Harrison's Principles of Internal Medicine 21st Edition Neurologic Disorders PDF

 21st Edition ® P R I N C I P L E S O F INTERNAL...

 21st Edition ® P R I N C I P L E S O F INTERNAL MEDICINE HPIM 21e_FM_VOL1_pi-pxl.indd 1 21/01/22 7:01 PM  Robert Lindsay, Blossom Samuels Irene Litvan, William W. Seeley, Bruce L. Miller xv 412 Paget’s Disease and Other Dysplasias of Bone............... 3209 435 Parkinson’s Disease....................................................... 3386 Rajesh K. Jain, Tamara J. Vokes C. Warren Olanow, Anthony H.V. Schapira 436 Tremor, Chorea, and Other Movement Disorders........... 3400 SECTION 5 Disorders of Intermediary Metabolism C. Warren Olanow, Christine Klein CONTENTS 413 Heritable Disorders of Connective Tissue...................... 3217 437 Amyotrophic Lateral Sclerosis and Other Motor Joan C. Marini, Fransiska Malfait Neuron Diseases........................................................... 3410 414 Hemochromatosis......................................................... 3230 Robert H. Brown, Jr. Lawrie W. Powell, David M. Frazer 438 Prion Diseases.............................................................. 3416 415 Wilson’s Disease........................................................... 3235 Stanley B. Prusiner, Michael Geschwind Stephen G. Kaler 439 Ataxic Disorders........................................................... 3422 416 The Porphyrias............................................................. 3237 Roger N. Rosenberg Robert J. Desnick, Manisha Balwani 440 Disorders of the Autonomic Nervous System................... 3427 417 Disorders of Purine and Pyrimidine Metabolism........... 3248 Richard J. Barohn, John W. Engstrom John N. Mecchella, Christopher M. Burns 441 Trigeminal Neuralgia, Bell’s Palsy, and Other 418 Lysosomal Storage Diseases.......................................... 3254 Cranial Nerve Disorders............................................... 3436 Robert J. Hopkin, Gregory A. Grabowski Vanja C. Douglas, Stephen L. Hauser 419 Glycogen Storage Diseases and Other Inherited 442 Diseases of the Spinal Cord........................................... 3445 Disorders of Carbohydrate Metabolism......................... 3261 Stephen L. Hauser Priya S. Kishnani 443 Concussion and Other Traumatic Brain Injuries............ 3456 420 Inherited Disorders of Amino Acid Metabolism Geoffrey T. Manley, Benjamin L. Brett, Michael McCrea in Adults....................................................................... 3268 444 Multiple Sclerosis......................................................... 3462 Nicola Longo Bruce A. C. Cree, Stephen L. Hauser 421 Inherited Defects of Membrane Transport.................... 3274 445 Neuromyelitis Optica.................................................... 3477 Nicola Longo Bruce A. C. Cree, Stephen L. Hauser PART 13 Neurologic Disorders SECTION 3 Nerve and Muscle Disorders 446 Peripheral Neuropathy.................................................. 3480 Anthony A. Amato, Richard J. Barohn SECTION 1 Diagnosis of Neurologic Disorders 447 Guillain-Barré Syndrome and Other 422 Approach to the Patient with Neurologic Disease.......... 3277 Immune-Mediated Neuropathies................................... 3501 Daniel H. Lowenstein, S. Andrew Josephson, Stephen L. Hauser Stephen L. Hauser, Anthony A. Amato 423 Neuroimaging in Neurologic Disorders......................... 3282 448 Myasthenia Gravis and Other Diseases of the William P. Dillon Neuromuscular Junction............................................... 3509 424 Pathobiology of Neurologic Diseases............................. 3293 Anthony A. Amato Stephen L. Hauser, Arnold R. Kriegstein, Stanley B. Prusiner 449 Muscular Dystrophies and Other Muscle Diseases........ 3516 Anthony A. Amato, Robert H. Brown, Jr. SECTION 2 Diseases of the Central Nervous System 425 Seizures and Epilepsy.................................................... 3305 SECTION 4 Myalgic Encephalomyelitis/Chronic Vikram R. Rao, Daniel H. Lowenstein Fatigue Syndrome 426 Introduction to Cerebrovascular Diseases...................... 3324 450 Myalgic Encephalomyelitis/Chronic Fatigue Wade S. Smith, S. Claiborne Johnston, J. Claude Hemphill, III Syndrome..................................................................... 3532 427 Ischemic Stroke............................................................ 3335 Elizabeth R. Unger, Jin-Mann S. Lin, Jeanne Bertolli Wade S. Smith, S. Claiborne Johnston, J. Claude Hemphill, III 428 Intracranial Hemorrhage............................................... 3348 SECTION 5 Psychiatric and Addiction Disorders Wade S. Smith, J. Claude Hemphill, III, S. Claiborne Johnston 451 Biology of Psychiatric Disorders.................................... 3534 429 Subarachnoid Hemorrhage........................................... 3353 Robert O. Messing, Eric J. Nestler, Matthew W. State J. Claude Hemphill, III,Wade S. Smith, Daryl R. Gress 452 Psychiatric Disorders.................................................... 3540 430 Migraine and Other Primary Headache Victor I. Reus Disorders...................................................................... 3357 453 Alcohol and Alcohol Use Disorders............................... 3556 Peter J. Goadsby Marc A. Schuckit 431 Alzheimer’s Disease...................................................... 3370 454 Nicotine Addiction....................................................... 3563 Gil D. Rabinovici, William W. Seeley, Bruce L. Miller David M. Burns 432 Frontotemporal Dementia............................................ 3378 455 Marijuana and Marijuana Use Disorders....................... 3567 William W. Seeley, Bruce L. Miller Nora D. Volkow, Aidan Hampson, Ruben Baler 433 Vascular Dementia........................................................ 3381 456 Opioid-Related Disorders............................................. 3569 Steven M. Greenberg, William W. Seeley Thomas R. Kosten, Colin N. Haile 434 Dementia with Lewy Bodies.......................................... 3385 457 Cocaine, Other Psychostimulants, and Hallucinogens............................................................... 3573 Karran A. Phillips, Wilson M. Compton HPIM 21e_FM_VOL1_pi-pxl.indd 15 21/01/22 7:01 PM  Neurologic Disorders PART 13 The first clues to defining the anatomic area of involvement appear Section 1 Diagnosis of Neurologic in the history, and the examination is then directed to confirm or rule Disorders out these impressions and to clarify uncertainties. A more detailed examination of a particular region of the CNS or PNS is often indi- cated. For example, the examination of a patient who presents with 422 with a history of ascending paresthesias and weakness should be directed Approach to the Patient toward deciding, among other things, if the lesion is in the spinal cord Neurologic Disease or peripheral nerves. Focal back pain, a spinal cord sensory level, and incontinence suggest a spinal cord origin, whereas a stocking-glove Daniel H. Lowenstein, S. Andrew pattern of sensory loss suggests peripheral nerve disease; areflexia usually indicates peripheral neuropathy but may also be present with Josephson, Stephen L. Hauser so-called spinal shock in acute spinal cord disorders. Deciding “where the lesion is” accomplishes the task of limiting the possible etiologies to a manageable, finite number. In addition, Neurologic diseases are common and costly. According to estimates this strategy safeguards against making serious errors. Symptoms of by the World Health Organization, neurologic disorders affect more recurrent vertigo, diplopia, and nystagmus should not trigger “multiple than 1 billion people worldwide, constitute 12% of the global bur- sclerosis” as an answer (etiology) but “brainstem” or “pons” (location); den of disease, and cause 14% of global deaths (Table 422-1). These then a diagnosis of brainstem arteriovenous malformation will not be numbers are only expected to increase as the world’s