Neurology_Adams

Neurology_Adams. Meningococcal meningitis occurs most often in children and adolescents but is also encountered throughout much of adult life, with a sharp decline in incidence after the age of 50 years. Pneumococcal meningitis predominates in the very young and in older adults. Perhaps the greatest change in the epidemiology of bacterial meningitis, aside from the one related to H. influenzae vaccination, has been the increasing incidence of nosocomial infections, accounting for 40 percent of cases in large urban hospitals (Durand et al); staphylococcus and gram-negative bacilli account for a large proportion of these. The yearly incidence rate (per 100,000 population) of the responsible pathogens is approximately as follows: S. pneumoniae, 1.1; N. meningitidis, 0.6; group B streptococcus (mainly in newborns), 0.3; L. monocytogenes, 0.2; and


Neurology_Adams

Neurology_Adams. S. pneumoniae, 1.1; N. meningitidis, 0.6; group B streptococcus (mainly in newborns), 0.3; L. monocytogenes, 0.2; and H. influenzae, 0.2. In an epidemiologic survey of bacterial meningitis in the United States from 1998 to 2007, Thigpen and colleagues found the relative order of the various organisms to be much the same and again emphasized the decrease in incidence of the disease due mainly to the H. influenza vaccination program. They estimated the recent overall incidence of bacterial meningitis in the United States to be 4,100 cases annually, resulting in 500 deaths. Their article is recommended for its detailed analysis of age, race, and underlying medical conditions.


Neurology_Adams

Neurology_Adams. The most common meningeal pathogens are normal inhabitants of the nasopharynx in a significant part of the population and depend on antiphagocytic capsular or surface antigens for survival in the tissues of the infected host. To a large extent they express their pathogenicity by extracellular proliferation. It is evident from the frequency with which the carrier state is detected that nasal colonization is not a sufficient explanation of infection of the meninges. Factors that predispose the colonized patient to invasion of the bloodstream, which is the usual route by which these bacteria reach the meninges, are obscure but include antecedent viral infections of the upper respiratory passages or, in the case of S. pneumoniae, infections of the lung. Once blood-borne, pneumococci, H. influenzae, and meningococci possess a predilection for the meninges, although the precise factors that determine this tropism are not known. Whether the organisms enter the CSF via the choroid plexus or


Neurology_Adams

Neurology_Adams. and meningococci possess a predilection for the meninges, although the precise factors that determine this tropism are not known. Whether the organisms enter the CSF via the choroid plexus or meningeal vessels is also unknown. It has been variously postulated that the entry of bacteria into the subarachnoid space is facilitated by disruption of the blood–CSF barrier by trauma, circulating endotoxins, or an initial viral infection of the meninges. These organisms, being commensal in most persons, create immunity, but bacteria may nonetheless penetrate the mucosa. Certain features of the organisms enhance their ability to cause infection; this is particularly true of the meningococcus (Rosenstein et al).


Neurology_Adams

Neurology_Adams. Avenues other than the bloodstream by which bacteria can gain access to the meninges include congenital neuroectodermal defects; craniotomy and spinal operative sites; diseases of the middle ear and paranasal sinuses, particularly perilymphatic fistulas; skull fractures; and, in cases of recurrent infection, dural tears from remote minor or major trauma. Occasionally, a brain abscess may rupture into the subarachnoid space or ventricles, thus infecting the meninges. The isolation of anaerobic streptococci, Bacteroides, Actinomyces, or a mixture of microorganisms from the CSF should suggest the possibility of a brain abscess with associated meningitis.


Neurology_Adams

Neurology_Adams. The early clinical effects of acute bacterial meningitis are fever, headache, usually severe, and stiffness of the neck (resistance to passive movement on forward bending), and less often initially, generalized convulsions and a disorder of consciousness (i.e., confusion, drowsiness, stupor, and coma). Flexion at the hip and knee in response to forward flexion of the neck (Brudzinski sign) and resistance to completely extending the legs with the hips flexed (Kernig sign) have the same significance as stiff neck but are less consistently elicitable. Basically, all of these signs are part of a flexor protective reflex (one of the “nocifensive” responses in Fulton’s terms). Stiffness of the neck that is part of paratonic or extrapyramidal rigidity should not be mistaken for that of meningeal irritation. The former is more or less equal in all directions of movement, in distinction to that of meningitis, which is present only or predominantly on forward flexion. Whether it is stiffness in


Neurology_Adams

Neurology_Adams. irritation. The former is more or less equal in all directions of movement, in distinction to that of meningitis, which is present only or predominantly on forward flexion. Whether it is stiffness in the initial few degrees of flexion of the neck or in the subsequent part of the movement that is more specific for meningitis has been debated; our experience has been that the latter is more sensitive but also occurs in other disorders; thus the first may be more specific for meningitis.


Neurology_Adams

Neurology_Adams. Diagnosis of meningitis may be difficult when the initial manifestations consist only of fever and headache, when stiffness of the neck has not yet developed, or when there is only pain in the neck or abdomen or a febrile confusional state or delirium. Also, stiffness of the neck may not be apparent in the stuporous or comatose patient or in the infant or the elderly, as indicated further on. These signs and symptoms comprising the meningitic syndrome are common to the three main types of bacterial meningitis, but certain clinical features and the setting in which each of them occurs correlate more closely with one type than another.


