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Contents Authorsix Prefacexiii
5. Aphasia, Apraxia, & Agnosia
John C.M. Brust, MD Aphasia37 Apraxia39 Agnosia40
Section I. Neurologic Investigations 1.Electroencephalography
6. Hearing Loss & Dizziness
Tina Shih, MD General Considerations 1 When to Order 1 Findings1 Continuous EEG Monitoring 3
Mark W. Green, MD, FAAN & Anna Pace, MD Approach to the Patient with Headache 66 Primary Headache Syndromes 66 Migraine66 Tension-Type Headache 72 Trigeminal Autonomic Cephalgias 73 Other Important Headache Syndromes 75 Medication Overuse Headache 75 New Daily Persistent Headache 75 Secondary Headaches 76 Meningitis76 Sinus Headache 76 Ocular Causes of Headache 76 Hypertension76 Subarachnoid Hemorrhage 76 Brain Tumor 77 Cerebral Venous Sinus Thrombosis 77 Idiopathic Intracranial Hypertension 77 Intracranial Hypotension 77 Giant Cell Arteritis 77 Exertional Headache 78 Sexually Induced Headache 78 Cardiac Cephalalgia 78
Maria J. Borja, MD & John P. Loh, MD Plain Films 14 Computed Tomography 14 Magnetic Resonance Imaging 17 Advanced Magnetic Resonance Imaging Techniques 24 Myelography & Postmyelography Computed Tomography24 Catheter Angiography 26 Interventional Neuroradiology 27 Ultrasonography27 Nuclear Medicine 29
Section II. Neurologic Disorders 4.Coma
John C.M. Brust, MD General Considerations 31 Pathogenesis31 Clinical Findings 31 Differential Diagnosis 33
Professor of Neurology, Columbia University College of Physicians & Surgeons, New York, New York Coma; Aphasia, Apraxia, & Agnosia; Disorders of Cerebrospinal Fluid Dynamics; Alcoholism; Drug Dependence
Internal Medicine Resident, New York Medical College, Metropolitan Hospital Center, New York, New York Bacterial, Fungal, & Parasitic Infections of the Nervous System
Richard A. Bernstein, MD, PhD
Northwestern Medicine Distinguished Physician in Vascular Neurology, Professor of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois Cerebrovascular Disease: Hemorrhagic Stroke
Philip Chang, MD
Maria J. Borja, MD
Professor of Neurology and Pediatrics at CUMC, Division of Pediatric Neurology, Columbia University Medical Centers, New York, New York Neurologic Disorders of Childhood & Adolescence
Vascular Neurology Fellow, Northwestern University, Feinberg School of Medicine, Chicago, Illinois Cerebrovascular Disease: Hemorrhagic Stroke
Claudia A. Chiriboga, MD, MPH
Assistant Professor of Neuroradiology, Department of Radiology, New York University School of Medicine, New York, New York Neuroradiology
Ugonma N. Chukwueke, MD
Dana-Farber Cancer Institute, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts Paraneoplastic Neurologic Syndromes
Thomas H. Brannagan III, MD
Professor of Neurology, Director, Peripheral Neuropathy Center, Columbia University College of Physicians and Surgeons, Co-director, Electromyography lab, New York-Presbyterian Hospital New York, New York Peripheral Neuropathies
Bruce A.C. Cree, MD, PhD, MAS
George A. Zimmermann Endowed Professor in Multiple Sclerosis, Professor of Clinical Neurology, Clinical Research Director, UCSF Weill Institute for Neurosciences, Department of Neurology, University of California San Francisco, San Francisco, California Multiple Sclerosis & Demyelinating Diseases
Carl Bazil, MD, PhD
Caitlin Tynan Doyle Professor of Neurology at CPMC Director, Division of Epilepsy and Sleep, Columbia University College of Physicians and Surgeons, New York, New York Sleep Disorders
Juliana R. Dutra, MD
Division of Aging and Dementia, Department of Neurology, Columbia University Medical Center, New York, New York Dementia & Memory Loss
Susan B. Bressman, MD
Professor, Department of Neurology, Albert Einstein College of Medicine; Alan and John Mirken Chair, Department of Neurology, Beth Israel Medical Center, New York, New York Movement Disorders
Lydia B. Estanislao, MD
Instructor, Department of Neurology, Mt. Sinai School of Medicine, New York, New York HIV Neurology
Jeffrey N. Bruce, MD
Svetlana Faktorovich, MD
Edgar M. Housepian Professor of Neurological Surgery, Columbia University College of Physicians & Surgeons, New York, New York Central Nervous System Neoplasms
Assistant Professor of Neurology, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, New York, New York Myasthenia Gravis & Other Disorders of the Neuromuscular Junction
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Blair Ford, MD
Barbara S. Koppel, MD
Howard L. Geyer, MD, PhD
William C. Kreisl, MD
Professor, Department of Neurology, Columbia University College of Physicians & Surgeons, New York, New York Movement Disorders Assistant Professor, Department of Neurology, Albert Einstein College of Medicine, Bronx, New York Movement Disorders
Soha N. Ghossaini, MD, FACS
ENT Associates of New York, New York Hearing Loss & Dizziness
Mark W. Green, MD, FAAN
Professor, Department of Neurology, Mount Sinai School of Medicine, New York, New York Headache and Facial Pain
Claire Henchcliffe, MD, DPhil
Associate Professor, Department of Neurology and Neuroscience, Weill Cornell Medical College, New York, New York Ataxia & Cerebellar Disease
Michio Hirano, MD
Professor, Department of Neurology, Columbia University College of Physicians & Surgeons, New York, New York Motor Neuron Diseases; Mitochondrial Diseases
Lawrence S. Honig, MD, PhD
Professor of Clinical Neurology, Department of Neurology/ Taub Institute, Columbia University College of Physicians & Surgeons, New York, New York Dementia & Memory Loss; Prion Diseases
Edward Huey, MD
Assistant Professor of Psychiatry Columbia College of Physicians and Surgeons, Assistant Professor of Neurology, Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, New York, New York Dementia & Memory Loss