population ages. missed for lack of consideration. Similarly, the combination of optic Because therapies now exist for many neurologic disorders, a skill- neuritis and spastic ataxic paraparesis suggests optic nerve and spinal ful approach to diagnosis is essential. Errors commonly result from cord disease; multiple sclerosis (MS), CNS syphilis, and vitamin B12 an overreliance on costly neuroimaging procedures and laboratory deficiency are treatable disorders that can produce this syndrome. tests, which, while useful, do not substitute for an adequate history Once the question, “Where is the lesion?” is answered, then the ques- and examination. The proper approach begins with the patient and tion “What is the lesion?” can be addressed. focuses the clinical problem first in anatomic and then in patho- physiologic terms; only then should a specific neurologic diagnosis IDENTIFY THE PATHOPHYSIOLOGY be entertained. This method ensures that technology is judiciously Clues to the pathophysiology of the disease process may also be present applied, a correct diagnosis is established in an efficient manner, and in the history. Primary neuronal (gray matter) disorders often present as treatment is promptly initiated. early cognitive disturbances, movement disorders, or seizures, whereas white matter involvement produces “long tract” disorders of motor, THE NEUROLOGIC METHOD sensory, visual, and cerebellar pathways. Progressive and symmetric symptoms often have a metabolic or degenerative origin; in such cases DEFINE THE ANATOMY lesions are usually not sharply circumscribed. Thus, a patient with The first priority is to identify the region of the nervous system that is paraparesis and a clear spinal cord sensory level is unlikely to have likely to be responsible for the symptoms. Can the disorder be mapped vitamin B12 deficiency as the explanation. A Lhermitte symptom (electric to one specific location, is it multifocal, or is a diffuse process present? shock–like sensations evoked by neck flexion) is due to ectopic impulse Are the symptoms restricted to the nervous system, or do they arise in generation in white matter pathways and occurs with demyelination in the context of a systemic illness? Is the problem in the central nervous the cervical spinal cord; among many possible causes, this symptom may system (CNS), the peripheral nervous system (PNS), or both? In the indicate MS in a young adult or compressive cervical spondylosis in an CNS, is the cerebral cortex, basal ganglia, brainstem, cerebellum, or older person. Symptoms that worsen after exposure to heat or exercise spinal cord responsible? Are the pain-sensitive meninges involved? may indicate conduction block in demyelinated axons, as occurs in MS. In the PNS, could the disorder be located in peripheral nerves and, if A patient with recurrent episodes of diplopia and dysarthria associated so, are motor or sensory nerves primarily affected, or is a lesion in the with exercise or fatigue may have a disorder of neuromuscular transmis- neuromuscular junction or muscle more likely? sion such as myasthenia gravis. Slowly advancing visual scotoma with luminous edges, termed fortification spectra, indicates spreading cortical TABLE 422-1 Global Disability-Adjusted Life-Years (DALYs) and depression, typically with migraine. Number of Annual Deaths for Selected Neurologic Disorders in 2019 DISORDER DALYs DEATHS THE NEUROLOGIC HISTORY Low-back and neck pain 85,766,442 — Attention to the description of the symptoms experienced by the patient and substantiated by family members and others often permits Cerebrovascular diseases 143,232,184 6,552,725 an accurate localization and determination of the probable cause, even Meningitis and encephalitis 21,120,604 326,117 before the neurologic examination is performed. The history also helps Migraine 42,077,666 — focus the neurologic examination that follows. Each complaint should Epilepsy 13,077,624 114,010 be pursued as far as possible to identify the location of the lesion, the Dementia 25,276,989 1,623,256 likely underlying pathophysiology, and potential etiologies. For exam- Parkinson’s disease 6,292,616 362,907 ple, a patient complains of weakness of the right arm. What are the associated features? Does the patient have difficulty with brushing hair % of total DALYs or deaths for all 13.7% 16.1% causes that are neurologic or reaching upward (proximal) or fastening buttons or opening a plas- tic bottle (distal)? Negative associations may also be crucial. A right- % change of DALYs or deaths for 41.0% 0.0% neurologic disorders between 2015 handed patient with a right hemiparesis without a language deficit and 2019 likely has a lesion (internal capsule, brainstem, or spinal cord) different from that of a patient with a right hemiparesis and aphasia (left hemi- Source: Data from Global Burden of Disease Study 2019 (GBD 2019) Data Resources http://ghdx.healthdata.org/gbd-2019 and GBD 2019 Diseases and Injuries sphere). Other pertinent features of the history include the following: Collaborators. Global burden of 369 diseases and injuries in 204 countries and territories, 1990-2019: a systematic analysis for the Global Burden of Disease Study 1. Temporal course of the illness. It is important to determine the pre- 2019. Lancet 396:1204, 2020. cise time of appearance and rate of progression of the symptoms HPIM21e_Part13_p3277-p3578.indd 3277 21/01/22 7:49 AM  3278 experienced by the patient. The rapid onset of a neurologic com- and fibromuscular dysplasia. Various neurologic disorders occur plaint, occurring within seconds or minutes, usually indicates a with dysthyroid states or other endocrinopathies. It is especially vascular event, a seizure, or migraine. The onset of sensory symp- important to look for the presence of systemic diseases in patients toms located in one extremity that spread over a few seconds to with peripheral neuropathy. Most patients with coma in a hospital adjacent portions of that extremity and then to the other regions of setting have a metabolic, toxic, or infectious cause. the body suggests a seizure. A similar but slower temporal march of 6. Drug use and abuse and toxin exposure. It is essential to inquire symptoms accompanied by headache, nausea, or visual disturbance about the history of drug use, both prescribed and illicit. Sedatives, suggests migraine. Less well-localized symptoms that are maximum antidepressants, and other psychoactive medications are frequently at onset and persist for seconds, minutes, or much less commonly associated with acute confusional states, especially in the elderly. hours, point to the possibility of a transient ischemic attack (TIA). Aminoglycoside antibiotics may exacerbate symptoms of weakness The presence of “positive” sensory symptoms (e.g., tingling or sensa- in patients with disorders of neuromuscular transmission, such as tions that are difficult to describe) or involuntary motor movements myasthenia gravis, and may cause dizziness secondary to ototoxicity. suggests a seizure; in contrast, transient loss of function (negative Vincristine and other antineoplastic drugs can cause peripheral neu- symptoms) suggests a TIA. A stuttering onset where symptoms ropathy, and immunosuppressive agents such as cyclosporine can appear, stabilize, and then progress over hours or days also suggests produce encephalopathy. Excessive vitamin ingestion can lead to cerebrovascular disease; an additional history of transient remission disease; examples include vitamin A and intracranial hypertension or regression indicates that the process is more likely due to ische- (“pseudotumor cerebri”) or pyridoxine and peripheral neuropathy. mia rather than hemorrhage. A gradual evolution of symptoms over Many patients are unaware that over-the-counter sleeping pills, cold PART 13 hours or days suggests a toxic, metabolic, infectious, or inflamma- preparations, and diet pills are actually drugs. Alcohol, the most tory process. Progressing symptoms associated with the systemic prevalent neurotoxin, is often not recognized as such by patients, manifestations of fever, stiff neck, and altered level of consciousness and other drugs of abuse such as cocaine, methamphetamine, and imply an infectious process. Relapsing and remitting symptoms heroin can cause a wide range of neurologic abnormalities. A his- Neurologic Disorders involving different levels of the nervous system suggest MS or tory of environmental or industrial exposure to neurotoxins may other inflammatory processes. Slowly progressive symptoms with- provide an essential clue; consultation with the patient’s coworkers out remissions are characteristic of neurodegenerative disorders, or employer may be required. chronic infections, gradual intoxications, and neoplasms. 