Ancillary Diagnostic Tests for Neurologic Patients:
After determining that the patient has a neurologic disease, localizing the disease process,
and forming a differential diagnosis, a diagnostic plan can be developed. This will include tests
to ascertain the nature of the neurologic disease, but also include tests to evaluate any
discrepancies in the physical examination. Some test should be performed on every neurologic
patient while other tests must be selected based upon the location of the neurologic lesion or
lesions. The former tests are called the minimum data base.
The Minimum Data Base:
A complete blood count (CBC) including a measure of chronic inflammation such as
plasma fibrinogen should be performed on all patients. The presence of polycythemia or anemia,
the presence of alterations in plasma proteins and the presence of inflammatory disease or
possibility of disseminated intravascular coagulation (DIC) can be assessed, initially, through the
CBC. The presence of reduced or elevated white blood cells (WBCs) may indicate infection
with viral or bacterial pathogens. Myeloproliferative diseases may produce characteristic
changes in the WBC. Increases in circulating nucleated red blood cells (RBCs) may indicate
lead poisoning or the presence of hemangiosarcoma.
Serum chemistry profiles allow screening for metabolic and toxic conditions which
could result in neurologic sequela. Since any disease which effects the body can affect the
nervous system, wither directly or indirectly through metabolic intoxication, assessment of the
bodies health through screening tests is important in understanding neurologic disease. As will
be seen in seizure disorders, the changes reflected in the chemistry profile may help differentiate
between an active seizure disease and epilepsy. To this end, the electrolytes (Na, K, Cl, Ca and
PO4) are important in muscle and nerve strength and reactivity. Assessments of BUN,
cholesterol and albumin can help assess liver function. If all of these parameters are low, one
should suspect a portosystemic shunt with diminished liver function. Elevations of cholesterol
may help suggest endocrine abnormalities such as hypothyroidism or Cushing’s disease.
Elevated globulins might indicate autoimmune disease or, in the case of cats, the presence of
feline infectious peritonitis.
Additional serum chemistries beyond routine screening tests may be indicated based
upon the location of the lesion and the nature of the neurologic disease. For example, in
seizures, all cases should also have serum cholinesterase levels run (to rule out organophosphate
intoxication) and serum bile acid levels determined (to rule out liver dysfunction and as a baseline
for possible future examines after anticonvulsant medications have been started). Dogs and
cats with muscle pain or weakness may need additional serum muscle enzyme tests and
determination of serum T4, T3 and TSH concentrations.
A urinalysis can help complete the assessment of the patient’s health. Since many
neurologic patients exhibit urinary retention or incontinence, this can be important in monitoring
for urinary tract infection. Examination for ammonium biurate crystals can help establish
diminished liver function, while the presence of calcium oxalate crystals might confirm ethylene
glycol intoxication.
Appropriate parasite screens should be performed where indicated. Heartworm
infection can result in neurologic and muscular diseases in endemic areas. Heavily parasitized
young animals can become anemic or hypoglycemic as a result of the infestation, resulting in
seizures or other neurologic conditions.
Routine radiographs of the chest and abdomen are indicated where disease is
suspicioned based upon the physical examination. They may also be indicated in animals over
6-8 years of age, even in the absence of overt physical changes. When neoplasia is on the
differential, then they are warranted. If the chest or abdomen are riddled with cancer, extensive
workup for the concurrent neurologic disease may not be indicated. In addition to abdominal
radiography, abdominal ultrasound examination may help determine the cause of the problem,
even when abdominal radiographs do not show obvious lesions.
Other Physical Examinations:
Fundoscopic examination may provide important information about the nervous system,
since the retina and optic disc are the only parts of the nervous system which can be directly
visualized. With CNS infection, active chorioretinitis might be seen. In the dog, this may mean
fungal infection (aspergillosis or cryptococcoses), protozoal infection (toxoplasmosis or
neosporidiosis) or canine distemper. In cats, it may lead to the diagnosis of cryptococcoses,
toxoplasmosis or viral diseases (FeLV or FIP).
Otoscopic examination may help in diagnosing problems in the ears and is especially
important in assessing animals with vestibular disease.
