Merritts neurology 10th ed l rowland (williams wilkins, 2000)

Merritt's Neurology 10th Edition (June 2000): by H Houston Textbook of Neurology Merritt (Editor), Lewis P Rowland (Editor), Randy Rowland By Lippincott Williams & Wilkins Publishers By OkDoKeY Merritt's Neurology CONTENTS Contributing Authors Preface Abbreviations SECTION I SYMPTOMS OF NEUROLOGIC DISORDERS Chapter Delirium and Dementia Scott A Small and Richard Mayeux Chapter Aphasia, Apraxia, and Agnosia J P Mohr Chapter Syncope and Seizure Timothy A Pedley and Dewey K Ziegler Chapter Coma John C.M Brust Chapter Diagnosis of Pain and Paresthesias Lewis P Rowland Chapter Dizziness and Hearing Loss Jack J.Wazen Chapter Impaired Vision Myles M Behrens Chapter Headache Neil H Raskin Chapter Involuntary Movements Stanley Fahn Chapter 10 Syndromes Caused by Weak Muscles Lewis P Rowland Chapter 11 Gait Disorders Sid Gilman Chapter 12 Signs and Symptoms in Neurologic Diagnosis Lewis P Rowland SECTION II HOW TO SELECT DIAGNOSTIC TESTS Chapter 13 Computed Tomography and Magnetic Resonance Imaging Robert DeLaPaz and Stephen Chan Chapter 14 Electroencephalography and Evoked Potentials Ronald G.Emerson,Thaddeus S.Walczak, and Timothy A.Pedley Chapter 15 Electromyography and Nerve Conduction Studies in Neuromuscular Disease Dale J Lange and Werner Trojaborg Chapter 16 Neurovascular Imaging J P Mohr and Robert DeLaPaz Chapter 17 Lumbar Puncture and Cerebrospinal Fluid Examination Robert A Fishman Chapter 18 Muscle and Nerve Biopsy Arthur P Hays Chapter 19 Neuropsychologic Evaluation Yaakov Stern Chapter 20 DNA Diagnosis Lewis P Rowland SECTION III INFECTIONS OF THE NERVOUS SYSTEM Chapter 21 Bacterial Infections James R.Miller and Burk Jubelt Chapter 22 Focal Infections Gary L Bernardini Chapter 23 Viral Infections Burk Jubelt and James R Miller Chapter 24 Acquired Immunodeficiency Syndrome Carolyn Barley Britton Chapter 25 Fungal and Yeast Infections Leon D.Prockop Chapter 26 Neurosarcoidosis John C.M Brust Chapter 27 Spirochete Infections: Neurosyphilis Lewis P.Rowland and Leonidas Stefanis Chapter 28 Spirochete Infections: Leptospirosis James R Miller Chapter 29 Spirochete Infections: Lyme Disease James R Miller Chapter 30 Parasitic Infections Burk Jubelt and James R Miller Chapter 31 Bacterial Toxins James R Miller Chapter 32 Reye Syndrome Darryl C De Vivo Chapter 33 Prion Diseases Burk Jubelt Chapter 34 Whipple Disease Elan D Louis SECTION IV VASCULAR DISEASES Chapter 35 Pathogenesis, Classification, and Epidemiology of Cerebrovascular Disease Ralph L Sacco Chapter 36 Examination of the Patient with Cerebrovascular Disease Randolph S.Marshall Chapter 37 Transient Ischemic Attack John C.M.Brust Chapter 38 Cerebral Infarction John C.M.Brust Chapter 39 Cerebral and Cerebellar Hemorrhage J P Mohr and Christian Stapf Chapter 40 Genetics of Stroke Alexander Halim and Ralph L Sacco Chapter 41 Other Cerebrovascular Syndromes Frank M Yatsu Chapter 42 Differential Diagnosis of Stroke Mitchell S.V Elkind and J.P Mohr Chapter 43 Stroke in Children Arnold P Gold and Abba L Cargan Chapter 44 Treatment and Prevention of Stroke Frank M Yatsu Chapter 45 Subarachnoid Hemorrhage Stephan A Mayer, Gary L Bernardini, John C.M Brust, and Robert A Solomon Chapter 46 Cerebral Veins and Sinuses Robert A Fishman Chapter 47 Vascular Disease of the Spinal Cord Leon A Weisberg SECTION V DISORDERS OF CEREBROSPINAL AND BRAIN FLUIDS Chapter 48 Hydrocephalus Leon D Prockop Chapter 49 Brain Edema and Disorders of Intracranial Pressure Robert A Fishman Chapter 50 Superficial Siderosis of the Central Nervous System Robert A Fishman Chapter 51 Hyperosmolar Hyperglycemic Nonketotic Syndrome Leon D.Prockop and Stephan A.Mayer SECTION VI TUMORS Chapter 52 General Considerations Casilda M Balmaceda Chapter 53 Tumors of the Skull And Cranial Nerves Jeffrey N.Bruce, Casilda M.Balmaceda, and Michael R.Fetell Chapter 54 Tumors of the Meninges Casilda M Balmaceda , Michael B Sisti, and Jeffrey N Bruce Chapter 55 Gliomas Casilda M Balmaceda and Robert L Fine Chapter 56 Lymphomas Casilda M Balmaceda Chapter 57 Pineal Region Tumors Jeffrey N Bruce, Casilda M Balmaceda, Bennett M Stein, and Michael R Fetell Chapter 58 Tumors of the Pituitary Gland Jeffrey N Bruce, Michael R Fetell, and Pamela U Freda Chapter 59 Congenital and Childhood Central Nervous System Tumors James H Garvin Jr and Neil A Feldstein Chapter 60 Vascular Tumors and Malformations Robert A Solomon, John Pile-Spellman, and J P Mohr Chapter 61 Metastatic Tumors Casilda M Balmaceda Chapter 62 Spinal Tumors Paul C McCormick, Michael R Fetell, and Lewis P Rowland SECTION VII TRAUMA Chapter 63 Head Injury Stephan A Mayer and Lewis P Rowland Chapter 64 Spinal Injury Joseph T.Marotta Chapter 65 Intervertebral Disks and Radiculopathy Paul C McCormick Chapter 66 Cervical Spondylotic Myelopathy Lewis P.Rowland and Paul C McCormick Chapter 67 Lumbar Spondylosis Lewis P Rowland and Paul C McCormick Chapter 68 Peripheral and Cranial Nerve Lesions Dale J Lange, Werner Trojaborg, and Lewis P Rowland Chapter 69 Thoracic Outlet Syndrome Lewis P Rowland Chapter 70 Neuropathic Pain and Posttraumatic Pain Syndromes James H Halsey Chapter 71 Radiation Injury Casilda M Balmaceda and Steven R Isaacson Chapter 72 Electrical and Lightning Injury Lewis P Rowland Chapter 73 Decompression Sickness Leon D Prockop SECTION VIII BIRTH INJURIES AND DEVELOPMENTAL ABNORMALITIES Chapter 74 Neonatal Neurology M Richard Koenigsberger and Ram Kairam Chapter 75 Floppy Infant Syndrome Thornton B.A Mason, II and Darryl C De Vivo Chapter 76 Static Disorders of Brain Development Isabelle Rapin Chapter 77 Laurence-Moon-Biedl Syndrome Melvin Greer Chapter 78 Structural Malformations Melvin Greer Chapter 79 Marcus Gunn and Möbius Syndromes Lewis P Rowland SECTION IX GENETIC DISEASES OF THE CENTRAL NERVOUS SYSTEM Chapter 80 Chromosomal Diseases Ching H Wang Chapter 81 Disorders of Amino Acid Metabolism John H Menkes Chapter 82 Disorders of Purine Metabolism Lewis P Rowland Chapter 83 Lysosomal and Other Storage Diseases William G Johnson Chapter 84 Disorders of Carbohydrate Metabolism Salvatore DiMauro Chapter 85 Glucose Transporter Protein Syndrome Darryl C De Vivo Chapter 86 Hyperammonemia Rosario R Trifiletti and Douglas R Nordli, Jr Chapter 87 Peroxisomal Diseases: Adrenoleukodystrophy, Zellweger Syndrome, and Refsum Disease Mia MacCollin and Darryl C De Vivo Chapter 88 Organic Acidurias Stefano Di Donato and Graziella Uziel Chapter 89 Disorders of Metal Metabolism John H Menkes Chapter 90 Acute Intermittent Porphyria Lewis P Rowland Chapter 91 Neurological Syndromes with Acanthocytes Timothy A Pedley and Lewis P Rowland Chapter 92 Xeroderma Pigmentosum Lewis P Rowland Chapter 93 Cerebral Degenerations of Childhood Eveline C Traeger and Isabelle Rapin Chapter 94 Diffuse Sclerosis Lewis P Rowland Chapter 95 Differential Diagnosis Eveline C Traeger and Isabelle Rapin SECTION X DISORDERS OF MITOCHONDRIAL DNA Chapter 96 Mitochondrial Encephalomyopathies: Diseases of Mitochondrial DNA Salvatore DiMauro, Eric A Schon, Michio Hirano, and Lewis P Rowland Chapter 97 Leber Hereditary Optic Neuropathy Myles M Behrens and Michio Hirano Chapter 98 Mitochondrial Diseases with Mutations of Nuclear DNA Darryl C De Vivo and Michio Hirano SECTION XI NEUROCUTANEOUS DISORDERS Chapter 99 Neurofibromatosis Arnold P Gold Chapter 100 Encephalotrigeminal Angiomatosis Arnold P Gold Chapter 101 Incontinentia Pigmenti Arnold P Gold Chapter 102 Tuberous Sclerosis Arnold P Gold SECTION XII PERIPHERAL NEUROPATHIES Chapter 103 General Considerations Norman Latov Chapter 104 Hereditary Neuropathies Robert E Lovelace and Lewis P Rowland Chapter 105 Acquired Neuropathies Dale J Lange, Norman Latov and Werner Trojaborg SECTION XIII DEMENTIAS Chapter 106 Alzheimer Disease and Related Dementias Scott A Small and Richard Mayeux SECTION XIV ATAXIAS Chapter 107 Hereditary Ataxias Susan B Bressman, Timothy Lynch, and Roger N Rosenberg SECTION XV MOVEMENT DISORDERS Chapter 108 Huntington Disease Stanley Fahn Chapter 109 Sydenham and Other Forms of Chorea Stanley Fahn Chapter 110 Myoclonus Stanley Fahn Chapter 111 Gilles de la Tourette Syndrome Stanley Fahn Chapter 112 Dystonia Stanley Fahn and Susan B Bressman Chapter 113 Essential Tremor Elan D Louis and Paul E Greene Chapter 114 Parkinsonism Stanley Fahn and Serge Przedborski Chapter 115 Progressive Supranuclear Palsy Paul E Greene Chapter 116 Tardive Dyskinesia and Other Neuroleptic-Induced Syndromes Stanley Fahn and Robert E Burke SECTION XVI SPINAL CORD DISEASES Chapter 117 Hereditary and Acquired Spastic Paraplegia Lewis P Rowland Chapter 118 Hereditary and Acquired Motor Neuron Diseases Lewis P Rowland Chapter 119 Syringomyelia Elliott L Mancall and Paul C McCormick SECTION XVII DISORDERS OF THE NEUROMUSCULAR JUNCTION Chapter 120 Myasthenia Gravis Audrey S Penn and Lewis P Rowland Chapter 121 Lambert-Eaton Syndrome Audrey S Penn Chapter 122 Botulism and Antibiotic-Induced Neuromuscular Disorders Audrey S Penn Chapter 123 Acute Quadriplegic Myopathy Michio Hirano SECTION XVIII MYOPATHIES Chapter 124 Identifying Disorders of the Motor Unit Lewis P Rowland Chapter 125 Progressive Muscular Dystrophies Lewis P Rowland Chapter 126 Familial Periodic Paralysis Lewis P Rowland Chapter 127 Congenital Disorders of Muscle Lewis P Rowland Chapter 128 Myoglobinuria Lewis P Rowland Chapter 129 Muscle Cramps and Stiffness Robert B Layzer and Lewis P Rowland Chapter 130 Dermatomyositis Lewis P Rowland Chapter 131 Polymyositis, Inclusion Body Myositis, and Related Myopathies Lewis P Rowland Chapter 132 Myositis Ossificans Lewis P Rowland SECTION XIX DEMYELINATING DISEASES Chapter 133 Multiple Sclerosis James R Miller Chapter 134 Marchiafava-Bignami Disease James R Miller Chapter 135 Central Pontine Myelinolysis Gary L Bernardini and Elliott L Mancall SECTION XX AUTONOMIC DISORDERS Chapter 136 Neurogenic Orthostatic Hypotension and Autonomic Failure Louis H Weimer Chapter 137 Acute Autonomic Neuropathy Louis H Weimer Chapter 138 Familial Dysautonomia Alan M Aron SECTION XXI PAROXYSMAL DISORDERS Chapter 139 Migraine and Other Headaches Neil H Raskin Chapter 140 Epilepsy Timothy A Pedley, Carl W Bazil, and Martha J Morrell Chapter 141 Febrile Seizures Douglas R Nordli, Jr and Timothy A Pedley Chapter 142 Neonatal Seizures Douglas R Nordli, Jr and Timothy A Pedley Chapter 143 Transient Global Amnesia John C.M Brust Chapter 144 Meniere Syndrome Jack J Wazen Chapter 145 Sleep Disorders June M Fry SECTION XXII SYSTEMIC DISEASES AND GENERAL MEDICINE Chapter 146 Endocrine Diseases Gary M Abrams and Earl A Zimmerman Chapter 147 Hematologic and Related Diseases Kyriakos P Papadopoulos and Casilda M Balmaceda Chapter 148 Hepatic Disease Neil H Raskin and Lewis P Rowland Chapter 149 Cerebral Complications of Cardiac Surgery Eric J Heyer and Lewis P Rowland Chapter 150 Bone Disease Roger N Rosenberg Chapter 151 Renal Disease Neil H Raskin Chapter 152 Respiratory Care: Diagnosis and Management Stephan A Mayer and Matthew E Fink Chapter 153 Paraneoplastic Syndromes Lewis P Rowland Chapter 154 Nutritional Disorders: Vitamin B12 Deficiency, Malabsorption, and Malnutrition Lewis P Rowland and Bradford P Worrall Chapter 155 Vasculitis Syndromes Lewis P Rowland Chapter 156 Neurologic Disease During Pregnancy Alison M Pack and Martha J Morrell SECTION XXIII ENVIRONMENTAL NEUROLOGY Chapter 157 Alcoholism John C.M Brust Chapter 158 Drug Dependence John C.M Brust Chapter 159 Iatrogenic Disease Lewis P Rowland Chapter 160 Complications of Cancer Chemotherapy Massimo Corbo and Casilda M Balmaceda Chapter 161 Occupational and Environmental Neurotoxicology Lewis P Rowland Chapter 162 Abuse of Children Claudia A Chiriboga Chapter 163 Falls in the Elderly Lewis P Rowland SECTION XXIV REHABILITATION Chapter 164 Neurologic Rehabilitation Laura Lennihan and Glenn M Seliger SECTION XXV ETHICAL AND LEGAL GUIDELINES Chapter 165 End-of-Life Issues in Neurology Lewis P Rowland CONTRIBUTORING AUTHORS Gary M Abrams, M.D Associate Professor Department of Neurology University of California 505 Parnassus Avenue San Francisco, California 94143, and Chief, Department of Neurology/Rehabilitation University of California, San Francisco/Mt Zion Medical Center 1600 Divisadero Street San Francisco, California 94115 Alan M Aron, M.D Professor of Pediatrics and Clinical Neurology Departments of Neurology and Pediatrics Mount Sinai-New York University Medical Center, and Director, Attending Neurologist, and Attending Pediatrician Department of Pediatric Neurology Mount Sinai Hospital One Gustave Levy Place New York, New York 10029 Casilda M Balmaceda, M.D Assistant Professor of Neurology Columbia University College of Physicians and Surgeons Assistant Attending Neurologist New York-Presbyterian Hospital Neurological Institute Columbia-Presbyterian Medical Center 710 West 168th Street New York, New York 10032 Carl W Bazil, M.D., Ph.D Assistant Professor of Neurology Columbia University College of Physicians and Surgeons Assistant Attending Neurologist New York-Presbyterian Hospital Neurological Institute Columbia-Presbyterian Medical Center 710 West 168th Street New York, New York 10032 Myles M Behrens, M.D Professor of Clinical Ophthalmology Columbia University College of Physicians and Surgeons Attending Ophthalmologist New York-Presbyterian Hospital Eye Institute Room 114 635 165th Street, Box 71 New York, New York 10032 Gary L Bernardini, M.D., Ph.D Associate