A wide range of tools are available to assist the clinician in the diagnosis of neurologic disease in children. These tests can make important contributions to elucidation of the patient's illness. Unfortunately, all tests have their limitations, and some entail significant risks to the patient. Therefore, it is important to know the values, limitations, and risks of the more commonly used procedures so that a rational approach to the investigation of suspected neurologic disease can be made. This article is written as a brief guide on when to use and when not to use these diagnostic tests. I have included approximate costs that represent price ranges in the New York area.
Skull x-rays, except for the minuscule amount of radiation they emit, are benign and painless. A routine skull series costs between $40 and $80. Routine films include a posteroanterior view, two lateral films, and a Townes view. This test is valuable in head trauma for diagnosing fractures when they are depressed or cross a suture line. Fractures behind the ear (basilar skull fractures) are almost impossible to see on skull films and are better diagnosed by the presence of blood or cerebrospinal fluid coming from the ear and, several days after the fracture, by a discoloration behind the ear (Battle's sign). Head injuries without a fracture can cause serious injury to the patient's brain, so no evidence of fracture affords the physician little indication of whether head trauma is serious or not. The clinical picture is a more accurate guide.
Congenital abnormalities of the skull can be diagnosed by skull x-rays. For example, craniosynostosis, either partial or complete (Crouzon's disease), shows up as prematurely closed sutures with "heaping up" at the suture lines. Spread sutures are seen in cases of abnormal expansion of the intracranial contents, leading to increased intracranial pressure - such as hydrocephalus, subdural hematoma, or brain tumor. This is most easily seen before the age of 10 or 12. After that, the sutures are so tight that the increased intracranial pressure is seen as erosion of the posterior clinoids. Skull x-rays usually give no indication as to the cause of the intracranial pressure. If it is due to a tumor, it does not show where the tumor is, Furthermore, some supra tenton al tumors and brain-stem gliomas do not give rise to increased intracranial pressure until late in the course of the disease, so skull x-rays will be normal. Thus, a skull x-ray is a very poor way of diagnosing a tumor. Clinical examination and other procedures are required. The exception to this is a craniopharyngioma. Sixty to 80 per cent of these tumors show calcifications in the supraclinoid region.
Speckled calcifications are seen in the periventricular region in intrauterine infections, such as cytomegalic inclusion cell disease and toxoplasmosis. The calcifications may not be present at birth, but appear by six months or one year of age. Calcifications are occasionally seen in chronic subdural hematomas, old hemorrhages, and oligodendrogliomas. Skull x-rays are generally useless in minimal cerebral dysfunction.
In this procedure a tracer amount of radioactive material, usually technetium, is injected intravenously, and a posteroanterior and two lateral scans are taken. Abnormalities are seen as either increased or decreased uptake. If there is breakdown of the blood-brain barrier (e.g., a brain abscess), the uptake is increased. If the vasculature in a region is altered (e.g., a tumor), there is an increased uptake. Porencephalic cysts, which lack proper vasculature, can, if large enough, show up as decreased uptake. Infarctions after about one week or intracerebral hemorrhage will show up as increased uptake. Thus, the cause of the lesion is difficult to elucidate on the brain scan alone. Moderate or large arteriovenous malformations (AVM) are best seen with flow scanning. In this procedure, the scan is done after the injection. Because of the "sump" effect of an AVM, blood arrives at it earlier than the normal vasculature. Thus, the pickup can be easily seen. Subdural hematomas are also best seen with a flow scan.
Brain scans require that the patient lie still for a fairly long time. Thus, infants and young children have to be sedated. The risks of the procedure are minimal. They are the risks of sedation and an allergic response to the technetium. The cost of the procedure is about $100 to $150. Brain scans are excellent in the diagnosis of a brain abscess. They are good screening procedures in diagnosing vascular tumors in the supratentorial region, such as meningiomas or metastatic tumors. Unfortunately, a very large number of pediatrie brain tumors are in the posterior fossa. Because the neck is very vascular, uptake is normally heavy in the posterior fossa. Thus, increased uptake can be difficult to assess. Furthermore, brain-stem gliomas and cystic cerebellar astrocytomas, two common childhood tumors, are not vascular. Even the supratentorial tumors are not too vascular in childhood. Thus, a normal brain scan does not rule out a tumor; if one is clinically suspected, further testing must be done. If the brain scan is abnormal, more elaborate procedures will usually have to be done to better localize the lesion and to rule out false positives.
This test is benign and painless. It costs about $50 to $75 to do. It is overused. The EEG reflects the electrical patterns of the underlying brain. The electrical patterns represent a summation of the physicalchemical interactions in the brain, recorded through the skull and scalp from the outermost portions of the cerebral cortex. Superimposed on these electrical patterns are such artifacts as eye and head movements, which may obscure the underlying record to the extent that it cannot be interpreted. To minimize this, the patient should be cooperative and quiet. Sedation may be required to obtain cooperation. This, however, introduces another artifact - namely, the effect of drugs on the electrical pattern. The EEG changes with age and state of consciousness. Generally, it gets faster with increasing age and slower with a decreasing level of consciousness. Finally, metabolic factors - such as temperature, thyroid function, and electrolyte changes - can alter the pattern of the EEG.
