Print
Email
Other Neurologic Infections
The varicella-zoster virus is neurotropic. After many years of latency, it may be reactivated (by unknown mechanisms) and primarily affects the dorsal root ganglion cells of spinal nerves and the sensory ganglia of cranial nerves, certainly the gasserian (V) ganglion and perhaps the geniculate (VII). At the spinal level, the involvement is usually unilateral, and 75% of cases occur in the abdominal or upper thoracic regions. The virus occasionally attacks anterior horn cells of the spinal cord. Edema, monocytic infiltration, and perivascular cuffing with neuronal degeneration are seen histologically, with later fibrosis and secondary degeneration of the distal part of the nerve fiber.
Among elderly patients, recurrent herpes should put one on guard for the presence of an underlying malignancy, lymphoma, or immune deficiency syndrome. Chickenpox
With herpes zoster viruses, burning or shooting pain with local hyperalgesia within the affected dermatomes is followed in 3 or 4 days by a typical vesicular eruption that fades over the next few days, with scarring and depigmentation of the skin. Within the affected area the skin may be anesthetic but at the same time painful or itchy. Motor involvement may affect the face, eye, diaphragm, or limb musculature. Postherpetic neuralgia is exceedingly painful. During the acute phase, valacyclovir and famciclovir both reduce the rate of postherpetic neuralgia.
Herpes zoster ophthalmicus may produce the feared complications of corneal damage and secondary infection. The eye should be treated immediately with topical idoxuridine. The region of the forehead and eye may be exceedingly painful at the time of diagnosis, and postherpetic neuralgia may follow. When herpes zoster attacks the VII nerve, the V nerve is often involved as well, which explains why there are vesicles in the auricle and inside the mouth. Intracranial CNS involvement is uncommon, but arteritis causing stroke, and meningoencephalitis do occasionally occur.
CMVs are members of the herpesvirus family. They may cause eye and brain damage in utero, and adults (especially if immunocompromised) may develop meningoencephalitis, retinitis, or polyneuropathy. Ganciclovir has been used to treat serious CMV infections.
Poliomyelitis is still prevalent throughout much of the world, and children who have not been immunized in the most advanced nations are susceptible to infection. Thus primary care physicians must remain informed about its clinical presentation and acute management. The neurotropic poliovirus has three serotypes, of which type 1 is the most common. Spread from person to person is by fecal contamination. After entering the gastrointestinal (GI) tract, the virus passes into the blood stream to invade the nervous system. The incubation period is 7 to 14 days, and in nonimmunized populations the disease may be either epidemic or sporadic. Subclinical infection frequently occurs and produces immunity; this is also the basis of live virus immunization.
If the poliovirus invades the nervous system, a minor illness occurs, with headache, drowsiness, fever, and mild GI symptoms. The illness may stop at that stage, or after 1 or 2 days of apparent remission severe muscle pains, meningism, and delirium progress within 24 hours to sudden asymmetric or generalized paralysis (the paralytic form of the major illness). The muscles are tender, and fasciculations may be seen (and felt) in the earliest stages. After a week, some degree of improvement usually begins. Truncal and bulbar involvement may give rise to severe respiratory and bulbar paralysis that requires artificial ventilation and skilled nursing attention in an intensive care unit. The lower motor neuron lesions produced may eventually progress to contractures, trophic changes, failure of limb growth, and eventual joint disorganization.
A nonparalytic form of the major illness also occurs, with signs of meningoencephalitis (as in the paralytic form) but without anterior horn cell involvement.
In the earliest stages, the disease can only be easily diagnosed during an epidemic because the mild symptoms resemble many other nonspecific viral illnesses. A paretic illness can also be caused by other enteroviruses, in which case the prognosis is much better. Weakness may also occur in association with other inflammatory bone or joint diseases.
Other fast-advancing peripheral motor neuropathies include those caused by porphyria, Guillain-Barré syndrome, and polyarteritis nodosa. Lower motor neuron lesions seldom complicate other CNS infections, although mumps may rarely produce encephalomyelitis. Even in these days, however, the presence of an acute infective illness associated with signs of anterior horn cell involvement must always make one suspect poliomyelitis.
The development of new weakness, muscle atrophy, fatigue, and pain decades after acute poliomyelitis, accompanied by a mixed picture of active and chronic denervation on an electromyogram (EMG), suggests the diagnosis of postpolio syndrome. This condition appears to be due to the late death of neurones that regrew or sprouted after the initial illness, but the reason why they die at this late stage remains unknown.