7. Formulating an impression of the patient. Use the opportunity while 2. Patients’ descriptions of the complaint. The same words often taking the history to form an impression of the patient. Is the infor- mean different things to different patients. “Dizziness” may imply mation forthcoming, or does it take a circuitous course? Is there impending syncope, a sense of disequilibrium, or true spinning evidence of anxiety, depression, or hypochondriasis? Are there any vertigo. “Numbness” may mean a complete loss of feeling, a positive clues to problems with language, memory, insight, comportment, or sensation such as tingling, or even weakness. “Blurred vision” may behavior? The neurologic assessment begins as soon as the patient be used to describe unilateral visual loss, as in transient monocular comes into the room and the first introduction is made. blindness, or diplopia. The interpretation of the true meaning of the words used by patients to describe symptoms obviously becomes even more complex when there are differences in primary languages THE NEUROLOGIC EXAMINATION and cultures. The neurologic examination is challenging and complex; it has many 3. Corroboration of the history by others. It is almost always helpful to components and includes a number of skills that can be mastered only obtain additional information from family, friends, or other observ- through repeated use of the same techniques on a large number of indi- ers to corroborate or expand the patient’s description. Memory loss, viduals with and without neurologic disease. Mastery of the complete aphasia, loss of insight, intoxication, and other factors may impair neurologic examination is usually important only for physicians in the patient’s capacity to communicate normally with the examiner neurology and associated specialties. However, knowledge of the basics or prevent openness about factors that have contributed to the of the examination, especially those components that are effective in illness. Episodes of loss of consciousness necessitate that details be screening for neurologic dysfunction, is essential for all clinicians, sought from observers to ascertain precisely what has happened especially generalists. during the event. There is no single, universally accepted sequence of the examina- 4. Family history. Many neurologic disorders have an underlying tion that must be followed, but most clinicians begin with assessment genetic component. The presence of a Mendelian disorder, such as of mental status followed by the cranial nerves (CN), motor system, Huntington’s disease or Charcot-Marie-Tooth neuropathy, is often reflexes, sensory system, coordination, and gait. Whether the examina- obvious if family data are available. More detailed questions about tion is basic or comprehensive, it is essential that it is performed in an family history are often necessary in polygenic disorders such as MS, orderly and systematic fashion to avoid errors and serious omissions. migraine, and many types of epilepsy. It is important to elicit family Thus, the best way to learn and gain expertise in the examination is to history about all illnesses, in addition to neurologic and psychiatric choose one’s own approach and practice it frequently and do it in the disorders. A familial propensity to hypertension or heart disease is same exact sequence each time. relevant in a patient who presents with a stroke. Numerous inherited The detailed description that follows describes the more commonly neurologic diseases are associated with multisystem manifestations used parts of the neurologic examination, with a particular emphasis that may provide clues to the correct diagnosis (e.g., neurofibroma- on the components that are considered most helpful for the assessment tosis, Wilson’s disease, mitochondrial disorders). of common neurologic problems. Each section also includes a brief 5. Medical illnesses. Many neurologic diseases occur in the context of description of the minimal examination necessary to adequately screen systemic disorders. Diabetes mellitus, hypertension, and abnormali- for abnormalities in a patient who has no symptoms suggesting neu- ties of blood lipids predispose to cerebrovascular disease. A solitary rologic dysfunction. A screening examination done in this way can be mass lesion in the brain may be an abscess in a patient with valvular completed in 3–5 min. Video demonstrations of the neurologic screening heart disease, a primary hemorrhage in a patient with a coagulop- examination (V6) and the detailed neurologic examination (V7) can be athy, a lymphoma or toxoplasmosis in a patient with AIDS, or a found in the Harrison’s Video Collection included in this textbook. metastasis in a patient with underlying cancer. Patients with malig- Several additional points about the examination are worth noting. nancy may also present with a neurologic paraneoplastic syndrome First, in recording observations, it is important to describe what is (Chap. 94) or complications from chemotherapy or radiotherapy. found rather than to apply a poorly defined medical term (e.g., “patient Marfan’s syndrome and related collagen disorders predispose to groans to sternal rub” rather than “obtunded”). Second, subtle CNS dissection of the cranial arteries and aneurysmal subarachnoid hem- abnormalities are best detected by carefully comparing a patient’s per- orrhage; the latter may also occur with polycystic kidney disease formance on tasks that require simultaneous activation of both cerebral HPIM21e_Part13_p3277-p3578.indd 3278 21/01/22 7:49 AM  hemispheres (e.g., eliciting a pronator drift of an outstretched arm with later; and (3) long-term memory is evaluated by determining how well 3279 the eyes closed; extinction on one side of bilaterally applied light touch, the patient is able to provide a coherent chronologic history of his or also with eyes closed; or decreased arm swing or a slight asymmetry her illness or personal events. when walking). Third, if the patient’s complaint is brought on by some Fund of information is assessed by asking questions about major activity, reproduce the activity in the office. If the complaint is of dizzi- historic or current events, with special attention to educational level ness when the head is turned in one direction, have the patient do this and life experiences. and also look for associated signs on examination (e.g., nystagmus or Abnormalities of insight and judgment are usually detected during dysmetria). If pain occurs after walking two blocks, have the patient the patient interview; a more detailed assessment can be elicited by ask- leave the office and walk this distance and immediately return, and ing the patient to describe how he or she would respond to situations repeat the relevant parts of the examination. Finally, the use of tests having a variety of potential outcomes (e.g., “What would you do if you that are individually tailored to the patient’s problem can be of value in found a wallet on the sidewalk?”). assessing changes over time. Tests of walking a 7.5-m (25-ft) distance Abstract thought can be tested by asking the patient to describe sim- (normal, 5–6 s; note