Chapter 4: The Relationship Between Neuroanatomy and Neurology

Neurology, more than any other specialty, rests on clinicoanatomic correlation. Patients do not arrive at the neurologist's office saying "the motor cortex in my right hemisphere is damaged," but they do tell, or show, the neurologist that there is weakness of the face and arm on the left. Since the nervous system is constructed in a modular manner, with different nerves, and different parts of the brain and spinal cord subserving different functions, it is often possible to infer, from a careful physical examination and history together with knowledge of neuroanatomy, which part of the nervous system is affected, even prior to ordering or viewing imaging studies. The neurologic clinician thus attempts, with each patient, to answer two questions: (1) Where is (are) the lesion(s)? and (2) What is (are) the lesion(s)?

Lesions of the central nervous system can be anatomic, with dysfunction resulting from structural damage (examples are provided by stroke, trauma, and brain tumors). Lesions can also be physiologic, reflecting physiologic dysfunction in the absence of demonstrable anatomic abnormalities. An example is provided by transient ischemic attacks, in which reversible loss of function of part of the brain occurs without structural damage to neurons or glial cells, as a result of metabolic changes caused by vascular insufficiency.

A knowledge of peripheral patterns of innervation, and of muscle actions, can also be highly important to the clinician interested in neurological disease. Each spinal ventral root, and each peripheral nerve, innervates a particular set of muscles, and these muscles have very specific actions (Appendix B). Similarly, each spinal dorsal root, and each peripheral nerve, provides sensory innervation to a particular part of the body (Appendix C). By assessing motor and sensory function, it is often possible to localize disease processes impairing spinal root function, or the function of specific nerves, with a high degree of precision.

This chapter gives a brief overview of clinical thinking in neurology and emphasizes the relationship between neuroanatomy and neurology. It has been included to help the reader begin to think as the clinician does and to place neuroanatomy, as outlined in the subsequent chapters, in a patient-oriented framework. Together with the Clinical Illustrations and Cases placed throughout this book and the Appendices, this chapter provides a clinical perspective on neuroanatomy.

In taking a history and examining the patient, the neurologic clinician elicits symptoms and signs. Symptoms are subjective experiences resulting from the disorder (ie, "I have a headache"; "The vision in my right eye became blurry a month ago"). Signs are objective abnormalities detected on examination (eg, a hyperactive reflex or abnormal eye movements).

The history may provide crucial information about diagnosis. For example, a patient was admitted to the hospital in a coma. His wife told the admitting physician that "my husband has high blood pressure but doesn't like to take his medicine. This morning he complained of the worst headache in his life. Then he passed out." On the basis of this history and a brief (but careful) examination, the physician rapidly reached a tentative diagnosis of subarachnoid hemorrhage (bleeding from an aneurysm, ie, a defect in a cerebral artery into the subarachnoid space). He confirmed this diagnostic impression with appropriate (but focused) imaging and laboratory tests and instituted appropriate therapy.

The astute clinical observer may be able to detect signs of neurologic disease by carefully observing the patients' spontaneous behavior as they walk into the room and tell their story. Even before touching the patient, the clinician may observe the "festinating" (shuffling, small-stepped) gait of Parkinson's disease, hemiparesis (weakness of one side of the body) resulting from a hemispheric lesion such as a stroke, or a third nerve palsy suggesting an intracranial mass. The way patients tell their story also may be informative; for example, it may reveal aphasia (difficulty with language), confusion, or impaired memory. Details of history taking and the neurologic examination are included in Appendix A.

In synthesizing the information obtained from the history and examination, the clinician usually keeps asking the questions, "Where is the lesion? What is the lesion?" This thinking process will usually result in the correct diagnosis. Several points should be kept in mind while one is going through the diagnostic process.

Neurologic Signs and Symptoms Often Reflect Focal Pathology of the Nervous System

It is well established that, with respect to many functions. Different parts of the nervous system subserve different functions. In turn, in many parts of the brain or spinal cord, even relatively small well-circumscribed lesions produce loss or severe impairment of a specific function. This effect reflects the principle of localized function within the nervous system.

There are numerous examples of localized function. (1) Aphasia (difficulty producing or understanding language) often results from damage to well-localized speech areas within the left cerebral hemisphere. (2) Control of fine movements of each hand is dependent on signals sent from a hand area within the motor cortex in the contralateral cerebral hemisphere. The motor cortex is organized in the form of a map, or "homunculus," reflecting control of different parts of the body by different parts of the motor cortex (see Chapter 10, especially Fig 10–14). A lesion affecting the hand area or the pathways that descend from it to the spinal cord can result in loss of skilled movements or even paralysis of the hand. (3) At a more basic level, many reflexes, which are tested as part of the neurologic examination, depend on circuits that run through particular parts of the nervous system. For example, the patellar reflex (knee jerk) depends on afferent and efferent nerve fibers in the femoral nerve and L3 and L4 spinal roots and the L3 and L4 spinal segments, where afferent Ia axons synapse with motor neurons that subserve the reflex. Damage to any part of this circuit (nerve, spinal roots, or L3 or L4 spinal segments) can interfere with the reflex.