Although coxsackievirus infection may cause aseptic meningitis, epidemic myalgia (Bornholm disease) is a more common manifestation. In this condition, the sudden onset of acute chest pain, with severe tenderness of the intercostal muscles in one or more spaces and great difficulty in breathing because of pleuritic pain, frequently raises suspicion of pulmonary embolism, pneumonia, or even myocardial infarction. The pain may occur so acutely that patients sometimes fear that they may have had a heart attack. Very few systemic signs are associated, and after a few days of useless symptomatic treatment, complete recovery occurs.
About 5% of patients with infectious mononucleosis develop neurologic complications as a result of inflammatory infiltrates and neuronal degeneration in the nervous system. The most common of these complications is aseptic meningitis, a benign and relatively transient disorder. Encephalitis and encephalomyelitis present with seizures, reduction in level of consciousness, raised ICP, focal neurologic signs, and meningism. A generalized peripheral neuropathy indistinguishable from Guillain-Barré syndrome is well recognized, but patients may also have mononeuropathies, and virtually every cranial nerve has been reported as affected. Less commonly, illnesses resembling Reye's syndrome, dysautonomia, brachial neuropathy, movement disorders, or a syndrome such as multiple sclerosis have been described.
The neurologic complications of influenza are usually indirect, taking the form of an acute postinfectious encephalomyelitis. Depression frequently occurs after influenza, and some patients with multiple sclerosis may have a relapse after even a mild attack. Neuralgic amyotrophy is another occasional complication.
Particularly in western North America, wood ticks may attach themselves to persons exploring the undergrowth, especially children. The tick can be found attached to the head or to any other hairy body parts. Its toxin may block neuromuscular transmission, causing a rapidly progressive, symmetric, flaccid paralysis, with signs resembling a severe myasthenic crisis.
The weakness may be so severe that respiratory and bulbar paralysis occur and the patient may die of respiratory insufficiency. The sudden onset of such profound weakness over the course of a day or less should make one think of tick paralysis. Treatment consists of removal of the tick, but it may be difficult to find and may require shaving the child or searching through the hair with a fine comb. With supportive measures, recovery should occur within a few days.
Although Clostridium tetani is not as widespread now as it was in the days of horse-drawn transport, tetanus still constitutes an important disease despite a fairly high level of immunization in Western communities. The organism enters a wound (which may be very small) or follows surgical procedures, otitis media, or puerperal or umbilical sepsis. Its toxin then ascends the peripheral motor nerves to block inhibitory postsynaptic potentials affecting the anterior horn cells.
After an incubation period of up to 3 weeks, patients develop pain and stiffness of the muscles (especially in the neck, back, and abdominal wall). Trismus, dysphagia, and reflex spasms are common, often beginning in the back, neck, and jaw muscles and lasting up to 30 seconds. The strong muscular contractions may induce hyperpyrexia, and respiratory arrest may occur. Laryngospasm, chest infections, and cardiac arrest are occasional lethal complications. Diagnosis is only achieved early if a high index of suspicion is maintained.
Treatment for tetanus is along several lines.
Human antitetanus immunoglobulin has replaced horse serum antitoxin, and 2000 to 4000 units are given intramuscularly, after which a course of intramuscular penicillin is necessary.
Tetanus toxoid is required to achieve active immunization.
The wound must be excised and cleaned, with all dead tissue removed.
Symptomatic treatment depends on the severity of the case. Mild cases will need only diazepam and sedatives. Respiratory difficulty requires tracheostomy and possibly curarization, as well as the above measures. The most severe cases must be anesthetized and paralyzed, so all patients must be transferred urgently to an intensive care unit. Many metabolic and urinary problems complicate the acute illness, and close nursing attention is essential.
Even in the best facilities, about 10% of patients with tetanus die, mainly because of complications. The most seriously affected patients are those with cephalic tetanus infection from invasion in the head and neck area, and those in whom symptoms begin within a few days of wounding.
The toxin of Clostridium botulinum impairs acetylcholine release at motor nerve endings. The source of this toxin is often improperly canned foods, although wounds are sometimes the portal of entry. In infants, progressive weakness, hypotonia, poor gag and suck reflexes, and constipation are the main signs. In adults, extraocular muscle, respiratory, facial, and bulbar palsies occur; the limbs are flaccid and paretic, and reflexes are lost. The pupils usually dilate and are poorly responsive. Treatment consists of urgent ventilatory support with neutralization of toxin using the specific trivalent (ABE) antiserum, penicillin, and cathartics.
