Brain Tumors, Metastatic Cancer, and Paraneoplastic Syndromes

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Chapter 19 Brain Tumors, Metastatic Cancer, and Paraneoplastic Syndromes

With their unpredictable onset and frequently tragic course, brain tumors command unique attention. Moreover, they seem to arise in children and adults in the prime of their life. Because brain tumors may produce depression, thought disorders, or cognitive impairment without any accompanying physical symptoms, they occasionally mimic psychiatric disturbances. Brain tumors remain the bête noire of psychiatry.

Varieties

Primary Brain Tumors

Primary brain tumors arise within the brain or spinal cord tissue (parenchyma) or their coverings (meninges) (Box 19-1). Pathologists have named them after their original cell line. The numerous, mostly small, glial cells, which normally provide the structural, biochemical, and immunologic support for the central nervous system (CNS), give rise to most tumors – gliomas. These tumors arise within the substance of the brain, i.e., in intraparenchymal or intra-axial locations. Meningeal cells give rise to the other large category of brain tumors, meningiomas. Because these tumors arise from the coverings of the CNS, rather than from actual brain or spinal cord tissue, they grow outside the brain, i.e., in extraparenchymal (extra-axial) locations. In contrast, CNS neurons rarely form tumors in adults.

Box 19-1

Primary Brain Tumors

Gliomas

Astrocyte Tumors

Astrocytoma
Glioblastoma

Oligodendroglioma

Meningioma*

Lymphoma

Medulloblastoma

Pituitary Adenoma*

Acoustic Neuroma*

*Relatively benign histology.

Of the various potential etiologies of primary brain tumors, studies have established that only ionizing radiation, certain neurocutaneous disorders (see Chapter 13), and various genetic mutations constitute risk factors. So far, data have not proven that cellphone use constitutes a risk factor.

Gliomas

Parenchymal tumors, gliomas, include oligodendrogliomas and astrocytomas. Oligodendrocytes, which normally produce the myelin covering that insulates CNS neurons,* may give rise to oligodendrogliomas. These tumors, which occur infrequently and grow slowly, produce similar manifestations to the more commonly occurring astrocytomas (see later).

Astrocytomas, which arise from astrocytes, strike children as well as adults. They do not invade surrounding tissue when they are low-grade, but originate anywhere in the CNS. They are the most common tumor in children. In children, relatively benign astrocytomas grow into cystic, noninvasive tumors in the cerebellum. Because neurosurgeons can readily remove an entire cerebellar astrocytoma without causing appreciable sequelae, the cure rate approaches 90% of this variety of tumor in children. However, in children, astrocytomas may arise in the brainstem, where they invade cranial nerve nuclei and long tracks. Brainstem astrocytomas tend to be highly malignant and not amenable to surgery.

For adults, astrocytomas occur predominantly in the cerebrum, infiltrate extensively, and often degenerate into glioblastomas. Total surgical removal is practical only when the surrounding brain can be sacrificed. For low-grade astrocytomas, combined surgery and radiotherapy prolong life for approximately 10 years.

Glioblastomas, the most malignant variety of astrocytoma, are the most frequently occurring brain tumor. They develop almost exclusively in the cerebrum. The prognosis is grim. These tumors not only grow rapidly and relentlessly, they infiltrate widely. Frontal lobe gliomas frequently cross the corpus callosum to produce the infamous “butterfly glioma” (Figs 19-1, A, 20-8, and 20-20). Contrary to many physicians’ expectations that brain tumors, like most other cancers, arise in the elderly, the age of patients at the time of a glioblastoma diagnosis averages only 54 years.

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FIGURE 19-1 A, A glioblastoma – the most malignant form of glioma – typically infiltrates along white-matter tracts. Sometimes it spreads through the heavily myelinated corpus callosum in a “butterfly” pattern (see Figs 20-8 and 20-20). B, Meningiomas arise from the meninges overlying the brain or spinal cord and grow slowly (see Fig. 20-10). They compress and irritate, but do not infiltrate, the central nervous system. C, Metastatic tumors, usually multiple and surrounded by edema, destroy large areas of brain and raise intracranial pressure (see Fig. 20-8). D, A subdural hematoma, typically located over one cerebral hemisphere (see Fig. 20-9), compresses the underlying brain and ventricles, and pushes away (shifts) midline structures. Large, acute, rapidly expanding subdural hematomas force the brainstem and ipsilateral oculomotor (third cranial) nerve through the tentorial notch. Such transtentorial herniation, which occurs with epidural as well as subdural hematomas (see Chapter 22), constitutes an immediately life-threatening condition. In contrast, small meningiomas and chronic subdural hematomas cause relatively few symptoms because they are extra-axial and exert little mass effect.

Radiotherapy, steroids, and chemotherapy may slow glioblastomas’ growth rate and provide a brief, physically comfortable period. Surgical excision rarely eliminates these tumors. In fact, many patients, especially the elderly and those with pronounced neurologic deficits, gain little from treatment. Glioblastoma patients survive for only about 15 months. Moreover, persistence of the tumor and side effects of treatment often produce progressive cognitive and emotional deterioration.

Meningiomas

Arising independently or as an integral part of neurofibromatosis type 1 (see Chapter 13), meningiomas usually create symptoms by compressing the underlying brain or spinal cord (see Figs 19-1, B and 20-10). They grow slowly and predominantly in middle-aged women. Because their expansion is insidious, meningiomas often grow quite large before they produce symptoms.

Neurologists frequently detect small meningiomas as an incidental finding on imaging studies of the brain. Small cerebral meningiomas usually remain asymptomatic and innocuous. They rarely require surgical removal. Neurologists generally follow patients harboring meningiomas with periodic clinical evaluation and magnetic resonance imaging (MRI) or computed tomography (CT). Even moderate-sized meningiomas located in certain areas may not produce symptoms. For example, meningiomas over the right frontal lobe can grow to an extraordinary size before they cause problems.

Primary Cerebral Lymphoma

In contrast to systemic lymphoma, which commonly spreads to the CNS, primary cerebral lymphoma arises within the brain and often in multiple sites. An impaired immune system is a powerful risk factor for primary cerebral lymphoma. Thus, these tumors complicate acquired immunodeficiency syndrome (AIDS), immunosuppressive therapy for organ transplant, and ataxia-telangiectasia.

On CT and MRI, primary cerebral lymphoma resembles cerebral toxoplasmosis (see Figs 20-11 and 20-21). The clinical features of cerebral toxoplasmosis, including focal neurologic deficits and seizures, overlap those of cerebral lymphoma. Although surgery cannot remove lymphomas, steroids often produce dramatic, although temporary, remissions.

Metastatic Tumors

Systemic tumors metastasize to the brain and spinal cord by hematogenous routes. They cannot spread through a lymphatic system because the brain, unlike almost all other organs, does not have one. Metastatic tumors tend to be multiple, surrounded by edema, and rapidly growing. Although individual tumors may each be small, their combined mass constitutes an oppressive intracerebral burden (see Figs 19-1, C and 20-8).

Cancer of the lung, breast, kidney, and skin (malignant melanomas) most often give rise to cerebral metastases. In contrast, because the portal vein diverts metastases to the liver, gastrointestinal, pelvic, and prostatic cancers spread to the brain rarely or only late in their course.

Approximately 15% of all cancer patients initially have symptoms of cerebral metastases; however, as treatment drives systemic tumors into long remissions, cerebral metastases, which usually do not respond to therapy, cause symptoms in a greater proportion of patients. Metastases resist systemic chemotherapy because the blood–brain barrier ironically blocks most medications from attacking them. Moreover, chemotherapy and radiotherapy have relatively little effect against metastatic tumors because, compared to the primary tumor, they are poorly differentiated. On the other hand, the discovery of a metastatic brain tumor is occasionally the first indication that a person has cancer.

Whatever the origin of cerebral metastases, conventional treatments, such as steroids and radiotherapy, provide palliative care. Stereotactic radiosurgery, which consists of a cobalt device, linear accelerator, or a cyclotron delivering a highly focused beam of radiation to metastases, alone or in conjunction with whole-brain radiation, usually shrinks the tumors. In cases involving a single metastasis, surgeons can help the patient, at least temporarily, by removing it. Nevertheless, most patients with metastatic brain tumors survive less than 9 months.

Initial Symptoms

Local Signs

By damaging surrounding tissue, brain tumors usually produce lateralized neurologic deficits, often called “local signs,” such as hemiparesis and dominant- or nondominant-hemisphere neuropsychologic disorders (see Chapter 8). Tumors arising in “eloquent” regions – cerebral cortex areas critical to motor or neuropsychologic function, such as Broca’s or Wernicke’s areas – produce obvious impairments. Tumors that are small, slowly growing, or located in “silent” regions of the brain, such as the right frontal lobe or either of the anterior temporal lobes, notoriously fail to produce symptoms. Tumors that arise from cranial nerves, although rare, almost immediately result in readily recognizable deficits. For example, optic nerve gliomas cause visual loss, and acoustic neuromas cause unilateral progressive hearing loss and tinnitus (see later).

Seizures in individuals older than 60 years are frequently the presenting feature of cerebral tumors. However, because strokes cause seizures nearly as often as tumors, a 60-year-old individual presenting with the first seizure is approximately equally likely to have sustained a stroke as have developed a brain tumor. When the etiology is either a brain tumor or stroke, seizures typically begin as a partial seizure that undergoes secondary generalization (see Chapter 10).

A brain tumor’s tendency to cause seizures also pertains to electroconvulsive therapy (ECT). For example, if a patient harboring a brain tumor were to undergo ECT, the procedure might give rise to multiple, uninterrupted, life-threatening seizures (status epilepticus). However, the benefits of ECT might outweigh the risks if the tumor were small enough not to cause neurologic deficits or surrounding cerebral edema. Large brain tumors, on the other hand, constitute an unequivocal problem regarding ECT. Not only might large brain tumors account for depressive symptoms, but also they might precipitate transtentorial herniation during ECT (Fig. 19-1, D). Thus, before their patients undergo ECT, neurologists order either an MRI or CT.

Signs of Increased Intracranial Pressure

In addition to damaging brain tissue, tumors may raise intracranial pressure through many mechanisms. They grow rapidly, constitute a large volume, accumulate surrounding edema, obstruct the flow of cerebrospinal fluid (CSF) through the ventricles, or impede CSF reabsorption through the arachnoid villi. Whatever the cause, increased pressure (pressures exceeding 200 mm H2O) creates symptoms and signs that may add to or supersede local ones.