Professor of Neurology Albany Medical College Director Neurological Intensive Care Unit Albany Medical Center 47 New Scotland Avenue Albany, New York 12208 Susan B Bressman, M.D Chair Department of Neurology Beth Israel Hospital Phillips Ambulatory Care Center 10 Union Square East, Suite 2Q New York, New York 10032 Carolyn Barley Britton, M.D Associate Professor of Clinical Neurology Columbia University College of Physicians and Surgeons Associate Attending Neurologist New York-Presbyterian Hospital Neurological Institute Columbia-Presbyterian Medical Center 710 West 168th Street New York, New York 10032 Jeffrey N Bruce, M.D Associate Professor of Neurological Surgery Associate Attending Neurological Surgeon Neurological Institute Columbia-Presbyterian Medical Center 710 West 168th Street New York, New York 10032 John C M Brust, M.D Professor of Clinical Neurology Department of Neurology Columbia University College of Physicians and Surgeons Attending Neurologist New York-Presbyterian Hospital 710 West 168th Street New York, New York 10032, and Director, Department of Neurology Harlem Hospital Center 506 Lenox Avenue New York, New York 10037 Robert E Burke, M.D Professor of Neurology Attending Neurologist Columbia University College of Physicians and Surgeons Black Building 650 West 168th Street, 3rd Floor New York, New York 10032 Abba L Cargan, M.D Assistant Professor of Neurology Columbia University College of Physicians and Surgeons Assistant Attending Neurologist New York-Presbyterian Hospital Neurological Institute Columbia-Presbyterian Medical Center 710 West 168th Street New York, New York 10032 Stephen Chan, M.D Assistant Professor of Radiology Assistant Attending Neurologist (Neuroradiology) Columbia University College of Physicians and Surgeons Milstein Hospital Building 177 Fort Washington Avenue New York, New York 10032 Claudia A Chiriboga, M.D Assistant Professor of Neurology Columbia University College of Physicians and Surgeons Assistant Attending Neurologist New York-Presbyterian Hospital Neurological Institute Columbia-Presbyterian Medical Center 710 West 168th Street New York, New York 10032 Massimo Corbo Assistant Professor of Neurology Department of Neurology San Raffaele Hospital Scientific Institute of Milan 20132 Milan, Italy Darryl C De Vivo, M.D Sidney Carter Professor of Neurology Professor of Pediatrics Columbia University College of Physicians and Surgeons Attending Neurologist and Pediatrician Chief, Division of Pediatric Neurology Neurological Institute Columbia-Presbyterian Medical Center 710 West 168th Street New York, New York 10032 Robert DeLaPaz, M.D Professor of Radiology Columbia University College of Physicians and Surgeons Attending Radiologist Director, Division of Neuroradiology New York-Presbyterian Hospital Milstein Hospital Building Columbia-Presbyterian Medical Center 177 Fort Washington Avenue New York, New York 10032 Stefano Di Donato, M.D Department of Pediatric Neurology Istituto Nazionale Neurologico C Besta Via Celoria, 11 Milano, 20133 Italy Salvatore DiMauro, M.D Lucy G Moses Professor Department of Neurology Columbia University College of Physicians and Surgeons 630 West 168th Street New York, New York 10032 Mitchell S.V Elkind, M.D Assistant Professor of Neurology Columbia University College of Physicians and Surgeons Assistant Attending Neurologist New York-Presbyterian Hospital Neurological Institute Columbia-Presbyterian Medical Center 710 West 168th Street New York, New York 10032 Ronald G Emerson, M.D Professor of Clinical Neurology and Clinical Pediatrics Columbia University College of Physicians and Surgeons Attending Neurologist New York-Presbyterian Hospital Columbia-Presbyterian Medical Center Neurological Institute 710 West 168th Street New York, New York 10032 Stanley Fahn, M.D H Houston Merritt Professor of Neurology Columbia University College of Physicians and Surgeons Attending Neurologist Chief, Division of Movement Disorder New York-Presbyterian Hospital Neurological Institute 710 West 168th Street New York, New York 10032 Neil A Feldstein, M.D Assistant Professor of Neurological Surgery Assistant Attending Neurosurgeon Neurological Institute Columbia-Presbyterian Medical Center 710 West 168th Street New York, New York 10032 Michael R Fetell, M.D Professor of Clinical Neurology and Neurosurgery Attending Neurologist Neurological Institute Columbia-Presbyterian Medical Center 710 West 168th Street New York, New York 10032 Robert L Fine, M.D Herbert Irving Associate Professor of Medicine Director, Medical Oncology Division Columbia University College of Physicians and Surgeons Associate Attending Physician in Medicine New York-Presbyterian Hospital 650 West 168th Street New York, New York 10032 Matthew E Fink, M.D Department of Neurology Albert Einstein College of Medicine President, Chief Executive Officer, and Attending Neurologist Beth Israel Medical Center First Avenue at 16th Street New York, New York 10003 Robert A Fishman, M.D Professor Emeritus Department of Neurology University of California, San Francisco, and Attending Neurologist Department of Neurology University of California, San Francisco Hospitals 505 Parnassus Avenue San Francisco, California 94143 Pamela U Freda Associate Professor of Clinical Medicine Department of Medicine Columbia University College of Physicians and Surgeons 630 West 168th Street New York, New York 10032, and Assistant Attending Physician Department of Medicine New York-Presbyterian Hospital 622 West 168th Street New York, New York 10032 June M Fry M.D., Ph.D Professor Department of Neurology MCP Hahnemann University 3200 Henry Avenue Philadelphia, Pennsylvania 19129, and Director of Sleep Medicine Department of Neurology Medical College of Pennsylvania Hospital 3300 Henry Avenue Measurement of blood lead levels is the time-honored diagnostic method even though technical variations render values somewhat uncertain in individual cases The mean whole blood level in adults who are not exposed to occupational hazards is less than µg/dL Standard recommendations now consider levels safe up to 30 µg/dL; some consider a higher safe limit, 50 µg/dL Workers are monitored closely if levels exceed 40 µg/dL The upper limit of lead in urine is 150 µg/g creatinine Peripheral neuropathy is usually accompanied by blood lead levels greater than 70 µg/dL In children, the warning mark is a blood lead level of 10 µg/dL, and estimates suggest that 1.7 million children still have higher levels Children with levels exceeding 10 µg/dL are more likely to be African-American, poor, and living in large cities For them, the major source of poisoning is lead paint, followed by contaminated soils and dust Chelation therapy commences with levels of 40 µg/dL Testing blood lead levels is recommended for children with presumed autism, attention deficit disorder, pervasive development disorder, mental retardation, or language problems The blood lead level is considered a more reliable indicator than the biochemical tests mentioned below A provocative test with Ca-EDTA has been advocated but has been used less and less often The patient is given 500 mg/m Ca-EDTA in 5% glucose infused in hour If urinary lead excretion in the next hours exceeds 60% of the amount of EDTA given, the test is positive, that is, the chelator is presumed to have combined with and mobilized excessive body stores of lead The test is cumbersome, and reliability is debated A diagnosis of lead intoxication is supported if blood zinc protoporphyrin exceeds 100 µg/dL or if urinary aminolevulinic acid excretion is higher than 15 mg/L With blood lead levels of 10 µg/dL, the activity of aminolevulinic acid dehydratase is low At higher lead levels, the activities of coproporphyrinogen oxidase and ferrochetalase are also low Anemia and basophilic stippling of erythrocytes are characteristic No other neurotoxin generates similarly specific biochemical abnormalities that can be used diagnostically Nerve conduction velocities are nonspecifically slow in lead and other neuropathies The diagnosis of arsenic intoxication is confirmed by urinary levels greater than 75 µg/dL Hair analysis has been used but is not deemed reliable The length-dependent neuropathy is primarily axonal with secondary demyelination After acute exposure, blood tests are not useful for detecting thallium because the metal is taken up by cells so rapidly that blood levels not rise Urinary thallium can be detected by atomic absorption spectrometry Normal urinary values are 0.3 to 0.8 µg/L and levels of 200 to 300 are seen in overt poisoning A provocative test depends on KCl, which is given orally in a dose of 45 mEq Potassium displaces thallium from tissue stores and blood levels rise, which can be detected by serial measurement of urinary content Prevention and Treatment Preventive measures have been most publicized for lead with special concern for the welfare of children Education programs, paint removal, and deleading house paints have all played a role Personnel involved in deleading must be protected Workers in industries at risk have been increasingly monitored and removed from exposure when blood lead levels begin to rise Motor nerve conduction studies have also been used Once symptoms of intoxication appear and the diagnosis of lead poisoning is clear, removal from exposure is mandatory Chelation therapy can be instituted For children with blood levels less than 45 µg/dL, oral treatment can be instituted with 2,3-dimercaptosuccinic acid and penicillamine For acute encephalopathy and blood levels more than 70 µg/dL, Ca-EDTA and dimercaprol (2,3-dimercaptopropanol), also called British anti-Lewisite (BAL), can be used together, starting with BAL, to mg/kg intramuscularly; this is followed by simultaneous but separate intramuscular injections of both chelators given every hours for the next to days For symptomatic neuropathy, Ca-EDTA can be used alone at doses of 50 to 75 mg/kg every 12 hours in a 3- to 5-day course and a 2- to 3-week rest between courses until the blood level is normal Treatment of the encephalopathy is also symptomatic or surgical Prevention of mercury intoxication requires monitoring in high-risk occupations, including dental offices, and correction of inadequate ventilation, avoiding vacuuming of spilled mercury, and removal of workers whose urinary level has increased fourfold or is more than 50 µg/L Control of industrial pollution may require major effort If the person is symptomatic, treatment commences with dimercaprol, which is given intramuscularly to mg/kg every hours for day 1, every 12 hours on day 2, and then once a day for the next days, followed by a 2-day interruption Other agents are 2,3-dimercaptosuccinic acid and 2,3-dimercapto-propane-1-sulfonate, a water-soluble form of BAL All agents are somewhat effective for organic and inorganic mercury poisoning BAL therapy is also used for acute arsenic poisoning and is most effective before symptoms of neuropathy appear BAL is considered more effective than penicillamine in treating the chronic neuropathy Hemodialysis is another treatment for the acute episode Aside from monitoring occupational exposure to thallium, an important preventive measure is protection of children against the ingestion of candylike pellets Treatment of acute poisoning depends in part on enhancing urinary and fecal excretion of thallium by giving laxatives and using Prussian Blue or activated charcoal to retard absorption Urinary excretion is enhanced by forced diuresis and administration of KCl; hemodialysis may be effective OTHER INTOXICATIONS Organophosphates Organophosphates, sometimes in combination with carbamates, are used as pesticides by more than 2.5 million agriculture workers and also by amateur gardeners Also exposed are those engaged in the manufacture of these compounds and military personnel who use or store compounds designed for chemical warfare It is estimated that 150,000 to 300,000 people have pesticide-induced illness each year Popular compounds include malathion, parathion, and others Most are lipid soluble and readily absorbed after ingestion, inhalation, or application to the skin They are powerful inhibitors of acetylcholinesterase Three clinical stages follow in sequence First, acute cholinergic crisis comprises nicotinic effects (limb weakness, fasciculation, tachycardia) and muscarinic manifestations (miosis, lacrimation, salivation) CNS signs include ataxia, seizures, altered consciousness, and sometimes coma Second, the intermediate syndrome appears in to days after exposure Weakness may be profound, affecting the proximal limbs, cranial muscles, neck flexors, and respiration; tendon reflexes are lost The differential diagnosis includes the Guillain-Barré syndrome, periodic paralysis, and myasthenia gravis Among survivors, recovery may be slow but is the rule Third, organophosphate-induced delayed neuropathy appears to weeks after exposure The syndrome was first described during the period of prohibition in the United States when illicit whiskey was made in home stills: 50,000 people consumed “Jamaica Ginger” or “Jinger Jake” that was later found to contain triorthocresyl phosphate Paresthesias and distal leg weakness appeared weeks later Triorthocresyl phosphate is not an anticholinesterase, but the syndrome was then seen after exposure to cholinergic organophosphates The disorder as been attributed to inhibition of “neuropathy target esterase,” disruption