Neurology_Adams

Neurology_Adams. Meningococcal meningitis should be suspected when the evolution is extremely rapid (delirium and stupor may supervene in a matter of hours), when the onset is attended by a petechial or purpuric rash or by large ecchymoses and lividity of the skin of the lower parts of the body, when there is circulatory shock, and especially during local outbreaks of meningitis. Because a petechial rash accompanies approximately 50 percent of meningococcal infections, its presence dictates immediate institution of antibiotic therapy, even though a similar rash may be observed with certain viral (echovirus serotype 9 and some other enteroviruses), rickettsia, as well as S. aureus infections, and, rarely, with other bacterial meningitides.


Neurology_Adams

Neurology_Adams. Pneumococcal meningitis is often preceded by an infection in the lungs, ears, sinuses, or heart valves. In addition, a pneumococcal etiology should be suspected in alcoholics, in splenectomized patients, in the very elderly, and in those with recurrent bacterial meningitis, dermal sinus tracts, sickle cell anemia (“autosplenectomized”), and basilar skull fracture. On the other hand, H. influenzae meningitis usually follows upper respiratory and ear infections in the uninocualted child.


Neurology_Adams

Neurology_Adams. Other specific bacterial etiologies are suggested by particular clinical settings. Meningitis in the presence furunculosis or following a neurosurgical procedure directs attention to the possibility of a coagulase-positive staphylococcal infection. Ventricular shunts or drains inserted for the relief of hydrocephalus are particularly prone to infection with coagulase-negative staphylococci and Proprionobacerium acnes and diphteroids. HIV infection, myeloproliferative or lymphoproliferative disorders, defects in cranial bones (tumor, osteomyelitis), rheumatologic diseases, metastatic cancer, and therapy with immunosuppressive agents are clinical conditions that favor invasion by such pathogens as Enterobacteriaceae, L. monocytogenes, A. calcoaceticus, Pseudomonas, and occasionally by parasites. In acute myelogenous leukemia patients, we have seen several instances of fatal Bacillus cereus meningitis (see Vodopivec et al).


Neurology_Adams

Neurology_Adams. Focal cerebral signs in the early stages of the disease, although seldom prominent, are most frequent in pneumococcal and H. influenzae meningitides as outlined by Adams and colleagues (1948). Some of the transitory focal cerebral signs may represent postictal phenomena (Todd paralysis); others may be related to an intense focal meningitis, for example, purulent material collected in one sylvian fissure. Seizures are encountered most often with H. influenzae meningitis. Although seizures are most common in infants and children, it is difficult to judge the significance, because young children may convulse with fever of any cause. Persistent focal cerebral lesions or intractable seizures usually develop in the second week of the meningeal infection and are caused by an infectious vasculitis, as described earlier, usually with occlusion of surface cerebral veins and consequent infarction of cerebral tissue. Cranial nerve abnormalities are particularly frequent with pneumococcal


Neurology_Adams

Neurology_Adams. as described earlier, usually with occlusion of surface cerebral veins and consequent infarction of cerebral tissue. Cranial nerve abnormalities are particularly frequent with pneumococcal meningitis, the result of invasion of the nerve by purulent exudate and possibly ischemic damage as the nerve traverses the subarachnoid space. Of course, bilateral abducens weakness can be due to increased intracranial pressure as a result of any form of meningitis.


Neurology_Adams

Neurology_Adams. Acute bacterial meningitis during the first month of life is said to be more frequent than in any subsequent 30-day period of life. It poses a number of special problems. Infants, of course, cannot complain of headache, stiff neck may be absent, and one has only the nonspecific signs of a systemic illness: fever, irritability, drowsiness, vomiting, convulsions, and a bulging fontanel to suggest the presence of meningeal infection. Signs of meningeal irritation do occur, but only late in the course of the illness. A high index of suspicion and liberal use of the lumbar puncture are the keys to early diagnosis. Lumbar puncture is ideally performed before any antibiotics are administered for other neonatal infections or, at a minimum, blood cultures should be obtained before treatment. An antibiotic regimen sufficient to control a septicemia may allow a meningeal infection to smolder and to flare up after antibiotic therapy for the systemic infection has been discontinued.


Neurology_Adams

Neurology_Adams. A number of other facts about the natural history of neonatal meningitis are noteworthy. It is more common in males than in females. Obstetric abnormalities in the third trimester (premature birth, prolonged labor, premature rupture of fetal membranes) occur frequently in mothers of infants who develop meningitis in the first weeks of life. The most significant factor in the pathogenesis of the meningitis is maternal infection (usually a urinary tract infection or puerperal fever of unknown cause). The infection in both mother and infant is most often caused by gram-negative enterobacteria, particularly E. coli, and group B streptococci, and less often to Pseudomonas, Listeria, S. aureus, or Staphylococcus epidermidis (formerly albus), and group A streptococci. Analysis of postmortem material indicates that in most cases infection occurs at or near the time of birth, although clinical signs of meningitis may not become evident until several days or a week later.


