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Rabies
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This disease also stands apart from other acute viral infections by virtue of the latent period that follows inoculation with the virus and its distinctive clinical and pathologic features Human examples of this disease are rare in the United States; between 1980 and 1997, only 34 such cases are known to have occurred; since 1960, there have never been more than 5 or so cases in any one year In some areas (Australia, Hawaii, Great Britain, and the Scandinavian peninsula), no indigenous cases have ever been reported; in India, however, there is a high incidence The importance of this disease derives from two facts: it has been almost invariably fatal once the characteristic clinical features appear; hence the survival of the infected individual depends upon the institution of speci c therapeutic measures before the infection becomes clinically evident Furthermore, each year 20,000 to 30,000 individuals are treated with rabies vaccine, having been bitten by animals that possibly were rabid, and although the incidence of complications with the newer rabies vaccination is much lower than before, a few serious reactions continue to be encountered (see below and also Chap 36) Etiology Practically all cases of rabies are the result of transdermal viral inoculation by an animal bite In undeveloped countries, where rabies is relatively common, the most frequent source is the rabid dog In western Europe and the United States, the most common rabid species are raccoons, skunks, foxes, and bats among wild animals and dogs and cats among domestic ones Because rabid animals commonly bite without provocation, the nature of the attack should be determined Also, the prevalence of animal rabies virus varies widely in the United States, and local presence of the
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VIRAL INFECTIONS OF THE NERVOUS SYSTEM, CHRONIC MENINGITIS, PRION DISEASES
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postexposure prophylaxis should be given Human rabies immune globulin (HRIG) is injected in a dose of 20 U/kg of body weight (one-half in ltrated around the wound and one-half intramuscularly) This provides passive immunization for 10 to 20 days, allowing time for active immunization Duck embryo vaccine (DEV) has been available for the latter purpose and has greatly reduced the danger of serious allergic reactions in the CNS (encephalomyelitis) from about 1 in 1000 cases (the one formerly used with equine vaccine) to 1 in 25,000 cases The more recently developed rabies vaccine grown on a human diploid cell line (human diploid cell vaccine, or HDCV) has reduced the doses needed to just 5 (from the 23 needed with DEV); these are given as 1-mL injections on the day of exposure and then on days 3, 7, 14, and 28 after the rst dose The HDCV vaccine has increased the rate of antibody response and reduced even further the allergic reactions by practically eliminating foreign protein A thorough trial of the new antiviral agents in patients already symptomatic has not been undertaken Persons at risk for rabies, such as animal handlers and laboratory workers, should receive pre-exposure vaccination with HDCV A preventative DNA rabies vaccine has been genetically engineered and is being tested for use in animal handlers and others at high risk
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Syndromes of Herpes Zoster
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Herpes zoster ( shingles, zona ) is a common viral infection of the nervous system occurring at an overall rate of 3 to 5 cases per 1000 persons per year, with higher rates in the elderly Shingles is distinctly rare in childhood It is characterized clinically by radicular pain, a vesicular cutaneous eruption, and, less often, by segmental sensory and delayed motor loss The pathologic changes consist of an acute in ammatory reaction in isolated spinal or cranial sensory ganglia and lesser degrees of reaction in the posterior and anterior roots, the posterior gray matter of the spinal cord, and the adjacent leptomeninges The neurologic implications of the segmental distribution of the rash were recognized by Richard Bright as long ago as 1831 In ammatory changes in the corresponding ganglia and related portions of the spinal nerves were rst described by von Barensprung in 1862 and were later studied extensively The concept that varicella and zoster are caused by the same agent was introduced by von Bokay in 1909 and was subsequently established by Weller and his associates (1954, 1958) The common agent, referred to as varicella or varicella zoster virus (VZV), is a DNA virus that is similar in structure to the virus of herpes simplex These and other historical