Sarah C. Janicki, MD, MPH
Instructor, Department of Neurology, Columbia University Medical Center, New York, New York Dementia & Memory Loss
Cheryl A. Jay, MD
Clinical Professor, Department of Neurology, University of California, San Francisco, San Francisco, California Systemic & Metabolic Disorders
Professor of Clinical Neurology, New York Medical College, New York, New York Bacterial, Fungal, & Parasitic Infections of the Nervous System Assistant Professor of Neurology, Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, New York, New York Dementia & Memory Loss
Andrew B. Lassman, MD
New York Presbyterian Hospital, Columbia University Medical Center, New York, New York Paraneoplastic Neurologic Syndromes
Marc Lazzaro, MD
Neurointerventional Fellow, Department of Neurology, Medical College of Wisconsin, Milwaukee, Wisconsin Cerebrovascular Disease: Ischemic Stroke
Dora Leung, MD
Assistant Professor of Clinical Neurology, Hospital for Special Surgery/Weill Cornell Medical College, New York, New York Electromyography, Nerve Conduction Studies, & Evoked Potentials
Jared Levin, MD
Albert Einstein College of Medicine, Bronx, New York Nontraumatic Disorders of the Spinal Cord
John P. Loh, MD
Assistant Professor, Department of Radiology, New York University School of Medicine, New York, New York Neuroradiology
Christopher E. Mandigo, MD
Department of Neurological Surgery, Columbia University College of Physicians & Surgeons, New York, New York Central Nervous System Neoplasms
Eric R. Marcus, MD
Professor of Clinical Psychiatry, Columbia University College of Physicians & Surgeons, Supervising and Training Analyst, Columbia University Center for Psychoanalytic Training and Research, New York, New York Psychiatric Disorders
Karen Marder, MD, MPH
Professor of Neurology, Columbia University College of Physicians & Surgeons, New York, New York Dementia & Memory Loss
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Authors Stephan A. Mayer, MD, FCCM
Associate Professor of Clinical Neurology, Columbia University College of Physicians & Surgeons, New York, New York Trauma
Lakshmi Nayak, MD
Dana-Farber Cancer Institute, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts Paraneoplastic Neurologic Syndromes
James M. Noble, MD, MS, CPH, FAAN
Harini Sarva, MD
Assistant Professor of Clinical Neurology, Parkinson’s Disease and Movement Disorders Institute, Department of Neurology, Weill Cornell Medicine, New York, New York Ataxia & Cerebellar Disease
Ned Sacktor, MD
Professor, Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland HIV Neurology
Associate Professor of Neurology, Taub Institute and Sergievsky Center, Columbia University Medical Center, New York, New York Dementia & Memory Loss; Viral Infections of the Nervous System
Deanna Saylor, MD, MHS
Santiago Ortega-Gutierrez, MD
Associate Professor, Department of Neurology, Sergievsky Center, Taub Institute, Columbia University College of Physicians & Surgeons, New York, New York 1st Department of Neurology, Aiginition Hospital, National and Kapodistrian University of Athens Medical School, Greece Dementia & Memory Loss
Neurology ICU Clinical Fellow, Department of Neurology, Columbia University College of Physicians & Surgeons, New York, New York Neurologic Intensive Care
Anna Pace, MD
Assistant Professor, Department of Neurology, Center for Headache and Pain Medicine Icahn School of Medicine at Mount Sinai, New York, New York Headache & Facial Pain
Marc C. Patterson, MD
Professor of Neurology, Pediatrics and Medical Genetics Chair, Division of Child and Adolescent Neurology, Mayo Clinic, Rochester, Minnesota Editor-in-Chief, Journal of Child Neurology and Child Neurology Open Editor, Journal of Inherited Metabolic Disease and JIMD Reports Neurologic Disorders of Childhood & Adolescence
Shanna K. Patterson, MD
FPA Medical Director, Director EMG Laboratory, Department of Neurology, Mount Sinai West and St. Luke’s Hospitals New York, New York Myasthenia Gravis & Other Disorders of the Neuromuscular Junction
Jeffrey Rumbaugh, MD, PhD
Assistant Professor, Department of Neurology, Emory University, Atlanta, Georgia HIV Neurology
Assistant Professor of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland HIV Neurology
Nikolaos Scarmeas, MD, MSc
Alan Z. Segal, MD
Associate Professor of Clinical Neurology, New York Presbyterian-Weill Cornell Medical College, New York, New York Neurologic Intensive Care
Jeffrey J. Sevigny, MD
Assistant Professor of Neurology, Department of Neurology, Beth Israel Medical Center, Albert Einstein College of Medicine, New York, New York HIV Neurology
Tina Shih, MD
Clinical Professor of Neurology, Department of Neurology, University of California, San Francisco, California Electroencephalography; Epilepsy & Seizures
Michelle Stern, MD
Associate Professor, Department of Physical Medicine and Rehabilitative Medicine, Albert Einstein College of Medicine, New York, New York Nontraumatic Disorders of the Spinal Cord
Kiran T. Thakur, MD
Assistant Professor of Neurology, Columbia University Medical Center, New York, New York Bacterial, Fungal, & Parasitic Infections of the Nervous System; Viral Infections of the Nervous System
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Alfredo D. Voloschin, MD
Assistant Professor, Department of Hematology and Oncology, Emory University, Atlanta, Georgia Paraneoplastic Syndromes
Katja Elfriede Wartenberg, MD, PhD Director, Neurocritical Care Unit Department of Neurology University of Leipzig, Leipzig, Germany Trauma
Jack J. Wazen, MD, FACS