Toxoplasmosis may occur as a congenital infection or may be acquired later in life, usually in immunosuppressed patients. This protozoan organism commonly affects the nervous system and produces an inflammatory reaction with formation of miliary granulomas. These may later calcify or undergo necrosis, resulting in hydrocephalus, or they may be completely asymptomatic.
Congenital toxoplasmosis may be evident shortly after birth. Failure to thrive, convulsions, spasticity, opisthotonos, and eye defects such as chorioretinitis or microphthalmos are possible presentations. Optic atrophy is a common later development, as is hydrocephalus. Some children do not develop symptoms until the age of 4 or 5, when hepatomegaly and splenomegaly are found. Radiographs of the skull often show scattered calcifications.
Acquired toxoplasmosis is often traceable to infected animals. Clinical features include skin lesions, pulmonary and lymphatic involvement, acute meningitis, encephalitis, myositis, and chronic granulomatous meningitis.
Laboratory findings will depend on the type and extent of involvement. The CSF may be under increased pressure, and the protein will usually be increased with a slight or moderate increase in mononuclear cells. Skull radiographs and funduscopy are often extremely helpful in making a diagnosis, but more definitive support comes from complement-fixation and fluorescent antibody tests.
Children with symptomatic congenital toxoplasmosis often have significant mental and neurologic defects, if they survive. In the adult form (which is much less common), the prognosis depends on the severity of the infection; patients with overt encephalitis do poorly. Treatment is with sulfonamides combined with pyrimethamine.
Although a request for specific serology is (or should be) routine on all patients admitted to neurologic wards, the overall return on these tests is relatively small. The request is still important because the prevalence of syphilis is probably increasing (in part associated with the spread of AIDS) but the number of patients who are coming for treatment is not, suggesting that we are going to be faced with an increasing number of cases of late and congenital syphilis in the future.
Serodiagnostic tests for syphilis may be classified as reagin tests and specific antitreponemal antibody tests. In the former group, the one most commonly used in North America is the rapid plasma reagin (RPR), a slide test that detects the presence of cardiolipin antigens. This is positive in between 75% and 95% of patients with primary, secondary, late, or latent syphilis. Unfortunately, false positive tests are common with reagin tests, being seen in conditions accompanied by abnormal globulins or excessive normal globulins. These include almost all of the collagen-vascular diseases, pregnancy, vaccination for smallpox, Hansen's disease
The specific antitreponemal antibody test in common use is the microtreponema pallidum hemagglutination test (MTPHA). It is the first to react in syphilis and is positive in about 95% of cases of primary, secondary, late, and latent syphilis. It can be performed on the CSF and the blood and is seldom positive in the conditions causing false-positive RPR reactions (except for yaws and pinta, when it may give a weak positive reaction).
One single positive serologic test for syphilis does not make the diagnosis, however, and clinical evidence or repeat testing by different methods is always necessary. In the following discussion, the classical patterns of syphilis are described (
The chancre is the only lesion that occurs in primary syphilis. This lesion, classically on the pudenda, appears after an incubation period of 3 weeks to 3 months. There may be some increase in CSF lymphocytes at this time, but no clinical signs appear.
The secondary syphilis stage follows immediately after the primary stage, 2 or 3 months after the appearance of the chancre. Constitutional symptoms are those of fever in association with a symmetric, nonitchy skin rash over all of the body, but particularly on the palms and soles. Snail-track ulcers (mucous patches on the mucosa of the mouth and genitalia), generalized lymphadenopathy, loss of hair, and iritis may occur. A meningoencephalitis presenting the usual features of fever, meningeal irritation, raised ICP, and occasionally with focal signs including seizures, is the main neurologic problem. The CSF shows a small increase in protein but a marked increase in lymphocytes, reduced glucose levels, and positive serologic reactions.
After the lesions of secondary syphilis clear, a latent stage occurs, even in untreated cases in which there are no signs of the underlying infection. Tertiary syphilis may appear years later and involves the skin, mouth, eyes, bones, joints, gut, or genitourinary system. Cardiovascular problems related to tertiary syphilis include aortitis, granulomas of the myocardium or arterial walls (gummas), or a generalized vasculitis; the nervous system may also show a variety of abnormalities. The three most common syndromes are described below. The diversity of involvement led to the old adage that syphilis is the great mimicker of virtually every known medical disease; lupus erythematosus and AIDS now have the same distinction.