assistance, if any), repetitive finger or toe tapping ilarities between various objects or concepts (e.g., apple and orange, (normal, 20–25 taps in 5 s), or handwriting are examples. desk and chair, poetry and sculpture) or to list items having the same attributes (e.g., a list of four-legged animals). MENTAL STATUS EXAMINATION Calculation ability is assessed by having the patient carry out a CHAPTER 422 Approach to the Patient with Neurologic Disease The bare minimum: During the interview, look for difficulties with computation that is appropriate to the patient’s age and education (e.g., communication and determine whether the patient has recall and serial subtraction of 7 from 100 or 3 from 20; or word problems involv- insight into recent and past events. ing simple arithmetic). The mental status examination is underway as soon as the physician CRANIAL NERVE EXAMINATION begins observing and speaking with the patient. If the history raises The bare minimum: Check the fundi, visual fields, pupil size and reac- any concern for abnormalities of higher cortical function or if cognitive tivity, extraocular movements, and facial movements. problems are observed during the interview, then detailed testing of the mental status is indicated. The patient’s ability to understand the The CNs are best examined in numerical order, except for grouping language used for the examination, cultural background, educational together CN III, IV, and VI because of their similar function. experience, sensory or motor problems, or comorbid conditions must be factored into the applicability of the tests and interpretation of CN I (Olfactory) Testing is often omitted unless there is suspicion for inferior frontal lobe disease (e.g., meningioma). With eyes closed, results. ask the patient to sniff a mild stimulus such as toothpaste or coffee and The Mini-Mental State Examination (MMSE) is a standardized identify the odorant. screening examination of cognitive function that is extremely easy to administer and takes flexors in the upper extremity and flexors > including radiofrequency and cold ablation and image-guided blood extensors in the lower extremity, and hyperreflexia. patches. Multidetector CTA (MDCTA) and gadolinium-enhanced b Weakness along with other abnormalities having a “lower motor neuron” pattern, i.e., flaccidity and hyporeflexia. MRA techniques have reduced the need for catheter-based angiogra- phy, which is now reserved for patients in whom small-vessel detail is and to select the laboratory tests most likely to be informative. The essential for diagnosis or for whom concurrent interventional therapy laboratory assessment may include (1) serum electrolytes; complete is planned (Table 423-1). blood count; and renal, hepatic, endocrine, and immune studies; (2) In general, MRI is more sensitive than CT for the detection of cerebrospinal fluid examination; (3) focused neuroimaging studies lesions affecting the peripheral and central nervous system (CNS). (Chap. 423); or (4) electrophysiologic studies. The anatomic localiza- Diffusion MR, a sequence sensitive to the microscopic motion of tion, mode of onset and course of illness, other medical data, and lab- water, is the most sensitive technique for detecting acute ischemic oratory findings are then integrated to establish an etiologic diagnosis. stroke of the brain or spinal cord, and is also useful in the detection The neurologic examination may be normal even in patients with and characterization of encephalitis, abscess, Creutzfeldt-Jacob dis- a serious neurologic disease, such as seizures, chronic meningitis, or a ease, cerebral tumors, and acute demyelinating lesions. CT, however, is TIA. A comatose patient may arrive with no available history, and in acquired more quickly, making it a pragmatic choice for uncooperative such cases, the approach is as described in Chap. 28. In other patients, patients, or those with suspected acute stroke, hemorrhage, and acute an inadequate history may be overcome by a succession of examina- intracranial or spinal trauma. CT is also more sensitive than MRI for tions from which the course of the illness can be inferred. In perplex- visualizing fine osseous detail and thus is appropriate for the initial ing cases it is useful to remember that uncommon presentations of imaging evaluation of conductive hearing loss, and lesions affecting the common diseases are more likely than rare etiologies. Thus, even in osseous skull and spine. MR may, however, add important diagnostic tertiary care settings, multiple strokes are usually due to emboli and not information regarding bone marrow infiltrative processes that can be vasculitis, and dementia with myoclonus is usually Alzheimer’s disease difficult to detect on CT. and not a prion disorder or a paraneoplastic illness. Finally, the most important task of a primary care physician faced with a patient who has COMPUTED TOMOGRAPHY a new neurologic complaint is to assess the urgency of referral to a spe- cialist. Here, the imperative is to rapidly identify patients likely to have TECHNIQUE nervous system infections, acute strokes, and spinal cord compression The CT image is a cross-sectional representation of anatomy created or other treatable mass lesions and arrange for immediate care. by a computer-generated analysis of the attenuation of x-ray beams passed through a section of the body. As the x-ray beam, collimated Acknowledgment to the desired slice width, rotates around the patient, it passes through The editors acknowledge the contributions of Joseph B. Martin to earlier selected regions in the body. X-rays that are not attenuated by body editions of this chapter. structures are detected by sensitive x-ray detectors aligned 180° from HPIM21e_Part13_p3277-p3578.indd 3282 21/01/22 7:49 AM  TABLE 423-1 Guidelines for the Use of CT, Ultrasound, and MRI be reformatted into various slice thicknesses and planes. Advantages 3283 of MDCT include shorter scan times and thus reduced patient and CONDITION RECOMMENDED TECHNIQUE organ motion, and the ability to acquire images dynamically during Hemorrhage the infusion of intravenous (IV) contrast, the basis of CTA and CT Acute parenchymal CT, MR perfusion (Figs. 423-1B and C). CTA is displayed in three dimen- Subacute/chronic MRI sions to yield angiogram-like images (Figs. 423-1C, 423-2E and F, Subarachnoid hemorrhage CT, CTA, lumbar puncture → angiography and see Fig. 420-3). Angiography > CTA, MRA IV iodinated contrast is used to identify vascular structures and Chronic subarachnoid blood MR with SWI to detect defects in the blood-brain barrier (BBB) that are caused by Aneurysm tumors, infarcts, and infections. In the normal CNS, only vessels and Ischemic infarction structures lacking a BBB (e.g., the pituitary gland, choroid plexus, Hemorrhagic infarction CT or MRI and dura) enhance after contrast administration. While helpful in Bland infarction MRI with diffusion > CT, CTA, angiography characterizing mass lesions as well as essential for the acquisition of Carotid or vertebral dissection MRI/MRA CTA studies, the decision to use contrast material should always be Vertebral basilar insufficiency CTA, MRI/MRA considered carefully as it carries a small risk of allergic reaction and Carotid stenosis CTA, MRA > US adds additional expense. CHAPTER 423 Neuroimaging in Neurologic Disorders Suspected mass lesion INDICATIONS Neoplasm, primary or metastatic MRI + contrast CT is the primary study of choice in the evaluation of an acute change Infection/abscess MRI + contrast in mental status, focal neurologic findings, acute trauma to the brain and  Immunosuppressed with focal MRI + contrast spine, suspected subarachnoid hemorrhage, and conductive hearing findings loss (Table 423-1). CT often is complementary to MR in the evalua- Vascular malformation MRI ± angiography tion of the skull base, orbit, and osseous structures of the spine. In the White matter disorders MRI spine, CT is useful in evaluating patients