As outlined in Chapter 4, the important question, “Where is the lesion?” (or “What is the precise location of the deficit?”), must be followed by the equally important question, “What is the lesion?” (or “What is the nature of the disease?”). The answers should lead to the differential diagnosis and correct diagnosis and should guide therapy.
THE LOCATION OF LESIONS
Where is the lesion?. In thinking about the location of the lesion, it is important to systematically survey the nervous system. Lesions can be located in one or more of the following anatomic sites:
Muscles. In muscle diseases, one sees weakness, sometimes with muscle atrophy. Deep tendon reflexes are usually depressed. Diseases of muscle include the dystrophies, which have specific genetic patterns and stages of onset and may preferentially involve certain muscle groups; and inflammatory disorders of muscle such as polymyositis. Diagnosis may be aided by measuring the level of enzymes (such as creatine phosphokinase) in the serum because damage to muscle fibers may lead to their release. Electromyography and muscle biopsy may help with diagnosis.
Motor end-plates. Disorders of the motor end-plate include myasthenia gravis and the Lambert-Eaton myasthenic syndrome. In these disorders, there is weakness, sometimes accompanied by abnormal fatigability resulting from abnormal function (eg, decreased effect of acetylcholine [ACh] on the post junctional muscle or decreased release of ACh) at the neuromuscular junction. Weakness may involve the limbs or trunk or muscles involved in chewing, swallowing, or eye movements. In addition to the characteristic clinical pattern, electromyography may be helpful in diagnosis.
Peripheral nerves. Peripheral nerve lesions may be differentiated from lesions of muscle or motor end-plate by clinical criteria, electrical tests, or biopsy. In many disorders of peripheral nerves, both motor (lower motor neuron) and sensory deficits are present, although in some cases motor or sensory function is impaired in a relatively pure way. In most peripheral neuropathies, functions subserved by the longest axons are impaired first, so that there is a “stocking-and-glove” pattern of sensory loss, together with loss of distal reflexes (such as the ankle jerks) and weakness of distal musculature (ie, intrinsic muscles of the feet), which is in severe cases accompanied by muscle atrophy.
Roots. A motor root lesion results in a precise segmental motor deficit, which in some cases (eg, plexus lesions) is mediated through several nerves. A single sensory deficit may be difficult to diagnose because of the adjacent overlapping dermatomes (see Fig 5–9). When a nerve root carrying axons mediating a deep tendon reflex is affected, the reflex may be depressed (see Table 5–5). Sensory root symptoms may include pain that is worsened with the Valsalva maneuver, the forced expiratory effort caused by laughing, sneezing, or coughing.
Spinal cord. The staggered pattern of decussation of the lateral corticospinal tract, dorsal column-medial lemniscal system, and spinothalamic tracts often permits localization of lesions within the spinal cord. Injury to the spinal cord, at a given level, may result in lower-motor-neuron signs and symptoms at that level, but will result in upper-motor-neuron abnormalities below the level of the lesion. Sensation may be impaired below the lesion; thus, the presence of a sensory level (ie, a dermatomal level below which sensation is impaired) can alert the clinician to the possibility of injury to the spinal cord. The injury may be located at the sensory level or above it.
Brain stem. Functional deficits in the long tracts that pass from the brain to the spinal cord or vice versa, together with cranial nerve signs and symptoms, suggest a lesion in the brain stem. As a result of the crowding of numerous fiber tracts and nuclei within the relatively compact brain stem, lesions at particular sites usually result in characteristic syndromes. Lesions in the medulla involve the last few cranial nerves, whereas lesions in the pons involve nerves V, VI, and VII, and lesions of the midbrain often involve nerve III and possibly nerve IV.
Cerebellum. Lesions in the cerebellum or its peduncles result in characteristic abnormalities of motor integration. There is usually impaired coordination and decreased muscle tone ipsilateral to a lesion in the cerebellar hemisphere.
Diencephalon. Hypothalamic lesions can be complex and can cause endocrinologic disturbances as well as visual abnormalities resulting from compression of neighboring optic tracts. Thalamic lesions often cause sensory dysfunction and may produce motor deficits as a result of compression of the neighboring internal capsule. Subthalamic lesions may cause abnormal movements such as hemiballismus. Epithalamic lesions are most frequently pineal region tumors, which can compress the cerebral aqueduct, thereby producing hydrocephalus.
Subcortical white matter. The presence of abnormal myelin (leukodystrophy, which is more common in infants and children than in adults) or the destruction of normal myelin (which can be caused by inflammatory disorders such as multiple sclerosis) results in abnormal axonal conduction and deficits of function. Disease may be diffuse, focal, or multifocal with a parallel pattern of clinical involvement.
Subcortical gray matter (basal ganglia). A variety of movement disorders, including Parkinson’s disease and Huntington’s disease, involve the basal ganglia. Tremors and other abnormal movements, abnormalities of tone (eg, cogwheel rigidity in Parkinson’s disease), and slowed movements (bradykinesia) are often seen. These disorders often affect the basal ganglia bilaterally, but if there is unilateral disease, the movement disorder will affect the contralateral limbs.
Cerebral cortex. Focal lesions may produce well-circumscribed deficits such as aphasia, hemi-inattention and neglect syndromes, or Gerstmann’s syndrome (see Chapter 21). In most patients, aphasia is due to the left hemisphere involvement. When the primary motor cortex is involved on one side, for example by a stroke or a tumor, there is usually a “crossed hemiparesis,” that is, upper-motor-neuron weakness of the contralateral limbs. Irritative lesions of the cortex may result in seizures, which can be focal or generalized.
Meninges. Hemorrhages in the subarachnoid, subdural, and epidural spaces have characteristic clinical and neuroradiologic features. Subarachnoid hemorrhage is often accompanied by severe headache (“worse headache of my life”). Subdural hemorrhages may occur acutely or chronically and can follow even trivial head injury, especially in elderly patients and young children. Epidural hemorrhages are often rapidly progressive and can produce sudden herniation of the brain. Infection of the subarachnoid space (meningitis) may present with signs of meningeal irritation (eg, stiff neck) as well as other neurologic deficits, and the diagnosis can often be confirmed by lumbar puncture.
