70 The Nervous Systemwps.aw.com/wps/media/objects/443/454059/08.Nervous.2p.pdf · The Nervous System The nervous system ... Rabies Encephalitis African sleeping sickness NERVOUS SYSTEM

The Nervous SystemThe nervous system is a highly complex and intercon-nected network of neurons and supporting neuroglia.Neural tissue is extremely delicate, and the character-istics of the extracellular environment must be keptwithin narrow homeostatic limits. When homeostaticregulatory mechanisms break down, under the stressof environmental factors, infection, or trauma, symp-toms of neurological disorders appear.

There are literally hundreds of different disordersof the nervous system. A neurological examinationattempts to trace the source of the problem throughevaluation of the sensory, motor, behavioral and cog-nitive functions of the nervous system. Figure A-25introduces several major categories of nervous systemdisorders. Many of these examples will be discussed inthe sections that follow. Table A-17 summarizes repre-sentative infectious diseases of the nervous system.

THE SYMPTOMS OFNEUROLOGICAL DISORDERSThe nervous system has varied and complex func-tions, and the systems of neurological disorders are

equally diverse. However, there are a few symptomsthat accompany many different disorders.

• Headache: The majority of headaches (roughly90 percent) are tension headaches due to mus-cle tension or migraine headaches that haveboth neurological and circulatory originsNeither of these conditions is life-threatening.

• Muscle weakness: Muscle weakness can have anunderlying neurologic basis, as noted in the sec-tion on muscle disorders (see Figure A-23, p. 64).The examiner must determine the origin of thesymptom. Myopathies (muscle disease) must bedifferentiated from neurologic diseases such asdemyelinating disorders, neuromuscular junc-tion dysfunction, and peripheral nerve damage.

• Paresthesias: Loss of feeling, numbness, or tin-gling sensations may develop following damageto (1) a sensory nerve (cranial or spinal nerve)or (2) sensory pathways inside the CNS. Theeffects may be temporary or permanent. Forexample, a pressure palsy (p. 80) may last afew minutes, whereas the paresthesia thatdevelops distal to an area of severe spinal corddamage (p. 75) will probably be permanent.

70 The Body Systems: Clinical and Applied Topics

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Tay-Sachs diseaseSpina bifidaHuntington’s diseaseHydrocephalusCerebral palsy

Secondary disorders

Congenital disorders

Degenerative disorders

Parkinson’s diseaseAlzheimer’s disease

Trauma

Tumors

NeuromasGliomasNeuroblastomasMeningiomas

Infection

DiphtheriaNeuritisShinglesHansen’s diseasePolioMeningitisRabiesEncephalitisAfrican sleeping sickness

NERVOUS SYSTEMDISORDERS

Cardiovascular system: Cerebrovascular disease Cerebrovascular accident (CVA) or stroke Aphasia

Immune problems: Multiple sclerosis

Spinal cord injuriesPeripheral nerve palsies

Cranial injuries: Epidural and subdural hemorrhages Concussions Contusions Lacerations

Figure A-25 Nervous System Disorders

Nervous.eap3am 8/20/02 3:10 PM Page 70

THE NEUROLOGICALEXAMINATION

During a physical examination, information aboutthe nervous system is obtained indirectly, byassessing sensory, motor, and intellectual func-tions. Examples of factors noted in the physicalexamination include:

• State of consciousness: There are many differ-ent levels of consciousness, ranging fromunconscious and incapable of being aroused, tofully alert and attentive, to hyperexcitable.

• Reflex activity: The general state of the nervoussystem, and especially the state of peripheralsensory and motor innervation, can be checkedby testing specific reflexes (p. 80). For example,the knee-jerk reflex will not be normal if dam-age has occurred in associated segments of thelumbar spinal cord, their spinal nerve roots, orthe peripheral nerves involved in the reflex.

• Abnormal speech patterns: Normal speechinvolves intellectual processing, motor coordi-nation at the speech centers of the brain, pre-cise respiratory control, regulation of tension inthe vocal cords, and adjustment of the muscu-lature of the palate and face. Problems with theselection, production, or use of words often fol-lows damage to the cerebral hemispheres, as ina stroke (p. 116).

• Abnormal motor patterns: An individual’s pos-ture, balance, and mode of walking, or gait, areuseful indicators of the level of motor coordina-tion. Clinicians also ask about abnormal invol-untary movements that may indicate a seizure, atemporary disorder of cerebral function (p. 77).

HeadachesAlmost everyone has experienced a headache atone time or another. Diagnosis and treatment posea number of problems, primarily because, as wenoted earlier, headaches can be produced by awide variety of underlying conditions. The mostcommon causes of headache are either vascular ormuscular problems.

Most headaches do not merit a visit to a neu-rologist. The vast majority of headaches are associ-ated with muscle tension, such as tight neckmuscles, but a variety of other factors may beresponsible. For example, headaches may developdue to one of the following problems:

1. CNS problems, such as infections (meningitis,encephalitis, rabies) or brain tumors

2. Trauma, such as a blow to the head (p. 45)

3. Cardiovascular disorders, such as a stroke (p. 116)

4. Metabolic disturbances, such as low blood sugar

5. Related muscle tension, such as stiff neck or tem-poromandibular joint (TMJ) syndrome

The Nervous System 71

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Table A-17 Examples of infectious Diseases of the Nervous System

Disease Organism(s) Description

Bacterial DiseasesHansen’s disease Mycobacterium leprae Progresses slowly; invades nerves and produces sensory loss and (leprosy) motor paralysis; cartilage and bone may degenerate.

Bacterial meningitis Inflammation of the spinal or cranial meningesHaemophilus influenzae Haemophilus meningitis; usually infects children (age 2 months–

5 years); vaccine availableNeisseria meningitidis Meningococcal meningitis; usually infects children and adults

(age 5–40 years); treatment with antibioticsStreptococcus pneumoniae Streptoccocal meningitis; usually infects adults over age 40; high

mortality rate (40%)Brain abscesses Various bacteria Infection increases in size and compresses the brain.

Viral DiseasesPoliomyelitis Polioviruses Polio has different forms; only one attacks motor neurons, leading

to paralysis of limbs and muscle atrophy. Vaccine is available.Rabies Rabies virus Virus invades the central nervous system through peripheral nerves.

Untreated cases are fatal; treatment involves rabies antitoxin.Encephalitis Various encephalitis Inflammation of the brain; fever and headache; no vaccine is

viruses available. Transmission occurs by mosquitoes. Eastern equine encephalitis is most lethal (50–75% mortality rate).

Parasitic DiseasesAfrican sleeping Trypanosoma brucei Caused by a flagellated protozoan; infection occurs through bite of sickness tsetse fly; infects blood, lymph nodes, and then nervous system.

Symptoms include headache, tiredness, weakness, and paralysis, before coma and death; no vaccine is available.


Migraine headaches affect roughly 5 percent ofthe population. An individual with a classicmigraine experiences visual or other sensory sig-nals that an attack is imminent. The headachepain may then be accompanied by disturbances invision or somatic sensation, extreme anxiety, nau-sea, or disorientation. The symptoms generally per-sist for several hours. A common migraine typicallylacks any warning signs.

Evidence indicates that migraine headachesbegin at a portion of the mesencephalon known asthe dorsal raphe. Electrical stimulation of the dor-sal raphe can produce changes in cerebral bloodflow; several drugs with anti-migraine action inhib-it neurons at this location. The most effective drugsstimulate a class of serotonin receptors that areabundant in the dorsal raphe.

The trigger for tension headaches probablyinvolves a combination of factors, but sustainedcontractions of the neck and facial muscles aremost commonly implicated. Tension headaches canlast for days or can occur daily over longer periods,typically without the throbbing, pulsing sensationscharacteristic of migraine headaches. Instead, theperson may complain of a feeling of pressure orviselike compression. Some tension headaches donot involve the muscles but accompany severedepression or anxiety.

Demyelination Disorders EAP p. 230

Demyelination disorders are linked by a commonsymptom: the destruction of myelinated axons inthe CNS and PNS. The mechanism responsible forthis symptom differs in each of these disorders. Wewill consider only the major categories of demyeli-nation disorders in this section.

