Giáo trình curent diagnosis and treatment neurology 3rd by brust

a LANGE medical book

CURRENT

Diagnosis & Treatment
Neurology
THIRD EDITION

Edited by
John C.M. Brust, MD
Professor of Neurology
Columbia University College of Physicians & Surgeons
New York, New York

New York Chicago San Francisco Athens London Madrid Mexico City 
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Brust_FM_p00i_pxiv.indd 1

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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

1

  6. Hearing Loss & Dizziness

Tina Shih, MD
General Considerations
1
When to Order

1
Findings1
Continuous EEG Monitoring
3

  2. Electromyography, Nerve Conduction
Studies, & Evoked Potentials
Dora Leung, MD
Electromyography & Nerve Conduction Studies
Nerve Conduction Studies
Needle Electromyography
Single-Fiber Electromyography
Evoked Potentials
Visual Evoked Potentials
Brainstem Auditory Evoked Potentials
Somatosensory Evoked Potentials

 3.Neuroradiology

41

Jack J. Wazen, MD, FACS, Soha N. Ghossaini, MD, FACS
& Benjamin J. Wycherly, MD
Hearing Loss
41
Tinnitus43
Dizziness44

4

  7. Epilepsy & Seizures

50

Tina Shih, MD
Incidence & Pathogenesis
50
Seizure Types
50
Epilepsy Syndromes
55
Clinical Findings
57
Differential Diagnosis
59
Treatment60
Prognosis65

4
4
8
11
12
12
12
12

8. Headache & Facial Pain

14

66

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

37

31

John C.M. Brust, MD
General Considerations
31
Pathogenesis31
Clinical Findings
31
Differential Diagnosis
33

iii

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iv

Contents

Carotid or Vertebral Artery Dissection &
Carotidynia78
Cold Stimulus Headache
78
Headaches Associated with Sleep
79
Pain in the Face, Pharynx, Joint, & Ear
79
Trigeminal Neuralgia
79
Glossopharyngeal Neuralgia
80
Yawning Headache
80
Eagle Syndrome
80
Red Ear Syndrome
80
Temporomandibular Joint Disorder
81
Primary Stabbing Headache
81
Nummular Headache
81

9. Dementia & Memory Loss

82

Karen Marder, MD, MPH, Lawrence S. Honig, MD, PhD,
William C. Kreisl, MD, Nikolaos Scarmeas, MD, MS,
Chen Zhao, MD, Edward Huey, MD, Juliana R. Dutra, MD,
James M. Noble, MD, MS, & Clinton B. Wright, MD, MPH
Alzheimer Disease
82
Mild Cognitive Impairment
89
Vascular Cognitive Impairment
90
Frontotemporal Dementias
92
Progressive Supranuclear Palsy
95
Corticobasal Degeneration
97
Parkinson Disease Dementia
99
Dementia with Lewy Bodies
101
Normal Pressure Hydrocephalus
103
Transient Global Amnesia
105
Huntington Disease
107

10. Cerebrovascular Disease: Ischemic

Stroke & Transient Ischemic Attack

109

Joshua Z. Willey, MD
General Considerations
109
Pathogenesis109
Clinical Findings
110
Acute Ischemic Stroke Treatment
113
Prevention117
Prognosis & Rehabilitation
119

11. Cerebrovascular Disease: Hemorrhagic
Stroke120
Richard A. Bernstein, MD, PhD & Philip Chang, MD
Intraparenchymal Hemorrhage
Subarachnoid Hemorrhage
Aneurysmal Subarachnoid Hemorrhage
Unruptured Intracranial Aneurysms
Infected (Mycotic) Aneurysms
Vascular Anomalies
Arteriovenous Malformations
Cavernous Malformations
Dural Arteriovenous Fistulas

Brust_FM_p00i_pxiv.indd 4

120
131
131
139
139
140
140
141
142

Vein of Galen Aneurysm
Developmental Venous Anomalies
Capillary Telangiectasias

12. Central Nervous System Neoplasms

142
142
143

144

Christopher E. Mandigo, MD & Jeffrey N. Bruce, MD
Brain Tumors
Primary Brain Tumors
Metastatic Tumors
Tumors of the Skull
Spinal Cord Tumors