The EEG is useful in the evaluation of a seizure disorder. A seizure that appears generalized clinically may have a focal component on the EEG. While this does not divulge the cause of the seizure, it may be the first clue that there is a structural lesion (cyst, scar, AVM, tumor) causing the seizure. A diagnosis of true petit mal should not be made in the absence of an EEG that shows a synchronous 3-per-second spike-and-wave abnormality in the context of a normal background. Infantile seizures may show hypsarrhythmia on the EEG, and this may determine that the patient should be treated with steroids or diazepam rather than with the standard anticonvulsants. Although the large majority of patients with seizure disorders have an abnormal EEG, a normal EEG does not rule out a seizure disorder. Furthermore, although there is a general correlation, the severity of the seizure disorder is not necessarily related to the degree of abnormality of the EEG.
The EEG is also useful in the diagnosis of acute or ongoing disease of the cerebral cortex. Thus, metabolic abnormalities, encephalopathies, and encephalitides frequently show diffuse slowing on the EEG. Brain abscesses, unilateral subdural hematomas, and tumors sometimes show focal abnormalities on the EEG. Unfortunately, subdural hematomas are frequently bilateral, and brain tumors in children are either deep to the cortex (craniopharyngioma) or in the posterior fossa; therefore, either they do not reflect themselves as abnormalities in the EEG or the abnormalities are diffuse and, thus, nonlocalizing. Furthermore, abnormalities do not indicate the cause.
In chronic conditions - such as mental retardation, cerebral palsy, or minimal cerebral dysfunction - unless associated with seizures, the EEG is generally of little value. It is true that many patients with chronic conditions have nonspecifically abnormal EEGs. However, an even larger number of patients have normal EEGs. Furthermore, the EEG gives no due as to the cause of the illness. It is also well to remember that about 15 per cent of the normal population have nonspecifically abnormal EEGs. Thus, a mildly abnormal EEG does not by itself signify brain dysfunction.
In summary, the EEG is a valuable tool in patients with seizures and in acute or ongoing conditions. It is not an adequate screening test for brain abscess, tumors, arteriovenous abnormalities, or subdural hematomas.
The spinal tap is a very useful examination and is quite safe, provided certain precautions are taken. It should not be performed until a complete neurologic evaluation, including funduscopic examination, has been carried out. If there is clinical evidence of increased intracranial pressure (papilledema, drowsiness, sixth nerve weakness, third nerve weakness, etc.), the test should be deferred until the cause of the increased intracranial pressure has been determined. If the increased pressure is due to a mass or dilated ventricles, the lumbar puncture is usually contraindicated, since it may lead to herniation of the brain. This can result in brain-stem dysfunction and even death. If, however, a diagnosis of meningitis, encephalitis, subarachnoid hemorrhage, or other encephalopathies is suspected, it can be crucial to both the diagnosis and treatment of the patient, and should be done immediately.
It is beyond the scope of this article to detail all of the findings in the numerous neurologic disorders that give rise to an abnormal spinal tap. In general, one monitors five things - pressure, color, protein, sugar, and cells and organisms. Pressure is increased in mass lesions, brain edema (secondary to anything from a contusion to a toxic encephalopathy to a meningitis), hydrocephalus, and subdural hematoma. In order for a valid pressure to be obtained, the patient should be quiet, lying on his side, and fully extended. Anesthesia can artificially raise the pressure. The normal color of cerebrospinal fluid is crystal dear. It may be cloudy - indicating an infection, usually bacterial - or it may be xanthochromic (yellow), indicating that there are breakdown products of blood. This is extremely important, since it indicates that intracranial hemorrhage has occurred. (It takes about three to four hours after intracranial hemorrhage for xanthochromia to occur.) A yellow coloring can also be seen with severe jaundice, and a faint yellow can be seen with a very high protein value.
To differentiate a "bloody tap" from intracranial hemorrhage, the fluid should be immediately spun down. In a bloody tap, since bleeding occurs immediately, no xanthochromia would be seen. In intracranial hemorrhage, however, the supernatant would be xanthochromic unless the hemorrhage immediately preceded the lumbar puncture . In old hemorrhages, xanthochromia may be seen without red blood cells. Fresh blood looks pink to red, depending on the amount. Protein values over 40 mg./100 ml. in the CSF are abnormal in children after the neonatal period. Protein is raised in tumors that communicate with the CSF, such as spinal cord tumors. Protein is also elevated in bacterial infections, carcinomatous or leukemic meningitis, subdural and subarachnoid hemorrhages, and the Guillain-Barré syndrome. It tends to be normal in viral meningitis and such tumors as brain-stem gliomas, which do not communicate with the CSF.
CSF glucose is usually about twothirds of the blood glucose. It tends to be lowered in bacterial, carcinomatous, or leukemic meningitis and in hypoglycemia; normal in solid tumors and viral meningirides; and elevated in hyperglycemia secondary to diabetes or intravenous glucose therapy.