As a corollary of the principle of localized function, it is often possible to predict, from neurologic signs and symptoms, which parts of the nervous system are involved. An accurate history and a careful examination can provide important clues about the localization of dysfunction in the nervous system.

Manifestations of Neurologic Disease May Be Negative or Positive

Negative manifestations result from loss of function (eg, hemiparesis, weakness of an eye muscle, impaired sensation, or loss of memory). Negative manifestations of neurologic disease may reflect damage to neurons (eg, in stroke, where there is often loss of neurons located within a particular vascular territory, and in Parkinson's disease, where there is degeneration of neurons in the substantia nigra) or to glial cells or myelin (eg, in multiple sclerosis, in which there is inflammatory damage to myelin). Positive abnormalities result from inappropriate excitation. These include, for example, seizures (caused by abnormal cortical discharge) and spasticity (from the loss of inhibition of motor neurons).

Lesions of Spinal Roots and Peripheral Nerves Can Cause Neurological Dysfunction

Injury to spinal roots, or to peripheral nerves, can produce characteristic patterns of clinical abnormality. Each dorsal root, and each peripheral nerve, provides sensory innervation for a particular part of the body (Appendix C). An irritative lesion, such as compression of a spinal dorsal root or of a peripheral nerve, can thus produce pain in a particular area of the body. Similarly, each ventral root, and each peripheral nerve, innervates a particular set of muscles; these muscles have well-defined actions that can be assessed in the clinic or at the bedside (Appendix B). Focal lesions of spinal roots (which can occur with spinal disc disease) or of peripheral nerve (which can occur as a result of localized penetrating injuries due to trauma, or to localized compression due to disorders such as carpal tunnel syndrome) can produce very characteristic patterns of pain, sensory loss, or weakness.

Lesions of White and Gray Matter Cause Neurologic Dysfunction

Damage to gray or white matter (or both) interferes with normal neurologic function. Lesions in gray matter interfere with the function of neuronal cell bodies and synapses, thereby leading to negative or positive abnormalities, as previously described. Lesions in white matter, on the other hand, interfere with axonal conduction and produce disconnection syndromes, which usually cause negative manifestations. Examples of these syndromes include optic neuritis (demyelination of the optic nerve), which interferes with vision; and infarction affecting pyramidal tract axons, which descend from the motor cortex in regions such as the internal capsule, which can cause "pure motor stroke" (Fig 4–1).

Some neurologic disorders affect primarily gray matter (eg, amyotrophic lateral sclerosis, a degenerative disease leading to the death of motor neurons in the cerebral cortex and gray matter of the spinal cord). Others primarily affect white matter (eg, multiple sclerosis). Still other disorders affect both gray and white matter (eg, large strokes, which lead to necrosis of the cerebral cortex and underlying white matter).

Neurologic Disease Can Result in Syndromes

A syndrome is a constellation of signs and symptoms frequently associated with each other and suggests that the signs and symptoms have a common origin. An example is Wallenberg's syndrome, which is characterized by vertigo, nausea, hoarseness, and dysphagia (difficulty swallowing). Other signs and symptoms include ipsilateral ataxia, ptosis, and meiosis; impairment of all sensory modalities over the ipsilateral face; and loss of pain and temperature sensitivity over the contralateral torso and limbs. This syndrome results from dysfunction of clustered nuclei and tracts in the lateral medulla and is usually due to infarction resulting from occlusion of the posterior inferior cerebellar artery, which irrigates these neighboring structures.

Neighborhood Signs May Help to Localize the Lesion

The brain and spinal cord contain many tracts and nuclei that are intimately associated with each other or are anatomic neighbors of each other. Particularly in the brain stem and spinal cord, where there is not much room, there is crowding of nuclei and fiber tracts. Many pathologic processes result in lesions that are larger than any single nucleus or tract. Combinations of signs and symptoms may help to localize the lesion. Figure 4–2 shows a section through the medulla of a patient with multiple sclerosis. The patient had a sensory loss in the legs (impaired touch-pressure sense and position sense) and weakness of the tongue. As an alternative to positing the presence of two separate lesions to account for these two abnormalities, the clinician should pose the question, "Might a single lesion account for both abnormalities?" Knowledge of brain stem neuroanatomy allowed the clinician to localize the lesion in the medial part of the medulla.