• Heavy metal poisoning: Chronic exposure toheavy metal ions, such as arsenic, lead, ormercury, can lead to damage of neuroglia andto demyelination. As demyelination occurs, theaffected axons deteriorate, and the conditionbecomes irreversible. Historians note severalexamples of heavy metal poisoning with wide-spread impact. For example, lead contamina-tion of drinking water has been cited as onefactor in the decline of the Roman Empire. Inthe seventeenth century, the great physicist SirIsaac Newton is thought to have suffered sever-al episodes of physical illness and mentalinstability brought on by his use of mercury inchemical experiments. Well into the nineteenthcentury, mercury used in the preparation of feltpresented a serious occupational hazard forthose employed in the manufacture of stylishhats. Over time, mercury absorbed through theskin and across the lungs accumulated in theCNS, producing neurological damage thataffected both physical and mental function.(This effect is the source of the expression “madas a hatter.”) More recently, Japanese fisher-men working in Minamata Bay, Japan, collect-ed and consumed seafood contaminated with


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mercury discharged from a nearby chemicalplant. Levels of mercury in their systems grad-ually rose to the point that clinical symptomsappeared in hundreds of people. Making mat-ters worse, mercury contamination of develop-ing embryos caused severe, crippling birthdefects.

• Diphtheria: Diphtheria (dif-TH¬-rƒ-uh; diph-theria, membrane + -ia, disease) is a diseasethat results from a bacterial infection of therespiratory tract. In addition to restricting air-flow and sometimes damaging the respiratorysurfaces, the bacteria produce a powerfultoxin that injures the kidneys and adrenalglands, among other tissues. In the nervoussystem, diphtheria toxin damages Schwanncells and destroys myelin sheaths in the PNS.This demyelination leads to sensory and motorproblems that may ultimately produce a fatalparalysis. The toxin also affects cardiac mus-cle cells, and heart enlargement and failuremay occur. The fatality rate for untreatedcases ranges from 35 to 90 percent, dependingon the site of infection and the subspecies ofbacterium. Because an effective vaccine exists,cases are relatively rare in countries with ade-quate health care.

• Multiple sclerosis: Multiple sclerosis (skler-«-sis; sklerosis, hardness), or MS, is a diseasecharacterized by recurrent incidents ofdemyelination affecting axons in the opticnerve, brain, and/or spinal cord. Commonsymptoms include partial loss of vision andproblems with speech, balance, and generalmotor coordination. The time between inci-dents and the degree of recovery varies fromcase to case. In about one-third of all cases,the disorder is progressive, and each incidentleaves a greater degree of functional impair-ment. The average age at the first attack is30–40; the incidence in women is 1.5 timesthat among men. Treatment with corticosteroidinjections and interferon slow the progressionof the disease in some patients. MS is dis-cussed in more detail in a later section (p. 82).

• Guillain-Barré syndrome: Guillain-Barré syn-drome is characterized by a progressive butreversible demyelination. Symptoms initiallyinvolve weakness of the legs, which spreadsrapidly to muscles of the trunk and arms.These symptoms usually increase in intensityfor 1–2 weeks before subsiding. The mortalityrate is low (under 5 percent), but there may besome permanent loss of motor function. Thecause is unknown, but because roughly two-thirds of Guillain-Barré patients develop symp-toms within two months after a viral infection,it is suspected that the condition may resultfrom a malfunction of the immune system.(The mechanism involved is considered inChapter 14 of the text; see p. 446.)


Drugs and Synaptic FunctionMany drugs interfere with key steps in the processof synaptic transmission. These drugs may (1) inter-fere with transmitter synthesis, (2) alter the rate oftransmitter release, (3) prevent transmitter inactiva-tion, or (4) prevent transmitter binding to receptors.The discussion that follows is limited to clinicallyimportant compounds that exert their effects atcholinergic synapses. Their sites of activity are indi-cated in Figure A-26.

Botulinus toxin is responsible for the primarysymptom of botulism, a widespread paralysis ofskeletal muscles. Botulinus toxin blocks therelease of ACh at the presynaptic membrane ofcholinergic neurons. The venom of the black widowspider has the opposite effect. It causes a massiverelease of ACh that produces intense muscularcramps and spasms.

Anticholinesterase drugs, sometimes calledcholinesterase inhibitors, block the breakdown ofACh by acetylcholinesterase. The result is an exag-gerated and prolonged stimulation of the postsy-naptic membrane. At the neuromuscular junctions,this abnormal stimulation produces an extendedand extreme state of contraction. Military nerve

gases block cholinesterase activity for weeks,although few persons exposed are likely to live longenough to regain normal synaptic function. Mostanimals utilize ACh as a neurotransmitter, andanticholinesterase drugs, such as malathion, are inwidespread use in pest-control projects.

Drugs such as atropine or d-tubocurarineprevent ACh from binding to the postsynapticreceptors. The latter compound is a derivative ofcurare, a plant extract used by certain SouthAmerican tribes to paralyze their prey. Curare andrelated compounds induce paralysis by preventingstimulation of the neuromuscular junction by ACh.Atropine can also be administered intentionally tocounteract the effects of anticholinesterase poison-ing. Other compounds, including nicotine, anactive ingredient in cigarette smoke, bind to thereceptor sites and stimulate the postsynaptic mem-brane. There are no enzymes to remove these com-pounds, and the effects are relatively prolonged.

Table A-18 provides additional information onspecific chemical compounds, their uses, and theirsites of action.

Spinal Anesthesia EAP p. 239

Injecting a local anesthetic around a nerve pro-duces a temporary blockage of nerve function. Thiscan be done peripherally, as when sewing up skinlacerations, or at sites around the spinal cord toobtain more widespread anesthetic effects.Although an epidural block, the injection of ananesthetic into the epidural space, has the advan-tage of affecting only the spinal nerves in theimmediate area of the injection, epidural anesthe-sia may be difficult to achieve in the upper cervical,midthoracic, and lumbar regions, where theepidural space is extremely narrow. Caudal anes-thesia involves the introduction of anesthetics intothe epidural space of the sacrum. Injection at thissite paralyzes lower abdominal and perineal struc-tures. Caudal anesthesia may be used instead ofepidural blocks in the lower lumbar or sacralregions to control pain during childbirth.

Local anesthetics may also be introduced intothe subarachnoid space of the spinal cord.However, the effects spread as CSF circulation anddiffusion distributes the anesthetic along the spinalcord. As a result, precise control of the regionaleffects can be difficult to achieve. Problems withoverdosing are seldom serious, because thediaphragmatic breathing muscles are controlled byupper cervical spinal nerves. Thus respiration con-tinues even when the thoracic and abdominal seg-ments have been paralyzed.

Epidural and SubduralHemorrhages EAP p. 240

The most common cases of epidural bleeding, orepidural hemorrhage, involve a traumatic arterialleak. The arterial blood pressure usually forcesconsiderable quantities of blood into the epidural


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Block membranechannels (TTX, STX)

Depress membrane sensitivity(lipid-soluble anesthetics)

Depolarize axonhillock (caffeine,

theobromine)

Demyelinate axons(arsenic, lead)

Block neurotrans-mitter release

(botulinus toxin)

Increase neurotrans-mitter release(spider venom)

Block neurotrans-mitter inactivation(anticholinesterase

drugs)

Prevent neurotransmitterbinding (atropine)

Stimulate receptors(nicotine)

FIGURE A-26 Mechanism of Drug Action at a CholinergicSynapseFactors that facilitate neural function and make neurons moreexcitable are shown in darker boxes. Factors that inhibit ordepress neural function are shown in lighter boxes.


space, distorting the underlying soft tissues of thebrain. The individual loses consciousness fromminutes to hours after the injury, and death fol-lows in untreated cases.

An epidural hemorrhage involving a damagedvein does not produce massive symptoms immedi-ately, and the individual may not develop symptomsuntil several hours to several days or even weeksafter the original incident. Consequently, the prob-lem may not be diagnosed until the nervous tissuehas been severely damaged by distortion, compres-sion, and secondary hemorrhaging. Epidural hem-orrhages are rare, occurring in fewer than 1 percentof head injuries. This is rather fortunate, for themortality rate is 100 percent in untreated cases andover 50 percent even after removal of the blood pooland closure of the damaged vessels.

In a subdural hemorrhage the blood accumu-lates between the dura and the arachnoid.

Subdural hemorrhages are roughly twice as com-mon as epidural hemorrhages. The most commonsource of blood is a small meningeal vein or one ofthe dural sinuses. Because the blood pressure issomewhat lower in the venous system, the extentand effects of this condition are more variable thanthose of the epidural hemorrhages.