of axonal transport, and a dying back neuropathy Although paresthesias may be noted, the disorder is dominantly motor Among survivors, upper motor neuron signs implicate the CNS, which in combination with profound lower motor neuron signs may simulate ALS except that there is no progression for years Exposure can be documented by levels of the drug or its metabolites in blood or urine Measurement of red cell or plasma cholinesterase is an indirect marker In electrodiagnostic studies there may be a repetitive response to a single nerve stimulus The acute disorder is a medical emergency risking death from respiratory paralysis If the patient has been splashed, clothing must be stripped and the skin washed thoroughly to prevent further absorption Gastric lavage may be needed Airway control and ventilation must be ensured and cardiac function monitored Atropine is the best antidote; subcutaneous doses of 0.5 to 1.0 mg are given every 15 minutes until an effect is observed in the form of dilated pupils, flushed face, dry mouth, and dry skin with cessation of sweating To suppress airway secretions, some give intravenous doses up to mg every hour Glycopyrrolate can be added to atropine Oxime therapy is also recommended in seriously ill patients These compounds reactivate acetylcholinesterase and should be given as soon as possible after exposure by continuous intravenous infusion Solvents and Organic Compounds Hexacarbon neuropathy results from mixtures that produce 2,5-hexanedione Outbreaks arise from industrial exposure to n-hexane, recreational abuse, and industrial exposure to methyl-n-butyl ketone Paresthesias and weakness appear distally in the legs and only later are the hands affected Acutely, the syndrome may resemble the Guillain-Barré syndrome, including slow conduction velocity Alternatively, progression may be slow Optic neuropathy is rare The characteristic pathologic change is neurofilamentous axonal swelling and distal axonal degeneration Effective measures have been taken to reduce industrial exposure and to eliminate the toxins from glues formerly used for glue sniffing Epidemics have largely disappeared Other organic compounds that induce axonal neuropathy by industrial exposure are acrylamide, carbon disulfide, methyl bromide, and triorthocresyl phosphate A current debate is whether house painters are at risk for solvent-induced behavioral disorders Carbon Monoxide Carbon monoxide intoxication is more often deliberate than accidental, about 600 a year accidentally in the United States and to 10 times more often in suicide attempts Accidents are caused predominantly by automobile exhausts and poorly ventilated gasoline-powered heaters Methylene chloride, a paint remover, is another source Toxicity results from issue hypoxia and direct damage to cellular structures CO competes with oxygen for binding to hemoglobin; it binds to other proteins, including myoglobin and cytochrome c oxidase Symptoms may be mild, simulating viral infection, or it may occur with another emergency, smoke inhalation Nonspecific symptoms may comprise headache, malaise, dizziness, nausea, difficulty concentrating, and dyspnea A delayed neuropsychiatric syndrome may follow acute exposure by to 240 days, with cognitive and personality changes, parkinsonism, and psychotic behavior Although the syndrome seems ominous, 50% to 75% of patients recover Diagnosis is made by finding high levels of carboxyhemoglobin However, serum levels may have fallen by the time the patient reaches the emergency room Measurement of CO in expired air can therefore be useful Blood taken at the scene by emergency technicians can be used Rescue from fires is of prime importance Hospital admission is reserved for the more seriously affected or those with other medical problems Oxygen is administered because it shortens the half-life of carboxyhemoglobin Hyperbaric oxygen therapy has been used with increasing frequency, but it is uncertain whether it hastens recovery or reduces the rate of late sequelae Coma is a clear indication for hyperbaric therapy Prevention is largely a matter of monitoring equipment, monitoring workers, and education about the hazards of running a motor vehicle in a closed space Nitrous Oxide Myelopathy (Layzer Syndrome) In 1978, Layzer described 15 patients; 14 were dentists Thirteen had abused nitrous oxide for months to several years; patients had been exposed only professionally, working in poorly ventilated offices Symptoms included early paresthesias, Lhermitte symptoms, ataxia, leg weakness, impotence, and sphincter disturbances Examination showed signs of sensorimotor polyneuropathy, often combined with signs implicating the posterior and lateral columns of the spinal cord in a pattern identical to that of subacute combined system disease (SCD) due to B 12 deficiency Electrodiagnostic tests showed axonal polyneuropathy; cerebrospinal fluid and other laboratory results were normal Layzer surmised that the gas interfered with the action of B 12 Subsequent experience proved him correct Additional cases were reported in abusers of nitrous oxide, and improvement was seen in weeks or months after exposure ceased Another version of the disorder was seen in people, including a vegetarian, who had hematologic evidence of B 12 deficiency but were asymptomatic until the neurologic disorder was precipitated by nitrous oxide anesthesia for surgery Magnetic resonance imaging shows the characteristic distribution of lesions in the spinal cord Scott et al (1981) reproduced the syndrome by maintaining monkeys in an atmosphere of nitrous oxide If the diet was supplemented with methionine, the disorder was prevented, but in controls, symptoms progressed to a moribund state; the spinal cord and peripheral nerves of the unsupplemented monkeys showed changes of SCD Inability to resynthesize methionine from homocysteine seemed responsible, and the primary lesion producing SCD in humans with pernicious anemia may also be impaired synthesis of methionine biosynthesis Cyanocobalamin is involved in the conversion of l-methylmalonyl coenzyme A to succinyl coenzyme A and the formation of methionine by methylation of homocysteine, a reaction essential for DNA synthesis and for maintenance of the myelin sheath by the methylation of myelin basic protein Active vitamin B 12 contains cobalt and nitrous oxide produces irreversible oxidation of the Co 2+, rendering B12 inactive Seafood Intoxication Ciguatera or the marine neurotoxic syndrome is the most common nonbacterial form of food poisoning in the United States and Canada It is caused by eating tropical reef fish that contain several toxins in edible parts; the toxins are thought to arise in dinoflagellates It is endemic in subtropical regions, and food shipped to other parts of the world spreads the disease The acute symptoms are gastrointestinal followed by sensory symptoms, paresthesias, and pruritus “Sensory inversion” describes the peculiarity that cold feels hot and vice versa Myalgia, fasciculations, areflexia, trismus, and carpopedal spasm may be noted Respiratory failure is exceptional Other systems may be involved prominently, including pain on sexual activity None of the physical findings is diagnostic, and there are no formal criteria for diagnosis Most associated toxins open sodium channels, but at least one affects calcium channels Peripheral nerve conduction velocities are often slow Bioassays for the ciguatoxins or immunochemical methods are being developed, but none has yet achieved approval by consensus Treatment is therefore symptomatic Shellfish poisoning can result from contamination of mollusks by saxitoxin, which blocks sodium channels The symptoms are similar to ciguatera but more severe, and respiratory depression is a threat The toxin originates in a dinoflagellate In the series of De Carvalho et al (1998), cerebellar ataxia was the dominant finding and peripheral nerve conduction was normal Recovery was rapid in those patients, but among those described by Gessner et al., of 11 patients were treated with mechanical ventilation and died Hypertension was also prominent Binding assays and liquid chromatography identified the toxin in serum and urine In Japan, the agent of puffer fish poisoning is tetrodotoxin Treatment of these conditions is symptomatic Methanol (Methyl Alcohol) Methanol intoxication is seen in drinkers who take it as a substitute for ethanol Acute poisoning was dominated by gastrointestinal symptoms, drunkenness, and coma Severe acidosis results from the conversion of methanol to formaldehyde and formic acid Viscera and brain show petechial hemorrhages and edema In the series of Liu et al (1998), the mortality rate was 36%; coma, seizures, and high methanol concentrations were predictors of poor prognosis Visual loss is attributed to retinal metabolism of methanol (rather than an action of circulating formic acid) because the local oxidation of methanol to formic acid parallels the depletion of retinal ATP Retinal glial cells may be the first target It has therefore been suggested that inhibitors of aldehyde dehydrogenase could be therapeutic; here it would mean the administration of ethanol to block the first step of the toxic metabolic pathway For similar reasons, administration of ethanol blocks the metabolism of methanol in the liver and unchanged toxin is excreted in the urine 4-Methylpyrazole (fomepizole) has also been used for this purpose Correction of acidosis and hemodialysis may be used Exposure to large amounts is fatal within 72 hours Vision is usually restored in survivors, who incur no other chronic neurologic symptoms Obsolete Epidemics Many syndromes described here could be eliminated if care were taken to protect the environment In fact, some epidemics pointed the way to correction For instance, the outbreak of subacute myelo-optic neuropathy was attributed to an oral antiparasitic agent, clioquinol The resulting peripheral neuropathy and blindness affected an estimated 10,000 people in Japan The practice has ceased, and there have been no new cases; investigations indicate that the drug is converted to a potent mitochondrial toxin Another transient outbreak was the eosinophilia-myalgia syndrome, which involved skin, muscle, lungs, and blood vessels and axonal neuropathy The disorder was attributed to a toxic contaminant in the preparation of tryptophan, which was taken as a health supplement That syndrome has also largely disappeared, but it seems likely that new epidemics will appear as new industries and new health fads arise SUGGESTED READINGS General Baker EL, Feldman RG, French JG Environmentally related disorders of the nervous system Med Clin North Am 1990;74:325–345 Bleecker ML, ed Occupational neurology and clinical neurotoxicology Baltimore: Williams& Wilkins, 1994 Feldman RG Occupational and environmental neurology Baltimore: Lippincott Raven, 1998 Goyer RA, Klaassen CD, Waalkes MP Metal toxicology San Diego: Academic Press, 1995 Kuncl RW, George EB Toxic neuropathies and myopathies Curr Opin Neurol 1993;6:695–704 Rom WN, ed Environmental and occupational medicine, 3rd ed Philadelphia: Lippincott Raven, 1998 Slikker W, Chang W, eds Handbook of developmental neurotoxicology New York: Academic Press, 1998 Spencer PS, Schaumburg HH, Ludolph A Experimental and clinical neurotoxicology, 2nd ed New York: Oxford University Press, 1999 Weiss B, O'Donaghue J Neurobehavioral toxicity Analysis and intervention New York: Raven Press, 1994 Aluminum Alfrey AC, Le Gendre GR, Kaehny WD The dialysis encephalopathy syndrome: possible aluminum intoxication N Engl J Med 1976;294:184–188 Cannata JB, Briggs JD, Junor BJR, et al Aluminum hydroxide intake: real risk of aluminum toxicity Br Med J 1983;286:1937–1938 Garruto RM, Strong MJ, Yanagihara R Experimental models of aluminum induced motor neuron degeneration Adv Neurol 1991;56:327–340 Longstreth WT Jr, Rosenstock L, Heyer NJ Potroom palsy? Neurologic disorders in three aluminum smelter workers Arch Intern Med 1985;145:1972–1975 Murray JC, Tanner CM, Sprague SM Aluminum neurotoxicity: a re evaluation Clin Neuropharmacol 1991;14:179–185 Rastegar A Dialysis dementia Neurobase La Jolla, CA: Arbor, 1999 Van Der Voet GB, Marani E, Tio S, et al Aluminum neurotoxicity Prog Histochem Cytochem 1991;23:235–241 White DM, Longstreth WT Jr, Rosenstock L, et al Neurologic syndrome in 25 workers from an aluminum smelting plant Arch Intern Med 1992;152:1443–1448 Arsenic Aposhian HV DMSA and DMPS—water soluble antidotes for heavy metal poisoning Annu Rev Pharmacol Toxicol 1983;23:193–215 Beckett WS, Moore JL, Keogh JP, et al Acute encephalopathy due to occupational exposure to arsenic Br J Ind Med 1986;43:66–67 Gerhardt RE, Crecelius EA, Hudson JB Moonshine related arsenic poisoning Arch Intern Med 1980;140:211–213 Huang SY, Chang CS, Tang JL, et al Acute and chronic arsenic poisoning associated with treatment of acute promyelocytic leukemia Br J Haematol 1998;103:1092–1095 Nickson R, McArthur J, Burgess W, et al Arsenic poisoning of Bangladesh groundwater [letter] Nature 1998;395:338 Quecedo E, Samartin O, Ferber MI, et al Mees lines: a clue for the diagnosis of arsenic poisoning [Letter] Arch Dermatol 1996;132:349–350 Lead Aub, JC, Fairhall LT, Minot A, et al Lead poisoning Medicine (Baltimore) 1925;4:1–250 Boothby JA, deJesus PV, Rowland LP Reversible forms of motor neuron disease—lead “neuritis.” Arch Neurol 1974;31:18–23 Byers RK Lead