Skull, vertebral column, and associated structures. Associated structures include the intervertebral disks, ligaments, and articulations. For example, metastatic tumors involving the vertebral column can produce spinal cord compression. Trauma often involves the skull and vertebral column as well as the brain and spinal cord.
THE NATURE OF LESIONS
What is the lesion?. A variety of pathologic processes can affect the nervous system. The following is a common neuropathologic classification of disorders:
Vascular disorders. Usually, with a sudden onset of signs and symptoms, cerebrovascular disease often occurs in the setting of hypertension. Stenosis or occlusion of the carotid artery in the neck, or of any of the arteries described in Chapter 12, may be responsible. Embolism, from ulcerated plaques in the carotid or from the heart (eg, in patients with atrial fibrillation or with endocarditis) can occlude more distal vessels such as the middle cerebral. Subarachnoid hemorrhage and intraparenchymal hemorrhage (often involving the basal ganglia, thalamus, pons, or cerebellum) occur in patients with hypertension. Subdural and epidural hemorrhages occur as a result of trauma, which can be trivial (and in many cases is not remembered) in the case of subdural hematoma.
Trauma. As previously noted, epidural and subdural hematomas can develop as a result of head injury. In addition, penetrating injuries can directly destroy brain tissue, produce vascular lesions, or introduce infections. Injury to the spine is a common cause of paraplegia and quadriplegia.
Tumors. Primary tumors of the brain and spinal cord, as well as metastases (eg, from breast, lung, and prostate tumors) produce symptoms by direct invasion (and destruction) of neural tissue, by compression of the brain and spinal cord, or by compression of the ventricles and cerebral aqueduct, which can lead to hydrocephalus. Classically, tumors of the central nervous system produce subacutely or chronically progressive deterioration, which, in contrast to vascular disorders, progresses over weeks, months, or years. Signs of increased intracranial pressure (eg, papilledema, sixth nerve palsy) may be present, and the patient may complain of increasing headache, which is sometimes worst in the morning.
Infections and inflammations. These disorders (eg, meningitis, abscess formation, encephalitis, and granulomas) may be accompanied by fever, especially if the onset is acute. Most infections and inflammations have characteristic signs, symptoms, and causes.
Toxic, deficiency, and metabolic disorders. A variety of intoxications, vitamin deficiencies (eg, B12 deficiency), and enzyme defects leading to abnormal lipid storage in neurons are examples of this heterogeneous group of disorders. Various substances in different amounts (too much or too little) can cause selective lesions involving particular nuclei or tracts. Vitamin B12 deficiency, for example, causes degeneration of axons in the dorsal and lateral columns of the spinal cord.
Demyelinating diseases. Multiple sclerosis is the prototype demyelinating disease. As expected for a disorder characterized by multiple lesions in the white matter, examination often provides evidence for involvement of several sites in the central nervous system. The cerebrospinal fluid (CSF) often shows characteristic abnormalities. Magnetic resonance imaging (MRI) scans are very useful in confirming the diagnosis.
Degenerative diseases. This heterogeneous group of diseases for which the cause has not yet been determined includes spinal, cerebellar, subcortical, and cortical degenerative disorders that are often characterized by specific functional deficits. Onset often occurs insidiously, so that the patient cannot determine date of the onset, and progression can continue over months or years.
Congenital malformations and perinatal disorders.
Exogenous factors (eg, infection or radiation of the motor cortex) or genetic and chromosomal factors can cause abnormalities of the brain or spinal cord in newborn infants. Hydrocephalus, Chiari malformation, cortical lesions, cerebral palsy, neural tumors, vascular abnormalities, and other syndromes may become apparent after birth.
Neuromuscular disorders. This group includes muscular dystrophies, congenital myopathies, neuromuscular junction disorders, transmitter deficiencies, and nerve lesions or neuropathies (inflammation, degeneration, and demyelination).
CASES
Case 1, Chapter 3
Abnormal, gradual tiring of the muscles for eye movement and chewing is suggestive of fatigue at the neuromuscular junction. The healthy neuromuscular junction can transmit at high frequencies so that this type of fatigue does not normally occur. The prominence of muscular fatigue suggested a diagnosis of myasthenia gravis in this patient. The absence of sensory deficits tends to confirm the diagnosis. Electromyography is a useful procedure for confirmation of the diagnosis; the muscle action potential, which provides a measure of the number of muscle cells that are contracting, decreases in size with repetitive stimulation in myasthenia gravis. In addition, antibodies to ACh receptors are often present and can provide a measure of the degree of disease activity. Injection of anticholinesterase drugs, such as neostigmine or edrophonium chloride, may reverse the fatigue and help to confirm the diagnosis. Treatment centers on the use of anticholinesterase drugs and immunosuppressants, including corticosteroids, which decrease the rate of anti-ACh receptor antibody production. In some patients, thymectomy is effective.
Comment: Myasthenia gravis often affects the extraocular and bulbar musculature. Myasthenia gravis should not be confused with the myasthenic syndrome (Lambert-Eaton syndrome), an autoimmune disease seen in the context of systemic neoplasms (especially those affecting the lung and breast). In the myasthenic syndrome, abnormal antibodies directed against presynaptic Ca2+ channels interfere with the release of ACh from the presynaptic ending at the neuromuscular junction.
Case 2, Chapter 5
Shoulder pain radiating into the arm suggests involvement at the C5 or C6 level. Recent weakness in the left extremities, abnormal reflexes in the legs, and decreased reflexes in the left arm suggest a lower-motor-neuron-type lesion close to the left C6 ventral root and an upper-motor-neuron lesion in the corticospinal tract (probably on both sides). The sensory deficits indicate a level of C6, or perhaps C7, bilaterally. The course of the disease shows a slow progression and recent deterioration, a series of events typical of an expanding mass that eventually compresses the spinal cord against the hard wall of the vertebral canal. Imaging studies showed a leftsided, intradural, extramedullary mass compressing and displacing the spinal cord at the C6-7 level.
The differential diagnosis includes a mass associated with spinal roots, meninges, and nerves; a tumor from the arachnoid (meningioma); and a nerve tumor (sometimes called a neuroma). Abscesses may form a mass, but the patient’s history does not suggest an infection.