Specific Neurologic Tests:
Despite the many different disease processes which can assault the nervous system, there
are a limited number of tests which can be used to help make the diagnosis. Many are indicated
not matter what the nervous system disorder, while others are indicated for specific neurologic
conditions. The include CSF tap and analysis, electroencephalogram (EEG), electromyogram
(EMG), brainstem auditory evoked response (BAER), skull or spinal radiographs, myelography
and magnetic resonance imaging (MRI). Skillful use of these test will, however, allow for the
diagnosis of the majority of neurologic conditions. Definitive diagnosis may be achieved by
biopsy techniques, including muscle, nerve or brain biopsies.
The CSF tap and analysis is one of the most important tests which can be performed in
assessing neurologic disease. It might be contraindicated in cases of recent or ongoing
hemorrhage and in cases the intracranial pressure is increased. However, in most cases, it
provides direct information about the CNS with minimal risk, being less than that of anesthesia.
Evaluation of CSF should include pressure (for cisternal taps), protein determination and
cytology. Additional test on CSF might be beneficial in certain diseases, such as
acetylcholinesterase levels and 2-D electrophoresis in degenerative myelopathy. In cases where
infection is suspected, titers can also be helpful in diagnosing the cause. CSF can be collected
from the cisterna magna or the lumbar cistern between L5 and L6. For most animals, a 22 ga
spinal needle is best for achieving the tap, varying in length between 1.5 to 3.5 inches.
Allowing
the CSF to flow by gravity and collecting into a syringe as it drips from the hub of the needle,
one cc of CSF can be collected for every 10 pounds of body weight. To run routine CSF
analysis and titers, requires approximately 1.5 cc of CSF. Cytologic examination plays an
important part of CSF analysis. Total counts can be useful, but we have found that close
inspection of the “reactivity” of the cells on cytology may be more important than the total
count. The best method to perform cytology is with the use of a cytocentrifuge. Since the cells
deteriorate rapidly in CSF, cytology and cells counts must be performed within 20 minutes of
drawing the sample.
The EEG tests the outer 3 mm of the cerebral cortex and measures the electrical
potentials between scalp electrodes. It can be used to test the forebrain and is an important
diagnostic tool for diseases characterized by changes in behavior and seizures. To perform the
EEG, the patient is anesthetized for any other neurologic tests which are being performed and,
then, the scalp electrodes are inserted and connected to an EEG machine (a filtered, amplifier
connected to a recording device). Once the connections are made, the recording is started and
the anesthesia is turned off. The EEG is then recorded while the patient recovers from
anesthesia. Performing the EEG in this manner induces some artifacts from the effects of
anesthesia (however, these are minimized by using the same anesthesia in all patients and
becoming familiar with the artifactual changes). On the other hand, it removes artifacts from
EMG activity and movements, typical of awake EEG recordings. The normal EEG has fast, low
amplitude activity (15-30 Hz and 5-15 :V, respectively). The presence of slow waves (alpha,
delta and theta waves) with high amplitude indicates abnormality.
Electromyographic examination test the integrity of the lower motor unit. The needle
EMG is performed by inserting an exploring electrode into the muscle to examine its intrinsic
electrical activity. It is best performed under anesthesia, whereby nerve stimulation studies can
also be performed. The presence of fibrillation potentials, fasciculation and bazaar high
frequency discharges indicates increased irritability of the muscle membrane, occurring in
disorders of the motor neuron, motor nerve, neuromuscular junction or muscle. Based upon the
distribution of the EMG changes, the location and nature of the neurologic disorder may be
indicated. Since muscle membrane irritability requires time to develop following denervation,
the needle EMG may be normal for 5-7 days following acute injury of the motor unit.
Another important part of the EMG is determined by electrical stimulation of peripheral
nerves. By stimulating at multiple sites along a motor nerve and recording the latency between
the stimulation and the beginning of the compound action potential, the motor nerve conduction
velocity can be determined. The distance between the stimulating electrodes at the two sites is
divided by the difference between the latencies from the 2 sites to give the motor conduction
velocity in meters per second (normal conduction is greater than 50 m/s). In addition to motor
conduction velocity, repetitive nerve stimulation can be performed. Normally, the muscle can
maintain activity at stimulation rates between 5-10 per second. In myasthenia gravis or subacute
organophosphate intoxication, there is a decremental response to repetitive stimulation.
The F wave is a low-amplitude wave seen several milliseconds following the compound action
potential and is thought to be produce by antedromal spread of the stimulation pulse to the cell
bodies of the nerve where it results in a secondary pulse traveling down the nerve to the muscle.