poisoning, review of the literature and report of 45 cases Pediatrics 1959;23:585–603 Davoli CT Childhood lead poisoning Neurobase La Jolla, CA: Arbor, 1999 Lifshitz M, Hashkanazi R, Phillip M The effect of 2,3 dimercaptosuccinic acid in the treatment of lead poisoning in adults Ann Med 1997;29:83–85 Needleman HL Lead at low dose and the behavior of children Acta Psychiatr Scand 1983;303[Suppl]:38–48 Pinkle JL, Brody DJ, Gunter EW, et al The decline in blood lead levels in the United States JAMA 1994;272:284–291 Porru S, Alessio L The use of chelating agents in occupational lead poisoning Occup Med 1996;46:41–48 Preuss HG A review of persistent, low grade lead challenge: neurological and cardiovascular consequences J Am Coll Nutr 1993;12:246–254 Rutter M Raised lead levels and impaired cognitive/behavioural functioning: a review of the evidence Dev Med Child Neurol 1980;42[Suppl]:1–36 Ryan D, Levy B, Pollack S, Walker B Jr Protecting children from lead poisoning and building healthy communities Am J Public Health 1999;89:822–827 Silbergeld EK Preventing lead poisoning in children Annu Rev Public Health 1997;18:187–210 Staudinger KC, Roth VS Occupational lead poisoning Am Fam Physician 1998;57:719–726, 731–732 Warren MJ, Cooper JB, Wood SP, Shoolingin Jordan PM Lead poisoning, haem synthesis, and aminolevulinic acid dehydratase Trends Biochem Sci 1998;23:217–221 Manganese Abd El Naby S, Hassanein M Neuropsychiatric manifestations of chronic manganese poisoning J Neurol Neurosurg Psychiatry 1965;28:282–288 Aschner M, Aschner JL Manganese neurotoxicity: cellular effects and blood brain barrier transport Neurosci Behav Rev 1991;15:333–340 Canavan MM, Cobb S, Drinker CK Chronic manganese poisoning Arch Neurol Psychiatry 1934;32:501–512 Chandra SV Psychiatric illness due to manganese poisoning Acta Psychiatr Scand 1983;303[Suppl]:49–54 Huang C, Chu NS, Lu CS, et al Long term progression in chronic manganism;10 years of follow up Neurology 1998;50:698–700 Rosenstock HA, Simons DG, Meyer JS Chronic manganism Neurologic and laboratory studies during treatment with levodopa JAMA 1971;217:1354–1358 Schuler P, Oyanguren H, Maturana V, et al Manganese poisoning Environmental and medical study at a Chilean mine Ind Med Surg 1957;26:167–173 Mercury Adams CR, Ziegler DK, Lin JT Mercury intoxication simulating amyotrophic lateral sclerosis JAMA 1983;250:642–643 Albers JW, Kallenbach LR, Fine LJ, et al Neurologic abnormalities and remote occupational elemental mercury exposure Ann Neurol 1988;24:651–659 Eto K Pathology of Minamata disease Toxicol Pathol 1997;25:614–623 Eyl TB Organic mercury food poisoning N Engl J Med 1971;284:706–709 Haley RM, Hom J, Roland PS, et al Evaluation of neurologic function in Gulf War veterans: a blinded case control study JAMA 1997;277:259–261 Hay WJ, Rickards AG, McMenemey WH, et al Organic mercurial encephalopathy J Neurol Neurosurg Psychiatry 1963;26:199–202 Korogi Y, Takahashi M, Okajima T, Eto K MR findings of Minamata disease—organic mercury poisoning J Magn Reson Imaging 1998;8:308–316 Kurland LT, Faro SN, Siedler H Minamata disease World Neurol 1960;1:370–390 Thallium Bank WJ, Pleasure DE, Suzuki K, et al Thallium poisoning Arch Neurol 1972;26:456–464 Mahoney W Retrobulbar neuritis due to thallium poisoning from depilatory cream JAMA 1932;98:618–620 Nordentoft T, Andersen EB, Mogensen PH Initial sensorimotor and delayed autonomic neuropathy in acute thallium poisoning Neurotoxicology 1998;19:421–426 Passarge C, Wieck HH Thallium polyneuritis Fortschr Neurol Psychiatr 1965;33:477–557 Rambar AC Acute thallium poisoning JAMA 1932;98:1372–1373 Rauws AG, van Heyst AN Check of Prussian blue for antidotal efficacy in thallium intoxication [Letter] Arch Toxicol 1979;43:153–154 Shabalina LP, Spiridonova VS Thallium as an industrial poison (review of literature) J Hyg Epidemiol Microbiol Immunol 1979;23:247–255 Smith DH, Doherty RA Thallotoxicosis: report of three cases in Massachusetts Pediatrics 1964;34:480–490 Stein MD, Perlstein MA Thallium poisoning Am J Dis Child 1959;98:80–85 Methyl Alcohol Bennet IL Jr, Cary FM, Mitchell GL, et al Acute methyl alcohol poisoning: a review based on experience in an outbreak of 323 cases Medicine (Baltimore) 1953;32:431–463 Burns MJ, Graudins A, Aaron CK, McMartin K, Brent J Treatment of methanol poisoning with intravenous methylpyrazole Ann Emerg Med 1997;30:829–832 Harrop GA Jr, Benedict EM Acute methyl alcohol poisoning associated with acidosis JAMA 1920;74:25–27 Liu JJ, Daya MR, Carrasquillo O, Kales SN Prognostic factors in patients with methanol intoxication J Toxicol Clin Toxicol 1998;36:175–181 Organic Solvents Allen N, Mendell JR, Billmaier DJ, et al Toxic polyneuropathy due to methyl n butyl ketone Arch Neurol 1975;32:209–218 Baker EL, Fine LJ Solvent neurotoxicity: the current evidence J Med 1986;28:126–129 Griffin JW Hexacarbon neuropathy Neurobase La Jolla, CA: Arbor, 1999 Juntunen J, Matikainen E, Antti Poika M, et al Nervous system effects of long term occupational exposure to toluene Acta Neurol Scand 1985;72:512–517 Lees Haley PR, Williams CW Neurotoxicity of chronic low dose exposure to organic solvents: a skeptical review J Clin Psychology 1997;53:699–712 Schaumberg HH, Spencer PS Clinical and experimental studies of distal axonopathy—a frequent form of brain and nerve damage produced by environmental chemical hazards Ann N Y Acad Sci 1979;329:14–29 Struwe G Psychiatric and neurological symptoms in workers occupationally exposed to organic solvents—results of a differential epidemiological study Acta Psychiatr Scand 1983;303[Suppl]:100–104 Organophosphate Insecticides Choi PT, Quinonez LG, Cook DJ, Baxter F, Whitehead L The use of glycopyrrolate in a case of intermediate syndrome following acute organophosphate poisoning Can J Anesth 1998;45:337–340 De Bleeker J The intermediate syndrome in organophosphate poisoning: an overview of experimental and clinical observations Clin Toxicol 1995;33:683–686 de Jager AEJ, van Weerden TW, Houthoff HJ, et al Polyneuropathy after massive exposure to parathion Neurology 1981;31:603–605 Ecobichon DJ, Davies JE, Doull J, et al Neurotoxic effects of pesticides In: Baker SR, Wilkinson CF, eds The effects of pesticides on human health Princeton, NJ: Princeton Scientific, 1990:131–199 Ecobichon DJ, Joy RM Pesticides and neurological diseases, 2nd ed Boca Raton, FL: CRC Press, 1994 Good JL, Khurana RK, Mayer RF, et al Pathophysiological studies of neuromuscular function in subacute organophosphate poisoning induced by phosmet J Neurol Neurosurg Psychiatry 1993;56:290–294 Landrigan P Illness in Gulf War veterans JAMA 1997;277:238–245 Lotti M, Moretto A, Zoppelari R, et al Inhibition of lymphocytic neuropathy target esterase predicts the development of organophosphate induced delayed polyneuropathy Arch Toxicol 1986;59:176–179 Moretto A, Lotti M Poisoning by organophosphorus insecticides and sensory neuropathy J Neurol Neurosurg Psychiatry 1998;64:463–468 Morgan JP, Penovich P Jamaica ginger paralysis 47 year follow up Arch Neurol 1978;35:530–532 Singh G, Mahajan R, Whig J The importance of electrodiagnostic studies in acute organophosphate poisoning J Neurol Sci 1998;157:191–200 Steenland K, Jenkins B, Ames RG, et al Chronic neurologic sequelae to organophosphate pesticide poisoning Am J Public Health 1994;84:731–736 Taylor JR, Selhorst JB, Houff S, et al Chlordecone intoxication in man Neurology 1978;28:626–630 Thiermann H, Mast U, Klimmeck R, et al Cholinesterase status, pharmacokinetics, and laboratory findings during obidoxime therapy in organophosphate poisoned patients Hum Exp Toxicol 1997;16:473–480 Tush GM, Anstead MI Pralidoxime continuous infusion in the treatment of organophosphorus poisoning Ann Pharmacother 1997;31:441–444 Wadia RS, Chitra S, Amin RB, et al Neurological manifestations of organophosphate insecticide poisoning J Neurol Neurosurg Psychiatry 1987;50:1442–1448 Carbon Monoxide Ernst A, Zibrak JD Carbon monoxide poisoning N Engl J Med 1998;339:1603–1608 Neurotoxic Seafood Poisoning DeCarvalho M, Jacinto J, Ramos N, et al Paralytic shellfish poisoning Clinical and electrophysiological observations J Neurol 1998;2245:551–554 DiNubile MJ, Hokama Y The ciguatera poisoning syndrome from farm raised salmon Ann Intern Med 1995;122:113–114 Gessner BD, Bell P, Doucette GJ, et al Hypertension and identification of toxin in human urine and serum following a cluster of mussel associated paralytic shellfish poisoning outbreaks Toxicon 1997;35:711–722 Payne CA, Payne SN Ciguatera Neurobase La Jolla, CA: Arbor, 1999 Yasumoto T, Satake M Chemistry, etiology and determination methods of ciguatera toxins Annu Rev Pharmacol Toxicol 1988;28:141–161 Nitrous Oxide Beltramello A, Puppini G, Cerini R, et al Subacute combined degeneration of the spinal cord after nitrous oxide anaesthesia: role of magnetic resonance imaging J Neurol Neurosurg Psychiatry 1998;64:563–564 Flippo TS, Holder WD Jr Neurologic degeneration associated with nitrous oxide anesthesia in patients with vitamin B 12 deficiency Arch Surg 1993;128:1391–1395 Gutmann L, Farrell B, Crosby TW, Johnsen D Nitrous oxide induced myelopathy neuropathy: potential for chronic misuse by dentists J Am Dent Assoc 1979;98:58–59 Hadzic A, Glab K, Sanborn KV, Thys DM Severe neurologic deficit after nitrous oxide anesthesia Anesthesiology 1995;83:863–866 Layzer RB Myeloneuropathy after prolonged exposure to nitrous oxide Lancet 1978;2:1227–1230 Pema PJ, Horak HA, Wyatt RH Myelopathy caused by nitrous oxide toxicity AJNR 1998;19:894–896 Rosener M, Dichgans J Severe combined degeneration of the spinal cord after nitrous oxide anaesthesia in a vegetarian [Letter] J Neurol Neurosurg Psychiatry 1996;60:354 Scott JM, Dinn JJ, Wilson P, Weir DG Pathogenesis of subacute combined degeneration: a result of methyl group deficiency Lancet 1981;2:334–337 Obsolete Epidemics Anonymous Eosinophilia myalgia syndrome: review and reappraisal of clinical, epidemiologic and animal studies symposium J Rheumatol 1996;46[Suppl]:1–110 Arbiser JL, Kraeft SK, van Leeuwen R, et al Clioquinol zinc chelate: a candidate causative agent of subacute myelo optic neuropathy Mol Med 1998;4:665–670 Burns SM, Lange DJ, Jaffe IA, Hays AP Axonal neuropathy in eosinophilia myalgia syndrome Muscle Nerve 1994;17:293–298 Emslie Smith AM, Mayeno AN, Nakano S, Gleich GJ 1,1 Ethylidenebis [tryptophan] induces pathologic alterations in muscle similar to those observed in the eosinophilia myalgia syndrome Neurology 1994;44:2390–2392 Martin RW, Duffy J, Engel AG, et al The clinical spectrum of the eosinophilis myalgia syndrome associated with l-tryptophan ingestion Ann Intern Med 1990;113:124–134 CHAPTER 162 ABUSE OF CHILDREN MERRITT’S NEUROLOGY CHAPTER 162 ABUSE OF CHILDREN CLAUDIA A CHIRIBOGA Pediatric Acquired Immunodeficiency Syndrome and Human Immunodeficiency Virus Infection Fetal Alcohol Syndrome Fetal Cocaine Effects The Battered Child Suggested Readings PEDIATRIC ACQUIRED IMMUNODEFICIENCY SYNDROME AND HUMAN IMMUNODEFICIENCY VIRUS INFECTION Woman and children are the fastest-growing population affected by the acquired immunodeficiency syndrome (AIDS) and the human immunodeficiency virus (HIV) Most children with AIDS in the United States are infected perinatally In inner cities, about 2% to 4% of live births are HIV-1 antibody positive Intravenous drug abuse and sexual contact with HIV-infected partners are the maternal risk factors in more than 85% of perinatal cases Most infections occur during the last trimester of pregnancy and time of delivery Risk factors for vertical transmission are recent maternal HIV seroconversion, high viral load, and maternal AIDS Premature infants are also at increased risk of infection Infection may result from exposure to blood and other body fluids at delivery or transmitted in breast milk Mother-to-child HIV transmission rates range from 14% to 30%; rates decrease to 8% with prenatal and neonatal zidovudine treatment Determination of HIV infection in children is complicated because maternal HIV antibody transfers across the placenta and may persist up to age 18 months HIV-seropositive children are considered HIV infected if they test positive for HIV on two separate occasions by either HIV culture or HIV polymerase chain reaction (PCR) or if they develop AIDS HIV-seropositive children who not meet these criteria are considered perinatally exposed, and HIV-seropositive children without AIDS and without laboratory evidence of infection who on testing after age months have negative antibody are seroreverters The 1994 revised classification system for HIV infection in children has four clinical categories: N, not symptomatic; A, mildly symptomatic; B, moderately symptomatic; and C, severely symptomatic, which includes all AIDS-defining conditions except lymphoid hyperplasia ( Table 162.1) These clinical categories are further classified immunologically depending on the child's age and absolute CD4 count: no evidence of suppression, moderate suppression, and severe suppression ( Table 162.2) For example, A2 indicates mild signs and symptoms of infection with moderate immunosuppression TABLE 162.1 REVISED CENTERS FOR DISEASE CONTROL AND PREVENTION CLINICAL CATEGORIES FOR CHILDREN WITH HUMAN IMMUNODEFICIENCY VIRUS (HIV) INFECTION TABLE 162.2 IMMUNOLOGICAL CATEGORIES BASED ON CHILD'S AGE-SPECIFIC CD4 + T LYMPHOCYTE COUNT AND PERCENT OF TOTAL LYMPHOCYTES Diagnostic Tests Because of early testing, most