Meningitis EAP p. 240

The warm, dark, nutrient-rich environment of themeninges provides ideal conditions for a variety ofbacteria and viruses. Microorganisms that causemeningitis include bacteria associated with middleear infections; pneumonia, streptococcal (“strep”),staphylococcal (“staph”), or meningococcal infec-tions; and tuberculosis. These pathogens may gainaccess to the meninges by traveling within bloodvessels or by entering at sites of vertebral or cranial


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Table A-18 Drugs Affecting Acetylcholine Activity at Synapses

Drug Mechanism Effects Remarks

Hemicholinium Blocks ACh synthesis Produces symptoms ofsynaptic fatigue

Botulinus toxin Blocks ACh release Paralyzes voluntary Produced by bacteria;directly muscles responsible for a deadly

type of food poisoningBarbiturates Decrease rate of ACh Muscular weakness, Administered as sedatives

release depression of CNS and anestheticsactivity

Procaine (Novocain®, Reduces membrane Prevents stimulation of Used as a local anestheticLidocaine) permeability to sodium sensory neuronsTetrodotoxin (TTX) Blocks sodium Eliminates production of Produced by some marine

Saxitoxin (STX) ion channels action potentials organisms duringCiguatoxin (CTX) normal metabolic activity

Neostigmine Prevents ACh inacti- Sustained contraction Used clinically to treatvation by cholin- of skeletal muscles; myasthenia gravis and toesterase other effects on cardiac counteract overdoses of

muscle, smooth muscle, tubocurarineInsecticides As above As above Related compounds used in

(malathion, military nerve gasesparathion, etc.),and nerve gases

d-tubocurarine Prevents ACh binding to Paralysis of voluntary Curare produced bypostsynaptic receptor muscles South American plantsites

Nicotine Binds to ACh receptor Low doses facilitate An active ingredient insites voluntary muscles; cigarette smoke; very

high doses cause addictiveparalysis

Succinylcholine Reduces sensitivity to ACh Paralysis of voluntary Used to produce muscularmuscles relaxation during surgery

Atropine Competes with ACh Reduced heart rate, Produced by deadlyfor binding sites on smooth muscle nightshade plantpostsynaptic membrane activity; skeletal

muscle weakness develops at high doses


injury. Headache, chills, high fever, disorientation,and rapid heart and respiratory rates appear ashigher centers are affected. Without treatment,delirium, coma, convulsions, and death may followwithin hours.

The most common clinical assessment involveschecking for a “stiff neck” by asking the patient totouch chin to chest. Meningitis affecting the cervi-cal portion of the spinal cord results in a markedincrease in the muscle tone of the extensor mus-cles of the neck. So many motor units become acti-vated that voluntary or involuntary flexion of theneck becomes painfully difficult if not impossible.

The mortality rate for viral and bacterialmeningitis ranges from 1 to 50 percent or higher,depending on the type of virus or bacteria, the ageand health of the patient, and other factors. Thereis no effective treatment for viral meningitis, butbacterial meningitis can be combated with antibi-otics and the maintenance of proper fluid and elec-trolyte balance. The incidence of the most commonform of bacterial meningitis, caused byHaemophilus influenzae, has been dramaticallyreduced by immunization.

Spinal Cord Injuries andExperimental Treatments EAP p. 240

At the outset, any severe injury to the spinal cordproduces a period of sensory and motor paralysistermed spinal shock. The skeletal muscles becomeflaccid; neither somatic nor visceral reflexes func-tion; and the brain no longer receives sensations oftouch, pain, heat, or cold. The location and severityof the injury determine how long these symptomspersist and how completely the individual recovers.

Violent jolts, such as those associated withblows or gunshot wounds near the spinal cord, maycause spinal concussion without visibly damagingthe spinal cord. Spinal concussion produces a peri-od of spinal shock, but the symptoms are only tem-porary and recovery may be complete in a matter ofhours. More serious injuries, such as vertebral frac-tures, usually involve physical damage to the spinalcord. In a spinal contusion hemorrhages occur inthe meninges, pressure rises in the cerebrospinalfluid, and the white matter of the spinal cord maydegenerate at the site of injury. Gradual recoveryover a period of weeks may leave some functionallosses. Recovery from a spinal laceration by verte-bral fragments or other foreign bodies will usuallybe far slower and less complete. Spinal compres-sion occurs when the spinal cord becomes physi-cally squeezed or distorted within the vertebralcanal. In a spinal transection the spinal cord iscompletely severed. At present surgical procedurescannot repair a severed spinal cord, but experimen-tal techniques may restore partial function.

Spinal cord injuries often involve some combi-nation of compression, laceration, contusion, andpartial transection. Relieving pressure and stabiliz-ing the affected area through surgery may prevent

further damage and allow the injured spinal cordto recover as much as possible.

Two avenues of research are being pursued,one biological and the other electronic.

Biological Methods. A major biological line ofinvestigation involves the introduction of stem cellsand the biochemical control of nerve growth andregeneration. Treated with embryonic stem cells atthe injury site 9 days after a crushing injury to thespine, laboratory rats recovered some limb mobilityand strength. Oligodendrocytes, astrocytes, andfunctional neurons developed at the injury site.Neural stem cells have also been proposed for thetreatment of strokes, Parkinson’s disease, andAlzheimer’s disease. The recent discovery that theadult brain contains inactive stem cells has openeda new line of investigation: What are the factorsthat activate resident stem cells?

Neurons are influenced by a combination ofgrowth promoters and growth inhibitors. Damagedmyelin sheaths apparently release an inhibitoryfactor that slows the repair process. Researchershave made an antibody, IN-1, that inactivates theinhibitory factor released in the damaged spinalcords of rats. The treatment stimulates repairs,even in severed spinal cords.

A partial listing of compounds known to affectnerve growth and regeneration includes nervegrowth factor (NGF), brain-derived neutrophicfactor (BDNF), neurotrophin-3 (NT-3), neu-rotrophin-4 (NT-4), glial growth factor, glial mat-uration factor, ciliary neurotrophic factor, andgrowth-associated protein 43 (GAP-43). Many ofthese factors have now been synthesized by meansof gene-splicing techniques, and sufficient quanti-ties are available to permit their use in experimentson humans and other mammals. Initial results arepromising, and these factors in various combina-tion are being evaluated for treatment of CNSinjuries and the chronic degeneration seen inAlzheimer’s disease and Parkinson’s disease.

Electrical Methods. Several research teams areexperimenting with the use of computers to stimu-late specific muscles and muscle groups electrically.The technique is called functional electrical stimula-tion, or FES. This approach commonly involvesimplanting a network of wires beneath the skin withtheir tips in skeletal muscle tissue. The wires areconnected to a small computer worn at the waist.The wires deliver minute electrical stimuli to themuscles, depolarizing their membranes and causingcontractions. With this equipment and lightweightbraces, quadriplegics have walked several hundredyards and paraplegics several thousand. TheParastep™ system, which uses a microcomputercontroller, is now undergoing clinical trials.

Equally impressive results have been obtainedusing a network of wires woven into the fabric ofclose-fitting garments. This provides the necessarystimulation without the complications and mainte-nance problems that accompany implanted wires. A


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paraplegic woman in a set of electronic “hot pants”completed several miles of the 1985 HonoluluMarathon, and more recently a paraplegic womanwalked down the aisle at her wedding.

Such technological solutions can provide only adegree of motor control without accompanying sen-sation. Everyone would prefer a biological procedurethat would restore the functional integrity of the ner-vous system. For now, however, computer-assistedprograms such as FES can improve the quality oflife for thousands of paralyzed individuals.

Hydrocephalus EAP p. 245

The adult brain is surrounded by the inflexiblebones of the cranium. The cranial cavity containstwo fluids, blood and cerebrospinal fluid (CSF), andthe relatively firm tissues of the brain. Because thetotal volume cannot change, when the volume ofblood or CSF increases, the volume of the brainmust decrease. In a subdural or epidural hemor-rhage the fluid volume increases as blood collectswithin the cranial cavity. The rising intracranialpressure compresses the brain, leading to neuraldysfunction that, if not treated, ends in uncon-sciousness and death.