Neurology_Adams

Neurology_Adams. In infants with meningitis, one should be prepared to find a unilateral or bilateral “sympathetic” subdural effusion regardless of bacterial type. Young age, rapid evolution of the illness, low polymorphonuclear cell count, and markedly elevated protein in the CSF correlate to some extent with the formation of effusions, according to Snedeker and coworkers. Also, these attributes greatly increase the likelihood of the meningitis being associated with neurologic signs. Transillumination of the skull is the simplest method of demonstrating the presence of an effusion, but CT and MRI are the definitive diagnostic tests. When aspirated, most of the effusions prove to be sterile. If recovery is delayed and neurologic signs persist, a succession of aspirations is required. Children in whom meningitis is complicated by subdural effusions are no more likely, according to authorative sources, to have residual neurologic signs and seizures than are those without effusions.


Neurology_Adams

Neurology_Adams. As already indicated, the lumbar puncture is an indispensable part of the examination of patients with the symptoms and signs of meningitis or of any patient in whom this diagnosis is suspected. Bacteremia is not a contraindication to lumbar puncture. The dilemma concerning the risk of promoting transtentorial or cerebellar herniation by lumbar puncture, even without a cerebral mass, as indicated in Chaps. 2 and 16, has been settled in favor of performing the tap if there is a reasonable suspicion of meningitis.


Neurology_Adams

Neurology_Adams. The highest estimates of risk of lumbar puncture come from studies such as those of Rennick, who reported a 4 percent incidence of clinical worsening among 445 children undergoing lumbar puncture for the diagnosis of acute meningitis; most other series give a lower number. It must be pointed out that cerebellar tonsillar herniation may occur in fulminant meningitis independent of lumbar puncture; therefore the risk of the procedure may be even less than usually stated. In an attempt to determine the utility of the CT scan performed prior to a lumbar puncture, Hasbun and colleagues were able to identify several clinical characteristics that were likely to be associated with an abnormality on the scan in patients with suspected meningitis; these included a recent seizure, coma or confusion, gaze palsy, and other findings. The more salient findings from this study in our opinion was that only 2 percent of 235 patients had a focal mass lesion that was judged a risk for lumbar puncture and


Neurology_Adams

Neurology_Adams. gaze palsy, and other findings. The more salient findings from this study in our opinion was that only 2 percent of 235 patients had a focal mass lesion that was judged a risk for lumbar puncture and none had herniation after the procedure; many had CT findings of interest, including some with diffuse mass effect. This study does not entirely clarify the issue of the safety of lumbar puncture but it emphasizes that patients who lack major neurologic findings are unlikely to have findings on the scan that will preclude lumbar puncture.


Neurology_Adams

Neurology_Adams. Therefore, if there is clinical evidence of a focal lesion with increased intracranial pressure, then CT or MRI scanning of the head, looking for a mass lesion, is may at times be a prudent first step, but in most cases this is not necessary and should not delay the administration of antibiotics.


Neurology_Adams

Neurology_Adams. Only a sizable brain abscess or substantial brain swelling entirely interdicts a lumbar puncture in suspected bacterial meningitis. Furthermore, the fact that death results from cerebral herniation in many fatal cases of bacterial meningitis does not, of course, mean that lumbar puncture precipitated the demise. When there are signs of impending herniation or indications of a dangerous configuration on cerebral images, one may wish to draw blood cultures and and institute empiric treatment rather than take the small risk of precipitation herniation with a lumbar puncture. Any coagulopathy that is deemed a risk for hemorrhagic complication of lumbar puncture should be rapidly reversed if possible.


Neurology_Adams

Neurology_Adams. The spinal fluid pressure is so consistently elevated (above 180 mm H2O) that a normal pressure on the initial lumbar puncture in a patient with suspected bacterial meningitis suggests another diagnosis or raises the possibility that the needle is partially occluded or the spinal subarachnoid space is blocked. Pressures over approximately 350 mm H2O suggest the presence of brain swelling and the potential for cerebellar herniation. Some neurologists favor the administration of intravenous mannitol if the pressure is this high, but this practice does not provide assurance that herniation will be avoided.


Neurology_Adams

Neurology_Adams. A pleocytosis in the spinal fluid is diagnostic of meningitis. The number of leukocytes ranges from 250 to 100,000/mm3, but the usual number is from 1,000 to 10,000. Occasionally, in pneumococcal and influenzal meningitis, the CSF may contain a large number of bacteria but few, if any, neutrophils for the first few hours. Cell counts of more than 50,000/mm3 raise the possibility of a brain abscess having ruptured into a ventricle. Neutrophils predominate (85 to 95 percent of the total), but an increasing proportion of mononuclear cells is found as the infection continues for days, and especially in partially treated meningitis. In the early stages, careful cytologic examination may disclose that some of the mononuclear cells are myelocytes or young neutrophils. Later, as treatment takes effect, the proportions of lymphocytes, plasma cells, and histiocytes steadily increase. However, there are rare instances of low numbers or absent cells in the spinal fluid with meningitis,


Neurology_Adams

Neurology_Adams. takes effect, the proportions of lymphocytes, plasma cells, and histiocytes steadily increase. However, there are rare instances of low numbers or absent cells in the spinal fluid with meningitis, particularly in the context of pronounced neutropenia and forms of immunosuppression.