Headache, while the most common symptom of increased intracranial pressure, still occurs in only one-half of patients. Although brain-tumor-induced headache lacks distinctive features, it usually resembles tension-type headache because it consists of diffuse, dull, relatively mild pain that initially responds to mild analgesics, including aspirin. Sometimes, a predominantly localized or unilateral headache points to a tumor’s location and mimics migraine. In any case, as pressure rises, headaches worsen, especially in the early-morning hours, and begin to awaken patients from sleep. Increasing intracranial pressure eventually produces nausea and vomiting, as well as increasing intense headache.

Despite the statistic that fewer than 1 out of 1000 people with headache harbors a brain tumor, both patient and physician frequently have great concerns – spoken or unspoken – that any headache may indicate a brain tumor. These concerns sometimes thwart diagnosis of a less threatening disorder, such as migraine or depression. Neurologists, dispensing with lengthy explanations or reassurances, often simply order a CT or MRI to exclude a tumor and move on with their evaluation and treatment plan.

Another sign of increased intracranial pressure, papilledema, occurs as pressure is transmitted along the optic nerve to the optic disks (Fig. 19-2). Although papilledema has a notorious association with brain tumors, it occurs late, if at all, in their course. In fact, among young adults, especially overweight females with menstrual irregularity, idiopathic intracranial hypertension (pseudotumor cerebri) is much more likely than a brain tumor to explain papilledema (see Chapter 9). In general, because only a small proportion of brain tumor patients have papilledema during an initial examination, its absence should not be taken as evidence against the presence of a brain tumor.

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FIGURE 19-2 Papilledema’s main features consist of reddening of the optic disk, which loses its distinct margin, and distension of the retinal veins. In addition, the disk is elevated and hemorrhages appear at its edge. (Compare this disk to the normal optic disk in Figure 4-4.)

In considering manifestations of brain tumors, meningiomas constitute a special category. Unlike gliomas, as discussed previously, small meningiomas are common and usually small. Even large ones may remain asymptomatic. Also, they arise and usually remain entirely in extra-axial locations and produce characteristic syndromes. For example, a meningioma arising from the falx, a parasagittal meningioma, can compress the medial motor cortex and cause spastic paresis of one or both legs. A meningioma arising from the sphenoid wing can damage the adjacent temporal lobe and, because of its proximity to the orbit, cause proptosis and paresis of eye movement. Likewise, an olfactory groove meningioma can compress the adjacent olfactory and optic nerves and the overlying frontal lobe (see Foster–Kennedy syndrome, Chapter 4), causing anosmia, unilateral blindness, and, when large, frontal lobe dysfunction (see Chapter 7).

Initial Mental Symptoms

Direct Effects of Tumors

As a preliminary practical point, most rapidly evolving tumor-related cognitive impairments or personality changes result from a glioblastoma. Another point is that tumors in the frontal lobe produce “frontal lobe personality changes,” consisting of psychomotor retardation, emotional dulling, loss of initiative, poor insight, and reduced capacity to execute complex mental tasks. This clinical picture, like the clinical picture of frontotemporal dementia (see Chapter 7), consists of disturbances in behavior and affect that overshadow cognitive impairments, and those disturbances in turn overshadow physical impairments.

In a somewhat opposite effect, frontal lobe tumors sometimes impair normal inhibitory systems. Patients with lack of inhibition (disinhibition) may overreact to an irritation, liberally use profanities, cry with little provocation, jump excitedly from topic to topic, and speak without tolerating interruptions. By way of contrast, parietal or occipital lobe, as well as right-sided far anterior frontal, tumors, unless they cause increased intracranial pressure, have relatively little effect on mood or cognitive function.

Overall, with numerous potential causes, depression is a frequent comorbidity of brain tumor. Depressive symptoms not only arise soon after diagnosis, but they increase in prevalence and severity during the ensuing illness, and predict a poor quality of life.

In brain tumor cases, a psychiatrist might attempt to determine the patient’s mood, cognitive capacity, neurologic deficits, and iatrogenic factors. With no standard guidelines for prescribing antidepressants or other psychotropics, psychiatrists must approach each situation entirely on an individual basis. In addition to prescribing a psychotropic and precluding ECT, psychiatrists might offer advice on alterations in mental status, guide pain management, assist in appointing a health care proxy, and help with decisions about end-of-life care.

Medication and Other Treatment

Opioids can cause delirium and undesirable changes in mood. On the other hand, insufficient opioids can lead to suffering, insomnia, and drug-seeking behavior. Benzodiazepines and hypnotics also present a quandary. They help control pain, anxiety, and insomnia, but may themselves cause mental dullness, confusion, and disruption of the sleep–wake cycle.

Other medications likely to induce mental status changes in cancer patients are antiepileptic drugs (AEDs), steroids, antiemetics, and antihistamines. Although physicians can usually predict common medications’ potential physical side effects, their mental side effects in cancer patients often arise insidiously and unexpectedly. For example, patients might have undiagnosed liver metastases that slow metabolism of medications and allow their unexpected accumulation. Similarly, because cancer patients often have lost body mass, physicians may inadvertently prescribe relatively large doses of a medicine. When cancer involves several organs, various specialists may each order different medicines that not only cause mental status abnormalities, but also may adversely interact.

Chemotherapy agents generally do not cause mental status changes because they cannot penetrate the blood–brain barrier. An exception occurs when physicians administer methotrexate intrathecally (into the subarachnoid space, usually through a lumbar puncture [LP]) because it often causes adverse CNS effects. Although intrathecal methotrexate, which is frequently administered in conjunction with cranial radiotherapy, may protect children from leukemic cells invading the CNS, it often induces short-term confusional states and occasional permanent learning disabilities and personality changes.

Many times chemotherapy penetrates the barrier and damages oligodendrocytes, which are the most vulnerable CNS cells. After 3 months to 5 years after treatment, loss of the oligodendrocytes leads to demyelination. Cancer survivors who sustain chemotherapy-induced CNS demyelination typically have cognitive decline and personality changes, paresis and spasticity, and ataxia and gait impairment – alone or in combination. Their MRIs show demyelination.

In contrast to chemotherapy-induced CNS demyelination, chemotherapy-induced peripheral neuropathy, from damage of either axons or the myelin-generating Schwann cells, usually occurs during or shortly after chemotherapy. Although severe enough at times to cause paresis and painful sensory impairment, chemotherapy-induced neuropathy tends to improve.

In an acute, often debilitating side effect, chemotherapy tends to induce nausea and vomiting (chemotherapy-induced emesis). This problem usually stems from chemotherapy agents triggering the brain’s chemoreceptor zone and its adjacent vomiting center. These zones are located in the area postrema of the medulla, which is one of the few regions of the brain unprotected by the blood–brain barrier. The absence of a blood–brain barrier leaves the chemoreceptor zone freely accessible to any blood-borne substance. Thus, if people inadvertently ingest toxins, such as in poisonous mushrooms, they will immediately vomit. From a medical perspective, morphine, heroin, and high doses of L-dopa, as well as several chemotherapeutic agents, activate the chemoreceptor zone and induce vomiting. On the other hand, both dopamine-blocking agents and 5-HT3 antagonists prevent chemotherapy-induced nausea and vomiting (see Chapter 21).

Depending on the radiation’s total dose and rapidity with which it is administered, radiotherapy sometimes causes inflammatory arteritis and necrosis. Small strokes, which begin to accumulate 6–18 months after a course of radiotherapy, lead to a stepwise progression of cognitive impairments and personality changes resembling vascular cognitive impairment (see Chapter 11). Hemiparesis and dysarthria often accompany neuropsychologic changes. MRIs of patients with radiation-induced cognitive impairments typically reveal white-matter changes (leukoencephalopathy). Overall, radiotherapy induces more cognitive impairment than most chemotherapy agents.

Whole-brain radiation administered to children for acute leukemia or brain tumors may result not only in cognitive impairment, but also in problems from hypothalamic–pituitary deficiency, particularly growth retardation, developmental delay, and late, incomplete puberty. Compared to young and middle-aged adults, children are more susceptible to radiation-induced cognitive impairment.

In an analogous complication, radiotherapy of the spine or mediastinum can strike the spinal cord and cause spinal cord radiation necrosis (radiation myelitis). Similarly, radiation of pituitary tumors may lead to necrosis of the adjacent pituitary gland. In this situation, radiation scatter may also cause necrosis of the nearby medial inferior temporal lobes. Young adult survivors of childhood non-CNS cancers, such as Hodgkin disease that required radiation of the chest and neck, also have an increased incidence of stroke. Their strokes occur because the extracranial portions of the carotid and vertebral arteries develop radiation-induced fibrosis that occludes the vessels.

Infections and Organ Failure

Immunosuppressive agents, radiotherapy, and various open ports, such as intravenous lines and urinary catheters, leave cancer patients susceptible to systemic infection. Bacteria, fungi, and opportunistic organisms frequently invade and proliferate, without provoking an immunologic response, and cause sepsis.

In addition, systemic cancer, infections, and various treatments often cause renal, pulmonary, or hepatic failure. Alone or together, sepsis and organ failure often lead to delirium. Perhaps owing to a comorbid depression, delirium in cancer patients may consist primarily of apathy, reticence, and sleep disturbance.

Infective agents sometimes invade the CNS, but not other organs. Because cancer patients often cannot respond with fever or leukocytosis to an infection, they may not show the usual markers. In fact, only 5% of cancer patients with meningitis will have the classic triad of fever, nuchal rigidity, and encephalopathy. Also, because of their immunocompromised state, cancer patients are susceptible to opportunistic infections. For example, progressive multifocal leukoencephalopathy (PML) probably results from a papovavirus that attacks CNS myelin. Indeed, CSF analysis in PML cases yields JC virus DNA. Usually complicating the late course of an illness, PML causes dementia and variable physical impairments, but not delirium, fever, or leukocytosis. PML has also complicated AIDS and immunosuppression therapy, including the multiple sclerosis treatment natalizumab (see Chapters 7, 15, and 20).

Ectopic Hormone Production

Sometimes tumors synthesize and excrete hormones, ectopic hormones, in unregulated, large quantities. For example, tumors may produce parathyroid hormone that causes hypercalcemia, or syndrome of inappropriate antidiuretic hormone secretion that causes hyponatremia. Ectopic hormone-induced metabolic aberrations often cause delirium and, if severe enough, seizures.