Director of Research, Ear Research Foundation, Silverstein Institute, Sarasota, Florida Hearing Loss & Dizziness
Louis H. Weimer, MD, FAAN, FANA
Professor of Neurology at CUMC, Columbia University College of Physicians & Surgeons, New York, New York Autonomic Disorders
Andrew J Westwood, MD, FRCP (Edin)
Assistant Professor of Clinical Neurology, Division of Epilepsy and Sleep Medicine, Department of Neurology, Columbia University, New York, New York Sleep Disorders
Olajide Williams, MD, MSc
Associate Professor of Neurology, Columbia University College of Physicians & Surgeons, New York, New York Nontraumatic Disorders of the Spinal Cord; Diseases of Muscle
Jennifer Williamson, MPH, MS, CGC
Senior Staff Associate of Research, Sergievsky Center, Columbia University College of Physicians & Surgeons, New York, New York Dementia & Memory Loss
Clinton B. Wright, MD
Associate Professor, Departments of Neurology, Epidemiology, and Public Health, University of Miami, Miami, Florida Dementia & Memory Loss
Benjamin J. Wycherly, MD
ProHealth Hearing & Balance, University of Connecticut, Division of Otolaryngology, Farmington, Connecticut Hearing Loss & Dizziness
Joshua Z. Willey, MD
Assistant Professor of Neurology, Columbia University Vagelos College of Physicians and Surgeons, New York, New York Cerebrovascular Disease: Ischemic Stroke & Transient Ischemic Attack
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Preface Seven years after the second edition of this book, the era of precision medicine is upon us. Assuming that any genetic mutation has the potential to cause disease, it has been predicted that a comprehensive medical textbook of the future will have at least 20,000 chapters, one for each of our coding genes. (Following already established trends, such a book will be electronic only.) In the meantime, clinicians continue to use more prosaic strategies in managing patients with neurologic disorders. Clinical conundrums persist, and management seldom addresses RNA splicing or histone acetylation. In fact, despite breathtaking scientific progress, most clinical decisions are made without understanding the root cause of the disorder in question. Calcitonin gene-related peptide antagonists might offer clues to the pathophysiology of migraine, but at the moment there is no consensus as to what migraine actually is. As with previous editions, the focus of this book is practical, and the principal intended audience is primary care physicians. Specialists (including neurologists), surgeons, nurses, and physicians’ assistants are also invited. Introductory chapters address specific symptoms and diagnostic procedures. Subsequent chapters are disease-specific and adhere to a standard format, beginning with Essentials of Diagnosis (to help a clinician get a sense of being in the right ballpark), followed by Symptoms and Signs, Diagnostic Studies, Treatment, and Prognosis. Tables are abundant, and references are up-to-date. If you seek guidance in selecting one of the growing number of medications available to treat multiple sclerosis, you will find it here. But if you want to know the role of interleukin-2 signaling in demyelinating disease, you need to look elsewhere. It is estimated that more than 20% of admissions to community hospitals in the United States involve patients with neurologic symptoms and signs. Too many non-neurologists are uneasy dealing with such patients. In steering a course between oversimplification and recondite detail, this book aims to instill clinical confidence and thereby, perhaps, to improve patient care. John C.M. Brust, MD
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Section I. Neurologic Investigations
Electroencephalography Tina Shih, MD
▶▶General Considerations Electroencephalography (EEG), a diagnostic test invented over a century ago, is still widely used today in the evaluation of patients with paroxysmal neurologic disorders such as seizures and epilepsy. Although brain electrical activity is very low in voltage (on the order of microvolts) in comparison with ambient noise (on the order of volts), EEG uses the technique of differential amplification to cancel out noise and increase the amplitude of the waveforms of interest. EEG compares the voltages recorded from two different brain regions and plots this result over time. A standard array of metal electrodes is placed on the scalp of the patient, and over a 30-minute period, brain electrical activity sampled from different regions of the cortex is recorded simultaneously. EEG thus provides both spatial and temporal information about brain activity. In the past, EEG was recorded on paper, and the electrical activity was displayed in a static manner. Today, the activity is recorded digitally, allowing the data to be displayed in multiple ways after the recording has been completed. EEG recordings use standard montages, which allow the comparison of recordings from individual electrodes with either adjacent electrodes or distant electrodes (Figure 1–1). Montages provide a means of viewing the data in an organized fashion; some montages enhance localized findings, whereas others highlight global or diffuse findings. For routine outpatient EEGs, an ideal recording environment is quiet, allowing the patient to achieve relaxed wakefulness and to fall asleep (Figure 1–2). During the EEG recording, hyperventilation (having the patient exhale repeatedly and deeply for 180 seconds) and photic stimulation (strobe light flashes for 10 seconds at a time, at different frequencies ranging from 1–25 Hz) are also performed, as both techniques can elicit abnormal EEG activity in certain patients.