The cellular elements should be examined immediately after centrifugation. Both red and white blood cells should be examined, and lymphocytes and polymorphonuclear cells should be counted. Polys are seen in bacterial infections, whereas lymphocytes predominate in viral meningitis or encephalitis. If carcinomatous or leukemic meningitis is suspected, cytologie evaluation by a competent cytologist should be requested. In deciding whether white cells come from blood or the CSF in a bloody tap, a handy little formula is that there is approximately one white cell per 1,000 red cells in the blood. If the CSF ratio is very different from that, it can be assumed that the white cells are from the CSF. Gram stains, as well as a culture and sensitivity test, should be performed on CSF. This, of course, is crucial in the determination of an offending bacterial agent and the appropriate therapy for its eradication.
Headaches do occur following spinal tap. Thus, it is a good idea to keep the patient on his back for several hours after the tap. On occasion, headaches do persist for a long time. They are characterized by pain on getting up and relief on lying down. They disappear with time. Occasionally, a nerve root is touched when the spinal canal is entered. This can cause temporary shooting sciatic pain. This disappears in time, and no therapy is required. Sterile techniques should be used to avoid introducing infection with the needle.
The echoenchephalogram is painless and safe. Each test costs $25 to $50. The routine echoencephalogram shows the position of the lateral ventricles. Thus, if they are shifted - as they are in supratentorial tumors, brain abscesses, or unilateral subdural hematomas - a shift is noted. Since many pediatrie tumors occur in the posterior fossa or in the midline of the middle fossa, there might be no shift in the lateral ventricles; thus it is not adequate to rule out a brain tumor. While a positive echoencephalogram may be helpful, a negative one certainly does not rule out a mass lesion or pathology.
ELECTROMYOGRAPHY AND NERVE CONDUCTION VELOCITY
This procedure is safe but quite uncomfortable. In electromyography, needles are stuck into the muscles sampled. The electrical pattern is sampled at insertion, at rest, and during contraction. Because of the discomfort, the very young patient usually has to be sedated. Electromyography is useful in differentiating myopathy from neuropathy. It is not useful in central nervous system disease. In neuropathy, fibrillations and fasciculations are seen at rest. During contraction, long-duration giant potentials are seen with a decrease in the number of potentials. In myopathy, the resting electromyogram is normal (silent) . During contraction, shortduration polyphasic potentials are seen. The amplitude is diminished as well. In myasthenia, fatigue of the muscles is seen. Nerve conduction velocity is normal in myopathy and decreased in peripheral neuropathy of the large fibers of the peripheral nerve.
A pneumoencephalogram is done by injecting air in the lumbar space, letting the air rise to the ventricles, and examining the ventricular size and distortion. With this procedure, enlargement of the ventricles, aqueductal stenosis, shifts of the ventricles secondary to tumors or other masses, and competency of the subarachnoid space can be seen. This test is one of the most accurate for hydrocephalus, tumors of the posterior fossa, and tumors around the pituitary and third ventricles. It is a painful test, so it requires either deep sedation or general anesthesia. It can be dangerous, especially if done in patients with increased intracranial pressure. Patients almost always develop a temporary headache and fever and even a stiff neck. The test requires special equipment and considerable experience in interpretation; therefore, it is best done by a neurologist, neurosurgeon, or neuroradiologist. The angiogram is also a complex test to perform and interpret, and should be done by someone experienced with the technique and the proper equipment. Contrast material is injected into the artery, and rapid-sequence films are taken in the posteroanterior and two lateral views. Arterial, capillary, and venous films are examined. Deviations from the normal vascular anatomy, early filling, early draining veins, and stains are looked for. The major complications are those of anesthesia, stroke in the distribution of the injected vessel, and thrombosis at the site of the injection. While the incidence of serious permanent sequelae is small, complications in the most experienced hands are 0.1 to 0.5 per cent. The pneumoencephalogram and angiogram are the "definitive" examinations for tumors, subdural hematomas, aneurysms, abscesses, or any other masses in the cranial vault. Since they carry significant risks, they should be done only if there are definite indications. They require hospitalization and have rather high morbidity and mortality.
Computerized axial tomography (the EMI scan) is a new test that is rapid, safe, and quite accurate for diagnosing intracranial masses. It costs $200 to $250, but is available in only a few centers at present. This is the first test to show the brain directly. It is noninvasive, and can be performed on outpatients. With it, one sees the brain density and the ventricles. Any mass abnormalities of the brain (e.g., clot, tumor, abscess) are of a density different from that of the normal brain, and therefore show up as relative lucencies or densities. Ventricular size and shifts are also noted. This test is so new that its diagnostic possibilities are constantly being evaluated and enlarged. It represents one of the most important advances in diagnostic neurology since the contrast studies, and will undoubtedly become more readily available in time.
This article was not intended to include all tests used in pediatrie neurology. For example, the myelogram and the muscle biopsy were not even mentioned. Nor was it intended to completely convey the uses and limitations of the tests. Entire books can be and have been written on each test. It is hoped, however, that some useful guidelines to the commonly used tests in pediatrie neurology have been provided.