HIV-positive children are identified soon after birth Viral load (i.e., quantified HIV DNA or RNA PCR) is more sensitive than viral cultures and p24 antigen in identifying HIV infection in asymptomatic newborns and infants By age to months, over 95% of HIV-infected children are identified by a positive PCR In newborns, a negative PCR test for HIV does not exclude infection but decreases the risk of HIV infection to 3% Viral load runs higher in asymptomatic children than in asymptomatic adults Sustained high viral load in adults predicts progression to AIDS High viral loads in early infancy predict early onset of symptomatic HIV disease HIV-1 syncytial-inducing phenotypes are linked to aggressive early symptomatic disease Clinical Manifestations Mild HIV infection includes diarrhea, unexplained persistent fever, lymphadenopathy, and parotitis Table 162.1 lists the range of signs of symptomatic HIV infection Lymphoid interstitial pneumonitis and recurrent bacterial infections are seen in children with AIDS but not in adults Severe manifestations in early infancy, such as progressive encephalopathy or opportunistic infections (e.g., Pneumocystis carinii), carry a poor prognosis for survival Mechanism of Action HIV infection is maintained by viral persistence in helper T lymphocytes and macrophages HIV strains with tropism for monocyte-derived macrophages have a predilection to infect cerebral vascular endothelium and central nervous system (CNS) Infected macrophages traverse the blood–brain barrier and infect microglial cells; neurons are spared from direct infestation Nonproductive infection of astrocytes is reported, but infection of other glial cells has not been firmly established Neuronal dropout is seen as the disease advances, but it is not known how HIV induces neural damage Postulated mechanisms include release of soluble neurotoxins by HIV-infected macrophages and lymphocytes (e.g., cytokines, quinolinic acid, viral antigens, or undefined viral products), neurotoxin amplification by astrocyte–macrophage interaction, and impaired blood–brain barrier function secondary to HIV-related endothelial damage These neurotoxins are thought to produce a reversible metabolic encephalopathy that may disappear with effective antiretroviral treatment Children with HIV encephalopathy who respond to antiretroviral therapy may show nonprogressive corticospinal tract sequelae Pathology Glial nodules and endothelial hyperplasia with calcification, dystrophic calcification, and perivascular mononuclear inflammation are common pathologic findings of subacute encephalitis in HIV-infected brains The glial nodule comprises a cluster of chronic inflammatory cells in the neurophil and is often associated with multinucleated giant cells that are presumed to arise from coalescent microglia Human Immunodeficiency Virus Encephalopathy Two types of encephalopathy are seen in children: progressive and static The evolution of the progressive encephalopathy may be fulminant, inexorably progressive, or stepwise Progressive encephalopathy is characterized by loss of developmental milestones, progressive pyramidal tract dysfunction, and acquired microcephaly or impaired brain growth The static encephalopathy is less well defined, and not all cases may be HIV induced The neurologic abnormalities commonly include abnormalities of muscle tone, hyperreflexia, clonus, and impaired head growth Hypotonia with corticospinal tract dysfunction may be seen in infants early in the course of the encephalopathy and evolves into a spastic diparesis; with newer antiretroviral treatments, progression to a spastic tetraparesis, with or without pseudobulbar palsy, is seldom seen Ataxia and rigidity are uncommon Progressive neurologic dysfunction is the first evidence of progression to AIDS in 10% of infected children There is always evidence of underlying HIV infection, such as immunologic compromise (low CD4 counts) or high viral load, at the time of onset of neurologic symptoms Many infected children exhibit global developmental delay, regardless of neurologic findings In young children, motor development is more impaired than mental development The incidence of neurologic abnormalities reported in HIV-infected cohorts before the advent of antiretroviral treatments was 30% Older HIV-infected children may show problems in visual-spatial processing functions and expressive language and may develop AIDS-dementia complex indistinguishable from that described in adults HIV-associated myelopathy, polyneuropathy, and myopathy are rare in children Spinal cord pathology shows demyelinating changes of the corticospinal tracts, vacuolar changes, or myelitis attributable to HIV Acute inflammatory demyelinating polyneuropathy is a rare complication in pediatric HIV Low-dose treatment with dideoxyinosine causes a painful sensory neuropathy in less than 10% of patients treated The neuropathy is dose related and usually reverts with cessation of treatment The mitochondrial myopathy induced by zidovudine has not been seen in children Focal Manifestations HIV brain infection is nonfocal and subcortical Seizures are not common Focal signs or seizures raises the possibility of neoplasm, strokes, or, less likely, opportunistic infections Primary Central Nervous System Lymphoma This is the most common cause of focal cerebral signs in HIV- infected children, found in 3% to 4% of cases Seizures are reported in about 33% of patients It may be difficult to differentiate this tumor from toxoplasma brain abscess; diagnosis requires brain biopsy Magnetic resonance imaging (MRI) spectroscopy may prove helpful in distinguishing CNS toxoplasmosis from lymphoma Stroke HIV infection produces inflammation of cerebral vessels, increasing the risk of stroke, which occurs at a rate of 1.3% a year in HIV-infected children More than 50% of strokes are hemorrhagic and occur with thrombocytopenia (especially immune thrombocytopenic purpura) or CNS neoplasia Nonhemorrhagic stroke and subarachnoid hemorrhage are attributable to an arteriopathy affecting the large vessels of the circle of Willis or meninges HIV-related strokes may be clinically silent, so the true incidence is probably higher Opportunistic Central Nervous System Infection Compared with adults, opportunistic CNS infection is infrequent in HIV-infected children, affecting primarily older children and adolescents Only a few have had progressive multifocal leukoencephalopathy Imaging In children with HIV encephalopathy, computed tomography or MRI may show diffuse cerebral atrophy or may be normal There may be foci of demyelination Frontal lobe or basal ganglia enhancement and calcifications are late manifestations of HIV encephalopathy and occur primarily in symptomatic infants ( Fig 162.1) HIV-related myelopathy on spinal MRI may show a high signal but is usually normal Bilateral cerebral lesions may mimic myelopathy and must be excluded with MRI or computed tomography Lesions of progressive multifocal leukoencephalopathy are commonly located in the parietooccipital or frontal region affecting both periventricular and subcortical white matter These lesions may be difficult to distinguish from HIV demyelination FIG 162.1 Computed tomography of an infant with human immunodeficiency virus encephalopathy showing cortical and subcortical atrophy, basal ganglia, and frontal lobe calcifications (Courtesy of Dr Ram Kairam.) Cerebrospinal Fluid Cerebrospinal fluid (CSF) examination is commonly normal in children with HIV infection In the absence of opportunistic infection, CSF findings in children with progressive encephalopathy are nonspecific, with a lymphocytic pleocytosis and elevated protein content Intra-blood–brain barrier synthesis of HIV-specific antibody or antigen detection in CSF has not been useful in predicting encephalopathy CSF viral load, although still experimental, may prove useful in determining HIV encephalopathy in children Antiretroviral Therapy Combination antiretroviral therapy is needed to avoid emergence of resistant HIV strains Triple combination antiretroviral therapies that include a protease inhibitor are effective in diminishing viral load and suppressing active viral replication This in turn correlates with increases in CD4 count, weight gain, improved morbidity (including CNS symptomatology), and mortality Whether high systemic viral load predicts the development of HIV encephalopathy has not been firmly established FETAL ALCOHOL SYNDROME The fetal alcohol syndrome (FAS) affects children of chronic alcoholic women but also occurs with binge drinking, as defined by five drinks or more on one occasion Fetal susceptibility to the effects of alcohol is greatest during the first trimester of pregnancy FAS is characterized by abnormalities of growth, CNS, and facial features; birth defects are common (Table 162.3) FAS rates in the United States are to per 1,000 live births and 2% to 4% among children of alcohol-abusing women FAS is confined to infants of alcohol-abusing women Most children with FAS are mildly or moderately retarded, with mean IQ scores of 65 to 70, but intellectual ability varies widely In families with several affected siblings, the youngest child is usually the most cognitively impaired Learning disabilities—in particular difficulty with arithmetic, speech delay, and hyperactivity—are commonly observed TABLE 162.3 FETAL ALCOHOL SYNDROME Less severe alcohol-related effects are associated with wide patterns of drinking These fetal alcohol effects are probably a lower point on the continuum of alcohol effects on the fetus Maternal alcohol abuse is associated with increased risk of spontaneous abortions, infant mortality, intrauterine growth retardation, and prematurity Birth defects are common Minor or major congenital anomalies occur in about a third of infants born to heavy drinkers, compared with 9% of minor anomalies in infants of women who abstain from alcohol Depressed birth weight has been seen with ingestion of as little as 100 g of alcohol a week (about drink a day); hampered brain growth may be seen with 20 mL (1.5 drinks) a day Decrease of alcohol intake during pregnancy is beneficial to the offspring, reducing rates of growth retardation and dysmorphic features Heavy alcohol exposure prenatally, but not mild or moderate exposure, has been linked to decrease in IQ scores, hyperactive behavior, attention problems, learning difficulties, and speech disorders Postnatal Alcohol Exposure Alcohol transferred through breast milk impairs motor development but not mental development at age year Ingestion of alcohol by children may lead to hypoglycemic seizures Withdrawal Syndrome Infants born to women who drink large amounts of alcohol during pregnancy may rarely exhibit signs of withdrawal Restlessness, agitation, tremulousness, opisthotonus, and seizures are seen shortly after birth and disappear within a few days FETAL COCAINE EFFECTS In U.S cities, about in every 10 newborns is exposed prenatally to cocaine The long-term consequences of fetal cocaine exposure to the developing nervous system are not well known Cocaine use during pregnancy has been linked to spontaneous abortion, abruptio placentae, stillbirth, and premature delivery These events may immediately follow large intakes of cocaine and are attributed to drug-induced vasoconstriction of intrauterine vessels Women who use cocaine tend to resort to prostitution, increasing risks for syphilis and HIV They also tend to lack prenatal care, adding to the risks of infant death, low birth weight, and prematurity Low birth weight and intrauterine growth retardation are common among cocaine-exposed infants Fetal brain growth is impaired independently of birth weight or gestational age Sudden infant death syndrome has also been linked to cocaine exposure in utero Neurobehavior State regulation difficulties are well described among cocaine-exposed newborns, although findings are inconsistent Some reports describe irritability, excitability, poor feeding, and sleep disturbances among cocaine and cocaine/methamphetamine infants, whereas others describe decreased organizational response and interactive behavior, even if the exposure to cocaine was limited to the first trimester of pregnancy Modulation of attention is impaired among cocaine-exposed infants who, unlike unexposed infants, prefer higher rates of stimuli when in a high level of arousal Exposed infants also show motor and movement abnormalities, including excessive tremor and hypertonia Dose-response effects of cocaine on state regulation and neurologic findings are reported in newborns Some studies show no neurobehavioral effects, however Strokes Experimentally, cocaine has a vasoconstrictive effect on fetal cerebral vessels and decreases cerebral blood flow Neonatal stroke and porencephaly have been associated with prenatal cocaine exposure Some cases may be related to other neonatal stroke risk factors that accompany fetal cocaine exposure, such as abruptio placentae or birth asphyxia Intracranial hemorrhage was not associated with cocaine in a prospective study of prematures Seizures Focal seizures may occur in cocaine-exposed newborns with strokes Electroencephalograms in cocaine-exposed infants show bursts of sharp waves and spikes that are often multifocal These findings not correlate with clinical seizures or neurologic abnormalities and may disappear in to 12 months Cocaine-exposed premature infants are at increased