Paraneoplastic Syndromes

Systemic cancer sometimes causes neurologic syndromes not by invading the nervous system, but by inciting antibody-mediated immune responses directed against the CNS, PNS, or neuromuscular junction. Neurologists previously aptly called these disorders “remote effects of carcinoma,” but now they term them paraneoplastic syndromes. Paraneoplastic syndromes seem to begin with the patient’s synthesizing antibodies against a tumor’s antigens. The antibodies cross-react with neurons’ intracellular components, cell surfaces, or synaptic receptors. Antibodies involved in paraneoplastic syndromes include ones directed against voltage-gated potassium channels (VGKC) and N-methyl-D-aspartate (NMDA) receptors. Of the numerous paraneoplastic syndromes, three are particularly relevant: Cerebellar degeneration, limbic encephalitis, and Lambert–Eaton myasthenic syndrome (LEMS). Their pathophysiology likely represents “molecular mimicry” that is analogous to antistreptococcal antibodies cross-reacting with basal ganglia to cause Sydenham chorea (see Chapter 18).

Patients with paraneoplastic syndromes often show symptoms several months before or after the discovery of an underlying tumor. When neurologists diagnose a paraneoplastic syndrome in a patient without a known malignancy, they often order positron emission tomography (PET) and other tests for an occult malignancy. If physicians detect the underlying tumor and patients undergo surgery or chemotherapy that removes or shrinks it, paraneoplastic syndromes usually subside. Alternatively, immunosuppressive treatments, such as steroids, plasmapheresis, or intravenous immunoglobulin, may reduce the symptoms.

Cerebellar Degeneration

The most well-established paraneoplastic syndrome consists of a subacute, generalized cerebellar degeneration associated with an underlying neoplasm. A gynecologic cancer, lymphoma, or, most often, small cell tumor of the lung usually incites the syndrome. In fact, cerebellar degeneration and other paraneoplastic syndromes complicate 1–3% of cases of small cell lung cancer. In this syndrome, blood tests reveal antineuronal antibodies, such as anti-Hu and anti-Cv2 antibodies, directed against the relevant CNS neurons.

Paraneoplastic Limbic Encephalitis

Limbic encephalitis, as a paraneoplastic phenomenon, results from an antibody-mediated limbic system inflammation. As its clinical hallmark, over several days to several weeks, individuals develop pronounced memory impairment (amnesia), often accompanied by irritability and behavioral disturbances. In addition, the temporal lobe inflammation causes partial complex seizures. Limbic encephalitis often heralds small cell carcinoma of the lung or testicular cancer, but it may also be a manifestation of occult, nonmalignant disorders.

Whatever the underlying disorder, neurologic tests usually reflect temporal lobe abnormalities. MRIs may show atrophy of the mesial temporal lobes and electroencephalograms (EEGs) show spikes or slow waves emanating from the temporal lobes. Serum often contains anti-VGKC, anti-Hu, anti-Ma2, or other antibodies that react with limbic system neurons.

Anti-NMDA Receptor Encephalitis

Anti-NMDA receptor encephalitis, which results from antibodies directed against NMDA receptors, is a variety of paraneoplastic limbic encephalitis. It typically presents, like other forms of limbic encephalitis, with several days of progressively severe amnesia and behavioral disturbances. Then psychosis, seizures, involuntary movements, and autonomic instability often occur and eclipse the prodrome. This disorder typically occurs in young adults, especially young women. Neurologists might initially suspect – in decreasing order of probability – herpes simplex encephalitis, bacterial meningitis, phencyclidine (PCP) or other illicit drug intoxication, an anti-VGKC antibody paraneoplastic syndrome, and variant Creutzfeldt–Jakob – or an acute psychosis.

In most cases the MRI initially shows no abnormalities; however, the CSF shows a lymphocytic pleocytosis. The CSF and serum contain antibodies to NMDA receptors. The antibody concentration, greater in the serum than CSF, roughly correlates with the severity of the illness. The CSF also contains oligoclonal bands, as it does in the CSF of cases of multiple sclerosis and other CNS inflammatory illnesses.

The classic example of anti-NMDA receptor encephalitis consists of amnesia with mood change and depersonalization, involuntary movements, and eventually seizures in a young woman found to be harboring an ovarian teratoma. Overall, almost 50% of young adult women with this disorder harbor an ovarian teratoma, which presumably has triggered an antibody response to its neural tissue.

Lambert–Eaton Myasthenic Syndrome

In LEMS, small cell lung cancer provokes antibodies directed against the presynaptic side of the neuromuscular junction where they impair release of acetylcholine (ACh) (see Chapter 6). The antibody-induced neuromuscular junction dysfunction in LEMS causes proximal limb muscle weakness, which patients partly overcome with repetitive actions. Their weakness has different qualities and different distribution than myasthenia gravis – the well-known disorder of the ACh receptors on the postsynaptic side of the neuromuscular junction. Patients with myasthenia primarily have facial and extraocular muscle weakness that worsens on exertion. Antibody tests and electromyograms readily distinguish these two neuromuscular junction disorders.

Diagnostic Tests for Brain Tumors

Physicians should consider brain tumors and related conditions without waiting for a patient to have deficits. They should not rely exclusively on the mental status examination to distinguish between psychiatric disorders and brain tumors. In addition, commonplace complaints of fatigue, weight loss, menstrual irregularity, or infertility might prompt evaluation for pituitary insufficiency.

Neurologists generally order CT or MRI of the brain, admittedly liberally, for patients who have intellectual decline, those over 50 years who show substantial emotional changes, most adults with headaches not attributable to migraine, cluster, or giant cell arteritis (see Chapter 9), or, as previously discussed, those with excessive concern. Neurologists often also suggest CT or MRI for patients with any new psychiatric illness severe enough to warrant hospitalization or ECT.

CT remains a satisfactory screening procedure in many situations (see Chapter 20). It is sensitive to most tumors and other mass lesions, rapidly performed, relatively inexpensive, permissible for patients with pacemakers, and tolerable for most with claustrophobia. It remains preferable for detecting acute intracranial bleeding, including subarachnoid hemorrhage, subdural hematomas, and intracerebral hemorrhages. CT will also detect fractures and other abnormalities of the skull. On the other hand, its ionizing radiation, at least in children, carries a risk of inducing a malignancy (see Chapter 20).

MRI, especially with gadolinium infusion, remains superior in detecting lesions that are small or located in areas encased by bone, such as optic gliomas, acoustic neuromas, pituitary adenomas, and some posterior fossa tumors. It can readily demonstrate white-matter abnormalities associated with brain tumors, such as radiation necrosis, chemotherapy-induced leukoencephalopathy, and PML. If CT suggests a tumor, MRI still remains necessary to determine its exact location, internal structure, and involvement of surrounding brain. PET can help differentiate cerebral radiation necrosis from tumor recurrence.

For detecting tumors or other mass lesions, an EEG, especially in comparison to CT and MRI, is simply inappropriate. Nevertheless, in brain tumor and other cancer patients, it remains a good diagnostic test for delirium, particularly hepatic encephalopathy. An EEG may also assist in the diagnosis of seizures.

Neurologists generally do not perform an LP to analyze CSF when they suspect a brain tumor or other intracranial mass lesion because, in such cases, the CSF profile lacks a distinctive profile and rarely reveals malignant cells (see Chapter 20). More important, with large, expanding supratentorial mass lesions, an LP can precipitate transtentorial herniation (Fig. 19-3). Neurologists perform an LP when patients may have either carcinomatous or chronic infectious meningitis. Testing requires large volumes of CSF for neoplastic cells, chemistry studies, fungi, and bacterial and fungal antigens. In an exception to the general rule of not performing an LP in patients with a cerebral lesion, neurologists may perform one to test the CSF for Epstein–Barr virus in an AIDS patient found to have a cerebral tumor because a positive result would indicate a cerebral lymphoma and obviate surgery. Similarly, they may perform one in cases of suspected PML to look for JC virus DNA.

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FIGURE 19-3 A patient in transtentorial herniation from a right-sided subdural hematoma (see Fig. 19-1, D) has coma, decerebrate (extensor) posture, Babinski signs, and a dilated right pupil. The right temporal lobe compressing the right-sided (ipsilateral) oculomotor nerve and brainstem through the tentorial notch causes this catastrophe.

Related Conditions

Pituitary Adenomas

Although clinicians often view pituitary adenomas as brain tumors, their symptoms, histology, and treatment differ considerably from those of glioblastomas, astrocytomas, and meningiomas. In classic studies, the usual manifestations of pituitary adenomas included profound mental, physical, and visual loss; however, those studies reported on patients whose symptoms resulted from large pituitary tumors that produced extraordinary levels of hormones, expanded out of the sella to encroach on the adjacent temporal lobes and optic chiasm, and obstructed the flow of CSF through the third ventricle. Physicians now routinely diagnose pituitary adenomas early in their course, while they remain microscopic in size, by using MRI and blood tests for hormone levels.

In both men and women, prolactinomas produce infertility, decreased libido, headache, and eventually characteristic visual field deficits. Additionally, in women, they produce amenorrhea and galactorrhea, and in men, erectile dysfunction and gynecomastia. Because their loss of libido encompasses the nonsexual as well as sexual aspects of their lives, patients with pituitary adenomas may appear depressed or cognitively impaired.

Most pituitary adenomas are either prolactinomas, which secrete prolactin, or chromophobe adenomas, which do not. Although prolactinomas usually remain microscopic, they sometimes grow larger than 10 mm, in which case neurologists consider them macroadenomas. Pituitary adenomas of that size may exert pressure on surrounding structures (Fig. 19-4). Their upward pressure on the diaphragm sellae usually causes bitemporal and generalized headache. Compressing the optic chiasm, which is above the diaphragm, causes the visual field deficits. Initially they cause bitemporal superior quadrantanopia and, with further enlargement, bitemporal hemianopsia (see Fig. 12-9).

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FIGURE 19-4 Pituitary adenomas grow laterally and inferiorly against the walls of the sella turcica and upward against the diaphragm sellae. Large adenomas compress the optic chiasm, which causes a distinctive bitemporal hemianopsia or bitemporal superior quadrantanopia (see Fig. 12-9).

MRI reveals almost all pituitary adenomas. Serum prolactin level determination usually shows elevations with prolactinomas and some chromophobe adenomas. Visual field testing helps detect those that have expanded out of the sella. Treatment varies with tumor type and size, presence of visual deficit, and institutional expertise, but the usual options include radiation, transsphenoidal microsurgery, and, with prolactin-secreting tumors, a dopamine agonist, such as bromocriptine or cabergoline. As in a previous caveat, treating large tumors with radiation or craniotomy risks causing panhypopituitarism and, from temporal lobe damage, memory impairment and seizures.