▶▶When to Order The EEG has multiple clinical applications. It can be used to confirm the diagnosis of seizures or epilepsy, either by
demonstrating interictal (between seizures) epileptiform activity or, serendipitously, by directly recording a seizure. The EEG is important in the classification of seizures and epilepsy syndromes, and it can uncover a previously unknown structural, functional, or metabolic abnormality, even when imaging is normal. The EEG is also useful in diagnosing nonconvulsive status epilepticus (interminable seizure activity during which the patient appears comatose from an unknown cause), revealing intermittent seizure activity as a potential factor in unexplained coma, confirming electrocerebral inactivity (ie, so-called brain death, see Chapter 4 for discussion concerning more reliable tests to confirm electrocerebral inactivity), diagnosing certain neurologic syndromes (eg, Creutzfeldt-Jakob disease, subacute sclerosing panencephalitis), and monitoring cerebral perfusion during carotid endarterectomy.
▶▶Findings The EEG report generally includes several observations: 1. Is the background activity normal or abnormal for age and state of the patient (wakefulness vs sleep)? Is the mixture of frequencies appropriate? Is there a normal organization of the waveforms? A normal adult EEG during wakefulness is characterized by an admixture of wave forms in the beta frequency range (13–25 Hz or cycles per second) and alpha frequency range (8–12 Hz), whereas slower frequency wave forms in the theta range (4–7 Hz) and delta range (<4 Hz) are observed in drowsiness and sleep. 2. Are there any focal features (findings only observed in one region)? Do the two hemispheres of the brain appear electrically symmetric? 3.Are there any epileptiform discharges (also known as spikes or sharp waves)? 4. Is sleep achieved? Is the sleep architecture appropriate? 5.Does hyperventilation or photic stimulation elicit any abnormalities?
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CHAPTER 1 Run 1: Longitudinal bipolar
Fp1 9 1
F4 17 6
7 18 Pz P4 8
Run 2: Transverse bipolar
T4 15 T6 16
1 2 3 4
Fp1-F3 F3-C3 C3-P3 P3-O1
5 6 7 8
Fp2-F4 F4-C4 C4-P4 P4-O2
9 10 11 12
Fp1-F7 F7-T3 T3-T5 T5-O1
13 14 15 16
Fp2-F8 F8-T4 T4-T6 T6-O2
19 20 21
LUC-A1 RLC-A2 ECG
Pg1 1 F7 4 A1 Left
Pg2 Fp2 3
12 13 T4
15 16 14 Pz P4 17 T6 T5 P3 18 20 19 O1 O2 Inion
1 2 3
F7-Fp1 Fp1-Fp2 Fp2-F8
4 5 6 7
F7-F3 F3-Fz Fz-F4 F4-F8
8 9 10 11 12 13
A1-T3 T3-C3 C3-Cz Cz-C4 C4-T4 T4-A2
14 15 16 17
T5-P3 P3-Pz Pz-P4 P4-T4
18 19 20
T5-O1 O1-O2 O2-T6
▲▲ Figure 1–1. Two commonly used EEG montages: longitudinal bipolar and transverse bipolar. (C = central; F = frontal; Fp = frontal polar; O = occipital; P = parietal; T = temporal. Odd numbers denote “left”-hemisphere electrodes and even numbers denote “right”-hemisphere electrodes.)
Fp1-F3 F3-C3 C3-P3 P3-01 Eye blinks
Fp2-F4 F4-C4 C4-P4 P4-O2
Alpha rhythm of 9 Hz
Fp1-F7 F7-T3 T3-T5 T5-O1 300 µV Fp2-F8 F8-T4
T4-T6 T6-O2 Fz-Cz Cz-Pz Technologist demonstrating that the patient is vigilantly awake 09/11/2001 10:55:17 MOR
09/11/2001 10:55:17 ANS, QUES.
▲▲ Figure 1–2. Normal awake EEG of a 7-year-old child (longitudinal bipolar montage). This 11-second epoch is presented using the longitudinal bipolar montage with the first four channels representing the left parasagittal electrodes and the next four channels representing the right parasagittal electrodes. Channels 9 through 11 are left temporal electrodes; channels 13 through 16 are right temporal electrodes. Channels 17 and 18 are over the vertex of the head. Note the V-like deflections in the bifrontal channels, which are secondary to eye blinks and the 8–9 Hz “alpha” rhythm in the occipital channels.