144
144
156
158
159

13. Paraneoplastic Neurologic Syndromes 161
Ugonma N. Chukwueke, MD, Alfredo D. Voloschin, MD,
Andrew B. Lassman, MD, & Lakshmi Nayak, MD
Paraneoplastic Cerebellar Degeneration
164
Paraneoplastic Encephalomyelitis and
Encephalitis165
Paraneoplastic Opsoclonus-Myoclonus
167
Paraneoplastic Myelitis
169
Paraneoplastic Motor Neuron Disease
169
Stiff Person Syndrome
170
Paraneoplastic Visual Syndromes
171
Peripheral Nerve Hyperexcitability
172
Paraneoplastic Peripheral Neuropathy
172
Paraneoplastic Syndromes of the Neuromuscular
Junction173
Dermatomyositis & Polymyositis

174
Acknowledgments174

14.Trauma
Katja E. Wartenberg, MD, PhD &
Stephan A. Mayer, MD
Head Trauma
Spinal Trauma

15. Movement Disorders

175

175
192

199

Blair Ford, MD, Howard Geyer, MD, PhD, &
Susan B. Bressman, MD
Parkinsonism & Parkinson Disease
199
Atypical Parkinsonian Syndromes
207
Progressive Supranuclear Palsy
207
Corticobasal Degeneration
208
Multiple System Atrophy
209

Essential Tremor
209
Dystonia211
Myoclonus217
Tourette Syndrome & Tic Disorders
219
Tardive Dyskinesia & Other
Drug-Related Movement Disorders
222
Acute Syndromes Caused by Neuroleptics
223
Neuroleptic-Induced Parkinsonism
224

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v

Contents
Tardive Syndromes
Neuroleptic Malignant Syndrome
Restless Legs Syndrome

16. Ataxia & Cerebellar Disease
Harini Sarva, MD & Claire Henchcliffe, MD, DPhil
Approach to the Ataxic Patient
Acquired Ataxias
Cerebellar Ischemic Stroke Syndromes
Cerebellar Hemorrhage

Toxins & Nutritional Deficiencies
Abnormal Homeostasis & Ataxia
Endocrine Disease & Ataxia
Cerebellar Neoplasms
Infectious Causes of Ataxia
Ataxia Associated with Inflammatory &
Autoimmune Disease
Gluten Ataxia
Ataxia of Paraneoplastic Origin
Multiple System Atrophy (Type C)
Inherited Ataxias
Autosomal Dominant Cerebellar Ataxias
Autosomal Recessive Cerebellar Ataxias
Cerebellar Ataxia in Mitochondrial Disorders
X-Linked Ataxias: Fragile X–Associated
Tremor & Ataxia Syndrome

224
226
227

229
229
232
232
233
233
234
234
234

234
234
235
235
236
237
237
242
246
248

17. Multiple Sclerosis & Demyelinating
Diseases250
Bruce A.C. Cree, MD, PhD, MAS
Multiple Sclerosis
250
Acute Transverse Myelitis
271
Neuromyelitis Optica Spectrum Disorder
273
Acute Disseminated Encephalomyelitis
275
Antimyelin Oligodendrocyte Glycoprotein
Demyelination276
Chronic Relapsing Inflammatory Optic
Neuropathy276

18. Nontraumatic Disorders of the
Spinal Cord

278

Olajide Williams, MD, MSc, Jared Levin, MD,
& Michelle Stern, MD
Spinal Cord Syndromes
278
Spinal Cord Tumors
280
Myelitis280
Spinal Epidural Abscess
281
Syringomyelia283
Spinal Cord Arteriovenous Shunts
284
Spinal Cord Infarction
285
Spinal Epidural & Subdural Hematomas
286

Brust_FM_p00i_pxiv.indd 5

Subacute Combined Degeneration
287
Amyotrophic Lateral Sclerosis & Other Motor
Neuron Diseases
287
Spinocerebellar Degeneration
287
Radiculopathy287
Lumbar Stenosis