Any alteration in the rate of cerebrospinal fluidproduction is normally matched by an increase inthe rate of removal at the arachnoid villi. If thisequilibrium is disturbed, clinical problems appearas the intracranial pressure changes. The volumeof cerebrospinal fluid will increase if the rate of for-mation accelerates or the rate of removal decreas-es. In either event the increased fluid volume leadsto compression and distortion of the brain.Increased rates of formation may accompany headinjuries, but the most common problems arise frommasses, such as tumors or abscesses, or fromdevelopmental abnormalities or scarring afterinfection. These conditions have the same effect:they restrict the normal circulation and reabsorp-tion of CSF. Because CSF production continues,the ventricles gradually expand, distorting the sur-rounding neural tissues and causing the deteriora-tion of brain function.

Infants are especially sensitive to alterations inCSF volume that increase intracranial pressure,because the arachnoid villi, which reabsorb CSF, donot appear until roughly 3 years of age. As in anadult, if intracranial pressure becomes abnormallyhigh, the ventricles will expand. But in an infantthe cranial sutures have yet to fuse, and the skullcan enlarge to accommodate the extra fluid volume.This can produce an enormously expanded skull, acondition called hydrocephalus, or “water on thebrain.” Infant hydrocephalus (Figure A-27) oftenresults from some interference with normal CSF cir-culation, such as blockage of the mesencephalicaqueduct or constriction of the connection betweenthe subarachnoid spaces of the cranial and spinalmeninges. Untreated infants often suffer somedegree of mental retardation. Successful treatmentusually involves the installation of a shunt, a


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bypass that either bypasses the blockage site ordrains the excess cerebrospinal fluid. In either case,the goal is reduction of the intracranial pressure.The shunt may be removed if (1) further growth ofthe brain eliminates the blockage or (2) theintracranial pressure decreases following the devel-opment of the arachnoid villi at 3 years of age.

Lumbar Punctureand Myelography EAP p. 245

Tissue samples, or biopsies, are taken from manyorgans to assist in diagnosis. For example, when aliver or skin disorder is suspected, small plugs oftissue are removed and examined for signs of infec-tion or cell damage, or used to diagnose a tumor.Unlike many other tissues, however, neural tissueconsists largely of cells rather than extracellularfluids or fibers. Tissue samples are seldomremoved for analysis, because any extracted ordamaged neurons will not be replaced. Instead,small volumes of cerebrospinal fluid (CSF) areextracted via a spinal tap and analyzed. CSF isintimately associated with the neural tissue of theCNS, and pathogens, cell debris, or metabolicwastes in the CNS will therefore be detectable inthe CSF.

With the vertebral column flexed, a needle canbe inserted between the lower lumbar vertebrae andinto the subarachnoid spaces with minimal risk tothe cauda equina. This procedure, known as a lum-bar puncture, can be used to remove 3–9 ml of CSFfrom the subarachnoid space or to introduce anes-thetic drugs.

Myelography involves the introduction ofradiopaque dyes into the CSF of the subarachnoidspace. Because the dyes are opaque to X-rays, theCSF appears white on an X-ray photograph, as in

Figure A-27 Hydrocephalus

This infant suffers from hydrocephalus, a condition usuallycaused by impaired circulation and removal of cerebrospinalfluid. CSF buildup in infancy leads to distortion of the brainand enlargement of the cranium.


Figure A-28. Any tumors, inflammations, or adhe-sions that distort or divert CSF circulation will beshown in silhouette.

In the event of severe infection, inflammation,or leukemia (cancer of the white blood cells),antibiotics, steroids, or anticancer drugs can beinjected into the subarachnoid space.

Amnesia EAP p. 250

Amnesia may occur suddenly or progressively, andrecovery may be complete, partial, or nonexistent,depending on the nature of the problem. In retro-grade amnesia (retro-, behind), the individual losesmemories of past events. Some degree of retrogradeamnesia often follows a head injury, and accidentvictims are frequently unable to remember themoments preceding a car wreck. In anterogradeamnesia (antero-, ahead), an individual may beunable to store additional memories, but earliermemories are intact and accessible. The problemappears to involve an inability to generate long-term memories. At least two drugs—diazepam(Valium) and Halcion—have been known to causebrief periods of anterograde amnesia. A personwith permanent anterograde amnesia lives in sur-roundings that are always new. Magazines can beread, chuckled over, and then reread a few minuteslater with equal pleasure, as if they had never beenseen before. Physicians and nurses must introducethemselves at every meeting, even if they have beenvisiting the patient for years.

Posttraumatic amnesia (PTA) often developsafter a head injury. The duration of the amnesiavaries depending on the severity of the injury. PTAcombines the characteristics of retrograde andanterograde amnesia; the individual can neitherremember the past nor consolidate memories of thepresent.

Seizures and Epilepsy EAP p. 251

A seizure is a temporary disorder of cerebral func-tion, accompanied by abnormal, involuntary move-ments, unusual sensations, and/or inappropriatebehavior. The individual may or may not lose con-sciousness for the duration of the attack. There aremany different types of seizures. Clinical conditionscharacterized by seizures are known as seizure dis-orders, or epilepsies. The term epilepsy refers tomore than 40 different conditions characterized bya recurring pattern of seizures over extended peri-ods. In roughly 75 percent of patients, no obviouscause can be determined.

Seizures of all kinds are accompanied by amarked change in the pattern of electrical activitymonitored in an electroencephalogram. The alter-ation begins in one portion of the cerebral cortexbut may subsequently spread to adjacent regions,potentially involving the entire cortical surface. Theneurons at the site of origin are abnormally sensi-tive. When they become active, they may facilitateand subsequently stimulate adjacent neurons. As a


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result, the abnormal electrical activity can spreadacross the entire cerebral cortex.

The extent of the cortical involvement deter-mines the nature of the observed symptoms. A focalseizure affects a relatively restricted cortical area,producing sensory and/or motor symptoms. Theindividual usually remains conscious throughout theattack. If the seizure occurs within a portion of theprimary motor cortex, the activation of pyramidalcells will produce uncontrollable movements. Themuscles affected or the specific sensations experi-enced provide an indication of the precise regioninvolved. In a temporal lobe seizure the distur-bance spreads to the sensory cortex and associationareas, so the individual also experiences unusualmemories, sights, smells, or sounds. Involvement ofthe limbic system may also produce sudden emo-tional changes. Often the individual will lose con-sciousness at some point during the incident.

Convulsive seizures are associated withuncontrolled muscle contractions. In a general-ized seizure the entire cortical surface is involved.

(a)

(b)

Figure A-28 Myelography

(a) Position and procedure used to introduce spinal anes-thetic or radiopaque dye. (b) A myelogram—an X-ray photo-graph of the spinal cord after introduction of a radiopaquedye into the CSF—showing the cauda equina in the lowerlumbar region.


Generalized seizures may range from prolonged,major events to brief, almost unnoticed incidents.Only two examples will be considered here, grandmal and petit mal seizures.

Most readers will think of an epileptic attack asinvolving powerful, uncoordinated muscular con-tractions affecting the face, eyes, and limbs. Theseare symptoms of a grand mal seizure. During agrand mal attack, the cortical activation begins at asingle focus and then spreads across the entiresurface. There may be no warning, but some indi-viduals experience a vague apprehension or aware-ness that a seizure is about to begin. There followsa sudden loss of consciousness, and the individualdrops to the floor as major muscle groups go intotonic contraction. The body remains rigid for sever-al seconds before a rhythmic series of contractionsoccurs in the limb muscles. Incontinence mayoccur. After the attack, subsides, the individualmay appear disoriented or sleep for several hours.Muscles or bones subjected to extreme stressesmay be damaged, and the person will probably berather sore for days after the incident.

Petit mal epileptic attacks are very brief (under10 seconds in duration) and involve few motorabnormalities. Typically the individual simply losesconsciousness suddenly, with no warning. It is asif an internal switch were thrown and the con-scious mind turned off. Because the individual is“not there” for brief periods during petit malattacks, the incidents are also known as absenceseizures. During the seizure there may be smallmotor activities, such as fluttering of the eyelids ortrembling of the hands.

Petit mal attacks usually begin between the ageof 6 and 14 years. They can occur hundreds oftimes per day, so that the child lives each day insmall segments separated by blank periods. Thevictim is aware of brief losses of consciousness thatoccur without warning but seldom seeks helpbecause of embarrassment. Often he or shebecomes extremely anxious about the timing offuture attacks. However, the motor signs are sominor as to go completely unnoticed by other fami-ly members, and the psychological stress causedby this condition is often overlooked. The initialdiagnosis is frequently made during counseling forlearning problems. (You have probably taken anexam after missing 1 or 2 lectures of 20. Imaginetaking an exam after missing every third minute ofevery lecture.)