risk of neonatal seizures Seizures are rare if there is no stroke Malformations Prenatal cocaine exposure has been linked with urogenital malformations, limb reduction deformities, and intestinal atresia and infarction Agenesis of the corpus callosum and septooptic dysplasia have also been noted These teratogenic effects may result from cocaine-induced vasoconstriction and fetal vascular disruption in early organogenesis Neurodevelopmental Impact In experiment models, prenatal cocaine has been reported to affect serotonin, norepinephrine, and dopaminergic systems Lower CSF levels of homovanillic acid found in human newborns exposed to cocaine suggest dopaminergic involvement In infancy, there may be a high incidence of spastic tetraparesis and diparesis that resolves by age 24 months (Table 162.4) In toddlers and school-aged children, prenatal cocaine exposure did not decrease cognitive abilities, except as mediated through cocaine effects on brain growth Cocaine-exposed children seem to suffer from an excess of neurobehavioral abnormalities, including irritability, impulsivity, and aggressive behavior, which may reflect coexisting maternal psychopathology rather than direct cocaine effects TABLE 162.4 COCAINE-RELATED EFFECTS Cocaine Exposure in Childhood Passive intoxication with cocaine may be caused by breast-feeding or passive inhalation of free-base cocaine (“crack”) Seizures are the chief manifestation of symptomatic intoxication, but intoxication may be unsuspected Urine toxicology screen to detect illicit substances is indicated in evaluating seizures in infants and children, regardless of socioeconomic status Withdrawal Symptoms There is no evidence of a cocaine-induced withdrawal syndrome Even with remote prenatal cocaine exposure, cocaine-exposed infants may show hypertonicity and tremor, which are probably cerebral manifestations of fetal cocaine effects THE BATTERED CHILD Child abuse may be physical or psychological Physical abuse includes skin burns, welts, bruises, bone fractures, head trauma, and failure to thrive Psychological abuse frequently accompanies physical abuse and may lead to growth, behavioral, and developmental impairments The shaken baby syndrome, an increasingly recognized form of physical abuse, is characterized by bilateral subdural hematomas or subarachnoid hemorrhage, retinal hemorrhages, and the absence of external signs of trauma It is seen in infants mostly under age year who are shaken repeatedly and violently The aggressor, usually a parent, shakes the crying infant until he or she quiets and later denies doing so Depressed mental status, seizures, and signs of increased intracranial pressure are common Neurogenic pulmonary edema may occur rarely Bilateral retinal hemorrhages, in the absence of a coagulopathy, are the most specific signs of shaken baby syndrome Hemorrhages may be flame shaped, round and intraretinal, preretinal, or vitreal The speed with which blood disappears varies by type: Flame-shaped hemorrhage disappears within a few days, but round intraretinal hemorrhage may last weeks Retinal folds occasionally are seen A dilated funduscopic examination should be performed quickly in any child with suspected child abuse to identify retinal hemorrhages before they disappear Shaken baby syndrome should be suspected with sudden infant death syndrome or near-miss sudden infant death syndrome, with sudden lethargy, with seizures of unknown cause, or if there is a discrepancy between the history and the clinical signs Broken ribs and chest bruises may be seen in infants held by the chest during shaking, and spiral fractures of the long bones or epiphysial separation may be seen in those shaken by the arms or legs A skeletal survey showing old fractures helps confirm abuse Infants with shaken baby syndrome may suffer neurologic sequelae, including hydrocephalus, blindness, developmental delay, mental retardation, microcephaly, and spastic tetraparesis SUGGESTED READINGS Caffey J The whiplash shaken baby syndrome: manual shaking by the extremities with whiplashed-induced intracranial and intraocular bleedings, linked with residual permanent brain damage and mental retardation Pediatrics 1974;54:396–403 Chasnoff IJ, Griffith DR, Freier C, et al Cocaine/polydrug use in pregnancy Pediatrics 1992;89:284–289 Chiriboga CA Neurological correlates of fetal cocaine exposure in cocaine and the developing brain Ann N Y Acad Sci 1998;846:109–125 Chiriboga CA, Brust JCM, Bateman D, Hauser WA Dose-response effect of fetal cocaine exposure on newborn neurological function Pediatrics 1999;103:79–85 Forsyth BW Primary care of children with HIV infection Curr Opin Pediatr 1995;7:502–512 Gendelman HE, Epstein LG HIV encephalopathy in children Curr Opin Pediatr 1995;7:655–662 Park YD, Belman AL, Kim TS, et al Stroke in pediatric acquired immunodeficiency syndrome Ann Neurol 1990;28:303–311 Pizzo PA, Wilfert CM Markers and determinant of disease progression in children with HIV infection The Pediatric AIDS Siena Workshop II J Acquir Immune Def Syndr Hum Retrovir 1995;8:30–44 1994 Revised classification system for human immunodeficiency virus (HIV) infection in children less than 13 years of age MMWR Morb Mortal Wkly Rep 1994;43:RR12 Streissguth AP Fetal alcohol syndrome: early and long-term consequences NIDA Res Monogr 1992;119:126–130 CHAPTER 163 FALLS IN THE ELDERLY MERRITT’S NEUROLOGY CHAPTER 163 FALLS IN THE ELDERLY LEWIS P ROWLAND Epidemiology Neurology of Falls Environmental Factors Prevention Suggested Readings Falls in the elderly are often taken for granted and considered an inevitable consequence of aging Analysis of the factors that lead to falls, however, raises the possibility of prevention The problem is certainly serious for individuals, families, and society ( Table 163.1) TABLE 163.1 FALLS IN THE ELDERLY EPIDEMIOLOGY It is estimated that 5% to 10% of falls in the elderly result in injury Most falls occur at home, but the rate of falling is higher in long-term care facilities Injury is the sixth leading cause of death after age 65, and most injuries result from a fall Although people over 65 comprise about 12% of the total population, they account for 74% of all deaths caused by falls Fatality rates increase with age in both men and women ( Table 163.2) TABLE 163.2 DEATH RATES FROM ACCIDENTAL FALLS IN 1982 The likelihood of admission to a nursing home increases with the number of falls an elderly person has had Once a person is in a nursing home, the use of antidepressants increases the likelihood of falls Falls are as likely among those who take selective serotonin reuptake inhibitors as among those taking tricyclics; use of newer drugs does not reduce the higher rates of falling NEUROLOGY OF FALLS Few falls seem to be related to syncope, drop attacks, transient ischemic attacks, or overt myopathy Instead, a propensity to falls is generated by the cumulative handicaps of poor vision, poor balance, unsteady gait, stooped posture, and impaired proprioception Sensitivity to drugs is another factor; falls are more frequent in people who take more than one drug Intuitively, it seems likely that the motor impairment of Parkinson disease or previous stroke would increase the likelihood of falls and so would the physical impediments of arthritis or the intellectual failure of dementia Disequilibrium of unknown cause increases the likelihood of falling The condition is identified as a triad: Impaired balance is a symptom; gait is impaired on examination; and no cause is discerned by medical, neurologic, and vestibular examination ENVIRONMENTAL FACTORS Most falls in the elderly are “accidental.” Examples include missing the last step on descent, slippery surfaces, poor lighting, unexpected appearance of a child or pet, and poorly fitting shoes PREVENTION In one study, 46% of fallers were repeaters The first fall led to loss of mobility and loss of confidence, making the next one more likely Interventions included walking aids, home nursing visits to assess environmental hazards (including lighting, stairs, bathrooms, and rugs), educating patients, care in taking medications, and physical therapy for gait and balance The list of medications should be reviewed periodically to be certain that all are needed; this is especially true of all psychoactive drugs In the Prevention of Falls in the Elderly Trial, these measures reduced the risk of falling and of recurrent falls and the likelihood of hospital admission Death rates from falls among people over 75 decreased by 50% between 1960 and 1980 SUGGESTED READINGS Avorn J Depression in the elderly—falls and pitfalls N Engl J Med 1998;339:918–20 Close J, Ellis M, Hooper R, Glucksman E, Jackson S, Swift C Prevention of Falls in the Elderly Trial (PROFET): a randomized controlled trial Fife TD, Baloh RW Disequilibrium of unknown cause in older people Ann Neurol 1993;34:694–702 Lancet 1999;353:93–97 Kerber KA, Enrietto JA, Jacobson KM, Baloh RW Disequilibrium in older people: a prospective study Neurology 1998;51:574–580 Lacomis D, Chad DA, Smith TW Myopathy in the elderly: evaluation of the histopathologic spectrum and the accuracy of clinical diagnosis Neurology 1993;43:825–828 Nutt JG, Marsden CD, Thompson PD Human walking and higher-level gait disorders, particularly in the elderly Neurology 1993;43:268–279 Saper CB “All fall down”: the mechanism of orthostatic hypotension in multiple systems atrophy and Parkinson's disease Ann Neurol 1998;43:149–151 Sorock GS Falls among the elderly: epidemiology and prevention Am J Prevent Med 1988;4:282–288 Thajeb P Gait disorders and multi-infarct dementia Acta Neurol Scand 1993;87:239–242 Thapa PB, Gideon P, Cost TW, Milam AB, Ray WA Antidepressants and the risk of falls among nursing homs residents N Engl J Med 1998;339:875–882 Tinetti ME, Speechley M Prevention of falls among the elderly N Engl J Med 1989;320:1055–1059 Tinetti ME, Williams CS Falls, injuries due to falls and the risk of admission to a nursing home N Engl J Med 1997;337:1279–1284 CHAPTER 164 NEUROLOGIC REHABILITATION MERRITT’S NEUROLOGY SECTION XXIV REHABILITATION CHAPTER 164 NEUROLOGIC REHABILITATION LAURA LENNIHAN AND GLENN M SELIGER Occupational Therapy Physical Therapy Dysphagia Therapy Language and Cognitive Therapies Incontinence Therapy Suggested Readings Neurologic disorders commonly cause temporary or permanent impairments that impede simple daily functions and complex intellectual and physical activities Neurologists play an important role in prescribing rehabilitation therapies to maximize functional recovery The proper selection and timing of these therapies make a substantial contribution to optimum quality of life for patient and family despite persistent neurologic impairments Although it is preferable for rehabilitation to begin soon after a neurologic injury, many people with chronic neurologic conditions have never received adequate rehabilitation therapy Nevertheless, if they are given proper training and equipment, they may still improve in personal independence, access to the community, or ease with which a caregiver assists them At a time when neurologists are assuming the role of principal care physicians, experience in neurorehabilitation is essential in the management continuum from acute to chronic neurologic disorders The World Health Organization definitions of impairment, disability, and handicap ( Table 164.1) provide a structure for understanding the impact of disease on personal independence and integration into society These criteria help to identify patients who may benefit from rehabilitation The planning and prescription of a rehabilitation program for a neurologically impaired individual requires characterization of the neurologic disorder with regard to natural history, localization, and extent of nervous system involvement; determination of functional disabilities caused by cognitive and physical impairments; and definition of these disabilities in the context of the patient's physical and social environment With this information, the type and intensity of rehabilitation therapies can be planned TABLE 164.1 WORLD HEALTH ORGANIZATION DEFINITION OF IMPAIRMENT, DISABILITY, AND HANDICAP Two principal approaches are used in rehabilitation therapy The first is to bypass the neurologic impediment by teaching adaptive techniques using preserved neurologic function For example, a person with a paralyzed arm can be trained in one-handed activities using the normal arm The second approach is to facilitate the return of neurologic function For example, the person with a paralyzed arm is given tasks to increase effective movement of that arm Both methods are usually applied in rehabilitation programs The efficacy of the first approach in improving functional independence and reducing disability is accepted The second approach is the focus of active clinical research In a primate model, restraint of the normal arm resulting in forced use of the paretic arm after motor cortex injury leads to better functional recovery of the affected arm than when the normal arm is unrestrained No functional recovery occurs if the paretic arm is restrained Case reports in humans similarly support the efficacy of this forced-use paradigm Gait training on a treadmill while a harness provides partial body weight support is thought to recruit spinal pattern generators for walking This technique may produce better balance, motor recovery, walking speed, and