292
Cervical Spondylotic Myelopathy
293
Issues in Rehabilitation of Spinal Cord–Injured
Patients294
Bladder Dysfunction
294
Bowel Dysfunction
294
Pressure Sores
295
Spasticity295
Autonomic Dysfunction
295
Contractures296
Sexual Dysfunction After Spinal Cord Injury 296
Deep Vein Thrombosis
296

19. Peripheral Neuropathies

297

Thomas H. Brannagan III, MD
Mononeuropathies299
Cranial Nerve Disorders
299
Upper Extremity Nerves
306
Lower Extremity Nerves

312
Multiple Mononeuropathy Syndromes
317
Acquired Polyneuropathies
318
Autoimmune Neuropathies
318
Infectious Polyneuropathy
325
Toxic & Metabolic Neuropathies
328
Neuropathies Associated with
330
Systemic Disease
330
Hereditary Peripheral Neuropathies
334

20. Motor Neuron Diseases

340

Neil A. Shneider, MD, PhD & Michio Hirano, MD
Amyotrophic Lateral Sclerosis
Lower Motor Neuron Disorders
Spinal Muscular Atrophy
Monomelic Amyotrophic Lateral Sclerosis
Kennedy Disease
Upper Motor Neuron Disorders
Hereditary Spastic Paraparesis

Primary Lateral Sclerosis

21. Autonomic Disorders

344
349
349
349
350
350
350
350

352

Louis H. Weimer, MD, FAAN, FANA
Dysautonomia352
Treatment of Orthostatic Hypotension
354
Disorders Associated with Autonomic Failure
355
Neurodegenerative Disorders & Parkinsonian
Syndromes355
Acute & Subacute Autonomic Neuropathies
356

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vi

Contents

Chronic Autonomic Neuropathies
Orthostatic Intolerance & Postural Orthostatic
Tachycardia Syndrome
Sudomotor (Sweating) Disorders
Autonomic Symptoms in Spinal
Cord Injury

22. Myasthenia Gravis & Other Disorders
of the Neuromuscular Junction

358
360
361
362

363

Svetlana Faktorovich, MD &
Shanna K. Patterson, MD
Neuromuscular Transmission
363
Myasthenia Gravis (Autoimmune Myasthenia)
363
Congenital Myasthenia Syndromes
371
Lambert-Eaton Myasthenic Syndrome
371

Botulism373
Tick Paralysis
374

23. Diseases of Muscle

375

Christina M. Ulane, MD, PhD &
Olajide Williams, MD
Myopathy375
Acquired Myopathies
377
Inflammatory Myopathies
377
Infectious Myopathies
382
Drug-Induced or Toxic Myopathies
384
Corticosteroid Myopathy
384
Cholesterol-Lowering Agent Myopathy
385
Alcoholic Myopathy
386
Myopathy in Critical Illness
387
Secondary Metabolic & Endocrine Myopathies
387
Hypokalemic Myopathy

387
Hypophosphatemic Myopathy
387
Chronic Renal Failure–Related Myopathies
388
Diabetic Muscle Infarction
388
Hypothyroid Myopathy
388
Hyperthyroid Myopathy
388
Hyperparathyroid Myopathy
389
Vitamin D–Related Myopathy
389
Cushing Disease
389
Primary Metabolic Myopathies
389
Mitochondrial Myopathies
391
Myoglobinuria391
Channelopathies391
Congenital Myopathies
392
Muscular Dystrophies
392
Congenital Muscular Dystrophies
392
Duchenne Muscular Dystrophy

392
Becker Muscular Dystrophy
394
Myotonic Dystrophy
395
Fascioscapulohumeral Dystrophy
396
Limb-Girdle Muscular Dystrophy
397
Emery-Dreifuss Muscular Dystrophy
397
Oculopharyngeal Muscular Dystrophy
398

Brust_FM_p00i_pxiv.indd 6

24. Mitochondrial Diseases

399

Michio Hirano, MD
Mitochondrial DNA Mutations
400
Kearns-Sayre Syndrome & Chronic Progressive
External Ophthalmoplegia
400
Melas Syndrome
402
Merrf Syndrome
403