Both petit mal and grand mal epilepsy can betreated with barbiturates or other anticonvulsivedrugs, such as phenytoin sodium (dilantin).

The Basal Nuclei and Parkinson’s Disease EAP p. 250

The basal nuclei contain two discrete populations ofneurons. One group stimulates motor neurons byreleasing acetylcholine (ACh), and the other inhibitsmotor neurons by the release of gamma aminobu-tyric acid (GABA). Under normal conditions the exci-

tatory neurons remain inactive, and the descendingtracts are primarily responsible for inhibiting motorneuron activity. If the descending tracts are severedin an accident, the loss of inhibitory control leads toa generalized state of muscular contraction knownas decerebrate rigidity.

The excitatory neurons are quiet because theyare continually exposed to the inhibitory effects ofthe neurotransmitter dopamine. This compound ismanufactured by neurons in the substantia nigraand carried to synapses in the basal nuclei. If theascending tract or the dopamine-producing neu-rons are damaged, this inhibition is lost and theexcitatory neurons become increasingly active. Thisincreased activity produces the motor symptoms ofParkinson’s disease, or paralysis agitans.

Parkinson’s disease is characterized by a pro-nounced increase in muscle tone. Voluntary move-ments become hesitant and jerky, a conditioncalled spasticity, for a movement cannot occuruntil one muscle group manages to overpower itsantagonists. Individuals with Parkinson’s diseaseshow spasticity during voluntary movement and acontinual tremor when at rest. A tremor repre-sents a tug of war between antagonistic musclegroups that produces a background shaking of thelimbs, in this case at a frequency of 4–6 cycles persecond. Individuals with Parkinson’s disease alsohave difficulty starting voluntary movements. Evenchanging one’s facial expression requires intenseconcentration, and the individual acquires a blank,static expression. Finally, the positioning andpreparatory adjustments normally performed auto-matically no longer occur. Every aspect of eachmovement must be voluntarily controlled, and theextra effort requires intense concentration thatmay prove tiring and extremely frustrating. In thelate stages of this condition, other CNS effects,such as depression, hallucinations, and dementiaoften appear.

Providing the basal nuclei with dopamine cansignificantly reduce the symptoms for two-thirds ofParkinson’s patients, but intravenous dopamineinjection is not effective, because the molecule can-not cross the blood-brain barrier. The most com-mon procedure involves the oral administration ofthe drug L-DOPA (levodopa), a related compoundthat crosses the capillaries and is then converted todopamine. Unfortunately, it appears that with pro-longed treatment, the capillaries become less per-meable to L-DOPA, so the required dosageincreases. Surgery to control Parkinson’s symptomshas focused on the destruction of large areas withinthe basal nuclei or thalamus to control the motorsymptoms of tremor and rigidity. The high rate ofsuccess for drug therapy has greatly reduced thenumber of surgical procedures. In 2001, electricalstimulation of the deep brain subthalamic nucleusby implanted wires and a pacemaker-like powerpack to dramatically improved motor function insome patients. Recent attempts to transplant tis-sues producing dopamine or related compoundsinto the basal nuclei have met with limited success.


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Variable results have been obtained with the trans-plantation of tissue from the adrenal gland. Thetransplantation of fetal tissue into adult brains hasbeen more successful. Most individuals withParkinson’s disease are elderly. However, since1983 an increasing number of young people havedeveloped this condition. In that year a drugappeared on the streets rumored to be “syntheticheroin.” The drug contained the contaminantnamed MPTP. This accidental by-product of thesynthetic process destroys neurons of the substan-tia nigra, eliminating the manufacture and trans-port of dopamine to the basal nuclei. As a result ofexposure to this drug, approximately 200 young,healthy adults developed symptoms of severeParkinson’s disease. Why MPTP targets these par-ticular neurons, and not all of the CNS neuronsthat produce dopamine, remains a mystery. MPTPhas been used to give experimental animalsParkinson’s disease. Testing the animals speeds thedevelopment of more effective treatments.

Huntington’s Disease EAP p. 250

Huntington’s disease is an inherited diseasemarked by a progressive deterioration of mentalabilities. There are approximately 25,000Americans with this condition. In Huntington’s dis-ease the basal nuclei show degenerative changes,as do the frontal lobes of the cerebral cortex. Thebasic problem is the destruction of ACh-secretingand GABA-secreting neurons in the basal nuclei.The cause of this deterioration is not known. Thefirst signs of the disease usually appear in earlyadulthood. As you would expect in view of theareas affected, the symptoms involve difficulties inperforming voluntary and involuntary patterns ofmovement and a gradual decline in intellectualabilities leading eventually to dementia and death.

Tests can now detect the presence of the genefor Huntington’s disease, which is an autosomaldominant gene located on chromosome 4. In peoplewith Huntington’s disease, a gene of uncertainfunction contains a variable number of repetitionsof the nucleotide sequence CAG. This DNA segmentappears to be unstable, and the number of repeti-tions can change from generation to generation.The duplication or deletion is thought to occur dur-ing gamete formation. The larger the number ofrepetitions, the earlier in life the symptoms appearand the more severe the symptoms. The linkbetween the multiple copies of the CAG nucleotideand the disorder has yet to be understood. There isno effective treatment. A victim’s children have a50 percent risk of receiving the gene and develop-ing Huntington’s disease.

Cerebellar Dysfunction EAP p. 253

Cerebellar function may be permanently altered bytrauma or a stroke, or temporarily by drugs suchas alcohol. Such alterations can produce distur-bances in motor control. In severe ataxia balanceproblems are so great that the individual cannot sit

or stand upright. Less-severe conditions cause anobvious unsteadiness and irregular patterns ofmovement. The individual often watches his or herfeet to see where they are going and controls ongo-ing movements by intense concentration and vol-untary effort. Reaching for something becomes amajor exertion, for the only information availablemust be gathered by sight or touch while the move-ment is taking place. Without the cerebellar abilityto adjust movements while they are occurring, theindividual becomes unable to anticipate the timecourse of a movement. Most often, a reachingmovement ends with the hand overshooting thetarget. This inability to anticipate and stop a move-ment precisely is called dysmetria (dis-MET-rƒ-uh;dys-, bad + metron, measure). In attempting to cor-rect the situation, the hand usually overshootsagain in the opposite direction, and then again.This leaves the hand oscillating back and forthuntil either the object can be grasped or theattempt is abandoned. This oscillatory movement isknown as an intention tremor.

Clinicians check for ataxia by watching an indi-vidual walk in a straight line; the usual test fordysmetria involves touching the tip of the index fin-ger to the tip of the nose. Because many drugsimpair cerebellar performance, the same tests areused by police officers to check drivers suspectedof alcohol or other drug abuse.

Shingles and Hansen’s DiseaseEAP p. 257

In shingles, or herpes zoster, the herpes varicella-zoster virus attacks neurons within the dorsalroots of spinal nerves and sensory ganglia of cra-nial nerves. This disorder produces a painful rashwhose distribution corresponds to that of theaffected sensory nerves (Figure A-29). Shinglesdevelops in adults who were first exposed to thevirus as children. The initial infection producessymptoms known as chicken pox. After thisencounter the virus remains dormant within neu-rons of the anterior gray horns of the spinal cord. Itis not known what triggers reactivation of thispathogen. Fortunately for those affected, attacks ofshingles usually heal and leave behind onlyunpleasant memories.

Most people suffer only a single episode ofshingles in their adult lives. However, the problemmay recur in people with weakened immune sys-tems, including those with AIDS or some forms ofcancer. Treatment typically involves large doses ofthe antiviral drug acyclovir (Zovirax).

The condition traditionally called leprosy, nowmore commonly known as Hansen’s disease, is aninfectious disease caused by a bacterium,Mycobacterium leprae. It is a disease that progress-es slowly, and symptoms may not appear for up to30 years after infection. The bacterium invadesperipheral nerves, especially those in the skin, pro-ducing sensory losses. Over time motor paralysisdevelops, and the combination of sensory and


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motor loss can lead to recurring injuries and infec-tions. The eyes, nose, hands, and feet may developdeformities as a result of neglected injuries. Thereare several forms of this disease; peripheral nervesare always affected, but some forms also involveextensive skin and mucous membrane lesions.