endurance compared with conventional gait training with patients bearing their full body weight Current research on the neurobiology of recovery from central nervous system injury and the efficacy of treatments to improve the speed and completeness of recovery is relevant to the practice of neurorehabilitation For example, norepinephrine plays an important role in modulating central nervous system recovery In animal models of focal brain injury and in people with strokes, amphetamine administered coincident with physical therapy has resulted in better motor recovery than in placebo-treated subjects Drugs with central catecholamine antagonist activity, such as haloperidol, prazosin, or clonidine, interfere with motor recovery in animals Enhancement of activity of the inhibitory neurotransmitter GABA by drugs such as diazapam, phenytoin, or phenobarbital also reduces neurologic recovery in animals In a retrospective study, stroke patients who received either class of drug had poorer motor recovery than those who did not Functional outcome is improved by treatment in a comprehensive rehabilitation program Stroke patients who receive rehabilitation therapies on a stroke rehabilitation unit have better functional outcomes and shorter hospital stays than those treated on a general neurology ward Similarly, stroke patients admitted to hospital-based acute rehabilitation programs have better functional recovery and are more likely to return home than those treated in a subacute rehabilitation program at a skilled nursing facility A comprehensive inpatient neurorehabilitation program requires an interdisciplinary team: physician, physical therapist, occupational therapist, speech therapist, neuropsychologist, social worker, and rehabilitation nurse The physician, as team leader, defines the type and prognosis of the neurologic disorder; is responsible for coordination of rehabilitation services and setting of realistic treatment goals; and provides medical care, especially for the prevention and treatment of complications of a disabling disorder, for instance, deep vein thrombosis or reflex sympathetic dystrophy The physical therapist's role is to maximize leg function and mobility The occupational therapist promotes maximum independence in activities of daily living by improving arm function and cognitive skills The speech therapist characterizes and treats specific language-based cognitive dysfunction and evaluates and treats dysphagia and dysarthria The neuropsychologist defines cognitive problems and monitors improvement The rehabilitation nurse, in addition to providing medical nursing care, incorporates into the patients' daily routines skills learned in therapy and institutes treatments to restore sphincter continence The social worker implements the discharge plan All team members participate in formulating a discharge plan and in educating and training patient and family in preparation for return home OCCUPATIONAL THERAPY Neurologic injury that interferes with use of the arms and hands can be profoundly disabling Weakness, loss of sensation, ataxia, abnormal tone, and involuntary movements, alone or in combination, can lead to inability to carry out basic activities of daily living, to drive a car, or to work Occupational therapy promotes recovery from neurologic injury; prevents permanent disability from complications of temporary neurologic impairments, such as wrist-flexor contractures from a radial nerve palsy; teaches new techniques to perform self-care and other tasks; prescribes equipment to increase use of the impaired arm and hand; and, when the impairment is unilateral, teaches performance of one-handed techniques by the normal arm The approach to restoring function to the neurologically impaired arm is determined in part by central or peripheral site of injury For example, treatment of weakness caused by an upper motor neuron lesion focuses on reestablishing movement at one joint in isolation from movement at other joints; strengthening exercises follow later Strengthening programs are usually instituted early for peripheral injuries, but it is important not to overwork muscles recovering from a nerve injury because weakness may worsen Wrist and ankle weights can be used to dampen arm and leg ataxia Improving motor skills is only one of the important components in enhancing performance of the activities of daily living, such as dressing, toileting, washing, grooming, feeding, and community skills Training to overcome visual and perceptual difficulties, unilateral spatial neglect, memory impairment, inattentiveness, and poor safety judgment may also be important The occupational therapist selects adaptive equipment and trains patient and family to compensate Advanced programs may include learning special occupational skills or to drive with the left hand and foot PHYSICAL THERAPY Interference with mobility by neurologic disease can be reduced or eliminated by strengthening exercises, gait and balance training, spasticity reduction through stretching or medication, surgical release of shortened tendons, bracing, assistive devices (e.g., cane, walker), and use of a wheelchair Techniques and orthotics are chosen to maximize safe and independent mobility; to optimize energy efficiency; to prevent decubitus skin ulcers, tendon contractures, and falls; and to enhance recovery Leg and trunk weakness, impaired postural reflexes, ataxia, proprioceptive loss, and hemineglect may all interfere with walking Even though a person may not be able to walk immediately after neurologic injury, ambulation usually becomes possible through a combination of bracing at the ankle and sometimes the knee and use of a walker or cane When ambulation is not possible, mobility is attained through training in the use of a wheelchair of the correct size and height, with a special seat to prevent skin breakdown and cushions for trunk support DYSPHAGIA THERAPY Facial, lingual, masticatory, pharyngeal, esophageal, and respiratory muscles participate in swallowing Neurologic disorders that disturb coordinated contraction of any of these muscles can cause dysphagia and, secondarily, airway obstruction, aspiration pneumonia, and malnutrition Dysphagia evaluation is indicated for patients with any of these complications; who report coughing, choking, or nasal regurgitation while eating; are dysarthric; or have a disease commonly associated with dysphagia, such as motor neuron disease or myasthenia gravis This evaluation includes characterization of the neurologic disorder and bedside and fluoroscopic observation of swallowing foods of different consistencies, from thin liquids to chewy meat Restriction of the diet to consistencies that can be swallowed without aspiration reduces the risk of dysphagia complications The speech therapist teaches techniques that improve coordinated swallowing and reduce the risk of aspiration, such as tucking the chin before swallowing to close the larynx and open the upper esophagus and swallowing twice after each bite of food to clear the pharynx LANGUAGE AND COGNITIVE THERAPIES Brain injuries that cause behavioral, language, and other cognitive dysfunctions may be focal and discrete or generalized and diffuse In focal injuries, the neurologic dysfunctions may be restricted, with other brain functions preserved, for instance, Broca aphasia with intact attention, memory, and concentration In contrast, diffuse injury may affect several areas of cognitive function The therapeutic approach needs to be tailored to the nature and complexity of the symptoms The first step in implementing a cognitive rehabilitation program is to define the neurobehavioral impediments and how they interfere with function For example, a short attention span may prevent participation in group activities such as business meetings, or memory impairment may lead to failure at school Speech therapy for aphasia is a specialized part of cognitive rehabilitation The speech therapist defines receptive and expressive dysfunction and identifies areas of strength and weaknesses in language Areas of strength may then be used for compensatory purposes For instance, if an aphasic patient's written language skills are preserved better than verbal expression, writing may be useful for communication Training in use of visual imagery as an internal cue may help to overcome the word blocking of Broca aphasia A picture board may circumvent an expressive language deficit The use of computer-assisted communication for aphasia is an area of active rehabilitation research Visual imagery to create memory cues may improve performance on memory tests Breaking a task into individual steps and then teaching one step at a time helps to overcome constructional problems In diffuse or multifocal brain injury that impairs attention and behavior and many aspects of cognition and language, a structured program that permits few distractions is necessary Speech and occupational therapists collaborate on program development and implementation, and all members of the rehabilitation team contribute Several strategies may compensate for multiple problems For example, sensory reduction minimizes distractions by controlling the noise and activity in the environment; development of a rigidly structured daily routine helps to overcome poor planning and organizational skills Education of patient and family about aphasia and other cognitive problems helps to reduce frustration with impaired communication, memory, and abnormal behavior INCONTINENCE THERAPY Loss of control of bladder or bowel emptying is a devastating condition and should be addressed by any comprehensive neurorehabilitation program The cause of impaired emptying or sphincter incompetence, and therefore the treatment, depends on the site of the neural injury Evaluation includes clinical observations about incontinence and retention; search for nonneurologic factors, such as cystitis or mechanical problems, particularly urethral obstruction by prostatic enlargement; and cystometrographic measurements of bladder and sphincter functions The neurorehabilitation nurse plays a crucial role in the treatment of bladder and bowel disorders, including implementation of voiding programs and training patient and family to use urethral catheters Incontinence characterized by bladder hyperreflexia, in which the bladder contracts at low urine volumes and voluntary inhibition of bladder contraction and sphincter relaxation fails, commonly complicates cerebral, particularly frontal lobe, injury Lack of awareness or indifference may impede achievement of continence, but neurologic recovery usually reduces incontinence Scheduled voidings at 2-hour intervals contribute to regaining continence Bladder dyssynergia, in which bladder contraction and sphincter relaxation are dissociated and the bladder contracts against a closed sphincter, is usually a consequence of lower brainstem or spinal cord disorders Bladder emptying, if it occurs at all, is incomplete and occurs at high pressure Treatment includes bladder antispasmodic drugs and intermittent catheterization Hydronephrosis and renal failure are potential complications Peripheral nerve diseases involving the nerves innervating the bladder may cause bladder flaccidity Bladder emptying, at low pressures, is incomplete, and incontinence occurs between voluntary voidings Cholinergic agents may improve emptying, but intermittent catheterization is often necessary Immobility from any neurologic disorder and loss of cortical control over bowel movements due to spinal cord injury may cause severe obstipation and even bowel obstruction Prevention combines a high-fiber diet and stool softeners with laxatives or enemas timed to stimulate evacuation on a regular schedule SUGGESTED READINGS Bennett L, Knowlton GC Overwork weakness in partially denervated skeletal muscle Clin Orthop 1958;12:22–29 Goldstein LB, Matchar DB, Morgenlander JC, Davis JN Influence of drugs on the recovery of sensorimotor function after stroke J Neurol Rehab 1990;4:137–144 Good DC, Couch JR, eds Handbook of neurorehabilitation New York: Marcel Dekker, 1994 International classification of impairments, disabilities, and handicaps Geneva: World Health Organization, 1980 Kalra L, Dale P, Crome P Improving stroke rehabilitation: a controlled study Stroke 1993;24:1462–1467 Kramer AM, Steiner JF, Schlenker RE, et al Outcomes and costs after hip fracture and stroke A comparison of rehabilitation settings JAMA 1997;277:396–404 Selzer ME Neurological rehabilitation Ann Neurol 1992;32:695–699 Taub E, Miller NE, Novack TA, et al Technique to improve chronic motor deficit after stroke Arch Phys Med Rehabil 1993;74:347–354 Visintin M, Barbeau H, Korner-Bitensky N, Mayo NE A new approach to retrain gait in stroke patients through body weight support and treadmill stimulation Stroke 1998;29:1122–1128 Walker-Batson D, Smith P, Curtis S, Unwin H, Greenlee R Amphetamine paired with physical therapy accelerates motor recovery after stroke Stroke 1995;26:2254–2259 CHAPTER 165 END-OF-LIFE ISSUES IN NEUROLOGY MERRITT’S NEUROLOGY XXV ETHICAL AND LEGAL GUIDELINES CHAPTER 165 END-OF-LIFE ISSUES IN NEUROLOGY LEWIS P ROWLAND Informed Consent Advance Directives Refusal of Life Sustaining Treatment Double Effect Palliative Care Physician Assisted Suicide Terminal Sedation Euthanasia An Overall View Suggested Readings Neurologic diseases have been at the center of discussions on