore not a reliable indicator of the state of brain health.  Similarly, medically induced comas intentionally suppress neuronal activity to promote recovery.  Therefore, EEG assessments of brain viability or brain death usually must be delayed for a few days after a severe injury or stroke.

Lumbar punctures or LPs involve sticking a needle into the space between two vertebrae, or back bones to extract a sample of the fluid which bathes the brain and spinal cord (the cerebrospinal fluid or CSF).  The fluid from around the brain and spinal cord is then tested for bacteria, viruses, markers of inflammation etc.  The reason for performing an LP is that the blood-brain/blood-spinal cord barrier goes both ways.  A lot of chemicals and infectious agents do not easily get into the brain, but a lot of the chemical markers used to identify diseases also do not easily get out.   Blood test are often not able to diagnose an infection or autoimmune attack in the brain, while testing the CSF can often diagnose the source of the problem.

Generally, LPs are not a favorite with patients.  Although the area of needle insertion is numbed so that the procedure itself is pretty painless, if the person moves at all for the next couple of hours they tend to get a really wicked headache.  On the plus side, most of the time when a doctor orders a LP, the person already has a bad headache, so the LP does not make things much worse.  Furthermore, if the problems that the person has been experiencing are due to a fluid buildup in the brain, removing some of the fluid with an LP will make things at least better until a shunt can be installed to solve the problem permanently.

Tissue biopsies involve removing a small piece of tissue and examining the cells under a microscope.  Biopsies may be used to identify infections, cancer or cancer subtypes, as well as the characteristic features of inherited neurodegenerative diseases or toxin induced nerve degeneration.  For a tissue biopsy of the brain or spinal cord, the precise location of the tissue to be taken is measured from an MRI. A biopsy needle is then lowered into that precise position using finely calibrated equipment. Usually the person is awake and talking with their doctors during this procedure in order for doctors to make sure that they are not damaging any important tissue. Patients are, however, administered antianxiety medication before and during the procure so that they are remarkably unbothered by the situation.  Nerve biopsies are much simpler to obtain and may be performed under local anesthesia.

The main limitation of tissue biopsies is the risk of infection and the fact that the results may be ambiguous or subject to interpretation.  In some cases, for example, a nerve biopsy may rule out some conditions but not be able to definitively identify the cause of the problem.