The diagnosis in this case was a nerve root tumor of the left C6 nerve. During neurosurgery, the tumor was completely removed, and the C6 sensory root was sacrificed. Pathologic studies showed a schwannoma. The patient’s recovery was complete and uneventful; 6 months after surgery, she danced at the junior prom.
Comment: MRI is now usually used to demonstrate such root tumors (Figs 25–1 and 25–2). It is crucial to request the most appropriate imaging tests. In this case, a careful examination permitted the patient’s neurologist to predict the presence of a lesion compressing the spinal cord and to request radiologic examination of the spine.
FIGURE 25–1 Magnetic resonance image of horizontal section through the neck and lower face (a different patient). The image shows a dumbbell-shaped tumor growing out of the spinal canal.
FIGURE 25–2 Magnetic resonance image (surface coil technique) of a parasagittal section through the lumbar spine in a patient with a root tumor (arrow).
Case 3, Chapter 5
Weakness, atrophy, cranial motor nerve deficits (difficulty in swallowing and in speaking), and fasciculations indicate extensive involvement of the motor system (see Chapter 23). The distribution of deficits over all the extremities suggests an extensive, generalized motor disorder. The abnormal reflexes suggest both lower- and upper-motor-neuron-type lesions. The absence of any sensory deficit strengthens a diagnosis of a pure motor disorder, and the results of the muscle biopsy confirm this.
The diagnosis is motor neuron disease, also known as amyotrophic lateral sclerosis and popularly called Lou Gehrig’s disease. Motor neurons in the spinal cord, brain stem, and motor cortex are gradually destroyed, resulting in progressive weakness. At this time the cause of motor neuron disease remains enigmatic and there is no cure (Fig 25–3).
FIGURE 25–3 Ventral view of the spinal cord (with the dura opened) of a patient with motor neuron disease (amyotrophic lateral sclerosis). Notice the reduction in size of the ventral roots (resulting from the degeneration of the axons of motor neurons) compared with the normal dorsal roots.
Case 4, Chapter 6
The cause—trauma—and the location—lower cervical spine—of the lesion are clear in this case. In the acute phase, traumatic involvement of the spinal cord usually produces spinal shock with flaccid paralysis, loss of temperature control, and hypotension. Precise neurologic localization of the extent of the lesion may be difficult. Plain films of the spine or CT scanning can be used to demonstrate the location and extent of the trauma to the bony spine. MRI provides information about the spinal cord itself.
The later neurologic examination showed lesions in the left corticospinal and spinothalamic tracts. There was a left lower-motor-neuron lesion around the C7 area. The lack of sensory deficit in the C7 segment can be explained by the segmental overlapping of dermatomes. Brown-Séquard syndrome was incompletely represented in this case because the dorsal column tract on the affected side was spared (see Figs 5–24 and 5–25).
The diagnosis is a traumatic lesion of the spinal cord at C7. Neurosurgical decompression of the bone fragments prevented further damage to the spinal cord, but the functional deficits caused by local cord destruction could not be corrected.
Case 5, Chapter 6
Trauma to the lower back, followed by pain down the sciatic region, is suggestive of sciatica. One of the underlying causes is herniation of the nucleus pulposus (the soft center of the intervertebral disk), which can cause a compressive radiculopathy (ie, compression of a nearby spinal root). The aggravation of pain by coughing, sneezing, straining, and bending backward (movements that increase abdominal pressure) and the stretching of dural root sleeves by leg raising are highly suggestive of root involvement (right L5 nerve). The location is confirmed by the presence of paresthesia in the patient’s right calf as well as the loss of the Achilles tendon reflex (L5, S1). Spasm of the paravertebral muscles and tenderness along the course of the sciatic nerve are common in this disorder.
Plain radiographs are useful only for showing a decrease in the height of the intervertebral disk space. The precise location of the lesion can best be shown by CT scanning or MRI (Figs 25–4 and 25–5).
FIGURE 25–4 Magnetic resonance image (surface coil technique) of a sagittal section through the lower lumbar spine of a patient with low back pain. Note the herniation of the nucleus pulposus at L4–5 compressing the cauda equina.
FIGURE 25–5 Photograph of a horizontal section through L4–5 intervertebral disk in a patient with low back pain. Note the lateral herniation of the nucleus pulposus. (Reproduced, with permission, from deGroot J: Correlative Neuroanatomy of Computed Tomography and Magnetic Resonance Imaging. Lea & Febiger, 21st ed. Appleton & Lange, 1991.)
The diagnosis is herniation of the nucleus pulposus at L5-S1. This patient responded well to conservative treatment (anti-inflammatory drugs, bed rest). Many patients show improvement as a result of conservative therapy. In some cases, there is a need for surgery with removal of the protruding disk fragment.
Case 6, Chapter 7
Careful analysis of the signs and symptoms shows that the following systems were involved: the vestibular system (dizziness and nystagmus); the trigeminal system, including the descending spinal tract of V (loss of pain sensation in the right half of the face); the spinothalamic system (contralateral pain deficit); the cerebellum (the inability to execute the right finger-to-nose test or to make rapid alternating movements and the presence of intention tremor and ataxia in the right lower extremity; see Appendix A); and the vagus nerve and ambiguous nucleus (hoarseness). The combination of these findings suggests a location in the posterior cranial fossa, probably in the brain stem. The combination of miosis, ptosis, enophthalmosis, and decreased sweating on one side of the face suggests Horner’s syndrome, caused by interruption of the sympathetic pathway. This pathway can be interrupted in the lateral brain stem fibers that descend from higher centers in the lateral column of the upper thoracic cord, the upper sympathetic ganglia, or the postsynaptic fibers of the carotid plexus (see Fig 20–7).
Because the patient’s disorder had a sudden onset and rapid course, a tumor was unlikely. The most frequent sudden neurologic deficits in the patient’s age group have a vascular basis: occlusion or bleeding. Of these, vascular occlusion (ischemic infarct) is the more common (see Chapter 12).