Dysfunction of the Nervous System Can Be due to Destruction or Compression of Neural Tissue or Compromise of the Ventricles or Vasculature

Several types of pathologic conditions can lead to dysfunction of the nervous system (Table 4–1). Destruction of neurons (or associated glial cells) occurs in disorders such as stroke (in which neurons are injured as a result of ischemia) and Parkinson's disease (in which degeneration of neurons occurs in one region of the brain stem, the substantia nigra). Destruction of axons secondary to trauma causes much of the dysfunction in spinal cord injury, and destruction of myelin as a result of inflammatory processes leads to the abnormal function in multiple sclerosis.

Compression can also cause dysfunction, without the invasion of the brain and spinal cord per se. This occurs, for example, in subdural hematoma, when an expanding blood clot, contained by the skull vault, compresses the adjacent brain, initially causing reversible dysfunction, before triggering the death of neural tissue. Early recognition and surgical drainage of the clot can lead to full recovery.

Finally, compromise of ventricular pathways or of the vasculature can lead to neurologic signs and symptoms. For example, a small cerebellar astrocytoma, critically located above the fourth ventricle, may compress the ventricle and obstruct the outflow of cerebrospinal fluid. The tumor may lead to obstructive hydrocephalus with widespread destructive effects on both cerebral hemispheres. In this case, a small, critically placed mass produces widespread neural dysfunction as a result of its effect on the outflow tracts for cerebrospinal fluid.

Critically placed vascular lesions can also produce devastating effects on the nervous system. Because certain cerebral arteries nourish the same parts of the brain in all humans, occlusion of these arteries produces characteristic clinical syndromes. For example, occlusion of the carotid artery, owing to atherosclerosis in the neck, can lead to infarction of much of the cerebral hemisphere which it supplies. Occlusion of the posterior cerebral artery produces infarction of the occipital lobe which depends on it for nourishment.

Processes Causing Neurologic Disease

The modular organization of the brain and spinal cord, with different groups of neurons and bundles of axions (tracts) fulfilling different functions, makes it relatively straight forward to diagnose neurological disorders on the basis of the history and neurological examination.

Focal pathology causes signs and symptoms on the basis of a single, geographically contiguous lesion. The most common example is stroke, which occurs when ischemia within the territory of a particular artery leads to infarction of neural tissue in a well-defined area (Fig 4–3). Another example is provided by solitary brain tumors.

In thinking about a patient, the physician should ask, "Is there a single lesion that can account for the signs and symptoms?" In some cases a single, critically placed lesion can injure several fiber tracts and/or nuclei. By carefully assessing the patient's signs and symptoms, and asking whether there is a single site in the nervous system where a lesion can produce all of these abnormalities, the clinician may be able to help the radiologist to focus neuroimaging studies on areas that have a high likelihood of being involved.

Multifocal pathology results in damage to the nervous system at numerous separate sites. In multiple sclerosis, for example, lesions are disseminated throughout the nervous system in the spatial domain, and develop at different points in time. Figure 4–2 shows the multifocal nature of the pathology in a patient with multiple sclerosis. Another example is provided by leptomeningeal seeding of a tumor. As a result of dissemination throughout the subarachnoid space, tumor deposits can affect numerous spinal and cranial nerve roots distributed along the entire neuraxis and can also block cerebrospinal fluid outflow, thereby producing hydrocephalus.

Diffuse Process: Diffuse dysfunction of the nervous system can be produced by a number of toxins and metabolic abnormalities. In arriving at a diagnosis, the clinician must ask, "Is there a systemic disorder that can account for the patient's signs and symptoms?" Metabolic or toxic coma, for instance, can result in abnormal function of neurons throughout the nervous system.

Rostrocaudal Localization

In deciding on the rostrocaudal localization of the lesion, it is important for the clinician to determine the nuclei and fiber tracts that are affected and to consider the constellation of structures involved. Here, the clinician is aided by a design feature of the human nervous system: Each of the major motor (descending) and sensory (ascending) pathways decussates (ie, crosses from one side of the neuraxis to the other) at a specific level. The levels of decussation of three major pathways are summarized in Figure 4–4 and are discussed in Chapter 5. By examining the constellation of deficits in a given patient and relating them to appropriate tracts and nuclei, it is often possible for a clinician to place the lesion at the appropriate level along the rostrocaudal axis.

For example, consider a patient with weakness of the left leg. This condition could be caused by a lesion involving the nerves innervating the leg or by a lesion affecting the corticospinal pathway at any level from the cortex through the midbrain and down to the lumbar spinal cord. If the patient also had loss of vibratory and position sense of the left leg (indicating dysfunction in the dorsal column pathway) and loss of pain and temperature sensation over the right leg (indicating impaired function of the spinothalamic pathway), the clinician would then think about dysfunction of the left half of the spinal cord, above the decussation of the spinothalamic fibers. These fibers decussate within the spinal cord, close to the level where they enter the cord but below the medullary-cervical spinal cord junction, where the corticospinal tract decussates. Furthermore, normal function in the arms and trunk suggests normal function in cervical and thoracic parts of the spinal cord (which carry fibers for the arm and trunk). The combination of deficits could, in fact, be parsimoniously explained by a single lesion, located in the left side of the spinal cord.