In the meningovascular form of tertiary syphilis, a chronic basal meningitis results in increased ICP, cranial nerve lesions, or cerebral infarction. The CSF will show positive serology, increased protein and lymphocytes, and occasionally decreased sugar levels.
Tabes dorsalis is characterized by degenerative changes in the posterior roots and root entry zone of the spinal cord (
General paresis is a subacute meningoencephalitis and is characterized by progressive dementia with major frontal lobe signs and evidence of involvement of the
Optic atrophy and Argyll Robertson pupils are usually found. Seizures are frequent and may be the presenting problem. The basal ganglion and corticospinal lesions combine to produce severe dysarthria, with tremors of the tongue and lips and variable motor disturbances in the arms and legs (
Syphilitic gummas may be single or multiple. If they occur intracerebrally, they may mimic a brain tumor. If they are multiple and involve the meninges, the patient may present with dementia and focal neurologic signs.
In about 10% of cases, the children of mothers who have seropositive syphilis have nervous system involvement. Either meningovascular or parenchymatous (general paresis, tabes, optic atrophy) syndromes may occur. Seizures, mental retardation, gummas of the musculoskeletal system, bilateral painful joint effusions, osteochondritis, skin lesions, and abnormalities of the teeth are characteristic signs.
Given a positive RPR test on a patient, a further history and examination are required, with the specific aim of finding evidence of any disease that may cause a biological false-positive reaction. One should also seek historical evidence of a previous syphilitic infection. The RPR should be repeated and the MTPHA performed to have two separate positive serologic tests at different times. The CSF should be examined for cells, serology, sugar, and protein. Any abnormality of the CSF should suggest the possibility of neurosyphilis.
If the CSF serology is positive, CSF must be rechecked every 6 months after treatment for 2 years to ascertain that the infection has cleared, the best indicators of which are the levels of cells and protein in the CSF.
For early syphilis (primary, secondary, or latent for less than 1 year), a single injection of benzathine penicillin, 2.4 megaU intramuscularly or procaine penicillin, 600,000 units intramuscularly daily for 8 days is adequate treatment.
In late latent stages, however, benzathine penicillin, 2.4 megaU intramuscularly weekly for 3 weeks is required. CNS syphilis requires intravenous benzylpenicillin therapy for at least 10 days. In patients allergic to penicillin, tetracycline or erythromycin, 500 mg qid for 30 days, may be used. The latter is the drug of choice in women who are pregnant and in young children.
Lyme disease is caused by the spirochete Borrelia burgdorferi and is transmitted by a tick endemic in North America and Europe. Most cases occur in summer; the first manifestations are in the skin: a red macule or papule extending outward from the site of the tick bite, with central clearing (erythema chronicum migrans). Fatigue, malaise,
Chronic arthropathy is the usual feature of the late stages of the disease, but chronic progressive meningoencephalitis with multifocal signs also occurs at a late stage. A raised ESR, increased serum IgM, and the presence of serum cryoglobulins suggest the diagnosis, which may be confirmed by finding high Borrelial antibody levels in the serum or CSF. Early diagnosis is important because treatment with oral antibiotics may be effective then. When neurologic features are present, high-dose penicillin or ceftriaxone is the treatment of choice.
In 1957 an unusual disease (kuru) was described in the Fore tribe of New Guinea. Its cause was traced to cannibalism and to the ceremonial rubbing of the blood and brains of the deceased over the bodies of those taking part in the ritual. Brain material from those who had died of kuru was injected into chimpanzees; some 19 months later they developed evidence of the disease.
Using a concept developed by Siggurdson, a Scandinavian veterinarian, the researchers postulated a slow virus infection—one caused by a transmissible agent presumed to be a virus particle, with a very long incubation period and slow course to death. Other conditions in this category have now been recognized.
In retrospect, it need not surprise us that an infection may produce disease months or years later. It has long been known that warts are caused by a virus with a similarly prolonged latent phase, rabies is recognized as having a prolonged incubation period, and herpes zoster remains in dorsal root ganglia, often causing no clinical disease for many years. Other viruses capable of behaving thus include CMV, HIV, rubella, and infectious hepatitis.
Creutzfeldt-Jakob disease (CJD) is an unusual condition, clinically and pathologically almost identical with kuru; it is characterized by a spongiform degeneration of the cerebellar cortex, some subcortical structures, and the cerebellum in older adults.
