I.

Lumbar Puncture and Examination of Cerebrospinal Fluid The information yielded by examination of the cerebrospinal fluid (CSF) is crucial in the diagnosis of certain neurologic diseases, particularly infectious and inflammatory conditions, subarachnoid hemorrhage, and diseases that alter intracranial pressure. Indications for Lumbar Puncture To obtain pressure measurements and procure a sample of the CSF for cellular, cytologic, chemical, and bacteriologic examination. To aid in therapy by the administration of spinal anesthetics and occasionally, antibiotics or antitumor agents, or by reduction of CSF pressure. To inject a radiopaque substance, as in myelography, or a radioactive agent, as in radionuclide cisternography.
Characteristics of CSF Formulas Cells Protein Glucose 2050 mg%; usually WBC >50/mm3, 100250 lower than often greatly mg% half of increased blood glucose level Normal or WBC 10 50-200 slightly 100/mm3 mg% reduced 100<50, often WBC >25/mm3 1,000 markedly mg% reduced RBC >500/mm3; slight increase in WBC RBC 50 200/mm3; higher if ventricular rupture of blood Normal or few WBC 60-150 mg%

Multiple sclerosis Meningeal cancer

Normal or few WBC WBC 10 100/mm3

Normal or slightly increased Usually elevated

Normal Normal or depressed

Increased IgG fraction and oligoclonal bands Neoplastic cells in CSF; elevation of certain protein markers (e.g., 2microglobulin)

II.

Imaging Techniques of the Skull, Brain and Spine A. Computed Tomography In this procedure, conventional x-radiation is attenuated as it passes successively through the skull, CSF, cerebral gray and white matter, and blood vessels. The intensity of the exiting radiation relative to the incident radiation is measured, the data are integrated, and images are reconstructed by computer. B. Contrast Myelography By injecting 5 to 25 mL of a water-soluble radiopaque dye through an LP needle and then tipping the patient downward on a tilt table, the entire spinal subarachnoid space can be visualized. The procedure is almost as harmless as the LP except for cases of complete spinal block, in which high concentrations of dye near the block can cause pain and regional myoclonus. C. Magnetic Resonance Imaging An MRI examination is accomplished by placing the patient within a powerful magnetic field, causing certain endogenous isotopes (atoms) of the tissues and CSF to align themselves in the longitudinal orientation of the magnetic field. MRI also provides "slice" images of the brain in any plane, but it has the great advantages over CT of using non-ionizing energy and providing better resolution of different structures within the brain and other organs. For the visualization of most neurologic diseases, MRI is the best procedure. MRI imaging of the spine provides clear images of the vertebral bodies, intervertebral discs, spinal cord, and cauda equina and of syringomyelia

Condition

Other Features

Bacterial Infection

Gram stain shows organisms; pressure increased

Viral, fngal, spirochetal infection Tuberculosis infection

Subarachnoid hemorrhage

Normal

Special culture techniques required; pressure normal or slightly increased Special culture techniques and PCR may be needed to detect organisms Must be distinguished from traumatic lumbar puncture by presence of xanthochromia of spun sample; greatly increased pressure Pressure may be elevated Normal pressure unless brain swelling

Cerebral hemorrhage, trauma Ischemic stroke

50-150 mg% Normal

Normal Normal

and other lesions (herniated discs, tumors, epidural or subdural hemorrhages, areas of demyelination, and abscesses). It has replaced contrast myelography except in certain circumstances where very-high-resolution images of nerve roots and spinal cord are required.

extensions of these systems through the neck and into the cranial cavity. E. Magnetic Resonance and Computed Tomographic Angiography These are non-invasive techniques for visualizing the main intracranial arteries. They can reliably detect intracranial vascular lesions and extracranial carotid artery stenosis and are supplanting conventional angiography. Positron Emission Tomography This technique, commonly known as PET, measures the regional cerebral concentration of systemically administered radioactive tracers. Positron-emitting isotopes (usually 11C, 18F, 13N, and 15O) are produced in a cyclotron or linear accelerator and incorporated into biologically active compounds in the body. The technique was recently applied to specially labeled ligands of pathologic chemical species such as beta-amyloid, enabling imaging of the deposition of these proteins in the brain as an experimental method for detecting and following Alzheimer disease. The ability of the technique to quantitate neurotransmitters and their receptors also promises to be of importance in the study of Parkinson disease and other degenerative diseases.