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Electroencephalography The EEG report ends with the interpreter’s impression of whether the tracing is normal or abnormal and how these findings correspond to the patient’s clinical picture. It is important to realize that despite the application of EEG in certain clinical settings, findings are often nonspecific. The abnormality referred to as diffuse background slowing and disorganization can result from metabolic derangements, intoxication, or brain structural abnormalities involving both hemispheres (eg, head trauma, strokes, hydrocephalus, multiple sclerosis, or Alzheimer dementia). The EEG can also lack sensitivity, even in the face of glaring clinical abnormalities. Patients with clear memory impairment, language difficulties, and poor attention and concentration in mild-to-moderate Alzheimer dementia may have a normal EEG. Persistently normal tracings do not exclude the possibility of underlying epilepsy.
▶▶Continuous EEG Monitoring Because it is rare that a seizure will occur during a 30-minute recording, long-term EEG monitoring (with or without simultaneous video monitoring) has been developed to record and characterize seizures and other paroxysmal
spells. In a specialized nursing unit in the hospital or as an ambulatory outpatient recording, long-term monitoring is becoming more widely available. Concurrent video and EEG monitoring is considered the gold standard for diagnosis of seizures, epilepsy, and psychogenic nonepileptic seizures and for distinguishing other paroxysmal spells from seizures (eg, syncope, hypoglycemia, or breath-holding spells). Another major application for continuous video EEG monitoring is epilepsy presurgical evaluation—to determine whether a patient is a candidate for focal brain resection. Long-term monitoring is also increasingly used in the critical care arena, most commonly in cases of status epilepticus, but also in patients after craniotomy, stroke, or head trauma. Prolonged EEG recordings provide another means of continuously monitoring the neurologic status of patients, especially in situations where the bedside neurologic examination is limited (coma). Fisch B. Fisch and Spehlmann’s EEG Primer: Basic Principles of Digital and Analog EEG. 3rd ed. Amsterdam, The Netherlands: Elsevier BV; 1999. Rowan AJ, Tolunsky E. Primer of EEG: With a Mini-Atlas. Philadelphia, PA: Butterworth-Heinemann; 2003.
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Electromyography, Nerve Conduction Studies, & Evoked Potentials Dora Leung, MD
▼▼ELECTROMYOGRAPHY & NERVE
Nerve conduction studies and needle electromyography (EMG) provide objective physiologic assessment of peripheral nerves and muscles. These two parts of the examination are performed sequentially, and when a patient is referred to an EMG laboratory, the understanding is that electrodiagnostic evaluation will include both nerve conduction studies and EMG. Special studies are performed in selected patients when clinically indicated.
NERVE CONDUCTION STUDIES 1. Routine Studies
▶▶General Considerations Studies are performed on motor and sensory nerves, but only large myelinated fibers can be evaluated in nerve conduction studies (Figure 2–1). Most studies use surface recording electrodes because of ease and convenience.
▶▶Technique In motor conduction studies, an electrical stimulus is delivered to a skin location known to overlie a peripheral nerve based on anatomical landmarks, and motor responses are recorded from muscles innervated by that nerve (Table 2–1). For example, the median nerve can be stimulated at the wrist and then more proximally at the elbow, with the recording electrode placed over the abductor pollicis brevis muscle in the thenar eminence. The evoked response obtained from the electrical stimulation is called the compound motor action potential (CMAP) (Figures 2–2 and 2–3). By measuring the distance between the two stimulating sites and the difference between latency onset of the resultant CMAPs, the examiner can calculate the motor conduction velocity of that nerve segment.
Sensory nerve conduction studies directly assess sensory axons by recording a sensory nerve action potential (SNAP) proximal or distal to the site of stimulation (Figure 2–4; see also Table 2–1). If the stimulus site is distal and the recording electrode is proximal, the impulse is directed toward the spinal cord (orthodromic study). If the stimulation site is proximal and recording site is distal, the impulse is directed away from the spinal cord (antidromic study). SNAP responses usually have small amplitudes in the order of microvolts (as compared with millivolts in the motor responses), and multiple responses with averaging are required to separate background noise from the desired waveforms.
▶▶Electrodiagnostic Data Components that are evaluated in nerve conduction studies include distal latency, conduction velocity, amplitude, and duration.
A. Distal Latency Distal latency is measured in milliseconds and is the time between the onset of the stimulus to the onset of resulting action potential. Distal latencies of motor nerves are compared with standardized values and can indicate distal nerve lesions if prolonged as a result of demyelination. However, because of the conduction time required for a nerve impulse to cross the neuromuscular junction and generate the CMAP response, distal latency alone cannot be used to calculate motor conduction velocity. Motor conduction velocity requires an additional stimulation at a more proximal segment of the nerve. The conduction velocity is calculated by the measured distance between the two stimuli divided by the difference in the distal latencies of the motor evoked potentials (see Figure 2–3). In sensory nerves, because of the absence of neuromuscular junctions, velocity can be calculated directly from sensory latency; the measured distance between stimulation and recording sites is divided by the distal latency of the sensory potential (see Figure 2–4).
▲▲ Figure 2–1. Technique of nerve conduction studies. Electrode setup for (A) motor and (B) sensory conduction studies of the median nerve. (R1 = recording electrode; R2 = reference electrode; S = stimulation sites.)