with osseous spinal stenosis Demyelinating disease MRI ± contrast and spondylosis, but MRI is often preferred in those with neurologic Dementia MRI > CT deficits. CT is often acquired following intrathecal contrast injection to Trauma evaluate for spinal and intracranial cerebrospinal fluid (CSF) fistula, as Acute trauma CT well as the spinal subarachnoid space (CT myelography) in failed back Shear injury/chronic hemorrhage MRI + susceptibility-weighted imaging surgery syndromes. Headache/migraine CT/MRI Seizure COMPLICATIONS  First time, no focal neurologic MRI > CT CT is safe, fast, and reliable. Radiation exposure depends on the dose deficits used but is normally 2–5 mSv (millisievert) for a routine brain CT  With neurologic deficit, or CT, followed by MR study. For all patients, especially children, it is important to use as low a immunocompromised or cancer radiation dose as possible for diagnostic purposes. Where feasible, MR Partial complex/refractory MRI or ultrasound is preferred. With the advent of MDCT, CTA, and CT Cranial neuropathy MRI with contrast perfusion, the benefit must be weighed against the increased radiation Meningeal disease MRI with contrast doses associated with these techniques. Advances in postprocessing software now permit acceptable diagnostic CT scans at 30–40% lower Spine radiation doses. Low-back pain The most frequent complications are those associated with use of No neurologic deficits MRI or CT after >6 weeks IV contrast agents. While two broad categories of contrast media, ionic With focal deficits MRI > CT and nonionic, are in use, ionic agents have been largely replaced by Spinal stenosis MRI or CT safer nonionic compounds. Cervical spondylosis MRI, CT, CT myelography Contrast nephropathy is rare. It may result from hemodynamic Infection MRI + contrast, CT changes, renal tubular obstruction and cell damage, or immunologic Myelopathy MRI + contrast reactions to contrast agents. A rise in serum creatinine of at least Arteriovenous malformation MRI + contrast, angiography 44 μmol/L (0.5 mg/dL) within 48 h of contrast administration is often used as a definition of contrast nephropathy, although there is no Abbreviations: CT, computed tomography; CTA, CT angiography; MRA, magnetic accepted definition and other causes of acute renal failure must be resonance angiography; MRI, magnetic resonance imaging; SWI, susceptibility- weighted imaging. excluded. The prognosis is usually favorable, with serum creatinine levels returning to baseline within 1–2 weeks. Risk factors for contrast nephropathy include age (>80 years), preexisting renal disease (serum creatinine exceeding 2 mg/dL), solitary kidney, diabetes mellitus, dehy- the x-ray tube. A computer calculates a “back projection” image from dration, paraproteinemia, concurrent use of nephrotoxic medication the 360° x-ray attenuation profile. Greater x-ray attenuation (e.g., as or chemotherapeutic agents, and high contrast dose. Patients with caused by bone), results in areas of high “density” (whiter) on the scan, diabetes and those with mild renal failure should be well hydrated prior whereas soft-tissue structures that have poor attenuation of x-rays, to the administration of contrast agents; careful consideration should such as organs and air-filled cavities, are lower (blacker) in density. be given to alternative imaging techniques such as MRI, noncontrast The resolution of an image depends on the radiation dose, the detector CT, or ultrasound (US). Nonionic, low-osmolar media produce fewer size, collimation (slice thickness), the field of view, and the matrix size abnormalities in renal blood flow and less endothelial cell damage but of the display. A modern CT scanner is capable of obtaining sections as should still be used carefully in patients at risk for allergic reaction. thin as 0.5–1 mm with 0.4-mm in-plane resolution at a speed of 0.3 s Estimated glomerular filtration rate (eGFR) is a more reliable indicator per rotation; complete studies of the brain can be completed in 1–10 s. of renal function compared to creatinine alone because it takes into Multidetector CT (MDCT) is now standard. Single or multiple (from account age and sex. In one study, 15% of outpatients with a normal 4 to 320) solid-state detectors positioned opposite to the x-ray source serum creatinine had an estimated creatinine clearance of ≤50 mL/min result in multiple slices per revolution of the beam around the patient. per 1.73 m2 (normal is ≥90 mL/min per 1.73 m2). The exact eGFR In helical mode, the table moves continuously through the rotating threshold, below which withholding IV contrast should be consid- x-ray beam, generating a continuous “helix” of information that can ered, is controversial. The risk of contrast nephropathy is minimal in HPIM21e_Part13_p3277-p3578.indd 3283 21/01/22 7:49 AM  3284 A B C PART 13 FIGURE 423-1 Computed tomography (CT) angiography (CTA) of ruptured anterior cerebral artery aneurysm in a patient presenting with acute headache. A. Noncontrast CT demonstrates subarachnoid and intraventricular hemorrhage and mild obstructive hydrocephalus. B. Axial maximum-intensity projection from CTA demonstrates enlargement of the anterior cerebral artery (arrow). C. Three-dimensional surface reconstruction using a workstation confirms the anterior cerebral aneurysm and demonstrates its orientation and relationship to nearby vessels (arrow). CTA image is produced by 0.5- to 1-mm helical CT scans performed during a rapid bolus infusion of IV contrast medium. Neurologic Disorders patients with eGFR >30 mL/min per 1.73 m2; however, the majority of a nonionic agent should be used in conjunction with pretreatment these patients will have only a temporary rise in creatinine. The risk of with glucocorticoids and antihistamines (Table 423-2); however, pre- dialysis after receiving contrast significantly increases in patients with treatment does not guarantee safety. Patients with allergic reactions to eGFR 1 h after injection) risk is used at all, an eGFR of 30 mL/min per 1.73 m2 seems to have the reactions are frequent and probably related to T cell–mediated immune greatest level of evidence. reactions. These are typically urticarial but can occasionally be more If contrast must be administered to a patient with an eGFR 60 years iodine therapy for thyroid disease or cancer should not receive iodi- History of “kidney disease” as an adult, including tumor and transplant nated contrast media, if possible, because this will decrease the uptake Family history of kidney failure of the radioisotope into the tumor or thyroid (see the American College Diabetes mellitus treated with insulin or other prescribed medications of Radiology Manual on Contrast Media, 2021; https://www.acr.org/-/ Hypertension media/ACR/Files/Clinical-Resources/Contrast_Media.pdf). Paraproteinemia syndromes or diseases (e.g., myeloma) Collagen vascular disease (e.g., systemic lupus erythematosus [SLE], MAGNETIC RESONANCE IMAGING scleroderma, rheumatoid arthritis) Solid-organ transplant recipient TECHNIQUE If creatinine testing is required, a creatinine level within the prior MRI is a complex interaction between hydrogen protons in biologic 6 weeks is sufficient in most clinical settings. tissues, a static magnetic field (the magnet), and energy in the form of radiofrequency (Rf) waves of a specific frequency introduced by coils Allergy Immediate reactions following IV contrast media occur placed next to the body part of interest. Images are made by computer- through several mechanisms. The most severe reactions are related ized processing of resonance information received from protons (typ- to allergic hypersensitivity (anaphylaxis) and range from mild hives ically hydrogen) in the body. Field strength of the magnet is directly to bronchospasm and death. The pathogenesis of allergic hypersen- related to signal-to-noise ratio. While 1.5 Tesla (T) and 3-T magnets sitivity reactions is thought to include the release