CT and MRI Imaging Characteristics of Various Tissues Tissue CT Gray Scale MRI T1 Signal MRI T2 Signal Brain Gray Gray Gray Air Black Black Black CSF Black Black White Fat Black White Black Calcium White Black Black Bone Very white Black Black Extravasated White White Black blood Contrast Gray, gadolinium Inflammation White enhancing enhancing Edema Dark gray Gray White Gray or white and Gray or white and Tumor contrast gadolinium White enhancing enhancing D. Angiography This technique has evolved over the past 50 years to the point where it is a safe and valuable method for the diagnosis of aneurysms, vascular malformations, narrowed or occluded arteries and veins, arterial dissections, and angitis. Since the advent of CT and MRI, the use of angiography has practically been limited to the diagnosis of these vascular disorders, and refinements in the former two techniques (magnetic resonance angiography [MRA] and spiral and helical CT scanning) promise to eliminate even these applications of conventional x-ray angiography. Following local anesthesia, a needle is placed in the femoral or brachial artery; a cannula is then threaded through the needle and along the aorta and the arterial branches to be visualized. In this way, a contrast medium can be injected to visualize the arch of the aorta, the origins of the carotid and vertebral systems, and the

F.

G. Single-Photon Emission Computed Tomography This technique, which has evolved from PET, uses isotopes that do not require a cyclotron for their production. Radioligands (usually containing iodine) are incorporated into biologically active compounds, which, on decay, emit only a single photon. This procedure allows the study of regional cerebral blood flow under conditions of cerebral ischemia or during intense tissue metabolism. This has proved particularly true in helping to distinguish between Alzheimer dementia and a number of focal cerebral (lobar) atrophies, and in the localization of epileptic foci in patients who are candidates for cortical resection. Once injected, the isotope localizes rapidly in the brain, with regional absorption proportional to blood flow, and is then stable for an hour or more.

It is thus possible to inject the isotope at the time of the seizure onset, while the patient is undergoing video and electroencephalographic monitoring, and to scan the patient later. H. Ultrasonography In recent years this technique has been refined to the point where it has become a principal methodology for clinical study of the fetal and neonatal brain and an important ancillary test for the cerebral vessels in adults. Ultrasound has several advantages, notably that it is non-invasive, harmless (hence can be used repeatedly), convenient because of the portability of the instrument, and inexpensive. I. Electroencephalography The electroencephalographic examination, for many years is a standard laboratory procedure in the study and localization of all forms of cerebral disease, has to a large extent been supplanted by CT and MRI for the purposes of localization. The electroencephalograph records spontaneous electrical activity generated in the cerebral cortex. This activity reflects the electrical currents that flow in the extracellular spaces of the brain that are the summated effects of innumerable excitatory and inhibitory synaptic potentials upon cortical neurons. Electrodes, which are silver or silver-silver chloride discs 0.5 cm in diameter, are attached to the scalp by means of a conductive paste. The electroencephalograph has 8 to 32 or more amplifying units capable of recording from many areas of the scalp at the same time. Patients are usually examined with their eyes closed and while relaxed in a comfortable chair or bed. Consequently, the ordinary EEG represents the electrocerebral activity that is recorded under restricted circumstances, usually during the waking or sleeping state, from several parts of the cerebral convexities during an almost infinitesimal segment of the person's life. The proper interpretation of EEGs involves the recognition of several characteristic normal and abnormal patterns and background rhythms (in accordance with the age of the patient), the detection of asymmetries and periodic changes in rhythm, and, importantly, the differentiation of artifacts from genuine abnormalities.