Less commonly occurring pituitary growths secrete growth hormone, which can cause acromegaly, or adrenocorticotropin hormone, which can lead to Cushing syndrome. In addition to disfiguring patients, these tumors may cause endocrine changes that produce depression and, rarely, psychosis. These tumors usually remain as collections of hyperplastic cells rather than forming adenoma-like masses that encroach on the optic chiasm or cause headache.

In contrast to these relatively benign pituitary lesions, craniopharyngiomas are large, calcified, cystic, congenital lesion derived from Rathke’s pouch that arise in children as well as in adults. Unlike pituitary adenomas, craniopharyngiomas grow within the hypothalamus, which is located above the diaphragm sellae (see Fig. 19-4). Because craniopharyngiomas cause endocrine deficiency, affected children routinely have delayed or incomplete physical, sexual, and mental maturation; adults tend to have impaired libido, amenorrhea, and apathy; and both children and adults develop diabetes insipidus. When craniopharyngiomas press downward on the optic chiasm, the pressure causes optic atrophy and, as with pituitary tumors, bitemporal hemianopsia. If the tumors completely compress the third ventricle, the obstructive hydrocephalus that ensues leads to papilledema with headache, nausea, and vomiting – classic signs of increased intracranial pressure. Removing them frequently requires extensive surgery and radiotherapy.

Postpartum pituitary necrosis, widely known as Sheehan syndrome, also causes pituitary insufficiency. Although radiotherapy and several other conditions might cause pituitary infarction, Sheehan syndrome typically results from obstetric deliveries complicated by massive blood loss. In overt cases of Sheehan syndrome, postpartum women fail to lactate, remain hypotensive, lose weight, and undergo regression of secondary sexual characteristics. In subtle cases, which are more common, several months to several years after delivering, women have only scant menses, diminished libido, and constant weakness. Physicians may misinterpret their symptoms as postpartum depression or chronic fatigue syndrome.

Acoustic Neuromas

If the cells covering the acoustic (eighth cranial) nerve proliferate, they form a distinctive tumor – the acoustic neuroma or schwannoma. (The term “acoustic neuroma,” however, consists of an inaccuracy because Schwann cells, not neurons, proliferate.) Growing from the vestibular division of the acoustic nerve, schwannomas usually arise between the internal auditory canal and cerebellopontine angle where they may compress adjacent structures, particularly the fifth (trigeminal) and seventh (facial) cranial nerve, as well as damage the eight nerve. Although relatively benign, these tumors cause hearing impairment with predominant loss of speech discrimination and tinnitus. Although they may arise from the vestibular division of the nerve, these tumors rarely cause imbalance or vertigo. If acoustic neuromas grow to compress the fifth cranial nerve, patients experience sensory symptoms in their face, ranging from tingling to trigeminal neuralgia-like pain. If these tumors compress the seventh cranial nerve, patients lose facial muscle strength.

Most acoustic neuromas grow unilaterally and spontaneously. Bilateral acoustic neuromas, in contrast, characteristically are a manifestation of neurofibromatosis-type 2 (NF2), an autosomal dominant disorder of chromosome 22 (see Chapter 13). Gadolinium-enhanced MRI (see Fig. 20-27), auditory tests, and brainstem auditory-evoked responses (see Chapter 15) detect acoustic neuromas. Stereotactic radiosurgery with a gamma knife or linear accelerator treatments can remove acoustic neuromas while preserving most, if not all, hearing and facial strength.

Spine Metastases

Lung, breast, and other cancers often metastasize to the vertebrae and then grow into the spinal epidural space (Fig. 19-5). Epidural metastases characteristically cause severe pain not only in the affected region (local pain) but also along the path of the affected nerve roots (radicular pain). For example, patients with thoracic spine metastases typically have interscapular spine pain that radiates around the chest in a band-like pattern. Similarly, patients with lumbar spine metastases suffer from lower back pain that, unlike simple musculosketal pain, radiates down the legs.

image

FIGURE 19-5 Left, Vertebral metastases typically grow posteriorly to encroach on the spinal epidural space (arrows). Epidural metastases in the cervical and thoracic regions may cause spinal cord compression, which results in paraplegia or quadriplegia, loss of sensation (hypalgesia) below the level of the lesion, and incontinence. Epidural metastases in the lumbar region may compress the cauda equina (see Fig. 5-11). Right, Patients have “local pain” from destruction of the vertebrae and band-like “radiating pain,” which follows the course of the nerves (jagged arrows). The location of the pain and level of the hypalgesia indicate the site of an epidural metastatic tumor (see Fig. 2-15).

If cervical or thoracic epidural metastases grow large enough, they compress the spinal cord. Metastatic spinal cord compression causes not only local and radicular pain, but also quadriplegia or paraplegia, loss of sensation below the lesion, and urinary and fecal incontinence (see Chapters 2 and 16). In addition, although patients typically retain their cognitive capacity, their pain, physical incapacity, and undeniable progression of their illness often lead to depression.

Early diagnosis and treatment may prevent paraplegia; however, once this dreaded complication sets in, patients almost never regain their ability to walk. Neurologists usually rely on an MRI to confirm a clinical impression. Therapy usually consists of steroids, radiation, and, sometimes, decompressive laminectomy.

Other Causes of Limb Weakness in Cancer Patients

Certain cancers trigger paraneoplastic inflammatory conditions that affect the PNS solely, such as LEMS. In addition, lung, breast, ovarian, gastric, and other solid tumors provoke dermatomyositis, which consists of diffuse, proximal muscle weakness, muscle tenderness, and a heliotrope rash on the face and extensor skin surfaces.

Sometimes weakness is iatrogenic. For example, prolonged use of steroids, whether as a medication or an illicit bodybuilding supplement, may result in steroid myopathy or collapse of a hip or vertebrae. Similarly, long-term use of diuretics without potassium supplements results in hypokalemic myopathy. Various chemotherapy agents, such as vincristine, cause polyneuropathy that often includes a disturbing sensory component (see Chapter 5).

In contrast to the generalized weakness of these polyneuropathies, cancer-induced injuries of individual peripheral nerves, mononeuropathies, cause paresis and sensory loss limited to the distribution of those nerves (see Table 5-1). With cancer-induced loss of muscle bulk and subcutaneous fat, mild to moderate pressure – even the patient’s own weight – compresses peripheral nerves deprived of their protective cushions. Compression injuries most often damage the sciatic, peroneal, and radial nerves when bedridden patients remain in one position in bed or secured in a wheelchair for prolonged periods, or are pulled on to stretchers. Sometimes misplaced injections or other accidents injure these nerves.

When lung and breast cancer invades the nearby brachial plexus or pelvic cancer invades the neighboring lumbosacral plexus, patients suffer excruciating pain as well as paresis. Because tumor cells have actually invaded the nerves, routine treatments, such as radiotherapy and opioids, will provide only limited analgesia. Physicians must prescribe treatments for neuropathic pain (see Chapter 14).

Disorders That Resemble Brain Tumors

Strokes, as well as tumors, occur predominantly in older people and cause physical deficits, seizures, and cognitive impairment. Nevertheless, the course, many symptoms, and results of imaging studies of strokes and tumors differ so much that, in the final analysis, physicians almost always arrive at the correct diagnosis.

Subdural hematomas also occur frequently and mimic brain tumors. Head trauma is the most common cause of intracranial bleeding in the potential space between the dura (the thick layer of the meninges) and the underlying brain – the subdural space (see Figs 19-1, D and 20-9). Because subdural bleeding originates from veins, its pressure is low and volume relatively small. After the bleeding forms a hematoma, it accumulates fluid and enlarges. During subsequent weeks, subdural hematomas exert an increasingly greater mass effect that presses broadly against one or both cerebral hemispheres. Subdural hematomas produce headaches, confusion, personality change, dementia, and other nonspecific symptoms of generalized cerebral dysfunction – much more than lateralized signs.

For several reasons, older individuals are especially vulnerable to subdural hematomas. They tend to fall and suffer head injury. They often take aspirin or other medicines that have an anticoagulant effect. Once intracranial bleeding starts, it continues unchecked because an atrophied brain cannot compress the bleeding vessels. Also, because subdural hematomas typically produce insidious nonspecific symptoms and signs, rather than lateralized ones, the patient and family may fail to appreciate the significance of headaches and nonspecific symptoms.

Neurosurgeons may easily evacuate subdural hematomas, but frequently a conservative approach suffices. Prompt diagnosis and treatment usually restore cerebral function. In other words, subdural hematomas represent a correctable form of dementia.

Arteriovenous malformations (AVMs) – a potential source of headaches and seizures, as well as intracerebral hemorrhage – consist of congenital vascular anomalies of large veins and arteries directly joined without the normal intervening capillary bed. Although a neurosurgeon might be able to resect the AVM, the surgery generally requires removal of the normal surrounding brain. Interventional neuroradiologists may obliterate the malformation by infusing epoxies or solid particles. If that procedure only shrinks the AVM, it will still be more amenable to neurosurgical resection.

Because intracranial bleeding is common and an emergency situation, physicians should know the causes and implication of bleeding into the different intracranial regions: Venous bleeding, usually under low pressure, generally accumulates in the subdural space. Head-trauma-induced arterial bleeding, which is under high pressure, collects in the epidural space. Rupture of a berry aneurysm, which is also under high pressure, leads to bleeding in the subarachnoid space. Uncontrolled hypertension or cocaine use may lead to bleeding in the basal ganglia, thalamus, pons, or cerebellum. AVMs may bleed into any part of the brain.

Bacterial abscesses usually result from sepsis originating in intravenous drug abuse, dental procedures, sinusitis, endocarditis, or immunodeficiency. They typically present with signs of a cerebral mass lesion rather than a systemic infection. In their clinical appearance and imaging studies, abscesses resemble brain tumors (see Fig. 20-15).

Although bacteria are the infecting organisms in most abscesses, toxoplasmosis is usually responsible in patients with AIDS. Cerebral toxoplasmosis differs from ordinary bacterial abscesses in that it occurs in multiple sites, but concentrates in the basal ganglia. Thus, unlike almost all other mass lesions, toxoplasmosis routinely presents with chorea, hemiballismus, or other involuntary movement disorder.