Transverse Localization

In localizing the lesion, the clinician must also consider its placement in the transverse plane, that is, within the cross section of the brain or spinal cord. Here again, neighborhood signs are important. In the previously described patient with a spinal cord lesion, the dorsal and lateral white matter columns in the spinal cord must be involved because the dorsal column pathway and corticospinal tract are involved. Moreover, the clinician can predict that the lesion is centered in the left half of the spinal cord because there is no evidence of dysfunction of the corticospinal tract, dorsal column system, or spinothalamic tract on the right side in this patient.

The pathologic nature of a lesion may be inferred from the examination and history. The age of the patient must be considered. Cerebrovascular disease, for example, is more common in individuals older than 50; in contrast, multiple sclerosis tends to be a disease of the second and third decades.

The gender of the patient may provide important information. Duchenne's muscular dystrophy, for instance, is a sex-linked disorder that occurs only in males. Carcinomas of the prostate (a male disease) and of the breast (predominantly a female disease) commonly metastasize to the vertebral column, and these metastases can cause spinal cord compression.

The general medical context can also provide important information: Is the patient a smoker? Lung and breast tumors, for example, commonly metastasize to the nervous system. The development of hemiparesis in an otherwise healthy, nonsmoking 75-year-old is most likely the result of cerebrovascular disease. In a smoker with a lesion seen on chest x-ray, on the other hand, hemiparesis may result from a metastasis in the brain.

Time Course of the Illness

The patient's history will often include information about the time course of the illness that may provide clues about its nature. Brief episodes of dysfunction lasting minutes to hours, occurring throughout the life of the patient, may represent seizures or migraine attacks (Fig 4–5A). A recent-onset cluster of brief episodes or a crescendo pattern of neurologic dysfunction, on the other hand, may represent nonstable evolving disease. For example, transient ischemic attacks (TIAs; brief episodes of neurologic dysfunction followed by full recovery, resulting from reversible ischemia) are the harbingers of stroke in some patients. A pattern of recent-onset headaches on wakening, increasing in intensity, may be caused by the presence of an expanding brain tumor (Fig 4–5B). A relapsing-remitting course, in which the patient experiences bouts of dysfunction lasting days to weeks followed by functional recovery, is characteristic of multiple sclerosis (Fig 4–5C). Sudden onset of a fixed deficit (over minutes or hours) is characteristic of ischemic stroke and intracerebral hemorrhage (Fig 4–5D). Slowly progressive dysfunction evolves over years and is suggestive of neurodegenerative diseases, such as Alzheimer's or Parkinson's (Fig 4–5E). Subacutely progressive dysfunction, which advances over weeks to months, is often seen with brain tumors (Fig 4–5F). The time course can provide helpful information, as illustrated in Clinical Illustrations 4–1, 4–2 which underscores the importance of a good history, and show how the tempo of disease onset can give clues about the disease process.

A careful synthesis of the clinical data permits the clinician to arrive at a differential diagnosis (ie, a list of diagnostic possibilities that fit with the patient's clinical picture). Armed with a working knowledge of correlative neuroanatomy, the clinician should not have to blindly "rule out" a multitude of diseases. On the contrary, by focusing on the questions "Where is the lesion?" and "What is the lesion?", clinicians can usually identify a logical and limited field of diagnostic choices that have a high probability of explaining the patient's clinical picture. This field of possibilities can be further delimited, and the diagnosis refined, via neuroimaging.

Neuroimaging investigations include plain x-rays; dye studies, such as angiography (to visualize cerebral vessels); computed tomography scanning; and magnetic resonance imaging (MRI). In obtaining neuroimaging studies, the radiologist is usually guided by clinical information. It is important for the clinician to specify the nature of the deficit that is being investigated and the parts of the nervous system in which a pathologic lesion is being considered. This approach helps in choosing the most appropriate imaging procedure and in "targeting" the imaging studies on the correct part of the nervous system.

Although neuroimaging presents an extremely powerful set of tools, they do not always, in and of themselves, provide the correct diagnosis. The results of neuroimaging must be interpreted in light of history and clinical examination and in terms of neuroanatomy. This is illustrated in the idealized case histories (combining aspects from many patients in a large clinical experience) presented in Clinical Illustrations 4–3 and 4–4.

In collecting a history, performing an examination, and implementing treatment, the clinician is "acting" not only as doctor to patient but also as caregiver to another human being. Listening is very important. Neurologic clinicians do not just treat cases or diseases; they treat people. An example is provided in Clinical Illustration 4–5.