features of herpes zoster have been reviewed by DennyBrown and Adams and by Weller and their colleagues Pathology and Pathogenesis The pathologic changes in VZV infection are unique and consist of one or more of the following: (1) an in ammatory reaction in several unilateral adjacent sensory ganglia of the spinal or cranial nerves, frequently of such intensity as to cause necrosis of all or part of the ganglion, with or without hemorrhage; (2) an in ammatory reaction in the spinal roots and peripheral nerve contiguous with the involved ganglia; (3) a less common poliomyelitis that closely resembles acute anterior poliomyelitis but is readily distinguished by its unilaterality, segmental localization, and greater involvement of the dorsal horn, root, and ganglion; and (4) a relatively mild leptomeningitis, largely limited to the involved spinal or cranial segments and nerve roots These pathologic changes are the substratum of the neuralgic pains, the pleocytosis, and the local palsies that may attend and follow the VZV infection There may also be a delayed cerebral vasculitis (see further on) As to pathogenesis, herpes zoster represents a spontaneous reactivation of VZV infection, which becomes latent in the neurons of sensory ganglia following a primary infection with chickenpox (Hope-Simpson) This hypothesis is consistent with the differences in the clinical manifestations of chickenpox and herpes zoster, even though both are caused by the same virus Chickenpox is highly contagious by respiratory aerosol, has a well-marked seasonal incidence (winter and spring), and tends to occur in epidemics Zoster, on the other hand, is not communicable (except to a person who has not had chickenpox), occurs sporadically throughout the year, and shows no increase in incidence during epidemics of chickenpox In patients with zoster, there is practically always a past history of chickenpox Such a history may be lacking in rare instances of herpes zoster in infants, but in these cases there has usually been prenatal maternal contact with VZV VZV DNA is localized primarily in trigeminal and thoracic ganglion cells, corresponding to the dermatomes in which chickenpox lesions are maximal and that are most commonly involved by VZV (Mahalingam et al) The supposition is that in both zoster and varicella infections the virus makes its way from the cutaneous
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Acute Cerebellitis (Acute Ataxia of Childhood)
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A special comment should be made here concerning the dramatic syndrome of acute ataxia that occurs in the context of an infectious illness The syndrome was originally described by Westphal in 1872 following smallpox and typhoid fever in adults, but Batten is credited with drawing attention to the more common ataxic illness that occurs after certain childhood infections such as measles, pertussis, and scarlet fever Currently, acute ataxia of childhood is most often associated with chickenpox (one-quarter of 73 consecutive cases reported by Connolly et al), but it can occur during or after any of the childhood exanthems, as well as in association with infections due to enteroviruses (mainly Coxsackie), EBV, Mycoplasma, CMV, Q fever, vaccinia, a number of vaccinations, rarely with HSV, and also after nondescript respiratory infections (see Weiss and Guberman) The condition is far less frequent in adults, but we encounter a case every 2 years or so in adolescents and individuals in their twenties; besides a late case of varicella, the most common preceding organisms in these individuals have been EBV and Mycoplasma The syndrome, which is essentially a meningocerebellitis, appears relatively abruptly, over a day or so, and consists of limb and gait ataxia and often dysarthria and nystagmus Additional signs include increased limb tone, Babinski signs, or confusion The fever of the original infection may have abated, or it may persist through the early stages of the ataxic illness As a rule, there is a mild pleocytosis; the CSF protein is elevated or may be normal The MRI is normal in the majority of cases but some show enhancement with gadolinium of the cerebellar cortical ribbon Most patients make a slow recovery, but permanent residua are known to follow Because the benign nature of the illness has precluded extensive pathologic study, there is still uncertainty regarding the infectious or postinfectious nature of these ataxic illnesses Some cases have shown an in ammatory pathology most suggestive of a postinfectious process (see Chap 36), but the nding of fragments of VZV and Mycoplasma genomes in the spinal uid by means of DNA ampli cation techniques favors a primary infectious encephalitis, at least in some instances
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