Patients with neurocysticercosis, the neurologic component of cysticercosis, usually have multiple intracerebral cysts that have originated from a gastrointestinal tapeworm (Taenia solium) infestation. Although each cyst may be small, their total number occupies a considerable space. They also tend to block CSF flow and thus cause obstructive hydrocephalus. Moreover, as they die, their fluid contents leak and provoke an inflammatory response in the surrounding brain. This irritation, as well as their mass effect, often causes seizures. Thus, patients with neurocysticercosis may present with dementia, symptoms and signs of increased intracranial pressure, or, most often, seizures. Almost all patients show cognitive impairment and about 13%, dementia. Because cysticercosis is endemic in Central and South America and the Indian subcontinent, immigrants from these regions often harbor neurocysticercosis. CT and MRI readily detect the cysts (see Fig. 20-12). Whatever the antibiotic regimen, neurologists almost always add AEDs.

Tuberculosis causes intracerebral masses, tuberculomas, particularly in AIDS patients and citizens of the Indian subcontinent. CT and MRI can also detect tuberculomas, even when the clinical evaluation does not suggest the diagnosis.

As another disorder that mimics brain tumor, idiopathic intracranial hypertension (pseudotumor cerebri) produces headache, papilledema, and, in severe cases, sixth cranial nerve palsies; however, it does not affect cognitive capacity or produce seizures (see before and Chapter 9).

References

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Darnell RB, Posner JB. Paraneoplastic syndromes involving the nervous system. N Engl J Med. 2003;349:1543–1554.

DeAndrade DC, Rodrigues CI, Abraham R. Cognitive impairment and dementia in neurocysticercosis. Neurology. 2010;74:1288–1295.

Duffner PK. Long-term effects of radiation therapy on cognitive and endocrine function in children with leukemia and brain tumors. Neurology. 2004;10:293–310.

Kayser MS, Kohler CG, Dalmau J. Psychiatric manifestations of paraneoplastic disorders. Am J Psychiatry. 2010;16667:1039.

Litofsky NS, Farace E, Anderson F, et al. Depression in patients with high-grade glioma: Results of the Glioma Outcomes Project. Neurosurgery. 2004;54:358–366.

Morris B, Partap S, Yeom K, et al. Cerebrovascular disease in childhood cancer survivors. Neurology. 2009;73:1906–1913.

Pelletier G, Verhoef MJ, Khatri N, et al. Quality of life in brain tumor patients: The relative contributions of depression, fatigue, emotional distress, and existential issues. J Neurooncol. 2002;57:41–49.

Ross L, Johansen C, Dalton SO, et al. Psychiatric hospitalization among survivors of cancer in childhood or adolescence. N Engl J Med. 2003;349:650–657.

Safdieh JE, Mead PA, Sepkowitz KA, et al. Bacterial and fungal meningitis in patients with cancer. Neurology. 2008;70:943–947.

Tess AV, Smetna GW. Medical evaluation of patients undergoing electroconvulsive therapy. N Engl J Med. 2009;360:1437–1444.

Torres IJ, Mundt AJ, Sweeney PJ, et al. A longitudinal neuropsychological study of partial brain radiation in adults with brain tumors. Neurology. 2003;60:1113–1118.

Zaidat OO, Ruff RL. Treatment of spinal epidural metastasis improves patient survival and functional state. Neurology. 2002;58:1360–1366.

Chapter 19Questions and Answers

1. After having 2 weeks of progressively greater difficulty with playing soccer and paying attention in school, a 7-year-old boy develops a severe headache, nausea, and vomiting. His examination shows papilledema and ataxia. Of the following, which is the most likely cause?

a. Migraine
b. Pseudotumor cerebri
c. Glioblastoma
d. Astrocytoma of the cerebellum

Answer:

d. The combination of headache, nausea, vomiting, and, most significantly, papilledema suggests hydrocephalus. The preceding ataxia, indicated by his diminished athletic ability, suggests that the problem originated in the cerebellum. Most likely, a cerebellar astrocytoma grew large enough to block cerebrospinal fluid (CSF) flow through the fourth ventricle, causing obstructive hydrocephalus. Among children with brain tumors, cerebellar astrocytomas occur frequently. Although basilar migraine attacks can cause nausea, vomiting, and ataxia, they do not last for 6 weeks or cause papilledema. Pseudotumor cerebri is a condition almost exclusively of young women. Glioblastomas develop almost only in older adults. A traumatic subdural hematoma, from an athletic injury or conceivably child abuse, is a credible explanation for the child’s symptoms and signs.

2. A primary care physician referred a 60-year-old construction worker for evaluation of episodes of impaired consciousness lasting 1–3 minutes. During them, the patient mutters nonsensically and makes kissing movements. He has diabetes and hypertension, and has smoked two packs of cigarettes daily since enlisting in the Navy at 17 years. A neurologist finds that the patient has a left superior quadrantanopia, right dysmetria, and right intention tremor. Electroencephalographic (EEG) monitoring confirms that the episodes represent partial complex seizures originating from the right temporal lobe. Of the following conditions, which is the most likely illness?

a. Subdural hematomas
b. Metastatic carcinoma in the right temporal lobe and right cerebellar hemisphere
c. Glioblastoma of the left temporal lobe
d. Strokes in the right temporal lobe and right cerebellar hemisphere
e. Multiple sclerosis (MS)

Answer:

b. Although neurologists try to attribute all of a patient’s symptoms and signs to a single location, this patient’s symptoms and signs require separate explanations. The seizures and superior quadrantanopsia are attributable to the right temporal lobe. The right-sided dysmetria and intention tremor are attributable to the right cerebellum. These multiple lesions are probably manifestations of metastatic cancer, but alternative explanations include multiple embolic strokes and abscesses. Strokes may cause mild, transient headaches. While subdural hematomas often occur over both cerebral hemispheres, they rarely cause seizures or occur in the posterior fossa. He is too old to have developed MS. Moreover, headaches and seizures are not initial symptoms of MS.

3. Which of the following patients is most likely to develop cerebral gliomas?

a. A 30-year-old woman with multiple café-au-lait spots
b. A 21-year-old woman with bilateral acoustic neuromas
c. A 21-year-old man with mental retardation, epilepsy, and adenoma sebaceum
d. A 30-year-old man with a vascular malformation in the distribution of the trigeminal nerve

Answer:

c. The patient with the mental retardation, epilepsy, and adenoma sebaceum has tuberous sclerosis. The cerebral tubers, which are a component of this illness, often undergo malignant transformation into gliomas. The woman with the café-au-lait spots has neurofibromatosis type 1 (NF1), which is often complicated by meningiomas, as well as neuromas of peripheral nerves. The woman with the acoustic neuromas probably has neurofibromatosis type 2 (NF2). The man with the vascular malformation has Sturge–Weber syndrome, which is not associated with neoplasms.

4. A 50-year-old woman has an impaired ability to hear when she places her telephone receiver against her right ear. She also has right-sided tinnitus and loss of auditory acuity. Her neurologic examination is otherwise normal. Of the following, which one is the most likely illness?

a. Left temporal lobe meningioma
b. Psychogenic factors
c. MS
d. A cerebellopontine angle tumor

Answer:

d. Acoustic neuroma, the most common cerebellopontine angle tumor, typically causes speech discrimination impairment, tinnitus, and the gradual loss of auditory acuity. Because acoustic neuromas develop slowly, they do not cause vertigo. Lesions of the cerebral hemispheres or the brainstem, including MS plaques, do not cause auditory disturbances. As discussed in the previous case, bilateral acoustic neuromas are a typical manifestation of NF2.

5. During the previous 2 years, a 55-year-old woman with multiple café-au-lait spots developed slowly increasing severe paresis of the left leg, which had hyperactive deep tendon reflexes (DTRs) and a Babinski sign. Before undergoing further evaluation, she had a seizure that began with clonic movements of the left foot, then leg, and finally the arm. On examination, she has left hemiparesis, hyperactive DTRs, and a Babinski sign. Of the following, which is the most likely illness?

a. Right cerebral glioblastoma
b. Right cerebral meningioma
c. Left cerebral glioblastoma
d. Left cerebral meningioma

Answer:

b. The evolution of a hemiparesis over a relatively long time, especially when it is accompanied by a partial (motor) seizure, suggests a cerebral tumor. A meningioma is more likely than a glioblastoma in view of the chronicity of the hemiparesis and her probably having NF1. Moreover, meningiomas are more common in women than men.

6. Which of the following is least likely to cause headaches in the elderly?

a. Subdural hematoma
b. Open-angle glaucoma
c. Brain tumors
d. Temporal arteritis
e. Nitroglycerin and other vasodilator medications

Answer:

b. Open-angle glaucoma is not associated with headaches. The other conditions often cause headaches in the elderly. In addition, headache may be a symptom of depression and other psychiatric disorder.

7. Brain tumors often produce headaches that are worse in the early morning, waking patients from sleep. Which four of the following headaches also typically begin in the early morning?

a. Muscle contraction tension
b. Pseudotumor cerebri
c. Migraine
d. Trigeminal neuralgia
e. Postconcussive syndrome
f. Cluster headache
g. Sleep apnea-induced headache
h. Caffeine withdrawal

Answer:

c, f, g, h. Migraine and cluster headaches characteristically develop during rapid eye movement sleep, which occurs predominantly in the early morning. Hypoxia and carbon dioxide retention also cause headache.

8. An obese 22-year-old woman has moderately severe, generalized headaches. She has papilledema and paresis of abduction of her right eye but no other neurologic abnormalities. Routine blood and chemistry tests are normal. Computed tomography (CT) shows small ventricles but no mass lesion. What would be the most appropriate next step?

a. Magnetic resonance imaging (MRI)
b. EEG
c. Lumbar puncture (LP) to measure the opening pressure and withdraw CSF
d. None of the above

Answer:

c. The patient almost certainly has pseudotumor cerebri, which is technically known as idiopathic intracranial hypertension. The increased intracranial pressure stretches the sixth nerve and immobilizes the abducens muscle. Because the sixth nerve problem does not reflect a mass lesion, neurologists often call it a “false localizing sign.” Given the clinical picture and normal CT, MRI is not necessary. Instead, physicians should perform an LP to diagnose pseudotumor cerebri and exclude the unlikely possibility of chronic meningitis. In pseudotumor, the CSF pressure is usually above 300 mm H2O, which is a marked elevation. Chronic papilledema, from this or any other condition, will lead to optic atrophy and then blindness. Pseudotumor is one of the rare situations where an LP is performed despite papilledema or suspicion of increased intracranial pressure.