Only about 5 percent of those exposed developsymptoms; people living in the Tropics are at great-est risk. There are about 2000 cases in the UnitedStates, and an estimated 12–20 million cases world-wide. If detected before deformities occur, the dis-ease can usually be treated successfully with drugssuch as rifampin and dapsone. Treated individualsare not infectious, and the practice of confining “lep-ers” in isolated compounds has been discontinued.

Palsies EAP p. 258

Peripheral nerve palsies, or peripheral neu-ropathies, are characterized by regional losses ofsensory and motor function as the result of nervetrauma or compression. Brachial palsies resultfrom injuries to the brachial plexus or its branch-es. Crural palsies involve the nerves of the lum-bosacral plexus.

Although palsies may appear for several rea-sons, the pressure palsies are especially interest-ing. A familiar but mild example is the experienceof having an arm or leg “fall asleep.” The limbbecomes numb, and afterwards an uncomfortable“pins-and-needles” sensation, or paresthesia,accompanies the return to normal function.

These incidents are seldom of clinical signifi-cance, but they provide graphic examples of theeffects of more serious palsies that can last fordays to months. In radial nerve palsy, pressure onthe back of the arm interrupts the function of theradial nerve, so that the extensors of the wrist andfingers are paralyzed. This condition is also knownas “Saturday night palsy,” for falling asleep on acouch with your arm over the seat back (orbeneath someone’s head) can produce the rightcombination of pressures. Students may also befamiliar with ulnar palsy, which can result fromprolonged contact between elbow and desk. The

ring and little fingers lose sensation, and the fin-gers cannot be adducted.

Men with large wallets in their hip pockets maydevelop symptoms of sciatic compression afterdriving or sitting in one position for extended peri-ods. As nerve function declines, the individualsnotice some lumbar or gluteal pain, a numbnessalong the back of the leg, and a weakness in the legmuscles. Similar symptoms result from compres-sion of the sciatic nerve by a distorted lumbarintervertebral disc. This condition is termed sciati-ca, and one or both legs may be affected, depend-ing on the site of compression. Finally, sitting withyour legs crossed may produce symptoms of a per-oneal palsy. Sensory losses from the top of the footand side of the leg are accompanied by a decreasedability to dorsiflex or evert the foot.

Reflexes and Diagnostic Testing EAP p. 258

Many reflexes can be assessed through carefulobservation and the use of simple tools. The proce-dures are easy to perform, and the results can pro-vide valuable information about damage to thespinal cord or spinal nerves. By testing a series ofspinal and cranial reflexes, a physician can assessthe function of sensory pathways and motor cen-ters throughout the spinal cord and brain.

Neurologists test many different reflexes; only afew are so generally useful that physicians makethem part of a standard physical examination.These reflexes are shown in Figure A-30.

The ankle jerk (Figure A-30a), biceps reflex(Figure A-30b), and triceps reflex (Figure A-30c) arestretch reflexes controlled by specific segments ofthe spinal cord. Testing these reflexes providesinformation about the corresponding spinal seg-ments. For example, a normal patellar reflex, orknee jerk, indicates that spinal nerves and spinalsegments L2-L4 are undamaged. The abdominalreflex (Figure A-30d), present in the normal adult,results from descending spinal facilitation. In thisreflex, a light stroking of the skin produces areflexive twitch in the abdominal muscles thatmoves the navel toward the stimulus. This reflexdisappears following damage to descending tracts.

Abnormal Reflex Activity EAP p. 258

In hyporeflexia normal reflexes are weak, butapparent, especially with reinforcement. In areflex-ia (¥-rƒ-FLEK-sƒ-uh; a-, without) normal reflexesfail to appear, even with reinforcement. Hyporeflexiaor areflexia may indicate temporary or permanentdamage to skeletal muscles, dorsal or ventral nerveroots, spinal nerves, the spinal cord, or the brain.

Hyperreflexia occurs when higher centersmaintain a high degree of facilitation along thespinal cord. Under these conditions reflexes areeasily triggered, and the responses may be grosslyexaggerated. This effect can also result fromspinal cord compression or diseases that target


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Figure A-29 Shingles

The left side of a person with shingles. The skin eruptionsfollow the distribution of dermatomal innervation.


higher centers or descending tracts. One potentialresult of hyperreflexia is the appearance of alter-nating contractions in opposing muscles. Whenone muscle contracts, it stimulates the stretchreceptors in the other. The stretch reflex thentriggers a contraction in that muscle, and thisstretches receptors in the original muscle. Thisself-perpetuating sequence, which can be repeat-ed indefinitely, is called clonus (KL«-nus). In ahyperreflexive person, a tap on the patellar ten-don will set up a cycle of kicks, rather than justone or two.

A more extreme hyperreflexia develops if themotor neurons of the spinal cord lose contact withhigher centers. Often, following a severe spinalinjury, the individual first experiences a temporaryperiod of areflexia known as spinal shock (p. 75).When the reflexes return, they respond in an exag-

gerated fashion, even to mild stimuli. For example,the lightest touch on the skin surface may producea massive withdrawal reflex. The reflex contrac-tions may occur in a series of intense musclespasms potentially strong enough to break bones.In the mass reflex, the entire spinal cord becomeshyperactive for several minutes, issuing exaggerat-ed skeletal muscle and visceral motor commands.

Multiple Sclerosis EAP p. 260

Multiple sclerosis (MS), introduced in the discus-sion of demyelination disorders, is a disease thatproduces muscular paralysis and sensory lossesthrough demyelination. The initial symptomsappear as the result of myelin degeneration withinthe white matter of the lateral and posteriorcolumns of the spinal cord or along tracts within


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(a) Ankle jerk

(c) Triceps reflex

(b) Biceps reflex

Figure A-30 Reflexes and Diagnostic Testing(d) Abdominal reflex


the brain. For example, spinal cord involvementmay produce weakness, tingling sensations, and aloss of “position sense” for the limbs. During subse-quent attacks the effects become more widespread,and the cumulative sensory and motor losses mayeventually lead to a generalized muscular paralysis.

Recent evidence suggests that this conditionmay be linked to a defect in the immune systemthat causes it to attack myelin sheaths. MS patientshave lymphocytes that do not respond normally toforeign proteins, and because several viral proteinshave amino acid sequences similar to those of nor-mal myelin, it has been proposed that MS resultsfrom a case of mistaken identity. For unknown rea-sons MS appears to be associated with cold andtemperate climates. It has been suggested that indi-viduals developing MS may have an inherited sus-ceptibility to the virus that is exaggerated byenvironmental conditions. The yearly incidencewithin the United States averages around 50 casesfor every 100,000 in the population. Improvementhas been noted in some patients treated with inter-feron, a peptide secreted by cells of the immunesystem, and recently corticosteroid treatment hasbeen linked to a slowdown in the progression of MS.

Alzheimer’s Disease EAP p. 268

In its characteristic form, Alzheimer’s disease pro-duces a gradual deterioration of mental organiza-tion. The afflicted individual loses memories, verbaland reading skills, and emotional control. Initialsymptoms are subtle—moodiness, irritability,depression, and a general lack of energy. Thesesymptoms are often ignored, overlooked, or dis-missed. Elderly relations may be viewed as “eccen-tric” or “irrascible,” and humored whenever possible.

As the condition progresses, however, itbecomes more difficult to ignore or accommodate.The victim has difficulty making decisions, evenminor ones. Mistakes—sometimes dangerousones—are made, either through bad judgment orsimple forgetfulness. For example, the personmight decide to make dinner, light the gas burner,place a pot on the stovetop, and go into the livingroom. Two hours later, the pot, still on the stove,melts into a shapeless blob and starts a fire thatdestroys the house.

As memory losses continue, the problemsbecome more severe. The affected person may for-get relatives, her home address, or how to use thetelephone. The memory loss often starts with aninability to store long-term memories, followed bythe loss of recently stored memories, and eventual-ly the loss of basic long-term memories, such asthe sound of the victim’s own name. The loss ofmemory affects both intellectual and motor abili-ties, and a patient with severe Alzheimer’s diseasehas difficulty in performing even the simplestmotor tasks. Although by this time victims are rela-tively unconcerned about their mental state ormotor abilities, the condition can have devastatingemotional effects on the immediate family.

Individuals with Alzheimer’s disease show apronounced decrease in the number of corticalneurons, especially in the frontal and temporallobes. This loss is correlated with inadequate AChproduction in the nucleus basalis of the cerebrum.Axons leaving this region project throughout thecerebral cortex, and when ACh productiondeclines, cortical function deteriorates.