Narp Syndrome & Maternally Inherited Leigh
Syndrome403
Leber Hereditary Optic Neuropathy
404
Nuclear DNA Mutations
405
Other Mitochondrial Disorders
406
Nucleoside Reverse-Transcriptase Inhibitor–
Induced Myopathy
406
Aminoglycoside-Induced Deafness
406

25. Neurologic Intensive Care

408

Santiago Ortega-Gutierrez, MD & Alan Z. Segal, MD
Increased Intracranial Pressure
408
Hypoxic-Ischemic Encephalopathy After
Cardiac Arrest
412
Neuromuscular Weakness in
Critical Illness
414

26. Bacterial, Fungal, & Parasitic Infections
of the Nervous System

416
Barbara S. Koppel, MD, Kiran T. Thakur, MD, &
Adedoyin Akinlonu, MD, MPH
Bacterial Infections
416
  Bacterial Meningitis
416
  Brain Abscess
424
  Subdural Empyema
428
  Epidural Abscess
429
  Intracranial Suppurative Thrombophlebitis 432
  Malignant Otitis Externa & Otitis Media
434
  Chronic & Recurrent Meningitis
435
Tuberculosis & Other Granulomatous
Infections438
  Central Nervous System Tuberculosis
438
  Leprosy (Mycobacterium Leprae)443
Infectious Toxins
443
 Tetanus
443
 Botulism
444
 Diphtheria

444
Fungal Infections
444
Spirochetal Infections
448
 Syphilis
448
  Nonsexually Transmitted Treponematoses 451
 Leptospirosis
451
  Lyme Disease (Neuroborreliosis)
452

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Contents
Rickettsial, Protozoal, & Helminthic Infections
  Rickettsial & Other Arthropod-Borne
 Infections
  Protozoal Infections
  Helminthic Infections

454
454
457
464

27. Viral Infections of the Nervous System 470
Kiran Thakur, MD & James M. Noble, MD, MS

Acute Viral Encephalitis
470
Viral Meningitis
475
Viral Central Nervous System Vasculopathies
476
Acute Viral Myelitis
477
Radiculitis & Ganglionitis
479
Chronic Viral Infections
480
Emerging and Reemerging Viral Neurotropic
Infections482

28. HIV Neurology

484

Deanna Saylor, MD, MHS, Ned Sacktor, MD,
Jeffrey Rumbaugh, MD, Jeffrey Sevigny, MD,
& Lydia B. Estanislao, MD
Central Nervous System Disorders Associated
with HIV484
Cryptococcal Meningitis
484
Toxoplasmosis of the Central Nervous System 486
Primary Central Nervous System Lymphoma 488
Progressive Multifocal Leukoencephalopathy 489
HIV-Associated Neurocognitive Disorder

490
HIV-Associated Myelopathy
492
HIV Meningitis
493
Varicella-Zoster Vasculitis
493
Cytomegalovirus Encephalitis
494
Peripheral Nervous System Complications
494
Cytomegalovirus Polyradiculopathy
494
Distal Symmetric Polyneuropathy
496
Mononeuropathy Multiplex
497
Acute Inflammatory Demyelinating
Polyneuropathy497
HIV-Associated Neuromuscular Weakness
Syndrome498
HIV-Associated Myopathy
498
HIV-Associated Motor Neuron Disease
499
Immune Reconstitution Inflammatory
Syndrome499

29. Prion Diseases

501

Lawrence S. Honig, MD, PhD
Creutzfeldt-Jakob Disease
501
Variant Creutzfeldt-Jakob Disease
503
Gerstmann-Sträussler-Scheinker Syndrome
504
Fatal Familial Insomnia
504
Kuru504
Treatment of Prion Diseases
505

Brust_FM_p00i_pxiv.indd 7

vii

30. Disorders of Cerebrospinal Fluid
Dynamics506
John C.M. Brust, MD
Obstructive Hydrocephalus
Intracranial Hypotension
Idiopathic Intracranial Hypertension