Neurology_Adams

Neurology_Adams. Substantial hemorrhage or substantial numbers of red cells in the CSF are uncommon in meningitis, the exceptions being anthrax meningitis (see Lanska) as well as certain viral infections (hantavirus, dengue fever, Ebola virus, etc.) and some cases of amebic meningoencephalitis.


Neurology_Adams

Neurology_Adams. The protein content is higher than 45 mg/dL in more than 90 percent of the cases; in most cases, it falls in the range of 100 to 500 mg/dL. The glucose content is diminished (hypoglycorrhachia), usually to a concentration less than 40 mg/dL, or less than 40 percent of the blood glucose concentration (measured concomitantly or within the previous hour), provided that the latter is less than 250 mg/dL. However, in atypical or culture-negative cases, other conditions associated with a reduced CSF glucose should be considered. These include hypoglycemia from any cause; sarcoidosis of the CNS; fungal or tuberculous meningitis; and some cases of subarachnoid hemorrhage, meningeal carcinomatosis, chemically induced inflammation from craniopharyngioma or teratoma, and meningeal gliomatosis. The factors that alter CSF glucose concentration, especially at the extremes of blood glucose, are discussed in Chap. 2.


Neurology_Adams

Neurology_Adams. A special problem pertains to identifying patients with a meningitic syndrome and CSF pleocytosis who do not, in fact, have bacterial meningitis but likely have a viral or other cause for their syndrome. This is driven by a desire to avoid exposure to high-potency intravenous antibiotics that are potentially dangerous may have side effects. To address this problem, Nigrovic and colleagues have developed a clinical prediction rule that classifies children at very low risk for bacterial meningitis if they have all of the following: negative CSF Gram stain, CSF absolute neutrophil count under 1,000 cells/mL, CSF protein under 80 mg/dL, peripheral absolute neutrophil count under 10,000 cells/mL, and no history of a seizure at or after the time of presentation. This rule was validated in a multicenter retrospective cohort study that encompassed 3,295 patients. Of those who were categorized at very low risk, only two had bacterial meningitis. Whether this low rate justifies withholding


Neurology_Adams

Neurology_Adams. multicenter retrospective cohort study that encompassed 3,295 patients. Of those who were categorized at very low risk, only two had bacterial meningitis. Whether this low rate justifies withholding antibiotics is, of course, a clinical judgement made at the bedside.


Neurology_Adams

Neurology_Adams. The Gram stain of the spinal fluid sediment permits identification of the causative agent in most cases of bacterial meningitis; pneumococci and H. influenzae are identified more readily than meningococci. Small numbers of gram-negative diplococci in leukocytes may be indistinguishable from fragmented nuclear material, which may also be gram-negative and of the same shape as bacteria. In such cases, a thin film of uncentrifuged CSF may lend itself more readily to morphologic interpretation than a smear of the sediment. The most common error in reading Gram-stained smears of CSF is the misinterpretation of precipitated dye or debris as gram-positive cocci or the confusion of pneumococci with H. influenzae. The latter organism may stain heavily at the poles, so that they resemble gram-positive diplococci, and older or rapidly growing pneumococci often lose their capacity to take a gram-positive stain.


Neurology_Adams

Neurology_Adams. Cultures of the spinal fluid, which prove to be positive in 70 to 90 percent of cases of bacterial meningitis, are best obtained by collecting the fluid in a sterile tube and immediately inoculating agar plates; tubes of thioglycolate (for anaerobes); and other media. The advantage of using broth media is that large amounts of CSF can be cultured. The importance of obtaining blood cultures is mentioned in the following text.


Neurology_Adams

Neurology_Adams. The problem of identifying causative organisms that cannot be easily cultured, particularly in patients who have received antibiotics, may be overcome by the application of special laboratory techniques. One of these is counterimmunoelectrophoresis (CIE), a sensitive test that permits the detection of bacterial antigens in the CSF in a matter of 30 to 60 min. It was in the past particularly useful in patients with partially treated meningitis, in whom the CSF still contains bacterial antigens but no organisms on a smear or grown in culture but it has been replaced by more sensitive methods described in the following text.


Neurology_Adams

Neurology_Adams. Several other serologic methods, radioimmunoassay (RIA) and latex-particle agglutination (LPA), as well as an enzyme-linked immunosorbent assay (ELISA), may be even more sensitive than CIE. An argument has been made that these procedures are not cost-effective, as—in virtually all instances in which the bacterial antigen can be detected—Gram stain also shows the organism. Gene amplification by the polymerase chain reaction (PCR) is the most recently developed and most sensitive technique. As it has become more widely available in clinical laboratories, rapid diagnosis has been facilitated but the use of carefully Gram-stained preparations still needs to be encouraged.