of mediators such are now widely available and have distinct advantages in the brain and as histamine, antibody-antigen reactions, and complement activation. musculoskeletal systems, even higher field magnets (7-T) and positron Severe allergic reactions occur in ~0.04% of patients receiving nonionic emission tomography (PET)-MR machines promise increased resolu- media, sixfold lower than with ionic media. Risk factors include a tion and anatomic-functional information on a variety of disorders. history of prior contrast reaction (fivefold increased likelihood), food Spatial localization is achieved by magnetic gradients surrounding the and or drug allergies, and atopy (asthma and hay fever). The predic- main magnet, which impart slight changes in magnetic field through- tive value of specific allergies, such as those to shellfish, once thought out the imaging volume. Rf pulses transiently excite the energy state important, actually is now recognized to be unreliable. Nonetheless, in of the hydrogen protons in the body. Rf is administered at a frequency patients with a history worrisome for potential allergic reaction, a non- specific for the field strength of the magnet. The subsequent return to contrast CT or MRI procedure should be considered as an alternative equilibrium energy state (relaxation) of the hydrogen protons results to contrast administration. If iodinated contrast is absolutely required, in a release of Rf energy (the echo), which is detected by the coils that HPIM21e_Part13_p3277-p3578.indd 3284 21/01/22 7:49 AM  3285 CHAPTER 423 Neuroimaging in Neurologic Disorders A B C D E F G H I FIGURE 423-2 Acute left hemiparesis due to right middle cerebral artery occlusion. A. Axial noncontrast computed tomography (CT) scan demonstrates high density within the right middle cerebral artery (arrow) associated with subtle low density involving the right putamen (arrowheads). B. Mean transit time CT perfusion parametric map indicating prolonged mean transit time involving the right middle cerebral territory (arrows). C. Cerebral blood volume (CBV) map shows reduced CBV involving an area within the defect shown in B, indicating a high likelihood of infarction (arrows). D. Axial maximum-intensity projection from a CT angiography (CTA) study through the circle of Willis demonstrates an abrupt occlusion of the proximal right middle cerebral artery (arrow). E. Sagittal reformation through the right internal carotid artery demonstrates a low- density lipid-laden plaque (arrowheads) narrowing the lumen (black arrow). F. Three-dimensional surface-rendered CTA image demonstrates calcification and narrowing of the right internal carotid artery (arrow), consistent with atherosclerotic disease. G. Coronal maximum-intensity projection from magnetic resonance angiography shows right middle cerebral artery (MCA) occlusion (arrow). H. and I. Axial diffusion-weighted image (H) and apparent diffusion-coefficient image (I) document the presence of a right middle cerebral artery infarction. HPIM21e_Part13_p3277-p3578.indd 3285 21/01/22 7:49 AM  3286 TABLE 423-2 Guidelines for Premedication of Patients with Prior Contrast Allergy 12 h prior to examination: Prednisone, 50 mg PO or methylprednisolone, 32 mg PO 2 h prior to examination:  Prednisone, 50 mg PO or methylprednisolone, 32 mg PO and cimetidine, 300 mg PO or ranitidine, 150 mg PO Immediately prior to examination: Benadryl, 50 mg IV (alternatively, can be given PO 2 h prior to exam) delivered the Rf pulses. Fourier analysis is used to transform the echo A into the information used to form an MR image. The MR image thus consists of a map of the distribution of hydrogen protons, with signal intensity imparted by both density of hydrogen protons and differences in the relaxation times (see below) of hydrogen protons on different PART 13 molecules. Although clinical MRI currently makes use of the ubiqui- tous hydrogen proton, sodium and carbon imaging and spectroscopy are also possible but have yet to be integrated into mainstream practice. T1 and T2 Relaxation Times The rate of return to equilibrium Neurologic Disorders of perturbed protons is called the relaxation rate. The relaxation rate varies among normal and pathologic tissues. The relaxation rate of a hydrogen proton in a tissue is influenced by local interactions with surrounding molecules and atomic neighbors. Two relaxation rates, T1 and T2, influence the signal intensity of the image. The T1 relaxation time is the time, measured in milliseconds, for 63% of the hydrogen protons to return to their normal equilibrium state, whereas the T2 B relaxation is the time for 63% of the protons to become dephased owing to interactions among nearby protons. The intensity and image FIGURE 423-3 Cerebral abscess in a patient with fever and a right hemiparesis. contrast of the signal within various tissues can be modulated by A. Coronal postcontrast T1-weighted image demonstrates a ring-enhancing mass altering acquisition parameters such as the interval between Rf pulses in the left frontal lobe. B. Axial diffusion-weighted image demonstrates restricted (TR) and the time between the Rf pulse and the signal reception (TE). diffusion (high signal intensity) within the lesion, which in this setting is highly T1-weighted (T1W) images are produced by keeping the TR and suggestive of cerebral abscess. TE relatively short, whereas using longer TR and TE times produces T2-weighted (T2W) images. Fat and subacute hemorrhage have rel- atively shorter T1 relaxation rates and thus higher signal intensity lesions or edema, especially those close to CSF-filled cisterns and sulci. than brain on T1W images. Structures containing more water, such Diffusion-weighted imaging is also routinely obtained in most brain as CSF and edema, have long T1 and T2 relaxation rates, resulting protocols. This sequence interrogates the microscopic motion of water, in relatively lower signal intensity on T1W images and higher signal which is restricted in areas of infarction, abscess, and some tumors. intensity on T2W images (Table 423-3). Gray matter contains 10–15% SWI is a gradient echo sequence that is very sensitive to alterations in more water than white matter, which accounts for much of the intrin- local magnetic field generated by blood, calcium, and air. SWI is also sic contrast between the two on MRI (Fig. 423-4A). T2W images are now routinely obtained and helps detect microhemorrhages, such as more sensitive than T1W images to edema, demyelination, infarction, is typical of amyloid angiopathy, hypertension, hemorrhagic metasta- and chronic hemorrhage, whereas T1W imaging is more sensitive to ses, traumatic brain injury, and thrombotic states (Fig. 423-5C). MR subacute hemorrhage and fat-containing structures. images can be generated in any plane without changing the patient’s Many different MR pulse sequences exist, and each can be obtained position. Each sequence, however, is currently obtained separately and in various planes (Figs. 423-2, 423-3, and 423-4). The selection of takes 1–10 min on average to complete. Three-dimensional volumetric a proper protocol that will best answer a clinical question depends imaging is also possible with MRI, resulting in a volume of data that on an accurate clinical history and indication for the examination. can be reformatted in any orientation to highlight certain disease pro- Fluid-attenuated inversion recovery (FLAIR) is a very useful pulse cesses. Perfusion techniques such as arterial spin labeling also provide sequence that produces T2W images in which the normally high quantitative imaging information regarding cerebral blood flow. signal intensity of CSF is suppressed (Fig. 423-4B). FLAIR images are MR Contrast Material The heavy-metal element gadolinium more sensitive than standard spin echo images for water-containing forms the basis of all currently approved IV MR contrast agents. Gadol- inium reduces the T1 and T2 relaxation times of nearby water