The only anatomic region where all these systems are contiguous is the lateral portion of the medulla; this is the site of the lesion: lateral medullary syndrome (Wallenberg’s syndrome). Damage to the lateral medulla results from occlusion of small branches of either the posterior inferior cerebellar or the vertebral artery. In 1895, Wallenberg described six patients with similar signs and symptoms and recognized the vascular basis of the disorder (Figs 25–6 and 25–7). Although Wallenberg’s syndrome commonly occurred as a complication of meningovascular compromise due to syphils in the preantibiotic era, this is now rare. Disease of small blood vessels due to hypertension can produce brain stem syndromes such as Wallenberg’s syndrome, and underscores the need for early recognition and textnet of high blood pressure.
FIGURE 25–6 Photograph of a section through the open medulla (from Wallenberg’s original publication). A large infarct is visible on the right and a smaller one on the left (arrows).
FIGURE 25–7 Left posterior inferior cerebellar artery occlusion (Wallenberg’s syndrome).
Case 7, Chapter 7
The patient’s signs and symptoms during his first examination suggest lesions in the left optic nerve or tract, nerve III or its nucleus, the vestibular system, the portion of the corticobulbar pathway that supplies the face, and the corticospinal tract. It would be difficult for one lesion to involve all these areas. Findings 4 months later showed additional deficits in the cerebellum or cerebellar peduncles as well as in the lower cranial nerves (VII, X, and XII, the nerves of articulation); once again, the lesions appeared in several systems or sites.
Signs and symptoms of multiple lesions at different times suggest a disseminated infectious disease, multiple infarcts, or a multifocal demyelinating disorder. The patient’s age was typical for onset of multiple sclerosis. Disseminated infection was unlikely in this patient because he had no fever. A CT image did not show multiple infarcts, but MR scanning revealed numerous lesions, consistent with multiple sclerosis. Increased latency of the visual evoked response, suggestive of demyelination along the visual pathway, was also consistent with this diagnosis. The lumbar puncture findings were within normal limits except for a slightly increased gamma globulin level and oligoclonal bands, which are suggestive of multiple sclerosis (Table 25–1). The age of the patient (third decade), the repeated attacks, and the multifocal nature of the deficits are indicative of multiple sclerosis (Figs 25–8 and 25–9).
TABLE 25–1 Frequency of Major Types of Intracranial Tumors.
FIGURE 25–8 Magnetic resonance image of a horizontal section through the head of a 28-year-old patient showing the lesions (arrowheads) of multiple sclerosis.
FIGURE 25–9 Areas of demyelination of the white matter (arrows) in the frontal lobe of a 54-year-old man with multiple sclerosis.
Comment: For reasons that are not yet understood, the risk of multiple sclerosis in populations living close to the equator between latitudes 40 °N and 40 °S is low. The time course of the disease varies; some patients remain relatively healthy after the first episode, other patients (like the one in this case) continue to have exacerbations followed by remissions, and yet others ex- perience a progressive course without remissions. The disease is usually most active in people between 10 and 45 years of age. The imaging procedure of choice is MRI, which readily demonstrates patches of inflammation or demyelination. Several treatments exist that slow the progression of multiple sclerosis. β-Interferon and COP-1 have been shown to reduce the rate of acquisition of new lesions.
Case 8, Chapter 8
All signs and symptoms are related to a lesion in the functional components of nerve VII (see Figs 8–13 and 8–14). Because there were no long-tract signs and no other cranial nerve deficits, it is unlikely that the lesion was in the brain stem, where the nuclei of nerve VII are located. Although the sudden onset of the problem may point to a vascular cause, this is unlikely because only one nerve was involved; the history suggests an isolated lesion of nerve VII.
The most probable diagnosis is peripheral facial paralysis (Bell’s palsy) (see Fig 8–14). As in this case, the paralysis is almost always unilateral. The syndrome always includes dysfunction of the brachial efferent fibers of the facial nerve, but visceral efferent and afferent fiber functions may also be lost. In most cases, the patient recovers spontaneously.
Peripheral facial paralysis occurs commonly in patients with diabetes (presumably as a result of ischemic damage to the facial nerve) and is also seen as a complication of Lyme disease. It can occur as a result of nerve damage from a tumor or in sarcoidosis and in various forms of meningitis, in which basilar inflammatory lesions can injure cranial nerves. A viral cause has been suggested in some patients.
Case 9, Chapter 8
Several causes of facial pain must be considered: pain from dental causes, sinusitis, migraine, tumors of the base of the skull and brain stem, tumors of the maxilla or nasopharynx, and other, rarer causes. Trigeminal neuralgia (severe episodic facial pain) can occur as a result of stroke, or in multiple sclerosis. These disorders can be ruled out by careful and complete examination, including a CT scan or MR imaging.
The description of brief attacks of very severe pain, triggered from a localized area in the face, in a patient who is otherwise found healthy points to a diagnosis of trigeminal neuralgia (tic douloureux). Medical treatment (with carbamazepine or phenytoin) may be effective. In cases of persistent painful attacks, neurosurgical treatment, aimed at relieving compression of the trigeminal nerve or root, is sometimes helpful.
Case 10, Chapter 9
The finding of bitemporal hemianopia is classical for an abnormal mass impinging on the optic chiasm. This may explain the complaint of worsening eyesight. The other signs and symptoms suggest pituitary dysfunction, probably of considerable duration. Additional tests could confirm this, showing lowered levels of gonadotrophic and thyrotropic hormones. The combination of headache and incipient papilledema indicated increased intracranial pressure, probably caused by a growing mass.
Differential diagnosis includes pituitary adenoma with pressure on the optic chiasm; a craniopharyngioma, a congenital tumor that can compress the pituitary gland, the optic chiasm, or both, and usually causes symptoms either before the age of 20 years or in old age; a tumor of the hypothalamus and pituitary stalk, which is unlikely because there were no other hypothalamic dysfunctions; and a gradually enlarging aneurysm of the anterior communicating artery, which is unlikely because there were endocrine dysfunctions.
Radiologic examination (CT or MRI) is often helpful in determining the precise location, characteristics, and extent of the neoplasm (Fig 25–10). The most likely diagnosis is pituitary adenoma. Treatment is neurosurgical removal of the tumor and hormone-substitution therapy.
FIGURE 25–10 Magnetic resonance image through the base of the brain in a patient with a pituitary adenoma (arrow). The tumor has grown downward into the sphenoid sinus and upward to the optic chiasm.