The H wave is another low-amplitude response several milliseconds after the F wave and
represents stimulation of the sensory fibers in the nerve and subsequent reflexive stimulation of
the motor neurons. Both the F wave and H wave may help examine the integrity of the central
connections of the peripheral nerves. In addition to motor nerve conduction velocities, sensory
nerve conduction can be measured. The sensory nerve is stimulated and a recording electrode
place proximally along the nerve records the passage of the impulse up the nerve. The distance
to the recording electrode is divided by the latency of the impulse recording to determine the
sensory conduction velocity.
The BAER records the electrical activity in the brainstem caused in response to auditory
clicks in the ears. The BAER is not affected by sedation or anesthesia, so patients who are
fractious can be sedated without affecting the results. The recording is made by placing a
ground electrode in the untested ear, a reference electrode in the ear to be tested and a recording
electrode over the vertex. The click is introduced in the ear to be tested and the electrical
activity generated is averaged to reduce random noise. Generally, 5-7 middle-latency, waves are
recorded, representing the transmission of auditory information through the vestibulocochlear
nerve, the cochlear nucleus, the nucleus of the trapezoid body, the lemniscal nucleus and caudal
colliculus, respectively. The BAER is used most frequency to test young animals for congenital
deafness, but may also be used to test the integrity of the brainstem auditory system.
Neuroradiology and imaging include routine radiographs of the skull and spinal
column. All neuro-imaging techniques are best performed under general anesthesia. Routine
radiographs of the skull may reveal fractures, congenital defects, otitis media and interna and
obvious neoplasia affecting the osseus structures of the skull. Routine spinal radiographs can
help identify fractures, congenital malformations, evidence of degenerative disc disease,
discospondylitis and neoplasia of the vertebra. However, many times the effects of the bony
changes on routine radiographs do not provide sufficient information about the neural damage
without the addition of special imaging techniques.
The most common of these techniques is myelography, performed by injecting contrast
agent into the subarachnoid space through a spinal needle. Most of the time, the injection is
made at the lumbar cistern and the contrast agent (Iohexol 180) is allowed to flow forward to fill
the subarachnoid space to beyond the lesion. For diseases in the thoracolumbar region 0.33
cc/kg of body weight is used, while 0.45 cc/kg of body weight is used for cervical disease. It is
best to use image-intensification to monitor the flow of the contrast agent and the dosage given
adjusted to effect. Since most contrast agents are irritative, most neurologist believe they should
not be performed in the face of obvious inflammation of the nervous system. In addition, this
irritation can result in seizures upon recovery from anesthesia, another reason not to inject more
than necessary to fill the subarachnoid space to the level of C1. Giving methylprednisolone
immediately following the contrast injection can reduce the incidence of pot-myelographic
seizure, probably due to helping to maintain intercellular glucose concentrations.
A number of other special imaging techniques have been applied to neuro-imaging
including computer assisted tomography (CAT) scans, radioisotopic brain scans, cerebral
angiography and ventriculography. Of these, only the MRI provides anatomic detail when
examining the nervous system. All portions of the CNS can be imaged by MRI. The MRI
provides evidence of increased tissue density and fluid accumulation, demonstrates anatomic
shifts in CNS structures, and (coupled with contrast studies) demonstrates breaks in the bloodbrain
barrier. For CNS neoplasia and for lumbosacral stenosis, MRI is the imaging method of
choice.
Diagnostic Plans:
Although the neurologic tests above can help diagnose neurologic disease, not all are
indicated for all conditions. For simplicity, the problems of the nervous system can be broken
into
1) diseases above the foramen magnum (diseases with head signs),
2) diseases of the spinal
column (diseases of quadriparesis or paraparesis) and
3) diseases of the peripheral nerves and
muscle.
For diseases of the head, the diagnostic plan includes:
1) minimum data base,
2) fundoscopic or otoscopic examination,
3) CSF tap and analysis,
4) skull radiographs,
5) EEG or BAER (EMG if cranial neuropathy), and
6) MRI or CT scan.
For diseases of the spine, the diagnostic plan includes:
1) minimum data base,
2) CSF tap and analysis,
3) spinal radiographs,
4) myelography,
5) EMG, and
6) MRI or CT scan.
For diseases of the peripheral nerves or muscle, the diagnostic plan includes:
1) minimum data base,
2) EMG,
3) special muscle enzymes, and
4) muscle and nerve biopsy.
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