Neurology_Adams

Neurology_Adams. In the past, much was made of the interesting finding that chloride concentrations in the CSF are usually low in meningitis, possibly reflecting dehydration and low serum chloride levels. In contrast, CSF lactate dehydrogenase (LDH), although also infrequently measured, can be of diagnostic and prognostic value. A rise in total LDH activity is consistently observed in patients with bacterial meningitis; most of this is because of fractions 4 and 5, which are derived from granulocytes. Fractions 1 and 2 of LDH, which are presumably derived from brain tissue, are only slightly elevated in bacterial meningitis but rise sharply in patients who develop neurologic sequelae or later die. Various enzymes in the CSF, derived from leukocytes, meningeal cells, or plasma, may also be increased in meningitis, but the clinical significance is unknown. Levels of lactic acid in the CSF (determined by either gas chromatography or enzymatic analysis) are also elevated in both bacterial and fungal


Neurology_Adams

Neurology_Adams. meningitis, but the clinical significance is unknown. Levels of lactic acid in the CSF (determined by either gas chromatography or enzymatic analysis) are also elevated in both bacterial and fungal meningitides (greater than 35 mg/dL) and may be helpful in distinguishing these disorders from viral meningitides, in which lactic acid levels remain normal; however, these ancillary tests are infrequently performed.


Neurology_Adams

Neurology_Adams. In addition to CSF cultures, blood cultures should be obtained if possible because they are positive in 40 to 60 percent of patients with H. influenzae, meningococcal, and pneumococcal meningitis, and may provide the only definite clue as to the causative agent. Routine cultures of the oropharynx are as often misleading as helpful, because pneumococci, H. influenzae, and meningococci are common in the throats of healthy persons. In contrast, cultures of the nasopharynx may aid in diagnosis, although often not in a timely way; the finding of encapsulated H. influenzae or groupable meningococci may provide the clue to the etiology of the meningeal infection. Conversely, the absence of such a finding prior to antibiotic treatment makes an H. influenzae and meningococcal etiology unlikely. The leukocyte count in the blood is generally elevated, and immature forms are usually present. Meningitis may be complicated after several days by severe hyponatremia, the result of inappropriate


Neurology_Adams

Neurology_Adams. The leukocyte count in the blood is generally elevated, and immature forms are usually present. Meningitis may be complicated after several days by severe hyponatremia, the result of inappropriate secretion of antidiuretic hormone (ADH).


Neurology_Adams

Neurology_Adams. In patients with bacterial meningitis, chest films are essential because they may disclose an area of pneumonia or abscess. Sinus and skull films may provide clues to the presence of cranial osteomyelitis, paranasal sinusitis, mastoiditis, or cranial osteomyelitis, but these structures are better visualized on CT scans, which have supplanted conventional films in most cases. The CT scan is particularly useful in detecting lesions that erode the skull or spine and provide a route for bacterial invasion, such as tumors or sinus wall defects, as well as in demonstrating a brain abscess or subdural empyema. MRI with gadolinium enhancement may display the meningeal exudate and cortical reaction, and both types of imaging, with appropriate techniques, will demonstrate venous occlusions and adjacent infarctions. The issues pertaining to an abscess and to brain swelling in meningitis have already been noted and are disucussed further on as well. We find it advisable to obtain some of these


Neurology_Adams

Neurology_Adams. infarctions. The issues pertaining to an abscess and to brain swelling in meningitis have already been noted and are disucussed further on as well. We find it advisable to obtain some of these imaging procedures.


Neurology_Adams

Neurology_Adams. Recurrent Bacterial Meningitis (See Chap. 32)


Neurology_Adams

Neurology_Adams. This is observed most frequently in patients who have had some type of shunting procedure for the treatment of hydrocephalus or who have an incompletely closed dural opening after cranial or spinal surgery. When the origin of the recurrence is inapparent, one should suspect a congenital neuroectodermal sinus or a fistulous connection between the nasal sinuses and the subarachnoid space. The fistula in these latter cases is more often traumatic than congenital in origin (e.g., a previous basilar skull fracture), although the interval between injury and the initial bout of meningitis may be several years. The site of trauma is in the frontal or ethmoid sinuses or the cribriform plate, and S. pneumoniae is the usual pathogen. Often it reflects the predominance of such strains in nasal carriers. These cases usually have a good prognosis; mortality is much lower than in ordinary cases of pneumococcal meningitis. Neurenteric cysts, although rare, are another source of recurrent meningitis.


Neurology_Adams

Neurology_Adams. CSF rhinorrhea (or otorrhea) is present in some cases of posttraumatic meningitis, but it may be transient and difficult to find. Suspicion of its presence is raised by the recent onset of anosmia or by the occurrence of a watery nasal discharge that is salty to the taste and increases in volume when the head is dependent. One way of confirming the presence of a CSF leak is to measure the glucose concentration of nasal secretions; ordinarily they contain little glucose, but in CSF rhinorrhea the amount of glucose approximates that obtained by lumbar puncture (two-thirds of the serum value). A “dipstick” used for urine testing is sometimes adequate but these are regrettably decresingly available on general hospital wards. Another bedside test for CSF rhinorrhea or otorrhea is to estimate the amount of protein in the fluid. A high protein, sufficient to make a handkerchief stiff on drying, suggests it is of nasal mucosal origin. If the fluid fails to cause a handkerchief to stiffen on


Neurology_Adams

Neurology_Adams. the amount of protein in the fluid. A high protein, sufficient to make a handkerchief stiff on drying, suggests it is of nasal mucosal origin. If the fluid fails to cause a handkerchief to stiffen on drying, a spinal fluid leak is suspected. The most specific and sensitive test for CSF otorrhea and rhinorrhea may be the finding of β2-transferrin (tau), in fluid collected in a polypropylene tube, a substance not found in fluids other than CSF.