506
508
508

31. Sleep Disorders

511

Andrew J. Westwood, MD & Carl Bazil, MD, PhD
Sleep Architecture
511
Sleep Testing
511
Insomnia512
Narcolepsy and Idiopathic Hypersomnia
514
Parasomnias515
Sleep-Related Breathing Disorders
517
Sleep-Related Movement Disorders
518
Circadian Rhythm Disorders
518

32. Systemic & Metabolic Disorders

520

Laura Lennihan, MD & Jason Diamond, MD
Nutritional Deficiencies
520
Electrolyte Disorders
521
Hyperglycemia & Hypoglycemia

522
Hypertensive Encephalopathy & Posterior
Reversible Encephalopathy Syndrome
523
Cardiac Disease
524
Pulmonary Disease
525
Liver Disease
525
Renal Disease
526
Pancreatic Disease
527
Endocrine Disorders
527
Hematologic Disorders
529
Bone & Joint Disorders
530
Neurosarcoidosis531
Vasculitis & Connective Tissue Disorders
532
Disordered Temperature Regulation
534
Medication-Induced Neurologic Effects
535
Biologic Neurotoxins
539
Neurotoxicity Caused by Heavy Metals &

Industrial Compounds
541

33.Alcoholism

544

John C.M. Brust, MD
Ethanol Intoxication
Ethanol Dependence & Withdrawal
Wernicke-Korsakoff Syndrome
Other Neurologic Complications of Alcoholism
Treatment of Chronic Alcoholism

544
545
546
547
548

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viii

Contents

34. Drug Dependence
John C.M. Brust, MD
Drugs of Dependence

Medical & Neurologic Complications of
Abused Substances

35. Psychiatric Disorders

551
551
555

558

Eric R. Marcus, MD
Approach to the Psychiatric Patient
558
Major Psychiatric Illnesses
559
Organic Brain Syndromes
559
Manic-Depressive Illnesses
559
Schizophrenia562
Anxiety Disorders
563
Chronic Anxiety
563
Panic Attacks
564
Personality Disorders
565

36. Neurologic Disorders of Childhood
& Adolescence
Claudia A. Chiriboga, MD, MPH &
Marc C. Patterson, MD, FRACP
Neonatal Neurologic Disorders
Hypoxic-Ischemic Encephalopathy
Intraventricular Hemorrhage

Brust_FM_p00i_pxiv.indd 8

566

Periventricular Leukoencephalomalacia
568
Neonatal Strokes
568
Developmental Disorders
569
Mental Retardation
569
Cerebral Palsy
571
Autistic Disorder & Pervasive Developmental
Disorder572
Learning Disabilities
573
Attention-Deficit/Hyperactivity Disorder
574
Genetic Disorders
577

Chromosomal Disorders
577
Inborn Errors of Metabolism
578
Congenital Brain Anomalies
581
Neurocutaneous Disorders
581
Neurofibromatosis Type 1
581
Neurofibromatosis Type 2
583
Tuberous Sclerosis Complex
583
Sturge-Weber Syndrome
584
Ataxia-Telangiectasia584
Index585
Color insert appears between pages 18 and 19.

566
566
567

14/11/18 11:34 AM


Authors
John C.M. Brust, MD

Adedoyin Akinlonu, MD, MPH

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

ix

Brust_FM_p00i_pxiv.indd 9

14/11/18 11:34 AM


x

Authors

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

Brust_FM_p00i_pxiv.indd 10

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

14/11/18 11:34 AM


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

xi

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

Brust_FM_p00i_pxiv.indd 11

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

14/11/18 11:34 AM


xii

Authors

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

Brust_FM_p00i_pxiv.indd 12

14/11/18 11:34 AM


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

xiii

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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

Brust_Ch01_p001-003.indd 1

1

1

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?