Clinical features include the subacute onset in later middle age of malaise, headache, weight loss, ataxia, twitching, behavioral disturbances, and personality change progressing to obvious dementia. Slowly progressive spasticity, dysphasia, cerebellar and extrapyramidal signs, fasciculations, and myoclonus, with marked "startle" effect, appear later. Ninety percent of patients die akinetic, cortically blind, mute, and eventually decorticate within a year. In this condition, the EEG is of diagnostic value because periodic abnormal discharges appear eventually in 75% of cases.
Gajdusek and others have been successful in transmitting the disease to chimpanzees through five consecutive passages, but the agent that is transmitted has not been isolated, although it is presumed to be a virus particle. There is no effective treatment.
There are three epidemiologic types of CJD known. Sporadic CJD, described in this chapter, accounts for 90% of the cases and may result from the spontaneous somatic mutation of a prion protein gene within the host. Familial CJD results from the inheritance of a defective form of the prion protein gene and accounts for 5% to 10% of cases. An unusual form, the infective form of CJD, accounts for less than 1% of cases. It can result from the transmission of infective material from a CJD case to another person via transplantation, cadaveric human growth hormone and gonadotrophin, and through contaminated neurosurgical instruments.
In the late 1980s and through the 1990s cases of a variant form of CJD disease have been reported from the United Kingdom. Epidemiologic evidence suggests that these cases are linked to bovine spongiform encephalopathy (BSE), perhaps as a result of consumption or other exposure to BSE-infected tissues. Patients with new variant CJD (nv-CJD) are younger than those with classic CJD (age range for nv-CJD is 19 to 41 years). This disease is progressive, leading to death in 7 to 23 months. Early and prominent behavioral changes dominate the clinical picture. Myoclonus and progressive dementia occur late. The typical EEG pattern of classic CJD is not seen in nv-CJD. Spongiform changes and prion protein plaques are distributed extensively throughout the cerebrum and cerebellum.
In the United Kingdom there was about one case per million population per year of nv-CJD. It has been theorized that nv-CJD might be the result of ingesting material from cows suffering from BSE, but this has not been proven. Although it is speculation, the theory closed down the British beef industry, which is now struggling to return, and has affected the blood donation system. Canada, again based on theory, now refuses to accept blood donations from those who have visited the United Kingdom in the last 16 years.
Subacute sclerosing panencephalitis (SSPE) is a delayed measles encephalitis associated with a defective immune response in the host. It is becoming less common, perhaps because of widespread measles immunization. Typically, children or young adults show mental and behavioral changes that lead to progressive dementia, myoclonic jerking, seizures, and increasing motor disability. The patients deteriorate and die in 1 to 3 years.
The EEG characteristically shows periodic slow wave and sharp wave discharges (
In most cases, the measles infection probably occurred up to 10 years before the onset of SSPE, so this condition is a convincing argument for the existence of persistent virus-induced autoimmune diseases of the nervous system. Children born with the congenital rubella syndrome may develop a similar disease, as do immunosuppressed patients (e.g., those with lymphomas).
Progressive multifocal leukoencephalopathy (PML) is a fatal brain disease seen only in immunosuppressed patients, in whom progressive demyelination occurs in the white matter of the cerebellar hemispheres and sometimes that of the brainstem, cerebellum, and spinal cord. The patchy areas of
This disorder is often a terminal event in patients with Hodgkin's disease or lymphoma, and occasionally in sarcoidosis, tuberculosis, and other conditions marked by immunologic incompetence. It is due to a polyoma viral infection acting as a slow virus. Patients die within 3 years after a progressive downhill course characterized by behavioral change and developing ataxia, aphasia, blindness, paralysis, and ultimately coma.
These are just a few examples of disease that had been considered to be degenerative in nature but are now known to be due to viruses acting in an unusual way. It appears that the virus can stay in the nervous system for prolonged periods before causing a progressive disease. It is also of interest that the brain lesions often look more degenerative than inflammatory or infective under the microscope, and one naturally begins to wonder about other "degenerative" processes, such as Alzheimer's disease, motor neuron disease, Parkinson's disease, and multiple sclerosis.
 |
Textbook of Primary Care Medicine, 3rd ed
By: T. Jock Murray, William Pryse-Phillips © 2005 ELSEVIER Inc. All Rights Reserved |
Related Learning Centers |
 |
 |
 |
Advertise | Terms of Use | Privacy Policy