9. A 45-year-old police officer, suffering from alcohol abuse and personality disturbances, has become obsessed with the idea that he has a brain tumor. Careful medical and neurologic examinations are normal. What would most neurologists do next?

a. Offer reassurance
b. Suggest psychotherapy
c. Give an antidepressant
d. Treat him for obsession
e. Order an MRI

Answer:

e. Even though brain tumors are rare in middle-aged people with a normal neurologic examination, especially when psychiatric disturbances can explain the symptom, most neurologists would order an MRI or CT for several reasons. At the onset, about 50% of patients with tumors have no overt physical neurologic deficits. Other structural lesions, such as an arteriovenous malformation or subdural hematoma, could be responsible for the patient’s symptoms. Furthermore, with a normal study, a neurologist can give more secure reassurance, feel protected in the event of a medicolegal problem, and refer the patient to a psychiatrist who, in turn, will probably feel more confident in accepting the patient.

10. A psychiatrist was asked to consult on a 60-year-old retired sanitation truck driver with lung cancer who developed confusion, disorientation, and agitation during his second week of hospitalization. He resisted a full neurologic examination, but a neurologist determined that he had no hemiparesis, papilledema, or nuchal rigidity. A noncontrast head CT was normal. The psychiatrist diagnosed delirium. Which one of the following is its least likely cause?

a. Hyperkalemia
b. Pneumonia
c. Liver metastases with hepatic encephalopathy
d. Withdrawal from alcohol or other substance
e. Inappropriate antidiuretic hormone secretion
f. Hypercalcemia
g. Liver metastases with slowed metabolism of medications

Answer:

a. The psychiatrist was correct: The patient has delirium. However, that diagnosis requires the physicians to determine its cause. Numerous conditions may cause delirium in cancer patients. The normal neurologic examination, although rudimentary, and normal noncontrast head CT indicate that he does not have cerebral metastases. Except for hyperkalemia, the other disorders frequently complicate lung cancer, even when it has not spread to the brain, and cause delirium. In addition, hospitalization of individuals who abuse alcohol or other substances may lead to withdrawal symptoms that can reach the point of delirium.

11. In the above case (Question 10), further testing discovered pneumonia. After a course of antibiotics, his delirium resolved. One month later, his delirium recurred and was more dangerous than the previous time. A CT revealed two ring-shaped lesions with surrounding edema in his cerebral hemispheres. An extensive evaluation found no other potential explanation. His primary care team solicited a psychiatry consultation. Which medication regimen should the psychiatrist recommend?

a. A major neuroleptic and steroids
b. A minor tranquilizer and steroids
c. Steroids
d. Hypnotics
e. An antiepileptic drug

Answer:

a. In this situation, a small dose of a neuroleptic will reduce the patient’s behavioral disturbances and reduce the risk of harm. Because steroids, such as dexamethasone, will reduce the edema and thus the volume of the lesions, they will bring about a rapid and dramatic, although temporary, improvement by reducing the size of the lesions.

12. A 65-year-old woman with the onset of dementia over 9 months has no physical or neurologic abnormalities except for frontal release signs and hyperactive DTRs. A complete laboratory and EEG evaluation reveals no specific abnormality. A CT shows atrophy and a small meningioma in the right parietal convexity. Which would be the most appropriate next step?

a. Have the tumor removed.
b. Tentatively diagnose Alzheimer disease and repeat the clinical evaluation and CT in 6–12 months.
c. Obtain an MRI.

Answer:

b. Her meningioma is irrelevant to her dementia. Meningiomas grow so slowly that they can be followed by periodic clinical examinations and scans. However, if meningiomas grow large enough to compress brain tissue or cause symptoms, neurosurgeons can remove them. Because a meningioma has a paucity of water and a great deal of calcium, MRIs help less than CTs in confirming that an intracranial lesion is a meningioma and in following its course.

13. A 75-year-old man, who has had dementia for 6 years, suddenly develops increased irritability and behavioral disturbances. He has no lateralized signs or indication of increased intracranial pressure. He is treated with a major tranquilizer. One week later, he becomes somnolent and has a seizure. He remains comatose with a left hemiparesis. No abnormalities are found on a general medical examination or routine laboratory tests, but a CT shows an extra-axial curved lucency and a shift of midline cerebral structures. Before any treatment can be instituted, the patient dies. An autopsy discloses cerebral atrophy and a large chronic subdural hematoma. Which of the following statements concerning subdural hematomas is false?

a. Subdural hematomas are apt to occur in the elderly, especially in those individuals who have a history of dementia and cerebral atrophy.
b. Subdural hematomas are usually located outside or overlying the brain, i.e., extra-axial.
c. Unless they are large or rapidly expanding, subdural hematomas may not cause lateralized signs or greatly raise intracranial pressure.
d. In chronic subdurals, CT portrays aged blood as less radiodense than brain, and in acute subdurals, fresh blood as more radiodense than brain. In other words, chronic hematomas are black (radiolucent) and fresh ones are white (radiodense). With acute bleeding into chronic subdurals, densities appear within lucent regions.
e. The trauma required to cause a subdural hematoma is usually so great that it causes loss of consciousness for 1 hour or longer.

Answer:

e. The elderly are more susceptible than young adults to developing subdurals for several reasons. Minimal or no trauma tears apart the delicate bridging veins of their meninges. With cerebral atrophy, the cerebral cortex cannot dampen overlying bleeding. The elderly often take aspirin, warfarin, or other medicines that impede clotting. Finally, elder abuse may cause the head trauma.

14. Which structure is not located in the posterior fossa?

a. Sphenoid wing
b. Chemoreceptors for vomiting
c. Vertebrobasilar artery system
d. Cerebellum
e. Fourth ventricle

Answer:

a.

15. Match the brain lesion (1–6) with the group(s) with the greatest risk (a–h).

1. Chronic subdural hematoma
2. Cerebellar astrocytoma
3. Cerebral lymphomas
4. Neurocysticercosis
5. Tuberculomas
6. Acoustic neuromas
a. Elderly individuals
b. Children
c. Residents of Central America
d. Residents of the Indian subcontinent
e. NF1
f. NF2
g. Trisomy 21
h. Acquired immunodeficiency syndrome (AIDS) patients

Answer:

1-a; 2-b; 3-h; 4-c; 5-d; 6-f.

16. Which one of the following does not usually indicate a pituitary adenoma?

a. Increased serum prolactin level
b. Cognitive impairment
c. Galactorrhea
d. Bitemporal hemianopsia
e. Decreased libido
f. Menstrual irregularity
g. Headaches
h. Bitemporal superior quadrantanopia
i. Infertility

Answer:

b. Because pituitary tumors can grow upwards to compress the optic chiasm and hypothalamus, they lead to headaches, visual field impairments, and panhypopituitarism. Also, certain pituitary tumors secrete prolactin.

17. Which of the following pituitary conditions is most likely to emerge in a 12-year-old child and delay growth, puberty, and social maturity?

a. Chromophobe adenoma
b. Prolactinoma
c. Cushing syndrome
d. Craniopharyngioma

Answer:

d. Unlike other pituitary region tumors, craniopharyngiomas are congenital lesions that produce symptoms in children and adults. These tumors are typically cystic and located in the hypothalamic region. Because of their high calcium content, skull X-rays as well as CT readily identify them. In children, craniopharyngiomas cause delayed puberty and poor school performance. When craniopharyngiomas are large, they cause visual impairments characteristic of pituitary tumors (e.g., bitemporal hemianopsia or superior quadrantanopia) and optic atrophy. They may also cause diabetes insipidus if they grow into the hypothalamus and obstructive hydrocephalus if they grow to occlude outflow from the third ventricle.

18. Of the following statements regarding paraneoplastic syndromes, which is true?

a. They only appear after the underlying cancer has metastasized.
b. They are only associated with small cell carcinoma of the lung and gynecologic cancers.
c. Immunosuppression often relieves the symptoms.
d. Neurologic paraneoplastic syndromes, such as Lambert–Eaton syndrome, cerebellar degeneration, and limbic encephalitis, result from antibodies directed against cell surface antigens.

Answer:

c. Immunosuppression, as well as chemotherapy, radiation, and other cancer treatments, frequently relieves paraneoplastic syndromes. If the underlying cancer is cured, they may completely remit. Paraneoplastic syndromes often appear weeks to months before a cancer is detectable and are associated with a wide variety of malignancies. Antineuronal antibodies probably cause Lambert–Eaton syndrome, cerebellar degeneration, and limbic encephalitis.

19. A 65-year-old man with metastatic prostate carcinoma has been in agony from bone metastases. He is agitated, verbose, and threatening in his demands for morphine. His behavior has become a major management problem, and his family is also becoming disruptive. CT, MRI, and blood tests have shown that the patient has no cerebral metastases, infection, hypercalcemia, or other metabolic aberrations. Which two recommendations should a psychiatry consultant make in response to this situation?

a. Help the primary physicians control the patient’s pain with as much narcotic (opioid medication) as he requires. Once the pain is controlled, the situation can be reassessed.
b. Stop all medications because they may be the cause of the behavioral disorder.
c. Immediately administer minor or major tranquilizers.
d. Before treating further, check with an MRI and LP for signs of cerebral metastases or opportunistic infections.

Answer:

a and possibly c. Prostatic cancer rarely spreads to the brain, but it commonly spreads to bone where metastases cause agonizing pain. However, hormone manipulation, radiotherapy, and opioids can partly or fully control the pain. If medicines do not adequately alleviate it, drug-seeking behavior will persist. Long-acting opioids, such as methadone, and ones delivered by patch or continuous intravenous infusion are particularly effective. Breakthrough pain may be alleviated by rescue doses of parenteral opioids, such as morphine. Judicious use of antidepressants, antiepileptic drugs, and tranquilizers may provide additional analgesia, mood improvement, and restful sleep.

20. What mechanism has been proposed to explain limbic encephalitis and other paraneoplastic syndromes?

a. Antibody formation
b. Viral infection
c. Endocrine disturbance
d. Toxins secreted by the tumor

Answer:

a. The etiology of paraneoplastic cerebellar degeneration, limbic encephalitis, and other paraneoplastic syndromes has been attributed to antibodies that react with neurons, i.e., antineuronal antibodies.

21. Which three lesions tend to arise in the extra-axial space?

a. Butterfly gliomas
b. Astrocytomas
c. Meningiomas
d. Epidural hematomas
e. Subdural hematomas
f. Medulloblastomas

Answer:

c, d, e.

22. Which two of the following are not functions of glial cells?

a. To provide structure for the spinal cord
b. To provide structure for the brain
c. To clear debris from infections and cerebrovascular accidents
d. To generate a myelin coat for central nervous system (CNS) neurons
e. To generate a myelin coat for peripheral nervous system (PNS) neurons
f. To generate electrochemical potentials

Answer:

e, f. Glial cells, such as astrocytes, normally provide physical structure, a nutritional network, and response to inflammation and cell death. Schwann cells generate the myelin coat for PNS neurons. Neurons generate electrochemical potentials.