Most cases of Alzheimer’s disease are associatedwith unusually large concentrations of neurofibril-lary tangles and plaques in the nucleus basalis, hip-pocampus, and parahippocampal gyrus. The tanglesare intracellular masses of abnormal microtubularproteins. The plaques are extracellular masses thatform around a core that consists of an abnormalprotein called beta-amyloid. Beta amyloid is alsofound in other tissues, including the skin, blood ves-sels, subcutaneous layer, and intestine. Familialcases of Alzheimer’s disease are associated withmutations on either chromosome 21 or a smallregion of chromosome 14. A number of experimentalprotocols are undergoing clinical trials, but as yetthere is no effective treatment for this condition.

PROBLEMS WITH SENSORYSYSTEMS EAP p. 278

A recurring theme of the text is that an understand-ing of how a system works enables you to predicthow things might go wrong. You are already familiarwith the organization and physiology of sensory sys-tems, and some of the most important clinical prob-lems were discussed in clinical comments on thepreceding pages. Placing the entire array into cate-gories provides an excellent example of a strategythat can be used to analyze any system in the body.

Every sensory system contains peripheralreceptors, afferent fibers, ascending tracts, nuclei,and areas of the cerebral cortex. Any malfunctionaffecting the system must involve one of those com-ponents. Any clinical diagnosis requires seekinganswers to a series of yes or no questions, elimi-nating one possibility at a time until the nature ofthe problem becomes apparent. Figure A-31 orga-nizes the disorders considered in this chapter intoa “trouble-shooting” format similar to that used todiagnose problems with automobiles or othermechanical devices.

The Control of Pain EAP p. 278

Pain management poses a number of problems forclinicians. Painful sensations can result from tis-sue damage or sensory nerve irritation; it mayoriginate where it is perceived, be referred fromanother location, or represent a false signal gen-erated along the sensory pathway (see Figure A-2,p. 12). The treatment differs in each case, and anaccurate diagnosis is an essential first step.

When pain results from tissue damage, themost effective solution is to stop the damage andend the stimulation. This is not always possible.


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Alternatively, the painful sensations can be sup-pressed at the injury site. Topical or locally injectedanesthetics inactivate nociceptors in the immediatearea. Aspirin and related analgesics reduce inflam-mation and suppress the release of irritating chem-icals, such as enzymes or prostaglandins, indamaged tissues.

Pain can also be suppressed by inhibition of thepain pathway. Analgesics related to morphinereduce pain by mimicking the action of endorphins.Surgical steps can be taken to control severe pain,including (1) the sensory innervation of an area canbe destroyed by an electric current, (2) the dorsalroots carrying the painful sensations can be cut (arhizotomy), (3) the ascending tracts in the spinalcord can be severed (a tractotomy), or (4) thalamic orlimbic centers can be stimulated or destroyed.These options, listed in order of increasing degree ofeffect, surgical complexity, and associated risk, areused only when other methods of pain control havefailed to provide relief.

The Chinese technique of acupuncture to con-trol pain has recently received considerable atten-tion. Fine needles are inserted at specific locationsand are either heated or twirled by the therapist.Several theories have been proposed to account for

the positive effects, but none is widely accepted. Ithas been suggested that the pain relief may followendorphin release, but it is not known howacupuncture stimulates endorphin release; theacupuncture points do not correspond to the distri-bution of any of the major peripheral nerves.

Many other aspects of pain generation and con-trol remain a mystery. Up to 30 percent of patientsexperience a significant reduction in pain afterreceiving a nonfunctional medication. It has beensuggested that this “placebo effect” results fromendorphin release triggered by the expectation ofpain relief. Although the medication has no directeffect, the indirect effect can be quite significant.

Assessment of TactileSensitivities EAP p. 279

Regional sensitivity to light touch can be checkedby gentle contact with a fingertip or a slender wispof cotton. The two-point discrimination test pro-vides a more detailed sensory map for tactile recep-tors. Two fine points of a drawing compass, bentpaper clip, or other object are applied to the skinsurface simultaneously. The subject then describesthe contact. When the points fall within a single


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QUESTION:

ls stimulusreaching receptors?

QUESTION:

Are receptorsresponding normally?

QUESTION:

Are receptorsphysically damaged?

QUESTION:

Are pathways intact and normal?

Problem involves inability tostimulate receptors

Problem results fromabnormal development

or receptor metabolism

Problem results fromtrauma or secondary

factors affectingreceptor cells

Problem involvesabnormality at the

cerebral cortex

Problem involvesabnormal pathway

function

No

No

No

No

Yes

Yes

Yes

Yes

Examples: Blindness or deafness due to cranial trauma or stroke

Examples: Glaucoma Acoustic nerve inflammation Syphilis involving spinal cord tracts

Examples: Deafness due to loud noises

Examples: Night blindness Color blindness Inherited deafness

Examples: Conductive deafness Cataracts Scarring of cornea

Figure A-32 A Flow Chart for the Analysis of Sensory Disorders


receptive field, the individual will report only onepoint of contact. A normal individual loses two-point discrimination at 1 mm (0.04 in.) on the sur-face of the tongue, at 2–3 mm (0.08–0.12 in.) onthe lips, at 3–5 mm (0.12–0.20 in.) on the backs ofthe hands and feet, and at 4–7 cm (1.6–2.75 in.)over the general body surface.

Vibration receptors are tested by applying thebase of a tuning fork to the skin. Damage to anindividual spinal nerve produces insensitivity tovibration along the paths of the related sensorynerves. If the sensory loss results from spinal corddamage, the injury site can often be located bywalking the tuning fork down the spinal column,resting its base on the vertebral spines.

Descriptive terms are used to indicate thedegree of sensitivity in the area considered.Anesthesia implies a total loss of sensation; theindividual cannot perceive touch, pressure, pain,or temperature sensations from that area.Hypesthesia is a reduction in sensitivity, andparesthesia is the presence of abnormal sensa-tions, such as the pins-and-needles sensationwhen an arm or leg “falls asleep” due to pressureon a peripheral nerve. (Several types of pressurepalsies producing temporary paresthesia were dis-cussed on p. 80.)

Conjunctivitis EAP p. 285

Problems with the accessory structures of the eyeand ear are more common causes of abnormal sen-sory function than damage to the receptors or theinnervation. The term conjunctivitis is more usefulas the description of a symptom than as a name fora specific disease. A great variety of pathogens,including bacteria, viruses, and fungi, can causeconjunctivitis, and a temporary form of the condi-tion may be produced by chemical or physical irri-tation (including even such mundane experiencesas prolonged crying or peeling an onion).

Chronic conjunctivitis, or trachoma, resultsfrom bacterial or viral invasion of the conjunctiva.Trachoma is often highly contagious. Severe casesmay disrupt the corneal surface and affect vision.The pathogen most often involved is Chlamydia tra-chomatis. Trachoma is a relatively common prob-lem in southwestern North America, North Africa,and the Middle East. The condition must be treatedwith topical and systemic antibiotics to preventscleral damage, eventual corneal damage, andvision loss.

Corneal Transplants EAP p. 285

The cornea has a very restricted ability to repairitself, so corneal injuries must be treated immedi-ately to prevent serious visual losses. To restorevision after corneal scarring, it is usually necessaryto replace the cornea through a corneal trans-plant. Corneal replacement is probably the mostcommon form of transplant surgery. Corneal trans-plants can be performed between unrelated indi-viduals because there are no corneal blood vessels,


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and white blood cells that would otherwise rejectthe graft are unlikely to enter the area. Cornealgrafts are obtained by posthumous donation; forbest results the tissues must be removed within 5hours after the donor’s death.

Glaucoma EAP p. 291

If aqueous humor cannot enter the canal ofSchlemm, the condition of glaucoma develops.Although drainage is impaired, production of aque-ous humor continues, and the intraocular pressurebegins to rise. The fibrous scleral coat cannotexpand significantly, so the increasing pressurebegins to distort soft tissues within the eye.

The optic nerve is not wrapped in connectivetissue, for it penetrates all three tunics. Whenintraocular pressures have risen to roughly twicenormal levels, distortion of the nerve fibers beginsto affect visual perception. If this condition is notcorrected, blindness eventually results.