issues at the end of life The American Academy of Neurology has set standards for the determination of cerebral death and for the persistent vegetative state (see Chapter 4) Amyotrophic lateral sclerosis and Alzheimer disease have been the focus of debates about assisted suicide Neurologic intensive care units face the issue of discontinuing mechanical ventilation Presymptomatic diagnosis is available for incurable conditions like Huntington disease, creating an ethical challenge These ethical issues could fill a separate book Here, we set forth some principles and definitions as an introduction for students and physicians as they learn to deal with the problems The fundamental ethical and legal guidelines are the basis for actions taken or avoided INFORMED CONSENT One basis for patient autonomy in decision making is informed consent A patient may accept or refuse a treatment or diagnostic test after learning about the anticipated benefits and risks and alternative choices This requires accurate information about prognosis ADVANCE DIRECTIVES Individuals may prepare legal documents that specify their preferences for end-of-life treatments under specific circumstances, and they may also appoint surrogate decision makers if the individual is not competent to make decisions at some future time Most states recognize living wills as instruments for these advance directives, which usually provide a prohibition against life-sustaining treatments that prolong the dying process if the person is in a terminal condition and can no longer make decisions In the interim, a competent person can change the advance directive at any time REFUSAL OF LIFE SUSTAINING TREATMENT The doctrine of informed consent includes the patient's right to refuse life-sustaining treatment Refusal is a decision not to provide consent, without which the physician usually cannot continue treatment Respect for patients' autonomy does not require acceptance of all decisions; the decision must be based on adequate understanding of the nature and consequences of the choice ( informed consent) without coercion and with capacity to make a reasoned decision The patient's right to consent or refuse is not abrogated when the patient loses the capacity to make decisions It becomes transferred to a legally authorized surrogate decision maker and the physician must ask the surrogate for consent or refusal on behalf of the patient The surrogate must follow the patient's previously expressed wishes as expressed in advance directives or other reliable statements If the patient's expressed wishes have not been explicitly stated, the surrogate must use the doctrine of substituted judgment, based on knowledge of the patient's general values and preferences If the surrogate has no such information, the surrogate must assess the anticipated benefits and burdens, based on the doctrine of best interest This may be problematic, however, because it is not based on the desires of the patient Despite widely held beliefs to the contrary, it is not necessary to consult legal counsel before withdrawing life-sustaining therapy DOUBLE EFFECT Some actions are morally and ethically acceptable and may have foreseeable but unintended and undesirable outcomes; the morality of the action depends on the morality of the intended outcome, not the unintended one According to the American Academy of Neurology Ethics Committee statement on assisted suicide, several conditions must be met: the action to be carried out must be morally or ethically acceptable or at least neutral, the good effect must not depend on the undesired or bad effect, and the good effect must be sufficient to justify the risk of the unintended outcome In practice, this principle makes it possible to administer sufficient analgesic and sedative medication to keep a patient comfortable even though the treatment will not prolong life The principle of double effect is the basis of the hospice program PALLIATIVE CARE According to the World Health Organization definition, palliative care is “the active total care of patients whose disease is not responsive to curative treatment, where the control of pain, of other symptoms and of psychological, social, and spiritual problems is paramount, and where the goal is the achievement of the best quality of life for patients and their families.” More directly stated, palliative care is “comfort care” or treatment intended to relieve pain and suffering rather than to cure the disease, restore the patient to health, or prolong life at all costs Oral or parenteral morphine is used in amounts sufficient to control pain and maintain comfort A hospice program is often the venue for palliative care This is sometimes carried out in a hospital or separate physical facility but is increasingly a home care program In the United States, a Medicare Disease-Related Group (DRG) provides reimbursement for the care of patients who are not expected to survive for more than months However, hospice care is used by only 17% of people who are dying, and three reasons are adduced: physicians are uncomfortable about talking with patients about terminal events long enough in advance, sometimes it is difficult to determine precisely the expected time of death, and hospices emphasize home care and family members may not be able to commit the time required or there may be no family members Most Americans die in hospitals (61%) or nursing homes (17%) Another drawback to the use of home or hospice care is the insensitivity of U.S physicians to the advance directives of their patients, as detected by the Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatment (support) Fifty percent of the physicians polled did not respect or did not know the advance directives; most do-not-resuscitate (DNR) orders were not written until 24 hours before death; and 40% of the patients had severe pain for several days before death In a follow-up study, there was no improvement in communication about patients' desires for resuscitation; in the time before death in an intensive care unit; or the incidence or timing of not resuscitate orders, which were not written in 50% of the patients surveyed Physicians misunderstood the desires of their patients against not resuscitate (80%) or the level of pain PHYSICIAN ASSISTED SUICIDE As specified by law in the state of Oregon, it is permissible for a physician to prescribe medication to be used by a patient for the purpose of suicide The physician may not actually administer the drug This law is restricted to Oregon and the practice is not legal in any other state Neurologic diseases generate problems for this policy Patients may be incompetent with Alzheimer disease and would be unable to give consent Other patients may lose the use of their hands from multiple sclerosis or amyotrophic lateral sclerosis Under these circumstances, the patients themselves cannot fill the prescription and take the drug; someone else must assist them physically, which would be euthanasia and specifically banned by the Oregon law Many authorities have debated the desirability of assisted suicide Medical and nursing organizations have uniformly opposed legalization TERMINAL SEDATION The right to forgo treatment includes food and water Pain or other discomfort can be ameliorated by standard palliative measures that may include sedation to unconsciousness The patient then dies as a result of the underlying disease, dehydration, or both It is believed that some form of terminal sedation is applied in up to 40% of deaths in U.S hospitals Discontinuing mechanical ventilation in an intensive care unit is another situation that calls for prevention or relief of suffering Some believe that terminal dehydration has a stronger moral basis than assisted suicide, based as it is on the right to refuse treatment A physician is morally obligated to honor a competent patient's refusal of food and water but is not obligated by a request for a lethal drug Nevertheless, detractors consider terminal sedation a form of “slow euthanasia.” EUTHANASIA If in compliance with a patient's request a physician administers a lethal drug by injection or other means, the act is “euthanasia,” which is illegal in the United States The public, physicians, and courts have had difficulty separating refusal or discontinuation of therapy, which are legal, from assisted suicide and euthanasia, which are not The distinction between assisted suicide and euthanasia is the most controversial of all The Supreme Court concluded that palliative care and terminal sedation are permissible but referred the question of physician-assisted suicide back to legislation by the states AN OVERALL VIEW The issues discussed here are among the most controversial in modern life Consensus is not easy to achieve, but views are changing and current practices are likely to change as well Already, pain control and palliative care have come to the fore and provide effective alternatives to assisted suicide Legal changes may be anticipated but not seem imminent SUGGESTED READINGS Almqvist EW, Block M, Brinkman R, Crauford D, Hayden M A worldwide assessment of the frequency of suicide, suicide attempts, or psychiatric hospitalization after predictive testing for Huntington disease Am J Hum Genet 1999;64:1293–1304 American Academy of Neurology Ethics and Humanities Subcommittee Certain aspects of the care and management of profoundly and irreversibly paralyzed patients with retained consciousness and cognition Neurology 1993;43:222–223 American Academy of Neurology Ethics and Humanities Subcommittee Palliative care in neurology Neurology 1996;46:870–872 American Academy of Neurology Ethics and Humanities Subcommittee Ethical issues in the management of the demented patient Neurology 1996;46:1180–1183 American Academy of Neurology Ethics and Humanities Subcommittee Assisted suicide, euthanasia, and the neurologist Neurology 1998; 50:596–598 American Academy of Neurology Quality Standards Subcommittee Practice parameter: assessment and management of patients in the persistent vegetative state Neurology 1995;45:1015–1018 Angell M The Supreme Court and assisted suicide—the ultimate right N Engl J Med 1997;336:50–53 Bernat JL Ethical issues in neurology Boston: Butterworth-Heinemann, 1994 Bernat JL The problem of physician-assisted suicide Semin Neurol 1997:17:271–280 Bird TD Outrageous fortune: the risk of suicide in genetic testing for Huntington disease Am J Hum Genet 1999;64:1289–1292 Burt RA The Supreme Court speaks—not assisted suicide but a constitutional right to palliative care N Engl J Med 1997;337:1234–1236 Doyle D, Hanks GC, Mac Donald N, eds Oxford textbook of palliative care, 2nd ed New York: Oxford University Press, 1998 Field MJ, Cassel CK, eds Institute of Medicine Approaching death: improving care at the end of life Washington, DC: National Academy Press, 1997 Foley KM Competent care for the dying instead of physician assisted suicide N Engl J Med 1997;336:54–58 Ganzini L, Johnston WS, McFarland BH, Tolle SW, Lee MA Attitudes of patients with amyotrophic lateral sclerosis and their care givers toward assisted suicide N Engl J Med 1998;339:967–973 Gostin LO Deciding life and death in the courtroom: from Quinlan to Cruzan, Glucksberg, and Vacco—a brief history and analysis of constitutional protection of the “right to die.” JAMA 1997:278:1523–1528 Mayer SA, Kossoff SB Withdrawal of life support in the neurological intensive care unit Neurology 1999;52:1602–1609 Meier DE, Morrison RS, Cassel CK Improving palliative care Ann Intern Med 1997;127:223–230 Miller FG, Meier DE Voluntary death: a comparison of terminal dehydration and physician-assisted suicide Ann Intern Med 1998;128:559–562 Multisociety task force on persistent vegetative state N Engl J Med 1994;330:1499–1508, 1572–1579 Newton HB, Malkin MG Ethical issues in neuro-oncology Semin Neurol 1997;17:219–226 Orentlicher D The Supreme Court and physician-assisted suicide—rejecting assisted suicide but embracing euthanasia N Engl J Med 1997;337:1236–1239 Payne SK, Taylor RM The persistent vegetative state and anencephaly: problematic paradigms for discussing futility and rationing Semin Neurol 1997;17:257–264 Quill TE, Lo B, Brock DW Palliative options of last resort: a comparison of voluntarily stopping eating and drinking, terminal sedation, physician-assisted suicide, and voluntary active euthanasia JAMA 1997; 278:2099–2104 Quill TE, Meier DE, Block SD, Billings JA The debate over physician-assisted suicide: empirical data and convergent views Ann Intern Med 1998;128:552–558 Rowland LP Assisted suicide and alternatives in amyotrophic lateral sclerosis N Engl J Med 1998;339:987–989 Ruffin TA Withdrawing life support How is the decision made? JAMA 1995;273:738–739 Youngner SJ Beyond DNR: Fine-tuning end-of-life decision making Neurology 1995;45:615–616 ... Unit Lewis P Rowland Chapter 125 Progressive Muscular Dystrophies Lewis P Rowland Chapter 126 Familial Periodic Paralysis Lewis P Rowland Chapter 127 Congenital Disorders of Muscle Lewis P Rowland. .. Departments of Neurology and Pediatrics University of California, Los Angeles Director of Pediatric Neurology Cedars Sinai Medical Center Los Angeles, California 90212 James R Miller, M.D Associate... personally dedicate it also to all the spouses and children of all the contributors, especially to Esther E Rowland; our children, Andrew, Steven, and Joy; and our grandchildren, Mikaela, David Liam,