Table 2–1. Nerves commonly tested in nerve conduction studies. Location
Commonly Studied Arms
Median (sensory and motor) Ulnar (sensory, and motor recording from abductor digiti minimi)
B. Conduction Velocity Conduction velocity studies measure the speed of impulse conduction in the largest and fastest fibers in the nerve tested. They may therefore fail to detect abnormalities in smaller sensory fibers.
C. Amplitude Amplitude is the height of the evoked responses, which is on the order of millivolts in motor responses and microvolts in sensory responses. In a CMAP, the amplitude reflects both the number of fibers generating the action potential and the efficiency of neuromuscular transmission. The CMAP amplitude often correlates clinically with patients’ symptoms; weakness and sensory loss caused by large fiber peripheral neuropathy may have low CMAP and SNAP amplitudes. In advanced peripheral neuropathy, sensory and/or motor responses may be absent.
D. Duration Duration refers to the total duration of an evoked response measured in milliseconds. It reflects the different conduction Distal latency Stimulus artifact
▲▲ Figure 2–2. Components of the motor action potential.
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CHAPTER 2 MCV = distance between S2 – S1/DL2 – DL1 = m/s
▲▲ Figure 2–3. Motor conduction study of the median nerve. (MCV = motor conduction velocity; R = recording site; S1 = distal stimulation site; S2 = proximal stimulation site.) rates of axons traveling in the nerve and contributing to the evoked response. Axons that contribute to the beginning of a motor response are the fastest. If the spread of velocities in the axons within a nerve increases, the duration of response will also increase, with a corresponding drop in amplitude because of dispersion and phase cancellation. However, the area of the response (CMAP or SNAP), which is a product of duration and amplitude measured in millivolt-millisecond (μV·ms) or microvolt-millisecond (µV·ms), reflects the number of activated axons and should be unchanged or only slightly decreased.
▶▶Advantages Sensory nerve conduction studies are especially useful because sensory nerves are affected earlier than motor nerves in most peripheral neuropathies. Sensory studies also help differentiate lesions proximal and distal to the dorsal root ganglion. Sensory responses are normal if a lesion is proximal to the dorsal root ganglion. Therefore, even when there is nerve root avulsion from trauma with corresponding anesthesia in that dermatome, sensory responses are normal as long as the dorsal root ganglion is intact. SCV = distance between R – S/DL = m/s
▲▲ Figure 2–4. Sensory conduction study of the median nerve. (DL = distal latency; R1 = recording electrode; R2 = reference electrode; S = stimulation site; SCV = sensory conduction study.)
Table 2–2. Sources that can affect nerve conduction studies. Factor
Type of Change or Error
Artificially slow nerve conduction velocity, caused by excessively cool limb temperature
Mild decrease in nerve conduction amplitudes and velocities associated with aging
Errors in interpretation due to anatomic variation
Lack of standardization Mistakes in electrode placement Variation in interelectrode distance
Submaximal stimulation Excessive stimulation Reversal of cathode/anode Movement artifact
Errors in measuring distance due to change in limb position between time of stimulation and measurement, resulting in inaccurate calculation of conduction velocity
2. Demyelinating neuropathy—In demyelinating neuropathy, CMAP and SNAP amplitudes can be normal with distal stimulation. If there is focal demyelination, the CMAP amplitude can be markedly reduced on proximal stimulation due to conduction failure across the demyelinated segment. Demyelination can also cause slowing without complete conduction failure or block; the CMAP will then have lower amplitude with longer than normal duration as a result of excessive temporal dispersion within the nerve. However, the area under the negative peak is less affected than the amplitude, indicating that the amplitude decrease is a result of dispersion rather than axonal loss.
2. Late Responses Routine nerve conduction studies can evaluate only distal segments of the nerve. In the leg, conduction studies evaluate the peroneal and tibial nerves up to the knee. Therefore, late responses such as F waves and H-reflex are used to evaluate the less-assessable proximal portions of the nerve.
A. F Waves
Motor and sensory conduction studies can be used to identify focal lesions and to distinguish peripheral neuropathy from myopathy and motor neuron diseases. They can also detect subclinical lesions (eg, Charcot-Marie-Tooth disease, carpal tunnel syndrome) and differentiate among inherited and acquired, axonal, and demyelinating polyneuropathy.
F waves are low-amplitude responses produced by antidromic stimulation of a small number of motor neurons during motor conduction studies. Because the nerve acts as an electric cable, stimulation not only results in CMAP response in the distal muscle, but the impulse is also transmitted proximally toward the spinal cord. A small population of motor neurons (about 2–3% of the total at that level) may then become activated and transmit a motor impulse back along the nerve to the recording muscle. The resulting evoked response, which can be viewed as “backfiring,” is much smaller in amplitude than the CMAP. Because each electrical stimulation activates a different subpopulation of motor neurons, consecutively recorded F waves vary in latency, amplitude, and duration. The F-wave latency is the time between the stimulus and onset of an F wave, and the minimal F-wave latency is the most commonly recorded parameter. Prolonged or absent F-wave latency can reflect a proximal lesion when distal nerve conduction is normal. F-wave study is especially useful if there is suspicion of demyelinating neuropathy in proximal segments. In Guillain-Barré syndrome, abnormal or absent F waves may be the earliest finding on nerve conduction studies. If the motor nerve conduction study is slowed distally due to underlying peripheral or entrapment neuropathy, F-wave latency can also be prolonged.