protons in the presence of a magnetic field, resulting in a high signal on T1W TABLE 423-3 Some Common Intensities on T1- and T2-Weighted MRI images and a low signal on T2W images (the latter requires a sufficient Sequences local concentration, usually in the form of an IV bolus). Unlike iodi- SIGNAL INTENSITY nated contrast agents, the effect of MR contrast agents depends on the presence of local hydrogen protons on which it must act to achieve the IMAGE TR TE CSF FAT BRAIN EDEMA desired effect. There are nine different gadolinium agents approved T1W Short Short Low High Low Low in the United States for use with MRI. These differ according to the T2W Long Long High High Medium High attached chelated moiety, which also affects the strength of chelation FLAIR (T2) Long Long Low High Medium High of the otherwise toxic gadolinium element. The chelating carrier mol- ecule for gadolinium can be classified by whether it is macrocyclic or Abbreviations: CSF, cerebrospinal fluid; FLAIR, fluid-attenuated inversion recovery; TE, interval between radiofrequency pulse and signal reception; TR, interval has linear geometry and whether it is ionic or nonionic. Macrocyclic between radiofrequency pulses; T1W and T2W, T1- and T2-weighted. ligands (Group 2 agents) are considered more stable as the gadolinium HPIM21e_Part13_p3277-p3578.indd 3286 21/01/22 7:49 AM  deposits are associated with histologic changes that would suggest 3287 neurotoxicity, even among agents with the highest rates of deposition. ALLERGIC HYPERSENSITIVITY Gadolinium-DTPA (diethylenetri- aminepentaacetic acid) does not normally cross the intact BBB imme- diately but will enhance lesions lacking a BBB (Fig. 423-3A) as well as areas of the brain that normally are devoid of the BBB (pituitary, dura, choroid plexus). However, gadolinium contrast slowly crosses an intact BBB over time and especially in the setting of reduced renal clearance or inflamed meninges. The agents are generally well toler- ated; overall adverse events after injection range from 0.07–2.4%. True allergic reactions are rare (0.004–0.7%) but have been reported. Severe A life-threatening reactions are exceedingly rare; in one report, only 55 reactions out of 20 million doses occurred. However, the adverse reaction rate in patients with a prior history of reaction to gadolinium is eight times higher than normal. Other risk factors include atopy or asthma (3.7%). There is no cross reactivity between different classes of CHAPTER 423 Neuroimaging in Neurologic Disorders contrast media; a prior reaction to gadolinium-based contrast does not predict a future reaction to iodinated contrast medium, or vice versa, more than any other unrelated allergy. Gadolinium contrast material can be administered safely to children as well as adults, although these agents are generally avoided in those aged 60 years 3. History of hypertension 4. History of diabetes 5. History of severe hepatic disease, liver transplantation, or pending liver transplantation; for these patients, it is recommended that the patient’s GFR assessment be nearly contemporaneous with the MR C examination. The incidence of NSF in patients with severe renal dysfunction FIGURE 423-4 Herpes simplex encephalitis in a patient presenting with altered (GFR 65 years. Acute seizures (i.e., occurring Metabolic disorders (uremia, hepatic failure, at the time of the stroke) are seen more often with embolic rather than electrolyte abnormalities, hypoglycemia, hemorrhagic or thrombotic stroke. Chronic seizures typically appear hyperglycemia) months to years after the initial event and are associated with all forms Alzheimer’s disease and other degenerative CNS of stroke. diseases Metabolic disturbances such as electrolyte imbalance, hypo- or Autoantibodies hyperglycemia, renal failure, and hepatic failure may cause seizures Abbreviation: CNS, central nervous system. at any age. Similarly, endocrine disorders, hematologic disorders, vas- culitides, and many other systemic diseases may cause seizures over a broad age range. A wide variety of medications and abused substances media, respiratory infection, or gastroenteritis. The seizure is likely to are known to precipitate seizures as well (Table 425-5). occur during the rising phase of the temperature curve (i.e., during the first day) rather than well into the course of the illness. A simple febrile BASIC MECHANISMS seizure is a single, isolated event, brief, and symmetric in appearance. Complex febrile seizures are characterized by repeated seizure activity, MECHANISMS OF SEIZURE INITIATION a duration >15 minutes, or by focal features. Approximately one-third AND PROPAGATION of patients with febrile seizures will have a recurrence, but 13 Hz); the alpha rhythm is attenuated when the eyes are opened seizure is based solely on clinical grounds—the examination and labora- (Fig. 425-3). During drowsiness, the alpha rhythm is also attenuated; tory studies are often normal. Questions should focus on the symptoms with light sleep, slower activity in the theta (4–7 Hz) and delta (15 s, postictal disorientation, muscle soreness, and sleepiness. In contrast, a syncopal episode is more likely if the Fp1-A1 event was provoked by acute pain or emotional stress or occurred F7-A1 immediately after arising from the lying or sitting position. Patients with syncope often describe a stereotyped transition from conscious- T3-A1 ness to unconsciousness that includes tiredness, sweating, nausea, T5-A1 and tunneling of vision, and they experience a relatively brief loss of consciousness. Headache or incontinence usually suggests a seizure but Fp2-A2 may on occasion also occur with syncope. A brief period (i.e., 1–10 s) F8-A2 of convulsive motor activity is frequently seen immediately at the onset of a syncopal episode, especially if the patient remains in an upright T4-A2 posture after fainting (e.g., in a dentist’s chair) and therefore has a sus- T6-A2 tained decrease in cerebral perfusion. Rarely, a syncopal episode can C TABLE 425-7 Features That Distinguish Generalized Tonic-Clonic Seizure from Syncope FIGURE 425-4 Electrographic seizures. A. Onset of a tonic seizure showing generalized repetitive sharp activity with synchronous onset over both FEATURES SEIZURE SYNCOPE hemispheres. B. Burst of repetitive spikes occurring with sudden onset in the Immediate precipitating Usually none Emotional stress, right temporal region during a clinical spell characterized by transient impairment factors Valsalva, orthostatic of awareness. C. Generalized 3-Hz spike-wave activity occurring synchronously hypotension, cardiac over both hemispheres during an absence seizure. Horizontal calibration: 1 s; etiologies vertical calibration: 400 μV in A, 200 μV in B, and 750 μV in C. (Reproduced with Premonitory symptoms None or aura (e.g., odd Tiredness, nausea, permission from MJ Aminoff: Aminoff’s Electrodiagnosis in Clinical Neurology, odor) diaphoresis, tunneling 6th ed. Oxford: Elsevier Saunders, 2012.) of vision Posture at onset Variable Usually erect Transition to Often immediate Gradual over secondsa in older patients with a history suggesting an undiagnosed genetic unconsciousness epilepsy syndrome that began early in life. Duration of Minutes Seconds unconsciousness DIFFERENTIAL DIAGNOSIS OF SEIZURES Duration of tonic or clonic 30–60 s Never >15 s Disorders that may mimic seizures are listed in Table 425-6. In most movements cases, seizures can be distinguished from other conditions by meticu- Facial appearance during Cyanosis, frothing at Pallor lous attention to the history and relevant laboratory studies. On occa- event mouth sion, additional studies such as video-EEG monitoring, sleep studies, Disorientation and Many minutes to hours 48 h in duration were excluded from this study. Stereotactic body radiotherapy, which delivers high doses of focused radiation, is preferred for radioresistant tumor types and for patients requiring re-irradiation. Biopsy of the epidural mass