Neurology_Adams

Neurology_Adams. The site of a CSF leak can sometimes be demonstrated by injecting a dye, radioactive substance (radionuclide), or water-soluble contrast material into the spinal subarachnoid space and detecting its appearance in nasal secretions or observing its site of exit by CT scanning. This testing is best performed after the acute infection has subsided. Persistence of CSF rhinorrhea or a spinal CSF leak usually requires surgical repair.


Neurology_Adams

Neurology_Adams. The diagnosis of bacterial meningitis is usually not difficult in an immunocompetent individual. Viral meningitis (which is far more common than bacterial meningitis), subarachnoid hemorrhage, chemical meningitis (following lumbar puncture, spinal anesthesia, myelography, or rupture of a intracranial lesion containing irritative material, e.g., craniopharyngioma or dermoid), and tuberculous, leptospiral, sarcoid, and fungal meningoencephalitis, and allergic-immune reactions, for example, due to certain medications, enter into the differential diagnosis as well, as discussed in later sections.


Neurology_Adams

Neurology_Adams. Overwhelming sepsis itself, or the multiorgan failure that it engenders, may cause an encephalopathy but if there is meningitis, it is imperative, in deciding on the choice of antibiotics, to identify it early. The same can be said for the confused alcoholic patient. Too often, the symptoms are ascribed to alcohol intoxication or withdrawal, or to hepatic encephalopathy, until examination of the CSF reveals meningitis. Although this approach undoubtedly results in many negative spinal fluid examinations, it is preferable to the consequence of overlooking bacterial meningitis.


Neurology_Adams

Neurology_Adams. A number of nonbacterial meningitides must be considered in the differential diagnosis when the meningitis recurs repeatedly and all cultures are negative. Included in this group are Epstein-Barr virus (EBV) infections; Behçet disease, which is characterized by recurrent oropharyngeal mucosal ulceration, uveitis, orchitis, and meningitis; Mollaret meningitis, which consists of recurrent episodes of fever and headache in addition to signs of meningeal irritation (in many cases caused by herpes simplex, as discussed in Chap. 32); and the Vogt-Koyanagi-Harada syndrome, in which recurrent meningitis is associated with iridocyclitis and depigmentation of the hair and skin (poliosis and vitiligo). The CSF in these recurrent types may contain large numbers of lymphocytes or polymorphonuclear leukocytes but no bacteria, and the glucose content is not reduced (see discussion of Chronic Persistent and Recurrent Meningitis in Chap. 32). These recurrent syndromes rarely present in the fulminant


Neurology_Adams

Neurology_Adams. but no bacteria, and the glucose content is not reduced (see discussion of Chronic Persistent and Recurrent Meningitis in Chap. 32). These recurrent syndromes rarely present in the fulminant manner of acute bacterial meningitis but sometimes they do, and the CSF formulas can be similar, including a reduction in glucose concentration. Rarely, a fulminant case of cerebral angiitis or intravascular lymphoma will present with headache, fever, and confusion in conjunction with a meningeal inflammatory reaction.


Neurology_Adams

Neurology_Adams. Bacterial meningitis is a medical emergency. The first therapeutic measures are directed to maintain blood pressure and treating septic shock (volume replacement, pressor therapy). A premium is then placed on choosing an antibiotic that is known both to be bactericidal for the suspected organism and is able to enter the CSF in effective amounts. Treatment should begin while awaiting the results of diagnostic tests and may be altered later in accordance with the laboratory findings. Whereas penicillin formerly sufficed to treat almost all meningitides acquired outside the hospital, the initial choice of antibiotic has become increasingly complicated as resistant strains of meningitic bacteria have emerged. The selection of drugs to treat nosocomial infections also presents special difficulties.


Neurology_Adams

Neurology_Adams. In recent years, many reports have documented an increasing incidence of pneumococcal isolates that have a relatively high resistance to penicillin, reaching 50 percent in some European countries. Current estimates are that, in some areas of the United States, 15 percent of these isolates are penicillin-resistant to some degree (most have a relatively low level of resistance). In the 1970s, H. influenzae type B strains producing beta-lactamase, which are resistant to ampicillin and penicillin, were recognized. Currently, 30 percent of H. influenzae isolates produce the beta-lactamase enzyme, but almost all remain sensitive to third-generation cephalosporins (e.g., cefotaxime, ceftizoxime, ceftriaxone).


Neurology_Adams

Neurology_Adams. Recommendations for the institution of empiric treatment of meningitis have been reviewed by van de Beek and colleagues (2006) and by McGill and colleagues, often updated, often requiring updating and are summarized in modified form in Table 31-2. The choice of agents evolves based on epidemiology, patterns of resistance and geographic region, but the ones given here are a good approximation to current practice in developed countries.


Neurology_Adams

Neurology_Adams. In children and adults, third-generation cephalosporins such as ceftriaxone, combined with vancomycin is probably the best initial therapy for the three major types of community-acquired meningitides. In areas with low numbers of high-level penicillin-resistant pneumococci, it is possible to avoid adding vancomycin. Ampicillin should be added to the regimen in cases of suspected Listeria meningitis, particularly in an immunocompromised patient. Intravenous drug abusers have high rates of meningitis due to S. Aureus and should receive cefepime or ceftazidime with vancomycin. When serious allergy to penicillin and cephalosporins precludes their use, chloramphenicol may be a suitable alternative in some regions, but not for Listeria.