1. Axonal neuropathy—In axonal neuropathy, motor and sensory action potentials show low amplitudes, with conduction velocity either preserved or only mildly slowed. With nerve transection, distal motor and sensory responses can be normal during the first 2 days, but as wallerian degeneration proceeds, the response amplitude diminishes with time and becomes absent 7–10 days after injury.
The H-reflex is the electrophysiologic equivalent of the Achilles tendon reflex. By early childhood it is present only in gastrocnemius-soleus and flexor carpi radialis muscles. It is a motor-evoked response that is elicited by stimulating sensory fibers in a peripheral nerve, usually the tibial nerve. A long-duration (1 millisecond), low-voltage stimulus is used to activate large-diameter, fast-conducting sensory
▶▶Disadvantages The limitation of sensory conduction is that results are easily affected by other physiologic factors such as age, limb temperature, or limb edema (Table 2–2). In addition, because of technical limitations, the studies evaluate more proximal portions of the sensory nerve and not the most distal segments. For example, sensory studies of digital nerves supplied by median nerve assess the response in the fingers but not in the fingertips. Often in patients with focal or unilateral lesions, the contralateral limb is used as an internal control. The amplitude of a CMAP or SNAP is considered abnormal if it is less than 50% of the value in the contralateral side. Therefore, studies are usually performed bilaterally.
▶▶When to Order
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fibers at an intensity that is below the activation threshold of motor fibers. The action potential then propagates to the dorsal root ganglion and subsequently into the dorsal horn of the spinal cord, and through a monosynaptic pathway, anterior horn cells are activated, in turn activating the corresponding muscle (the soleus). Because the H-reflex is mediated primarily through the S1 root, asymmetry of latency between sides is often used to support a diagnosis of S1 radiculopathy or a proximal tibial nerve lesion. However, the H-reflex may be absent bilaterally in normal people.
34.5 mA 0.1 ms 3 Hz
A 35.0 mA 0.1 ms 3 Hz
3. Repetitive Stimulation Repetitive stimulation of motor nerves is indicated when there is suspicion of a neuromuscular junction disorder such as myasthenia gravis (Figure 2–5). In normal subjects, persistent stimulation at rates less than 5 Hz cause progressive decline in release of acetylcholine vesicles into the synaptic cleft. Normally, because there is a large excess of vesicles and neurotransmitters compared with the number of receptors, the decline does not result in reduced numbers of activated muscle fibers. In individuals with myasthenia gravis, reduced number of functional acetylcholine receptors results in failure of neuromuscular transmission with repetitive stimulation. Subsequently, fewer activated fibers result in progressively smaller CMAP amplitude; this is referred to as decremental response to repetitive stimulation. In myasthenia gravis, the drop in amplitude is progressive from the first to the fourth response, which is usually the nadir response, and more than 10% decline in amplitude is considered abnormal. Subsequent responses may show a slight recovery in amplitude. Usually a stimulation rate of 2–3 Hz is adequate to produce maximal decrement. Sustained maximal activation of the muscle being tested is similar to repetitive stimulation at high frequency and can also result in a decremental response, with the maximal decrement seen 3–4 minutes after the exercise (post-exercise exhaustion). Repetitive stimulation immediately after brief (15-second) exercise at maximal effort has the opposite effect and reverses the decrement that is seen at baseline before exercise (post-exercise facilitation). In normal subjects, postexercise facilitation never causes increased response (increment) greater than 50% of baseline. However, in patients with Lambert-Eaton myasthenic syndrome, a presynaptic disorder, the increment increase from post-exercise facilitation can be more than two- to threefold. This amplitude increase can also be seen with repetitive stimulation at a high rate (50 Hz).
▶▶General Considerations The needle study is an extension of clinical muscle testing. Almost any muscle can be examined, although to do so is not always practical or useful.
B 34.5 mA 0.1 ms 3 Hz
▲▲ Figure 2–5. Procedure for repetitive stimulation. Study of patient with myasthenia gravis is depicted here. A: Baseline repetitive stimulation: (1) Stabilize limb and obtain supramaximal response in distal nerve-muscle pain (eg, median-thenar or ulnar-hypothenar); (2) deliver 10 supramaximal stimuli at 3 Hz; (3) calculate % decrement between first and fourth potentials (shown here, 30% decrement). B: Post-exercise facilitation: (1) Perform voluntary maximal contraction of muscle being tested for 15 seconds; (2) deliver 10 stimuli at 3 Hz immediately after exercise; (3) calculate % decrement (here 2%) and look for increment. C: Post-exercise exhaustion: (1) Exercise using maximal force for 1 minute; (2) repeat train of stimulation at 3 Hz at 1, 2, 3, and 4 minutes after exercise; (3) calculate % decrement (here 45%) and, if no decrement, repeat study in the proximal system (accessorytrapezius or facial-nasalis).
▶▶Electrodiagnostic Data Needle EMG includes assessment of spontaneous activity; evaluation of motor unit amplitude, duration, and appearance; and recruitment pattern of the muscle.