is unnecessary in patients with known primary cancer, but it is indicated if a history of underly- ing cancer is lacking. Surgical treatment, either decompression by laminectomy or a spinal fixation procedure, is also indicated when signs of cord compression worsen despite radiotherapy; the maxi- mum-tolerated dose of radiotherapy has been delivered previously to the site; a vertebral compression fracture or spinal instability contributes to cord compression; or in cases of high-grade spinal cord compression from a radioresistant tumor. A good response to therapy can be expected in individuals who FIGURE 442-3 Magnetic resonance imaging of a thoracic meningioma. Coronal are ambulatory at presentation. Treatment usually prevents new T1-weighted postcontrast image through the thoracic spinal cord demonstrates weakness, and some recovery of motor function occurs in up to intense and uniform enhancement of a well-circumscribed extramedullary mass one-third of patients. Motor deficits (paraplegia or quadriplegia), (arrows) that displaces the spinal cord to the left. HPIM21e_Part13_p3277-p3578.indd 3448 21/01/22 7:50 AM  3449 CHAPTER 442 Diseases of the Spinal Cord A B FIGURE 442-4 Magnetic resonance imaging of an intramedullary astrocytoma. FIGURE 442-5 Magnetic resonance (MR) imaging of a spinal epidural abscess Sagittal T1-weighted postcontrast image through the cervical spine demonstrates due to tuberculosis. A. Sagittal T2-weighted free spin-echo MR sequence. A expansion of the upper cervical spine by a mass lesion emanating from within the hypointense mass replaces the posterior elements of C3 and extends epidurally to spinal cord at the cervicomedullary junction. Irregular peripheral enhancement compress the spinal cord (arrows). B. Sagittal T1-weighted image after contrast occurs within the mass (arrows). administration reveals a diffuse enhancement of the epidural process (arrows) with extension into the epidural space. Fever is typically but not invariably present, accompanied by elevated white blood cell count, sedimentation rate, and C-reactive protein. As paralysis in evolution, but it is unlikely to improve deficits of more the abscess expands, further spinal cord damage results from venous than several days in duration. Broad-spectrum antibiotics typically congestion and thrombosis. Once weakness and other signs of mye- vancomycin 15–20 mg/kg q12h (staphylococcus including MRSA, lopathy appear, progression may be rapid and irreversible. A more streptococcus), ceftriaxone 2 gm q24h (gram-negative bacilli), and chronic sterile granulomatous form of abscess is also known, usually when indicated metronidazole 30 mg/kg per day divided into q6h after treatment of an acute epidural infection. intervals (anaerobes) should be started empirically before surgery Risk factors include an impaired immune status (HIV, diabetes mel- and then modified on the basis of culture results; medication is litus, renal failure, alcoholism, malignancy), intravenous drug abuse, generally continued for 6–8 weeks. If surgery is contraindicated or if and infections of the skin or other tissues. Two-thirds of epidural there is a fixed paraplegia or quadriplegia that is unlikely to improve infections result from hematogenous spread of bacteria from the skin following surgery, long-term administration of systemic and oral (furunculosis), soft tissue (pharyngeal or dental abscesses; sinusitis), or antibiotics can be used; in such cases, the choice of antibiotics deep viscera (bacterial endocarditis). The remainder arises from direct may be guided by results of blood cultures. Surgical management extension of a local infection to the subdural space; examples of local remains the treatment of choice unless the abscess is limited in size predisposing conditions are vertebral osteomyelitis, decubitus ulcers, and causes few or no neurologic signs. lumbar puncture, epidural anesthesia, or spinal surgery. Most cases With prompt diagnosis and treatment of spinal epidural abscess, are due to Staphylococcus aureus; gram-negative bacilli, Streptococcus, up to two-thirds of patients experience significant recovery. anaerobes, and fungi can also cause epidural abscesses. Methicillin- resistant Staphylococcus aureus (MRSA) is an important consideration, Spinal Epidural Hematoma Hemorrhage into the epidural (or and therapy should be tailored to this possibility. Tuberculosis from an subdural) space causes acute focal or radicular pain followed by vari- adjacent vertebral source (Pott’s disease) remains an important cause able signs of a spinal cord or conus medullaris disorder. Therapeutic in the developing world. anticoagulation, trauma, tumor, or blood dyscrasias are predisposing MRI (Fig. 442-5) localizes the abscess and excludes other causes of conditions. Rare cases complicate lumbar puncture or epidural anes- myelopathy. Blood cultures are positive in more than half of cases, but thesia. MRI and CT confirm the clinical suspicion and can delineate direct aspiration of the abscess at surgery is often required for a micro- the extent of the bleeding. Treatment consists of prompt reversal of any biologic diagnosis. Lumbar puncture is only required if encephalopathy underlying clotting disorder and surgical decompression. Surgery may or other clinical signs raise the question of associated meningitis, a be followed by substantial recovery, especially in patients with some feature that is found in 90 mmHg, or lumbar drainage factor; anti-SSA; anti-SSB, complement levels; antiphospholipid and of spinal fluid, was reportedly helpful in a few published cases of cord anticardiolipin antibodies; p-ANCA; antimicrosomal and antithyroglobulin antibodies; if Sjögren’s syndrome suspected, Schirmer test, salivary gland infarction, but neither of these approaches has been studied system- scintigraphy, and salivary/lacrimal gland biopsy. atically. Prognosis following spinal cord infarction is influenced by 9. Paraneoplastic disorders: Antibody for amphiphysin, CRMP5, Hu, others. the severity of the deficits at presentation; patients with severe motor 10. Other: vitamin B12, copper, zinc. weakness and those with persistent areflexia usually do poorly, but in one recent large series some improvement over time occurred in many Abbreviations: ANA, antinuclear antibodies; CMV, cytomegalovirus; CRMP5, patients, with more than half ultimately regaining some ambulation. collapsin response mediator 5-IgG; CSF, cerebrospinal fluid; CT, computed tomography; EBV, Epstein-Barr virus; ENA, epithelial neutrophil-activating peptide; ESR, erythrocyte sedimentation rate; GFAP, glial fibrillary acidic protein; HHV, human Inflammatory and Immune Myelopathies (Myelitis) This herpes virus; HSV, herpes simplex virus; HTLV, human T-cell leukemia/lymphoma broad category includes the demyelinating conditions MS, NMO, and virus; MOG, myelin oligodendrocyte glycoprotein; MRI, magnetic resonance postinfectious myelitis, as well as sarcoidosis, systemic autoimmune imaging; O&P, ova and parasites; p-ANCA, perinuclear antineutrophilic cytoplasmic antibodies; PCR, polymerase chain reaction; RPR, rapid plasma reagin (test); VDRL, disease, and infections. In approximately one-quarter of cases of myeli- Venereal Disease Research Laboratory; VZV, varicella-zoster virus. tis, no underlying cause can be identified. Some will later manifest HPIM21e_Part13_p3277-p3578.indd 3450 21/01/22 7:50 AM  additional symptoms of an immune-mediated disease. Transverse and values are elevated in only a minority of cases), serum calcium, and 3451 myelitis refers to a pattern of extensive spinal cord injury, clinically a gallium scan may assist in the diagnosis. Initial treatment is with high manifest as bilateral sensory symptoms, unilateral or bilateral weak- doses of glucocorticoids, which need to be administered long term and ness, and bladder and/or bowel disturbance. In most of the developed tapered slowly while monitoring resolution of clinical and MRI signs