Neurology_Adams

Neurology_Adams. Isolation from the blood or CSF of a resistant organism requires the use of ceftriaxone with the addition of vancomycin and rifampin. N. meningitidis, at least in the United States, remains highly susceptible to penicillin and ampicillin. Regional variations and ongoing antibiotic-induced changes in the infecting microorganisms underscore the need for constant awareness of drug resistance in the physician’s local area, especially in the case of pneumococcal infections. Throughout the course of treatment, it is necessary to have access to a laboratory that can carry out rapid and detailed drug-resistance testing.


Neurology_Adams

Neurology_Adams. Nosocomial meningitis In cases of meningitis caused by coagulase-positive S. aureus, including those that occur after neurosurgery or major head injury, administration of vancomycin plus a third-generation cephalosporin (e.g., cefepime, ceftazadime, or meropenem) is a reasonable first approach. If Pseudomonas is considered possible, such as after neurosurgery, an antipseudomonal cephalosporin such as ceftazidime or cefepime should be added. Once the sensitivity of the organism has been determined, therapy may have to be altered or may be simplified by using vancomycin or nafcillin alone. These approaches have been reviewd by van de Beek and colleagues (2010). They note that the CSF cell count may be low in cases of ventricular catheter-associated meningitis. They also provide recommendations on the use of prophylactic antibiotics after a basilar skull fracture, a controversial problem that is reviewed in Chap. 34.


Neurology_Adams

Neurology_Adams. Table 31-3 lists the approximate dosages of the most used antibiotics, and Table 31-4 gives reasonable choices of antibiotic for the treatment of specific bacterial isolates.


Neurology_Adams

Neurology_Adams. Duration of therapy Most cases of bacterial meningitis should be treated for a period of 10 to 14 days except when there is a persistent parameningeal focus of infection (otitic or sinus origin), in which cases longer treatment may be needed. Antibiotics should be administered in full doses parenterally (preferably intravenously) throughout the period of treatment. Treatment failures with certain drugs, notably ampicillin, may be attributable to oral or intramuscular administration, resulting in inadequate concentrations in the CSF. Repeated lumbar punctures are not necessary to assess the effects of therapy as long as there is progressive clinical improvement. The CSF glucose may remain low for many days after other signs of infection have subsided and should occasion concern only if bacteria are present in the fluid and the patient remains febrile and ill.


Neurology_Adams

Neurology_Adams. Persistence of fever or the late appearance of drowsiness, hemiparesis, or seizures should raise the suspicion of subdural effusion, mastoiditis, venous sinus thrombosis, cortical vein or jugular phlebitis, or brain abscess; all require that therapy be continued for a longer period. Bacteriologic relapse after treatment is discontinued requires reinstitution of therapy and exploration for a persistent parameningeal focus of infection, such as in the spinal column.


Neurology_Adams

Neurology_Adams. Corticosteroids Controlled studies several decades ago were unable to demonstrate beneficial effects of corticosteroids in the treatment of bacterial meningitis. More recent studies have given another perspective of the therapeutic value of dexamethasone in children and adults with meningitis. In children, although mortality was not affected in the main study conducted by Lebel and colleagues, fever subsided more rapidly and the incidence of sensorineural deafness and other neurologic sequelae was reduced, particularly in those children with H. influenzae meningitis. On these grounds, it has been recommended that the treatment of childhood meningitis include dexamethasone in high doses (0.15 mg/kg qid for 4 days), instituted as soon as possible.


Neurology_Adams

Neurology_Adams. Despite conflicting results from earlier studies of corticosteroids in adults, the trial by deGans and van de Beck has demonstrated a reduction in mortality and improved overall outcome if dexamethasone 10 mg is given just before the first dose of antibiotics and then repeated q6h for 4 days. The improvement was largely in patients who were infected with pneumococcus. Seizures and coma were reduced in incidence as a result of the administration of corticosteroids, but neurologic sequelae, such as hearing loss, were not affected. Based on a number of smaller studies, authorities in the field of bacterial meningitis have endorsed the administration of dexamethasone in the doses mentioned above, particularly if they can be started before antibiotics, and in those with presumed pneumococcal infection in developed countries (see Tunkel and Scheld). They also, however, have advised against the use of the drug if there is septic shock.


Neurology_Adams

Neurology_Adams. Tunkel and Scheld). They also, however, have advised against the use of the drug if there is septic shock. In developing countries, especially those with high rates of HIV, the benefits of adjuvant dexamethasone have not been clear. Improved survival was limited to those who ultimately had bacteria isolated from the CSF, in contrast to those with suspected meningitis but negative cultures. Nevertheless, the incidence of deafness was reduced (Nguyen et al; Scarborough et al).