Case 11, Chapter 10
The mental impairment (disorientation, confusion, distractibility, and partial loss of memory) of this patient suggests a lesion in one or both frontal lobes. The right facial signs made a left-sided lesion probable, and this was confirmed by the electroencephalogram and imaging studies. The seizure also suggested an irritative lesion in or near the motor cortex.
The differential diagnosis based on the clinical presentation must include a slow-growing tumor, an unusual type of chronic infection (unlikely but not impossible with no history of fever), and a degenerative disorder (unlikely in the context of unilateral facial weakness). Headache was suggestive of a mass lesion. The imaging studies suggested a multifocal tumor or cerebral abscesses, and a brain biopsy was performed. The pathologic diagnosis was malignant glioma (Fig 25–11).
FIGURE 25–11 Coronal section through the brain of a patient with a hemispheric glial tumor. Histopathologic examination showed this to be a glioblastoma. Note the uncal and subfalcial herniations (arrowheads). A biopsy track is visible on the left (arrow).
The tumor was a glioblastoma with calcifications and regions of hemorrhage within it. The small hemorrhages found in the brain stem at autopsy were indicative of rapid herniation and were probably caused by tearing of small vessels in the midbrain and pons (Duret hemorrhages).
Comment: Modern imaging techniques are useful in determining the site, and often the type, of a mass (Figs 25–12 and 25–13). Gliomas are a frequent type of brain tumor in most age groups (Tables 25–1and 25–2). Astrocytoma is considered histologically to be the most benign glioma, and glioblastoma multiforme is considered the most malignant. There is a need for more effective treatments for gliomas.
FIGURE 25–12 Magnetic resonance image of a horizontal section through the head at the level of the lentiform nucleus in a patient with a glioma surrounded by edema (arrows).
FIGURE 25–13 Computed tomography image of a horizontal section through the head at the level of the lateral ventricles in a patient with glioblastoma multiforme. A small amount of blood lies in the bottom of a cystic portion of the tumor.
TABLE 25–2 Brain Tumor Types According to Age and Site.
Case 12, Chapter 10
The history of ear pain, draining ear, and fever suggests acute middle-ear infection. The subsequent worsening of the patient’s condition indicates that complications had occurred: involvement of the left facial nerve (in the middle ear), headache, dysphasia, and mental deterioration. All this suggests that the infection had penetrated the cranial cavity. Electroencephalography showed abnormal electrical activity suggestive of a mass lesion in the left frontotemporal region, and CT scanning revealed a mass.
The differential diagnosis includes otitis media with meningitis, which is unlikely because there was no stiffness of the neck; encephalitis caused by an intercurrent infection, which seems too coincidental to be likely; and cerebritis (which often evolves into a cerebral abscess) as a complication of a pyogenic infection. In this patient CT imaging confirmed the diagnosis of cerebral abscess (Fig 25–14).
FIGURE 25–14 Computed tomography image of a horizontal section through the temporal lobes, showing an epidural lesion and multiple rounded confluent masses in the right lobe.
Comment: Although this patient had fever, it can be absent in patients with brain abscesses. Absence of fever does not rule out the presence of this treatable condition.
The high mortality rate in patients with cerebral abscesses has been reduced by repeating the CT scan every 2 or 3 days to monitor both the effects of antibiotics and the ripening of the abscess so that surgical drainage can be performed at the right time. In patients with an impaired immune system (eg, in patients with AIDS), an infection can develop in any part of the body; in the brain, the agent is often Toxoplasma gondii (Fig 25–15).
FIGURE 25–15 Magnetic resonance image of a horizontal section through the lateral ventricles in a patient with AIDS. Notice the multiple high-intensity regions throughout both hemispheres, representing cerebral abscesses (arrows).
Case 13, Chapter 11
The history, temperature, and blood count suggest this to be an infection. Fever, poor appetite, and cough suggest a respiratory infection, and the neck stiffness points to meningeal irritation. It is likely that the initial infection developed into septicemia and spread to the central nervous system. The lumbar puncture findings are consistent with meningitis (see Table 25–1). The low level of glucose in the CSF, especially with a normal level of glucose in the blood, is characteristic of bacterial infection and a Gram-stained smear showed pneumococci.
The diagnosis is pneumococcal meningitis (Fig 25–16). Treatment consists of injecting the appropriate antibiotics intravenously. In addition, intrathecal injection may be considered.
FIGURE 25–16 Pneumococcal meningitis. The convexity of the brain is covered by a thick, yellow-green exudate in the subarachnoid space.
Comment: Prognosis of meningitis depends in large part on prompt diagnosis and treatment. Many authorities recommend immediate treatment with antibiotics, even prior to confirmation of the diagnosis by lumbar puncture and spinal fluid examination, which are carried out to definitively establish the diagnosis of meningitis, and to identify the infectious agent and its antibiotic sensitivity.
Pneumococcal meningitis and other forms of purulent meningitis usually extend over the hemispheres, whereas tuberculous meningitis is more caseous and is often located in the basal cisterns (Fig 25–17). In both types, the circulation of CSF may become impaired, leading to communicating hydrocephalus.
FIGURE 25–17 Basal view of the brain, showing tuberculous meningitis (arrows) in a 26-year-old man.
Case 14, Chapter 11
The history indicates trauma on the right side of the head and temporary loss of consciousness. Findings on early neurologic examination were unremarkable. At this stage, the differential diagnosis should include concussion, in which there is usually little or no loss of consciousness; contusion of the brain, which usually produces no deficits at first; and some type of intracranial hemorrhage. An immediate CT scan or MR image would have been useful to show intracranial blood. A skull film might have shown a fracture of the temporal bone but would not have shown the intracranial changes. In the absence of neuroradiologic procedures, close observation was indicated.
The vital signs were within normal limits at first but changed appreciably after a few hours. The combination of increasing blood pressure and decreasing pulse and respiratory rates is often indicative of increasing intracranial pressure (Cushing’s phenomenon). This patient should have been reexamined at frequent intervals.
There was a loss of consciousness after a lucid interval. Together with the increased intracranial pressure, this suggested a rapidly growing mass on the right side and within the skull. The loss of right-sided functions of nerve III is indicative of beginning brain herniation.