10/11/18 2:01 PM


2

CHAPTER 1
Run 1: Longitudinal bipolar

Pg1

F3

10

2

T3
Left

C3
3

11
T5

P3
4

12

Pg2
Fp2

Fp1
9
1

F7
A1

Nasion

5

13

F4
17 6

Fz

Cz

F8
14

C4

7
18
Pz
P4
8

O1

Run 2: Transverse bipolar

O2
Inion

A2

T4
15
T6
16

Right

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

17
18

Fz-Cz
Cz-Pz

19
20
21

LUC-A1
RLC-A2
ECG

Pg1
1
F7 4
A1
Left

8

T3

9

Fp1

F3

C3

5

10

Nasion

2

Fz
Cz

Pg2
Fp2 3

6 F47

F8

11

12 13
T4

C4

15

16
14
Pz
P4 17 T6
T5 P3
18
20
19
O1
O2
Inion

A2
Right

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

21

ECG

▲▲ 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

1s

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.

Brust_Ch01_p001-003.indd 2

10/11/18 2:01 PM


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

Brust_Ch01_p001-003.indd 3

3

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.

10/11/18 2:01 PM


4

2

Electromyography, Nerve
Conduction Studies, &
Evoked Potentials
Dora Leung, MD

▼▼ELECTROMYOGRAPHY & NERVE


CONDUCTION STUDIES

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.

Brust_Ch02_p004-013.indd 4

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).

13/11/18 11:26 AM


5

EMG, NERVE CONDUCTION STUDIES, & EVOKED POTENTIALS

S2

S1
R2

R2
R1

R1

S

A

B

▲▲ 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

Nerves

Commonly Studied
Arms

Median (sensory and motor)
Ulnar (sensory, and motor recording
from abductor digiti minimi)

Legs

Tibial (motor)
Peroneal (motor recording from
extensor digiti brevis)
Sural (sensory)

Less Commonly Studied

 

Motor

Ulnar (recording from first dorsal
interossei)
Radial
Musculocutaneous

Axillary
Peroneal (recording from tibialis
anterior)
Femoral

Sensory

Brust_Ch02_p004-013.indd 5

Radial
Dorsal ulnar cutaneous
Lateral antebrachial cutaneous
Superficial peroneal
Deep peroneal
Saphenous

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

Area

Amplitude

Duration

▲▲ Figure 2–2.  Components of the motor action potential.

13/11/18 11:26 AM


6

CHAPTER 2
MCV = distance between S2 – S1/DL2 – DL1 = m/s

S2

S1

R2

R1

Di

sta

nc

e

▲▲ 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

R2
R1

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.)

Brust_Ch02_p004-013.indd 6

13/11/18 11:26 AM


EMG, NERVE CONDUCTION STUDIES, & EVOKED POTENTIALS

Table 2–2.  Sources that can affect nerve conduction
studies.
Factor

Type of Change or Error

Limb temperature

Artificially slow nerve conduction velocity, caused by
excessively cool limb temperature

Patient age

Mild decrease in nerve conduction amplitudes and
velocities associated with aging

Nerve anomalies

Errors in interpretation due to anatomic variation

Technical problems

Lack of standardization
Mistakes in electrode placement
Variation in interelectrode distance

Stimulation problems

Submaximal stimulation
Excessive stimulation
Reversal of cathode/anode
Movement artifact

Measurement errors

Errors in measuring distance due to change in limb position between time of stimulation and measurement,
resulting in inaccurate calculation of conduction
velocity

7

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.

▶▶Findings

B. H-Reflex

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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8

CHAPTER 2

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.

2 mV/D

34.5 mA
0.1 ms
3 Hz

A
35.0 mA
0.1 ms
3 Hz

2 mV/D

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).

NEEDLE ELECTROMYOGRAPHY

▶▶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.

Brust_Ch02_p004-013.indd 8

B
34.5 mA
0.1 ms
3 Hz

2 mV/D

C

▲▲ 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

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9

EMG, NERVE CONDUCTION STUDIES, & EVOKED POTENTIALS
10 ms/D
1490.0 ms
50 µV/d

50 µV/d

8 ms/D
1307.3 ms
100 µV/d

Fibrillations

Positive sharp waves

Fasciculations

A

B

C

▲▲ 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

Brust_Ch02_p004-013.indd 9

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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10

CHAPTER 2

Degenerated
neuron/axon

Degenerated
muscle fibers

MUP

A

B

C

▲▲ 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

A

B

C

▲▲ Figure 2–8.  Recruitment patterns. A: Full. B: Reduced. C: Discrete.

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