A. Spontaneous Activity At rest, a normal muscle is electrically silent except in the region of the neuromuscular junctions, where spontaneous endplate potentials result from spontaneous continuous release of vesicles containing acetylcholine. Abnormal spontaneous activity
▲▲ Figure 2–6. Abnormal spontaneous potentials. A: Fibrillations. B: Positive sharp waves. C: Fasciculations. seen in muscles includes fibrillation potentials, positive sharp waves, and fasciculations (Figure 2–6). Fibrillations and positive sharp waves are spontaneous discharges of individual muscle fibers and have characteristic configurations. They are present in both neurogenic denervation and myopathic diseases, and they have similar pathologic significance. Fibrillations and positive sharp waves are seen about 2 weeks after nerve injury, indicating muscle denervation. In chronic neurogenic diseases such as peripheral neuropathy or motor neuron disease, these potentials can be persistent. Fibrillations and positive sharp waves are also present in myopathic conditions, especially inflammatory myopathies and muscular dystrophy, in which muscle necrosis can separate remaining muscle fibers from their nerve axons and effectively denervate them. Thus these abnormal spontaneous potentials by themselves cannot distinguish neuropathic from myopathic processes, and information from nerve conduction studies as well as motor unit and recruitment analysis are crucial for diagnosis. Fasciculations are abnormal, large, spontaneous discharges of single motor units. Their firing pattern is slow and irregular, and although their configuration may be identical to an activated motor unit, they are not under voluntary control. A fasciculation represents a motor unit (all the muscle fibers innervated by a motor neuron); its configuration is therefore larger in amplitude and more complex than a fibrillation or a positive sharp wave. Often visible on skin surface as small muscle movements that are insufficient to move the joint, fasciculations are characteristic of motor neuron diseases such as amyotrophic lateral sclerosis. They can also occur in chronic neurogenic conditions such as peripheral neuropathy or radiculopathy, and they can be a normal finding in small foot muscles and in patients with benign fasciculation syndrome. In addition to documenting the presence of abnormal spontaneous activity, it is important to note the frequency and abundance of these activities. The abundance of fibrillations and positive sharp waves on EMG corresponds with the severity of the denervation/myopathic process. Other abnormal spontaneous activities occur in certain diseases. Myotonic discharges are high-frequency repetitive discharges that wax and wane in amplitude to produce a
sound similar to revving up of a motorcycle engine. Myotonic discharges are seen in myotonic dystrophy, myotonia congenita, paramyotonia, familial periodic paralysis, and acid maltase deficiency. Complex repetitive discharges are highfrequency discharges that begin and end abruptly without the waxing and waning quality of myotonic discharges. They can be seen in both muscle and nerve diseases. Myokymia are grouped discharges occurring in a semi-rhythmic manner separated by periods of silence. Corresponding to continuous rippling or quivering in the muscle, they are often seen in facial muscles, especially in patients with multiple sclerosis, brainstem tumors, hypocalcemia, or post-radiation treatment. Cramps are painful involuntary muscle contractions that on EMG are seen as high-frequency motor unit action potential discharges. Cramps can be benign (eg, nocturnal or post-exercise cramps), but they are also associated with neuropathic and metabolic abnormalities.
B. Motor Unit Potentials Following evaluation of insertional and spontaneous activity, motor unit potentials (MUPs) are assessed (Figure 2–7). The normal extracellularly recorded MUP is a triphasic waveform with a duration of 5–15 milliseconds. Its amplitude varies with the size of the motor unit and its proximity to the recording needle. The number of fibers in each motor unit varies, from very few in muscles requiring fine control (eg, eye muscles) to hundreds in large muscles, such as calf muscles. Each motor unit territory measures about 5–10 mm in diameter, with many units overlapping each other. When a nerve impulse travels down a motor axon, all the muscle fibers in that motor unit fire almost simultaneously, producing the characteristic triphasic waveform. In initial voluntary contraction at low effort, small motor units are activated first, with an initial increase in power from higher firing frequency. However, as more force is required, this increased firing frequency is insufficient, and larger motor units are recruited on stronger contraction. To characterize whether a muscle is normal or whether it reflects a myopathic or a neurogenic disorder, quantitative EMG (QEMG) is needed. In QEMG, at least 20 MUPs are collected from one muscle and analyzed, and their values are
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Degenerated muscle fibers
▲▲ Figure 2–7. Comparison of (A) normal muscle fiber and motor unit potential with changes seen in (B) neuropathic and (C) myopathic diseases. compared with standardized values. Shorter mean duration and lower amplitudes suggest loss of motor fibers in the motor unit, as seen in myopathies. In neurogenic diseases, amplitude and duration increase due to reinnervation and expansion of MUP territory. Polyphasic MUPs result from temporal dispersion of the individual muscle fibers in the motor unit and can be seen in both myopathic and neuropathic conditions.
contraction (Figure 2–8). On maximal effort, the needle recording from a muscle shows a dense band of motor units that completely obliterates the baseline (full recruitment pattern; see Figure 2–8A). The amplitude of the recruitment pattern (the so-called envelope) normally is in the range of 2–4 mV. In myopathy, the number of motor units is unchanged, but the number of muscle fibers in each unit is decreased. Therefore, the density of the recruitment pattern is unchanged, but the amplitude of the envelope during maximal force is low. In addition, because motor units are small
C. Recruitment Pattern The recruitment pattern is the electrical summation of activated MUPs during a submaximal or maximal