23. Which three are actions of oligodendrocytes?

a. Occasionally become oligodendrogliomas
b. Generate myelin for the CNS
c. Generate myelin for the PNS
d. Generate action potentials
e. Act as a glial cell

Answer:

a, b, e. Oligodendrocytes are also the target of the demyelinating process in MS.

24. In which three aspects do brain tumors in children differ from those in adults?

a. Childhood tumors more often develop in posterior fossa structures.
b. Childhood astrocytomas are usually resectable.
c. In children, tumors often present with signs of hydrocephalus.
d. Metastatic tumors in children are as common as primary brain tumors.
e. Meningiomas are relatively common in children.
f. Pituitary adenomas are relatively common in children.

Answer:

a, b, c. Childhood astrocytomas often develop in the cerebellum, block CSF flow through the fourth ventricle, and thus cause hydrocephalus. Neurosurgeons routinely resect them and affect a complete cure. Medulloblastomas, which develop in the medulla, are unresectable. They remain resistant to chemotherapy and radiotherapy.

25. Match the condition that causes weakness (1–5) with the impairment of acetylcholine (ACh) transmission at neuromuscular junctions (a–d).

1. Myasthenia gravis
2. Lambert–Eaton syndrome
3. Botulism
4. Guillain–Barré syndrome
5. Botulinum toxin
a. Impaired release of ACh quanta from presynaptic neurons
b. Abnormalities of the ACh receptor on postsynaptic neurons
c. Enhanced reuptake of ACh into the presynaptic neurons
d. None of the above

Answer:

1-b; 2-a; 3-a; 4-d; 5-a.

26. Which statement is false regarding the chemoreceptor area of the brain?

a. It is located in the superior surface of the medulla.
b. It is located in the area postrema.
c. It is unprotected by the blood–brain barrier.
d. The area is inaccessible to most chemicals.

Answer:

d. The chemoreceptor area of the brain is situated on the superior surface of the medulla. Because it is devoid of the blood–brain barrier, it is immediately exposed to blood-borne substances. Morphine, heroin, many chemotherapeutic agents, numerous toxins and, in large doses, L-dopa provoke vomiting as soon as they contact it.

27. Serum prolactin levels that are transiently elevated above the baseline are a useful diagnostic test for seizures. Which five of the following conditions or medicines elevate the baseline serum prolactin level?

a. Chromophobe adenoma
b. Prolactinoma
c. Phenothiazines
d. Butyrophenones
e. Estrogens
f. Bromocriptine
g. Dopamine
h. Quetiapine
i. L-dopa
j. Cabergoline

Answer:

a–e. Numerous medications and prolactinomas raise serum prolactin concentrations. Generalized and some partial seizures increase the serum prolactin concentration – at least temporarily. Bromocriptine, cabergoline, dopamine, and L-dopa, in contrast, reduce it.

28. Which two are complications of performing electroconvulsive therapy (ECT) on a patient with an undetected meningioma?

a. Skin necrosis
b. Status epilepticus
c. Transtentorial herniation
d. Exacerbating Parkinson disease

Answer:

b, c. With proper precautions, including obtaining either a CT or MRI, ECT carries few neurologic risks. Brain tumors are an important neurologic counterindication, although it may not be an absolute one. The importance of a brain tumor in respect to ECT is that it might be the cause of the depression or other indication for ECT, it might lead to status epilepticus, and, if large, a tumor may swell and cause transtentorial herniation.

29–31 Match the varieties of hemorrhage with the most likely cause.

29. Subarachnoid hemorrhage

30. Subdural hematoma

31. Epidural hematoma

a. Middle meningeal artery laceration
b. Rupture of a berry aneurysm
c. Trauma of bridging meningeal veins

Answers:

29-b. Although trauma and mycotic aneurysms may cause a subarachnoid hemorrhage, the most frequent and important cause is rupture of an aneurysm arising from one of the arteries that comprise the circle of Willis.

30-c. Bleeding from small meningeal veins is the usual cause of subdural hematomas.

31-a. Lacerations of the middle meningeal artery, which often result from a fracture of the temporal bone, are usually the cause of epidural hematomas.

32. A 46-year-old woman with metastatic breast cancer develops a disconcerting numbness in the skin over the right lower chin. She has no weakness of face or jaw muscles and the remainder of her neurologic examination is normal. However, X-rays of her jaw reveal a lytic lesion in the right lower mandible. What is the diagnosis?

a. Mental neuropathy
b. Mononeuritis multiplex
c. A remote effect of carcinoma
d. A facial nerve injury

Answer:

a. The mental nerve, a branch of the trigeminal nerve, provides sensation from the skin overlying the chin. Damage to this nerve, “mental neuropathy” – an unfortunate coincidence of words – causes numbness of the skin of one side of the chin, i.e., the “numb chin sign.” In this case, a metastasis to the jaw at the site where the mental nerve passes through its foramen has caused the mental neuropathy. Trauma to the same region of the jaw could also produce mental neuropathy.

33. A family brings a 59-year-old high-school basketball coach for psychiatric consultation because he has become apathetic and markedly forgetful, but intermittently he becomes loud and inexplicably angry. An examination confirms that he has amnesia and personality changes. One month before this consultation, his physicians diagnosed small cell carcinoma of the lung. An MRI with and without gadolinium infusion of the head and three LPs show normal CSF chemistries, absence of cells, and an opening pressure of 150 mmH2O. The results of all his blood tests are also within normal limits. However, an EEG shows focal slowing and spikes over the temporal lobes. Which is the most likely explanation for his memory deficit and other abnormalities?

a. A depressive disorder
b. An inflammatory condition affecting the temporal lobes
c. Temporal lobe metastases that have remained undetected by the MRI
d. Partial complex seizures

Answer:

b. He probably has limbic encephalitis, which is a paraneoplastic syndrome associated with small cell carcinoma of the lung and testicular carcinoma. Limbic encephalitis is characterized by memory impairment and personality changes, but it may also lead to generalized cognitive impairment and seizures. Without the underlying lung carcinoma, herpes simplex encephalitis would be a credible diagnosis.

34. Which of the following organs is most resistant to ionizing radiation?

a. Bone marrow
b. Brain
c. Gastrointestinal tract
d. Lung

Answer:

b. The brain and other regions of the CNS are relatively resistant to ionizing radiation; however, ionizing radiation, in large or sustained doses, may lead to radiation necrosis or, in the long term, development of brain tumors. On the other hand, evidence so far does not implicate cell phone use as a cause of brain tumors.

35. A 59-year-old active professor of English presents with a 3-week history of dulled affect, sleeplessness, and mild morning headaches. Aspirin relieves the headaches. Six years before, following the death of his mother, he had prolonged mourning. On examination, he scores 28 on the Mini-Mental State Examination (MMSE), but he is inattentive and reticent. He has psychomotor impersistence, but no lateralized neurologic deficit. An MRI reveals a single large ring-shaped mass lesion in the right frontal lobe that compresses the anterior horn of the lateral ventricle and shifts midline structures to the left. Which is the most likely nature of the lesion?

a. Glioblastoma
b. Meningioma
c. Bacterial abscess
d. None of the above

Answer:

a. The large ring-shaped mass lesion revealed by the MRI indicates that his symptoms and signs are attributable to a glioblastoma. The possible episode of depression 6 years before is too distant to be relevant. A meningioma is unlikely in view of the rapidity of his symptoms and the MRI shows an intra-axial lesion. Although the clinical and MRI features are consistent with a bacterial abscess, he has no systemic symptoms of one. Nevertheless, many neurologists would request a biopsy. If the lesion, such as this one, were situated in the nondominant frontal lobe, a generous excision would provide the patient with a definite diagnosis and additional months of life with reduction of his headaches and other symptoms.

36. Eight months after completing whole-brain radiotherapy for metastatic lung cancer, a 47-year-old former newspaper reporter suddenly developed aphasia and right-sided hemiparesis. Her MRI showed an acute infarction in the distribution of a branch of her left middle cerebral artery and small residual metastatic tumors in the right frontal lobe and left cerebellum. Which is the most likely cause of the stroke?

a. Another metastatic tumor
b. Chemotherapy
c. Atherosclerosis
d. Radiation arteritis or necrosis

Answer:

d. Radiotherapy damages intracerebral arteries as well as the malignant tumor’s cells. Because of radiation arteritis, patients sometimes sustain one or more small strokes that cause combinations of cognitive, personality, and motor impairments between 6 and 18 months after completion of the treatment. In a relatively young person, the history, MRI appearance, and routine tests usually distinguish this condition from other causes of stroke in this age group, such as use of cocaine, hypertension, cardiac valvular disease, atrial fibrillation, and blood dyscrasias.

37. Which of the following statements concerning depression comorbid with brain tumors is true?

a. Depression develops before surgery and subsides after tumor resection.
b. Depression rarely occurs in brain tumor patients.
c. Depression arises immediately after surgery and subsequently increases in severity.
d. The presence of comorbid depression does not affect the patient’s quality of life.

Answer:

c. In brain tumor patients, depression not only arises immediately after surgery, but increases in severity during the ensuing course. Along with physical debility, treatment-induced fatigue, cognitive impairments, and other emotional changes, depressive symptoms predict a poor quality of life.

38. The surgical service solicits a psychiatric consultation because the patient, a 79-year-old man, suddenly became “depressed.” The psychiatrist determines that he had been making an uneventful recovery for the preceding 3 weeks following resection of extensive colon cancer. When the psychiatrist examines the patient, she finds that he is intermittently lethargic and often inattentive. When she captures his attention, she finds that he is incompletely oriented and has a poor memory. Although his white count is elevated, he has no fever, asterixis, nuchal rigidity, papilledema, or lateralized neurologic findings. A head CT shows no abnormality. Which is most likely responsible for his change in mental state?

a. Toxic-metabolic encephalopathy
b. Paraneoplastic limbic encephalitis
c. Cerebral metastases
d. Major depression

Answer:

a. The patient probably has delirium from a toxic-metabolic encephalopathy, which has several potential explanations: sepsis, electrolyte imbalance, and metastases to the liver. Even minimal toxic-metabolic aberrations in elderly patients cause marked changes in their mood and level of consciousness. A potentially misleading aspect is that overwhelming sepsis sometimes fails to raise the white blood count. After his primary care physicians correct the encephalopathy and determine the extent of tumor spread, they can reconsult the psychiatrist to evaluate the patient for depression.