The most likely diagnosis is epidural hemorrhage, perhaps with some intracerebral bleeding (contusion). Subdural hemorrhage is less likely because of the rapid pace of deterioration of the patient’s condition. Intracerebral hemorrhage can be ruled out by radiologic studies (Fig 25–18; see also Figs 12–26 and 12–27). CT or MRI is superior to lumbar puncture.
FIGURE 25–18 Computed tomography image through the head at the level of the external ears (bone window) in a patient with epidural hemorrhage. Note the fracture site (arrow) and nearby air bubbles.
Neurosurgical treatment of the bleeding and prompt removal of the epidural blood may be lifesaving.
Case 15, Chapter 12
The headache and painful stiff neck indicate a process irritating the basal meninges. This could be infectious, the result of bleeding in the subarachnoid space, or the result of meningeal spread from a primary tumor. The suddenness of the disease suggested a vascular cause. Intracranial hypertensive bleeding was unlikely in this normotensive patient, and there was no history of trauma. The severity of the disease, the slightly increased white blood count, and the increased erythrocyte sedimentation rate all pointed to a major abnormal vascular event, most likely a hemorrhage.
Blood in the subarachnoid space can irritate the meninges, cause neck stiffness and pain and vessel spasms, and affect the function of the cranial nerves. The motor deficits must be explained by involvement of the corticospinal tract. The most likely site is the left cerebral peduncle, where dysfunction of the cranial nerve III explains the eye findings. Severe bleeding in the subarachnoid space can also trigger displacement of the cerebrum, followed by transtentorial herniation. Compression of the cerebral peduncle and nerve III between the posterior cerebral and superior cerebellar arteries is often seen as a complication of an expanding supratentorial mass.
A lumbar puncture might have aggravated the beginning brain herniation, but if performed, it would have demonstrated frank blood in the CSF and established the diagnosis of acute subarachnoid hemorrhage (see Table 24–1). In this case, a CT image showed a high-density area in the cisterns, particularly on the right side (see Fig 12–21). In such cases, cerebral angiography can be performed a few days later, when a clot has sealed off the bleeding site.
The treatment of subarachnoid hemorrhage may include neurosurgical removal or containment of the cause of the bleeding: an aneurysm or a vascular malformation. It may also include interventional radiologic (endovascular) procedures that stabilize or occlude the abnormal vessel.
Case 16, Chapter 12
The history shows the patient to be an alcoholic who had possibly received trauma to the head when he fell. His level of consciousness had deteriorated, and he seemed to have had a seizure (incontinence and a bitten lip), both findings suggesting cerebral involvement. Neurologic examination suggested a lesion in or near the right motor cortex, and the lumbar puncture showed xanthochromia (fresh and old blood) in the CSF (see Table 24–1). All these findings indicated a hemorrhage; the time course favored subdural bleeding. Subarachnoid bleeding from a leaking aneurysm was less likely because trauma initiated the process in this patient. An arachnoid tear could have produced the bloody CSF, and subdural bleeding could occur with additional (mild) trauma. The CT image demonstrated this. The worsening of the patient’s condition was caused by imminent herniation of the brain, triggered by the blood mass, the drop in CSF pressure associated with lumbar puncture, or both.
The diagnosis is subacute right-sided subdural hemorrhage. Treatment consists of neurosurgical removal of the blood and closure of the bleeding veins.
Comment: Most subdural hematomas cover the upper part of the hemispheres, whereas epidural hematomas are often more circumscribed and located lower (compare Figs 12–25 and 12–26). Bilateral hematoma is not uncommon (Fig 25–19). When bilateral hematoma is found in a youngster, child abuse may be suspected.
FIGURE 25–19 Magnetic resonance image of a horizontal section at the level of the lateral ventricles of a patient with bilateral subdural hematoma and congested frontal sinuses. The patient had fallen down a flight of stairs.
Case 17, Chapter 13
The history indicates a motor disorder. In the absence of cerebellar signs and of corticospinal tract deficits, an abnormality in basal ganglia system function must be suspected. This is consistent with the findings of akinesia and unilateral tremor. All observations and test results were compatible with a dysfunction of the substantia nigra or its pathways.
The most likely diagnosis was Parkinson’s disease, and neuroradiologic examinations served only to exclude other disorders. Treatment consisted of physical therapy and appropriate administration of drugs such as levodopa. The patient had a moderately good response to therapy.
Comment: Neuropathology may confirm the diagnosis at autopsy by the finding of depigmentation of the substantia nigra (see Fig 13–10). Neuromelanin is normally absent in the midbrain and other brain stem sites up to the age of about 8 years.
Case 18, Chapter 13
The suddenness of the severe neurologic deficits in a patient with hypertension most likely indicates a vascular event, possibly an intracerebral hemorrhage. The patient’s complaint of headache tended to support the diagnosis of intracerebral hemorrhage. In cases such as this, the hematoma may be (in order of frequency) in the putamen, thalamus, pons, or cerebellum. The bleeding in this patient involved the motor system (face and corticospinal tract dysfunction). The most likely site of bleeding was either in the putamen, with spread to the globus pallidus and internal capsule, or in the pons, with involvement of the corticospinal and corticopontine systems. However, the unilaterality of the motor deficits pointed to bleeding in the basal ganglia and internal capsule rather than in the compact pons.
A lumbar puncture could be useful in ruling out a subarachnoid hemorrhage (case 15; see also Table 24–1). However, normal CSF findings would not help in differentiating other types of bleeding, and the procedure might contribute to herniation of the brain. The neuroradiologic procedure of choice is CT imaging, as shown in FIGURE 12–19 for another patient. MRI can also be helpful.
The diagnosis is hypertensive intracerebral hemorrhage in the right basal ganglia and adjacent structures. Treatment includes antihypertensive therapy, intensive care, and measures to relieve symptoms. As seen in FIGURE 25–20, the blood clot may be resorbed, leaving a cavity-like region of neuronal degeneration in its wake, in patients who survive.
FIGURE 25–20 Cystic degeneration involving principally the left caudate and lenticular nuclei.