Neurologic Conditions Causing Abnormal Electroencephalograms Epilepsy Focal Brain Lesions (Brain Tumor, Abscess, Subdural Hematoma, Stroke, and Encephalitis) Diseases that Cause Coma and States of Impaired Consciousness Diffuse Degenerative Diseases Other Diseases of the Cerebrum Multiple sclerosis and other demyelinating diseases Delirium tremens and Wernicke-Korsakoff disease Psychosis and Mental Retardation Hypokinetic delirium III. Evoked Potential The stimulation of sense organs or peripheral nerves evokes an electrical response in the corresponding cortical receptive areas and in a number of subcortical relay stations. The interpretation of evoked potentials (visual, auditory, and somatosensory) is based on the prolongation of the latencies of the waveforms after the stimulus, the interwave latencies, and asymmetries in timing. A. Visual Evoked Potentials It had been known that a light stimulus flashing on the retina often initiates a discernible waveform over the occipital lobes. This procedure, called pattern-shift visual evoked responses (PSVERs, or VERs) or pattern-reversal visual evoked potentials, has been widely adopted as one of the most delicate tests of lesions in the visual system. B. Brainstem Auditory Evoked Potentials The effects of auditory stimuli can be studied in the same way as visual ones by a procedure called brainstem auditory evoked responses or potentials (BAERs, or BAEPs). Between 1,000 and 2,000 clicks, delivered first to one ear and then to the other, are recorded through scalp electrodes and maximized by computer. A series of seven waves appears at the scalp within 10 ms after each stimulus.

BAEPs are a particularly sensitive means of detecting lesions of the eighth cranial nerve (acoustic neuroma and other tumors of the cerebellopontine angle) and of the auditory pathways of the brainstem.

C. Somatosensory Evoked Potentials Somatosensory evoked potentials (SEPs) are used in most clinical neurophysiology laboratories to confirm lesions in the somatic sensory systems. The technique consists of applying 5-per-second painless transcutaneous electrical stimuli to the median, peroneal, and tibial nerves and recording the evoked potentials (for the upper limb) as they pass the brachial plexus over the Erb point above the clavicle, over the C2 vertebra, and over the opposite parietal cortex, and (for the lower limb) sequentially over the lumbar roots of the cauda equina, the nuclei over the cervical spine, and the opposite parietal cortex. This test has been most helpful in establishing the existence of lesions in spinal roots, posterior columns, and brainstem in disorders such as the ruptured lumbar and cervical discs, multiple sclerosis, and lumbar and cervical spondylosis when the clinical data are uncertain. D. Magnetic Stimulation of the Motor System The technique has been used to understand the organization, function, and recovery of the motor cortex and the pathophysiology of stroke, multiple sclerosis, and amyotrophic lateral sclerosis. Although the degree of functional deficit does not precisely correlate with the degree of electrophysiologic change, one expects that refinements of this technique will be useful in evaluating the status of the corticospinal motor system as well as other cortically based functions. E. Endogenous Event-Related Evoked Potentials Among the very late brain electrical potentials (>100-ms latency), which can be extracted from background activity by computer methods, are a group that cannot be classified as

sensory or motor but rather as psychophysical responses to environmental stimuli. These responses are of very low voltage, often fleeting and inconsistent, and of unknown anatomic origin. A prolongation of the latency is found with aging and in dementia as well as with degenerative diseases such as Parkinson disease, progressive supranuclear palsy, and Huntington chorea. The amplitude is reduced in schizophrenia and depression.

IV. Psychometry, Perimetry, Audiometry, and Tests of Labyrinthine Function These methods are used in quantitating and defining the nature of the special psychologic or sensory deficits produced by disease of the nervous system. V. Genetic Testing Numerous genetic markers of heredofamilial disease have become available to the clinician and greatly advanced both diagnosis and categorization of hitherto obscure causes of disease. The main examples are analyses of DNA extracted from blood or other cells for the identification of mutations (e.g., muscular dystrophy, spinocerebellar atrophies, and genetically determined polyneuropathies) and the quantification of abnormally long repetitions of certain trinucleotide sequences, most often used for the diagnosis of Huntington chorea.

VI. Biopsy of Muscle, Nerve, Skin, Temporal Artery, Brain and Other Tissue The application of light, phase, and electron microscopy to the study of these tissues may be highly informative. Temporal artery biopsy is indicated when giant cell arteritis is suspected. Brain biopsy, aside from its main use in the direct sampling of a suspected neoplasm, may be diagnostic in cases of granulomatous angiitis, some forms of encephalitis, subacute spongiform encephalopathy (biopsy now performed infrequently because of the risk of transmitting the infectious agent), and a number of other rare diseases. Biopsy of the pachymeninges or leptomeninges may disclose vasculitis, sarcoidosis, other granulomatous infiltrations, or an obscure infection, but its sensitivity is low.

An important advance in recent years has been the use of CT- or MRI-guided stereotactic biopsy, which is particularly valuable in tumor diagnosis and exposes the patient to less risk than does a craniotomy and open biopsy.