39. A family brings their 74-year-old patriarch, who owns a diner, to the neurologist because he began offending his customers and forgetting their orders. Although he rarely drinks alcohol, he has smoked two packs of cigarettes daily since he came to this country as a teenager. He takes no medications. He has lost 20 lb. His neurologic examination shows pronounced memory impairment, but no lateralized signs or papilledema. An MRI detected no mass lesions, but the medial temporal lobes are smaller than normal. Routine blood tests show mild anemia, but no other abnormality. An EEG contains temporal spikes. Which test should the neurologist now order?

a. CT of the head
b. CT of the chest
c. CSF analysis by a spinal tap
d. Brain biopsy

Answer:

b. A man with a more than a 100 pack-year history of smoking cigarettes and an unexplained 20 lb weight loss deserves a CT of the chest for investigation of lung cancer – no matter the particular symptoms. His amnesia, MRI, and EEG point to temporal lobe damage. Most likely he has developed limbic encephalitis as the presenting feature of a small cell carcinoma of the lung. In addition to ordering the chest CT, his physician should order a paraneoplastic encephalitis panel. In contrast, CSF analysis would probably not reveal useful information in this situation, except possibly for suggesting Creutzfeldt–Jakob disease (where it may detect 14-3-3 protein). Creutzfeldt–Jakob disease is a reasonable alternative diagnosis, but he has no myoclonus.

40. A 29-year-old intravenous drug addict, known to have AIDS, comes to the emergency room with uncontrollable involuntary, uncoordinated, large-scale jerky movements of his left arm and leg. He remains alert and free of headache. An MRI shows multiple small ring-enhancing lesions predominantly in the basal ganglia. Which is the most likely etiology of the cerebral lesions?

a. Cerebral abscesses
b. Neurocysticercosis
c. Multiple cerebral hemorrhages
d. Multiple strokes

Answer:

a. He probably has toxoplasmosis, which has a predilection for the basal ganglia. Unlike other cerebral mass lesions, toxoplasmosis causes movement disorders, including, as in this case, hemiballismus. A mass lesion tracking across the corpus callosum and infiltrating both frontal lobes, in a “butterfly” pattern, suggests a glioblastoma invading both frontal lobes. Multiple cerebral cortical cysts indicate neurocysticercosis, but AIDS patients are not particularly vulnerable to this CNS infection.

41. While resecting a cerebral seizure focus or tumor, neurosurgeons are naturally reluctant to excise “eloquent” cerebral cortex – areas of the cortex critical for physical or neuropsychological function. Which of the following is the most eloquent region of the brain?

a. The anterior section of the right frontal lobe
b. The posterior section of the left frontal lobe
c. The anterior section of the right occipital lobe
d. The posterior section of the left occipital lobe

Answer:

b. Broca’s area, one of the most eloquent areas of the brain, is situated in the posterior section of the left frontal lobe. The occipital lobes contain the visual cortex, which is important but not as critical as the language cortex. Almost the entire right frontal lobe, anterior to the motor strip, and the anterior tips of the temporal lobes are “silent” – devoid of readily recognizable cognitive, sensory, or motor function. Surgeons may remove these areas with little overt consequence, although neuropsychologic testing may show mood and personality change.

42. Which is the most frequently occurring complication of radiation leukoencephalopathy in adults?

a. Cognitive impairment
b. Psychosis
c. Convulsions
d. None of the above

Answer:

a. Sometimes immediately, but more frequently after a several-year interval, whole-brain radiotherapy causes cognitive and physical impairments because it induces leukoencephalopathy.

43. When administered to children, radiation therapy may prevent the spread of acute leukemia to the CNS or obliterate unresectable tumors. However, the treatment has many potential complications. Which of the following is false?

a. Young children, compared to young and middle-aged adults, are resistant to radiation-induced cognitive impairment.
b. In young children, radiation therapy may lead to mental retardation.
c. In children, radiation therapy may lead to panhypopituitarism.
d. In children, radiation therapy may lead to growth retardation.

Answer:

a. Compared to older individuals, young children are more vulnerable to radiation-induced cognitive impairment.

44. A close friend brings a 68-year-old retired nurse for psychiatric evaluation for depression. The patient explained she has lost her liveliness, energy, and interest in other people during the previous 3–6 months. However, she denies memory and other cognitive impairments, headaches, and systemic symptoms. On examination, she scores 28 on the MMSE and has no physical neurologic abnormalities, but she has psychomotor retardation, emotional dulling, and reduced capacity to execute complex mental tasks. During the examination and more so afterwards, she spoke excessively, loudly, and aggressively. With which two conditions is her clinical presentation most consistent?

a. Frontal lobe tumor
b. Alzheimer disease
c. Dementia with Lewy bodies disease
d. Frontotemporal dementia
e. Creutzfeldt–Jakob disease
f. Vascular dementia

Answer:

a, d. Her dulling of affect, loss of inhibition, and loquaciousness, with relatively normal memory and cognitive capacity, indicate frontal lobe dysfunction rather than simply dementia. Also, she has no physical abnormalities that would point to Creutzfeldt–Jakob diseases, dementia with Lewy bodies disease, or vascular cognitive impairment. MRI would distinguish a frontal lobe tumor from frontotemporal dementia.

45. Which electrolyte disturbance is most likely to complicate the course of a patient who presents with a previously undiagnosed, rapidly expanding metastatic brain tumor?

a. Hypernatremia
b. Hyponatremia
c. Hyperkalemia
d. Hypokalemia

Answer:

b. Patients who sustain intracranial catastrophes, such as major traumatic brain injury, subarachnoid hemorrhage, or sudden elevation in intracranial pressure from a rapidly growing brain tumor, typically develop the syndrome of inappropriate antidiuretic hormone (SIADH) secretion. SIADH essentially dilutes the electrolytes and lowers the serum osmolality. Hyponatremia, the most pronounced effect, may lead to delirium, because of the intracranial catastrophe, or seizures. Physicians must slowly correct hyponatremia because too rapid correction may lead to demyelination of the pons, i.e., central pontine myelinolysis.

46. Which of the following is the most commonly occurring brain tumor in middle-aged women?

a. Glioblastoma
b. Meningioma
c. Acoustic neuroma
d. Astrocytoma

Answer:

b. Small meningiomas are commonplace in middle-aged individuals. Because they grow slowly and remain asymptomatic, they pose no immediate threat. Small meningiomas do not cause psychiatric symptoms. Neurologists generally follow them rather than immediately recommend surgery.

47. With which condition is the JC virus associated?

a. Progressive multifocal leukoencephalopathy (PML)
b. Primary cerebral lymphoma
c. Glioblastoma
d. Meningioma

Answer:

a. The JC virus is closely and probably causally related to PML. When CSF studies detect evidence of JC virus, neurologists usually omit a cerebral biopsy in the diagnosis of PML.

48. With which condition is the Epstein–Barr virus associated?

a. PML
b. Primary cerebral lymphoma
c. Glioblastoma
d. Meningioma

Answer:

a. The Epstein–Barr virus is associated with primary cerebral lymphoma in AIDS patients. The association is close, but before instituting radiation therapy, neurologists often insist on a biopsy of the lesion.

49. Six months after delivering her third child, a 28-year-old woman seeks a psychiatric consultation for “depression.” She reports loss of interest in her husband and their children. She describes having little appetite or energy, sleeping poorly, and losing interest in sex. Her weight has fallen to below her pre-pregnancy level. Her menses initially returned, but were scant. Then, 2 months before the visit, her menses stopped. Two weeks before the psychiatric consultation, a neurologic evaluation showed no visual field or visual acuity deficits, or other abnormalities. A head MRI, with views of the sella, was normal. Routine blood tests were normal except that the serum prolactin level was slightly elevated. Which is the most likely diagnosis?

a. Major depression
b. Postpartum pituitary insufficiency
c. Prolactinoma
d. None of the above

Answer:

b. Except for not having an obstetric complication, such as hemorrhage, this patient has typical pituitary insufficiency. Her symptoms mimic, to a certain extent, postpartum depression. Thus, endocrinologic evaluation is generally indicated in women who seem to have postpartum depression. With all the potential medical explanations for her symptoms and lack of some criteria, major depression is not a tenable diagnosis. The modest prolactin elevation and lack of a visible abnormality on MRI speak against a prolactinoma. Despite the indications of pituitary insufficiency, the presence of amenorrhea and elevated prolactin level indicate that another pregnancy may have occurred. In any case, she should undergo testing for pregnancy and use of birth control before the psychiatrist prescribes an antidepressant or the endocrinologist prescribes hormone replacement.

50. During a week’s vacation, after a strenuous first semester of college, a 19-year-old woman developed involuntary right arm and leg movements and then unexplained anxiety. While undergoing a medical evaluation, she developed partial complex seizures. Aside from a temperature of 100.0°F, she had no general medical abnormalities. She was confused and disoriented, and had a poor memory, but she had no meningeal or lateralized findings. Her CSF showed 25 lymphocytes and a slightly elevated protein concentration, but no antibodies to herpes simplex virus or any common bacteria. Toxicology studies were consistently negative. A transvaginal ultrasound detected an ovarian lesion. Which is the most likely diagnosis?

a. Anti-N-methyl-D-aspartic acid (NMDA) receptor encephalitis
b. Herpes simplex virus encephalitis
c. Metastatic ovarian carcinoma
d. Voltage-gated potassium channel (VGKC) antibody encephalitis

Answer:

a. She has a syndrome of the rapid onset of involuntary movements, seizures, and encephalopathy with CSF lymphocytic pleocytosis. With the finding of an ovarian lesion in a young adult woman without evidence of an infection, anti-NMDA receptor encephalitis is the most likely diagnosis. Detecting serum and CSF anti-NMDA antibodies would confirm the diagnosis. Because of its neuropsychiatric features, with anti-NMDA receptor antibodies, patients are first apt to present to psychiatrists. VGKC antibody encephalitis may also cause neuropsychiatric symptoms that often have the quality and severity mimicking acute schizophrenia; however, VGKC antibody encephalitis is not associated with ovarian lesions.

51. In the previous case, which is the most likely ovarian pathology?

a. Ectopic pregnancy
b. Ovarian cancer
c. Teratoma
d. Cyst

Answer:

c. Teratomas often underlie anti-NMDA antibody encephalitis in young women. The association is almost close enough to merit its designation as a syndrome. When it is present, removing the teratoma typically reverses the condition.

*Schwann cells produce the myelin insulation for the peripheral nervous system (PNS).

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