Case 19, Chapter 14
In the absence of cranial nerve signs and symptoms and cerebellar signs, the lesion must be in the spinal cord, on the right side, at the level of the lower-motor-neuron deficit, C6-8. The numbness and tingling suggested involvement of the spinal cord on the right side. Weakness in the right hand and loss of deep tendon reflexes in the right upper extremity indicated dysfunction of the lower-motor-neuron type. Loss of pain sensation suggested a lesion in the spinothalamic system. Peripheral nerve involvement was unlikely because the patient had upper-motor-neuron signs (an extensor plantar response and abnormally brisk reflexes on the right side indicating involvement of the corticospinal tract) and a dissociated sensory deficit. (The areas of loss of touch were different from those of loss of pain sensation.)
The differential diagnosis includes traumatic injury of the spinal cord, which is unlikely because there was no history of trauma in this case; myelitis, unlikely because there was no history of fever; and bleeding or thrombosis, unlikely because of the slowly progressive course and the distribution of the deficits. A plain film of the spine is not helpful in demonstrating intrinsic cord lesions; therefore, MRI or CT imaging is preferable. An MRI study was performed and showed enlargement of the spinal cord by cavitation, or cyst formation, most severe in the lower cervical segments (Fig 25–21).
FIGURE 25–21 Magnetic resonance image (surface coil technique) of a sagittal section through the thoracic spine of a patient with syringomyelia (arrows).
The diagnosis is syringomyelia. The cavity extended from C4 to C7 and involved the right cuneate tract as well as portions of the ventral horns, causing atrophy of the hand muscles (see Fig 5–27). Abnormal enlargement of the central canal is called hydromyelia. Draining the cavity neurosurgically can provide relief.
Comment: MRI findings in syringomyelia must be distinguished from those in the Arnold-Chiari malformation (Fig 25–22). The latter is a congenital disorder characterized by downward displacement of a small cerebellum, cavitation of the spinal cord, and other abnormalities.
FIGURE 25–22 Magnetic resonance image (surface coil technique) of a midsagittal section through the upper spine of a patient with Chiari and other malformations. (Compare with Fig 7–22.)
Case 20, Chapter 14
The patient was an alcoholic, as the history indicates. The symmetric motor deficits (lower-motor-neuron type) in all extremities and the sensory abnormalities in the distal portions of the limbs are highly suggestive of peripheral nerve involvement (Fig 25–23). The differential diagnosis includes spinal cord disease, but the distribution of the lesions is not compatible with the somatotopic organization of pathways in the cord.
FIGURE 25–23 Distribution of sensory and lower-motorneuron deficits in a patient with peripheral polyneuropathy. Notice the “stocking-and-glove” pattern of sensory loss.
The diagnosis is polyneuropathy, which in this case is caused by alcohol abuse. Hyperalgesia of the soles and calf muscles is characteristic of this type of nerve disease. (There are many other causes of polyneuropathy, and hyperalgesia is not always present.) Diabetes is a common cause of polyneuropathy, and was ruled out in this case by measurement of fasting blood glucose. The treatment in this case should include injections of vitamin B1(thiamine hydrochloride), institution of a vitamin-rich diet, and cessation of alcohol intake.
Case 21, Chapter 15
The history of an epileptiform attack in a 50-year-old woman indicates irritation of the cerebral cortex, and the results of examination (chronic papilledema) suggest a slow-growing, space-occupying lesion. The mental status is compatible with involvement of one or both frontal lobes. The loss of olfaction on the left side and the atrophy of the adjacent left optic nerve (which resulted in a pale optic disk) suggest that the lesion is located in the base of the left frontal lobe and is compressing the optic nerve. The associated cerebral edema explains the mild facial weakness and the effect on the motor pathways to the extremities.
The differential diagnosis is limited: The lesion may be an intrinsic brain tumor in the left frontal lobe or olfactory region, or it may be a meningeal tumor in that region. A CT scan or MR image would show the exact location of the tumor.
Neurosurgical removal and pathologic studies of the abnormal tissue resulted in the diagnosis of olfactory groove meningioma with associated Foster Kennedy’s syndrome on the left side. This syndrome consists of contralateral papilledema and ipsilateral optic atrophy caused by a mass in the low frontal region (Fig 25–24).
FIGURE 25–24 Olfactory groove meningioma. (From Scarff: Classic Syndromes of Brain Tumor. Annual Clinical Conference of the Chicago Medical Society, 1953.)
Comment: Meningiomas arise from abnormal arachnoid cells; therefore, this type of tumor occurs in many intracranial locations as well as in the spinal region. Frequent sites are on the convexity of the hemisphere and along the falx (Fig 25–25). Although the robust vascularity of meningiomas can make surgery difficult, they often can be removed surgically.
FIGURE 25–25 Computed tomography image, with contrast enhancement, of a horizontal section through the cerebral hemispheres. The absence of surrounding edema suggests a slowgrowing tumor, in this case a meningioma.
Case 22, Chapter 16
The key to determining the site of the lesion in this case is the long-standing impairment of cranial nerve VIII, evident first in the cochlear division and more recently in the vestibular division. The ensuing signs and symptoms all related to the adjacent cranial nerves (V, VI, and VII) or their nuclei and to the brain stem (corticospinal tracts and cerebellar peduncles). The initial complaints pointed to a lesion in the pontocerebellar angle, where nerves VII and VIII lie close to the brain stem. The long period of progressive worsening and the presence of papilledema made a slow-growing tumor likely.
Differential diagnosis includes a cranial nerve tumor, a tumor of the brain stem (eg, a glioma) or the adjacent arachnoid (eg, a meningioma), or another rare neoplasm. The lesion occurring most frequently in this region is a nerve VIII tumor. This type of tumor usually originates just inside the proximal end of the internal auditory meatus, where it later compresses the adjacent seventh nerve and widens the meatus. The tumor (usually a schwannoma) may grow to compress adjacent structures in the pontocerebellar angle (Fig 25–26). Treatment consists of surgical removal of the tumor. Function of nerve VIII may be permanently lost.
FIGURE 25–26 Nerve VIII tumor.
Case 23, Chapter 17
The syndrome of recurrent vertigo with tinnitus, nausea, and progressive deafness suggests an abnormality in the inner ear. Spontaneous nystagmus (horizontal or rotatory) is often present during an attack. The most likely diagnosis is Meniere’s disease. (Transient ischemic attacks caused by basilar artery stenosis must first be ruled out.) The disease is probably caused by an increase in the volume of labyrinthine fluid (endolymphatic hydrops). Bilateral involvement occurs in 50% of the patients. Caloric testing usually shows impaired vestibular function. The patient should be referred to an ear, nose, and throat specialist for treatment.