Glaucoma affects roughly 2 percent of the pop-ulation over 35, and in most cases the primary fac-tors responsible cannot be determined. Because itis a relatively common condition—over 2 millioncases in the United States alone—most eye examsinclude a test of intraocular pressure. Glaucomamay be treated by the application of drugs thatconstrict the pupil and tense the edge of the iris,making the surface more permeable to aqueoushumor. Surgical correction involves perforating thewall of the anterior chamber to encouragedrainage. This procedure is now performed by lasersurgery on an outpatient basis.

Otitis Media andMastoiditis EAP p. 297

Otitis media is an infection of the middle ear, fre-quently of bacterial origin. Acute otitis media typi-cally affects infants and children, and isoccasionally seen in adults. The pathogens usuallygain access via the auditory tube, usually duringan upper respiratory infection. As the pathogenpopulation rises in the tympanic cavity, whiteblood cells rush to the site, and the middle earbecomes filled with pus. Eventually the tympanummay rupture, producing a characteristic oozingfrom the external auditory canal. The bacteria canusually be controlled by antibiotics, the painreduced by analgesics, and the swelling reduced bydecongestants. In the United States it is rare forotitis media to progress to the stage at which tym-panic rupture occurs.

Otitis media is extremely common in underde-veloped countries where medical care and antibi-otics are not readily available. Both children andadults in these countries often suffer from chronicotitis media, a condition characterized by chronicor recurring bouts of infection. This condition pro-duces scarring or perforation of the tympanic mem-brane, which leads to some degree of hearing loss.Resulting damage to the inner ear or the auditoryossicles may further reduce auditory sensitivity.


deafness. If you put your fingers in your ears andtalk quietly, you can still hear yourself because thebones of the skull conduct the sound waves to thecochlea, bypassing the middle ear. In a bone con-duction test the physician places a vibrating tuningfork against the skull. If the subject hears thesound of the tuning fork in contact with the skull,but not when held next to the auditory meatus, theproblem must lie within the external or middle ear.If the subject remains unresponsive to either stim-ulus, the problem must be at the receptors oralong the auditory pathway.

Several effective treatments exist for conductivedeafness. A hearing aid overcomes the loss in sen-sitivity by simply increasing the intensity of sound.Surgery may repair the tympanic membrane or freedamaged or immobilized ossicles. Artificial ossiclesmay also be implanted if the originals are damagedbeyond repair.

There are few possible treatments for nervedeafness. Mild conditions may be overcome by theuse of a hearing aid if some functional hair cellsremain. In a cochlear implant a small battery-powered device is inserted beneath the skin behindthe mastoid process. Small wires run through theround window to reach the cochlear nerve, andwhen the implant “hears” a sound, it stimulates


Figure A-32 An Audiogram

If the pathogens leave the middle ear andinvade the air cells within the mastoid process,mastoiditis develops. The connecting passagewaysare very narrow, and as the infection progresses,the subject experiences severe earaches, fever, andswelling behind the ear in addition to symptoms ofotitis media. Prompt antibiotic therapy is needed,and if the problem remains, the person may have toundergo mastoidectomy (opening and drainage ofthe mastoid sinuses) The major risk of mastoiditisis the spread of the infection to the brain by theconnective tissue sheath of the facial nerve (N VII).Recurrent otitis media may be treated by myringoto-my (drainage of the middle ear through a surgicalopening in the tympanic membrane) with placementof a temporary tube in the tympanic membrane.

Vertigo EAP p. 299

The term vertigo describes an inappropriate senseof motion. This meaning distinguishes it from“dizziness,” a sensation of light-headedness anddisorientation that often precedes a fainting spell.Vertigo can result from abnormal conditions in theinner ear or from problems elsewhere along thesensory pathway. It can accompany CNS infection,and many people experience vertigo when theyhave high fevers.

Any event that sets endolymph into motion canstimulate the equilibrium receptors and producevertigo. Placing an ice pack in contact with thetemporal bone or flushing the external auditorycanal with cold water may chill the endolymph inthe outermost portions of the labyrinth and estab-lish a temperature-related circulation of fluid. Amild and temporary vertigo is the result.Consumption of excessive quantities of alcohol andexposure to certain drugs can also produce vertigoby changing the composition of the endolymph ordisturbing the hair cells.

Acute vertigo can also result from damagecaused by abnormal endolymph production, as inMénière’s disease. Probably the most commoncause of vertigo is motion sickness. Motion sicknessappears to develop when central processing sta-tions receive conflicting sensory information. Whenyou read in a boat or plane, for example, your eyes(which are tracking lines on a page) report that thebook isn’t moving, but your inner ear reports thatyour body is lurching and turning. Why and howthese conflicting reports result in nausea, vomiting,and other symptoms is not known.

Testing and Treating Hearing Deficits EAP p. 304

In the most common hearing test, a subject listensto sounds of varying frequency and intensity gener-ated at irregular intervals. A record is kept of theresponses, and the graphed record, or audiogram,is compared with that of an individual with normalhearing (Figure A-32). Bone conduction tests areused to discriminate between conductive and nerve

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the nerve directly. Increasing the number of wiresand varying their implantation sites make it possi-ble to create a number of different frequency sen-sations. Those sensations do not approximatenormal hearing, because there is as yet no way totarget the specific afferent fibers responsible forthe perception of a particular sound. Instead, arandom assortment of afferent fibers are stimulat-ed, and the individual learns to recognize themeaning and probable origin of the perceivedsound. Radio personality Rush Limbaugh received

a multichannel cochlear implant in 2002, and con-genitally deaf children with implants have learnednormal speech.

A new approach involves inducing the regener-ation of hair cells of the organ of Corti.Researchers working with other mammals havebeen able to induce hair-cell regeneration both incultured hair cells and in living animals. This is avery exciting area of research, and there is hopethat it may ultimately lead to an effective treat-ment for human nerve deafness.

CRITICAL-THINKING QUESTIONS4-1. Ten-year-old Christina falls while climbing

a tree and lands on her back. Her frightened par-ents take her to the local emergency room, whereshe is examined. Her knee-jerk reflex is normal,and she exhibits a plantar reflex (negative Babinskireflex). These results suggest that:

a. Christina has injured one of her descendingnerve tracts.b. Christina has injured one of her ascendingnerve tracts.c. Christina has a spinal injury in the lumbarregion.d. Christina has a spinal injury in the cervicalregion.e. Christina has suffered no damage to herspinal cord.

4-2. Susan brings her husband, Jim, age 32, tothe emergency room. Jim has been complaining of asevere headache for the last 12 hours. He has a tem-perature of 39°C (102°F) and a “stiff” neck and com-plains of pain when he moves his chin to chest. Hisreflexes are normal. A lumbar puncture is performed;the results of CSF analysis are reported as follows:

Analysis of CSF

• Microorganism: presence of Streptococcus pneu-moniae (bacteria) detected by rapid latex agglu-tination tests for bacterial antigens

• Pressure of CSF: 201 cm H2O• Color of CSF: cloudy• Glucose: 50 mg/dl• Protein: 47 mg/dl• Cell count (lymphocytes): 550 mm3

What is the likely diagnosis?

a. brain tumorb. meningitisc. cerebrovascular accidentd. multiple sclerosis

4-3. Tapping the calcaneal tendon of a normalindividual with a rubber hammer will produce areflex response. What response would you expect?What type of reflex is this? Describe the stepsinvolved in the reflex. Discuss other reflexes of thistype, and what can be learned by reflex testing.

4-4. Mrs. Glenn, 73 years old, has recentlyhad trouble controlling her movements. Even whenresting, she has continual, slight tremors andincreased muscle tone to the point of rigidity. Shevisits her physician, who conducts a series oftests, including an assessment of her reflexes.What change or changes would you expect to seein Mrs. Glenn’s spinal reflexes?

4-5. Chelsea is mountain climbing with a groupof friends when she slips, falls, and bumps the leftside of her head on a rock. She gets up slowly andis dazed but otherwise appears unhurt. She feelsable to proceed, and the climb continues. An hourlater, Chelsea gets a severe headache and experi-ences a ringing in her ears. She starts having trou-ble speaking and soon loses consciousness. Beforemedical personnel can reach the scene, Chelseadies. What was the likely cause of death?

4-6. Dave has a hypothalamic tumor that com-presses the right medial surface of the optic chi-asm posterior to the decussation. How would thiscondition affect his vision?

4-7. Mr. Romero, 62 years old, has troublehearing people during conversations, and his fami-ly persuades him to have his hearing tested. Howcan the physician determine whether Mr. Romero’sproblem results from nerve deafness or conductivedeafness?


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