Case 24, Chapter 19
Fever, malaise, and headache may suggest a subacute intracranial infection. The patient’s “fits” indicate irritation of the cortex, possibly caused by edematous swelling of the brain. The lumbar puncture results confirmed the presence of infection and increased intracranial pressure; however, the basal meninges did not appear to be involved because there was no neck stiffness.
The dysphasia and memory loss, the defects seen on the MR scan, and the electroencephalographic findings all indicated temporal lobe involvement on both sides. The CT scan findings were compatible with swelling of these sites and showed some bleeding.
The differential diagnosis includes encephalitis, cerebritis, meningitis, and subarachnoid hemorrhage. Subarachnoid hemorrhage may be associated with a moderate rise in temperature and with seizures and loss of consciousness; however, the absence of blood in the CSF, the absence of neck stiffness, the presence of dysphasia, and the electroencephalographic findings make this diagnosis unlikely. Meningitis is unlikely because there was no neck stiffness and because the lumbar puncture specimen showed a white blood cell count with mostly lymphocytes rather than polymorphonuclear leukocytes (see Table 24–1). Moreover, red blood cells are not usually seen in the spinal fluid in meningitis. Although cerebritis associated with abscess formation is a possible diagnosis, it is unlikely because both temporal lobes were simultaneously involved; there was no primary infection such as otitis media, sinusitis, or endocarditis, and the predominance of lymphocytes suggests otherwise.
The most likely diagnosis is encephalitis. Localization in the temporal lobes, together with the CSF results and the findings on the MR image (see Fig 19–15), suggested a diagnosis of herpes simplex encephalitis. This diagnosis was confirmed by brain biopsy. In some cases, patients respond well to treatment with antiviral agents such as acyclovir, although residual amnesic defects, aphasia, dementia, and seizures are common.
Case 25, Chapter 20
The history indicates a slowly progressive process involving the lower cranial nerves (VIII, X, and XII), the brain stem nuclei of these nerves, and the cerebellar pathways, all predominantly on the right side. The ataxia and the increased level of protein in the CSF pointed to an intracranial location of the lesion. The hypersalivation, postural hypotension, and cranial nerve (or nuclei) signs can be explained by involvement of the lower brain stem, where the salivatory nuclei, vasomotor center, and pertinent cranial nerve nuclei are located.
The lesion is probably a brain stem tumor involving the right side of the stem more than the left and characterized by a slow progression over a period of 8 months. The ventricular enlargement seen on CT scan is compatible with a posterior fossa block of the CSF circulation. CT did not show the lesion itself because of bone artifacts. MRI, however, demonstrated a mass within the fourth ventricle, invading the nearby brain stem.
Treatment in this case consisted of subtotal removal of the mass. Histopathologic studies showed that the tumor was an ependymoma (Fig 25–27).
FIGURE 25–27 Midsagittal section through the brain of a patient with a brain stem tumor. Histologic findings showed the tumor to be an ependymoma.
Comment: The most common posterior fossa tumors in children are astrocytomas, medulloblastomas, and ependymomas. Different types of tumors may occur in older persons (Table 25–2 and Figs 25–27 to 25–29).
FIGURE 25–28 Computed tomography image, with contrast enhancement, of a horizontal section through the head. Notice the low-density cystic astrocytoma with a high-density nodule in the posterior fossa, representing a glioma of the cerebellum.
FIGURE 25–29 Magnetic resonance image of a midsagittal section through the head. The large mass that originates in the clivus and displaces the brain stem backward is a chordoma (arrows).
Case 26, Chapter 21
The history indicates a series of transient ischemic attacks, which are suggestive of cerebrovascular occlusive disease. The most common cause in elderly persons is arteriosclerosis. The sudden deterioration of the patient’s status was caused by thrombotic or embolic occlusion of a major cerebral vessel on the right side. Papilledema indicated an intracranial mass effect caused by swelling of the brain associated with an ischemic infarct. The flaccid paralysis and the sensory deficits suggested involvement of the blood supply to the sensory motor cortex or the underlying white matter in the right hemisphere. The left-sided neglect was consistent with a lesion affecting the right cerebral hemisphere.
The sudden nature of the disorder and the absence of a history of tumor or infections tend to eliminate neoplasm and infectious mass from the differential diagnosis. The distribution of the deficits suggests an infarct in the distribution of the right middle cerebral artery. The neuroradiologic examination clarified the extent of the ischemia as well as its vascular origin (Fig 25–30; see also Figs 12–14 and 12–15). The diagnosis is occlusion of the right middle cerebral artery.
FIGURE 25–30 Left internal carotid angiogram, arterial phase, lateral view, showing occlusion of the middle cerebral artery (arrow). The posterior artery is well filled (compare with Fig 22–4).
Case 27, Chapter 21
This patient’s history is consistent with a sensory seizure with predominantly visual symptoms; this suggests involvement of the occipital cortex. The sudden development of a right homonymous hemianopia was probably caused by a vascular event that involved the left visual pathway behind the optic chiasm. The history of heart disease suggests embolism, in which small thrombi detach from the heart and pass into the major cerebral vessels. There was no headache, so migraine was unlikely.
CT and MRI were helpful in confirming the diagnosis of embolic infarction of part of the left occipital lobe. Emboli passing to the brain often lodge in the largest vessels, the middle cerebral arteries. In this case, the infarct occurred in the territory of the posterior cerebral artery, which it may have reached by passage through a large (embryonic type) posterior communicating artery or by way of the vertebrobasilar system. Although angiography would help to determine this, there is debate about whether it should be done shortly after an infarct has occurred. Treatment of embolic infarction consists of controlled anticoagulation to prevent further emboli.
Comment: Emboli, including blood-borne metastases to the brain, most frequently lodge in the territory of the middle cerebral artery (Fig 25–31).
FIGURE 25–31 Computed tomography image of a horizontal section through the upper hemispheres of a patient with a known bronchial carcinoma.
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