Neurology_Adams

Neurology_Adams. Other forms of therapy There is no evidence that repeated drainage of CSF, a former practice, is therapeutically effective. In fact, increased CSF pressure in the acute phase of bacterial meningitis is largely a consequence of cerebral edema, in which case the lumbar puncture may predispose to cerebellar herniation. As already mentioned, a second lumbar puncture to gauge the effectiveness of treatment is generally not necessary, but it may be of value if the patient is worsening without explanation. Mannitol and urea have been employed with apparent success in cases of severe brain swelling with unusually high initial CSF pressures (400 mm H2O). Acting as osmotic diuretics, these agents enter cerebral tissue slowly, and their net effect is to decrease brain water. However, neither mannitol nor urea has been studied in controlled fashion in the management of meningitis. An adequate but not excessive amount of intravenous normal saline (and avoiding fluids with free water) should be


Neurology_Adams

Neurology_Adams. nor urea has been studied in controlled fashion in the management of meningitis. An adequate but not excessive amount of intravenous normal saline (and avoiding fluids with free water) should be given. Particular care should be taken with children to avoid hyponatremia and water intoxication—potential causes of brain swelling. Antiepileptic drugs need not be administered routinely but should be given if a seizure has occurred or possibly if there is evidence of cortical vein thrombosis.


Neurology_Adams

Neurology_Adams. Prophylaxis Household contacts of patients with meningococcal meningitis should be protected with antibiotic treatment. The risk of secondary cases is small for adolescents and adults, but ranges from 2 to 4 percent for those younger than 5 years of age and is probably higher in the elderly. A single dose of ciprofloxacin is effective. An alternative is a daily oral dose of rifampin—600 mg q12h in adults and 10 mg/kg q12h in children—for 2 days. If 2 weeks or more have elapsed since the index case was found, no prophylaxis is needed. As mentioned, immunization against H. influenzae is steadily reducing the incidence of meningitis from this organism. Also, many institutions housing young adults, such as colleges and the military, have instituted programs of immunization against N. meningitidis. Prognosis and Sequelae of Meningitis


Neurology_Adams

Neurology_Adams. Untreated, bacterial meningitis is usually fatal. The mortality rate of treated H. influenzae and meningococcal meningitis has remained approximately 5 percent for many years; in pneumococcal meningitis, the rate is considerably higher (approximately 15 percent), perhaps related to the older and sicker population that is affected. Fulminant meningococcemia, with or without meningitis, also has a high mortality rate because of the shock associated with adrenocortical hemorrhages (Waterhouse-Friderichsen syndrome). A disproportionate number of deaths from meningitis occur in infants and in the aged. The mortality rate is highest in neonates, from 40 to 75 percent in several reported series, and at least half of those who recover show serious neurologic sequelae. In adults, the presence of bacteremia, coma, seizures, and a variety of concomitant diseases—including alcoholism, diabetes mellitus, multiple myeloma, and head trauma—all worsen the prognosis. The triad of pneumococcal


Neurology_Adams

Neurology_Adams. of bacteremia, coma, seizures, and a variety of concomitant diseases—including alcoholism, diabetes mellitus, multiple myeloma, and head trauma—all worsen the prognosis. The triad of pneumococcal meningitis, pneumonia, and endocarditis (Osler triad) has a particularly high fatality rate.


Neurology_Adams

Neurology_Adams. Surprisingly often, it is impossible to explain the death of a patient with meningitis or at least to trace it to a single specific mechanism. The effects of overwhelming infection, with bacteremia and hypotension, or brain swelling and cerebellar herniation (see Rennick), are clearly implicated in some patients during the initial 48 h. These events may occur in bacterial meningitis of any etiology; however, they are far more frequent in meningococcal and pneumococcal infection. Some of the deaths occurring later in the course of the illness are attributable to respiratory failure, often consequent to aspiration pneumonia.


Neurology_Adams

Neurology_Adams. It has been stated that relatively few adult patients who recover from meningococcal meningitis show residual neurologic defects, whereas such defects are encountered in at least 25 percent of children with H. influenzae meningitis and up to 30 percent of child and adult patients with pneumococcal meningitis. Kastenbauer and Pfister, reporting on adults with pneumococcal meningitis, have emphasized that the mortality remains quite high and that cerebral venous or arterial thrombosis occurred in almost a third of cases, as discussed further on. They also had two patients with an associated myelitis. We have seen several instances of upper cervical cord and lower medullary infarction in bacterial meningitis; quadriparesis and respiratory failure were the result of compression from descent of the cerebellar tonsils (Ropper and Kanis). As already discussed, the role of lumbar puncture in promoting this complication of cerebellar herniation has not been clarified.


Neurology_Adams

Neurology_Adams. Among infants who survive H. influenzae meningitis, Ferry and coworkers, in a prospective study of 50 cases, found that about half were normal, whereas 9 percent had behavioral problems and about 30 percent had neurologic deficits (seizures or impairment of hearing, language, mentation, and motor function). In a report of a series of 185 children recovering from bacterial meningitis, Pomeroy and associates found that 69 were not normal neurologically at the end of a month; however, at the end of a year, only 18 were left with a hearing deficit, 13 with late seizures, and 8 with multiple deficits. The presence of a persistent neurologic deficit was the only independent predictor of later seizures. Dodge and colleagues in past decades found that 31 percent of children with pneumococcal meningitis were left with persistent sensorineural hearing loss; for meningococcal and H. influenzae meningitis, the figures were 10.5 and 6 percent, respectively. These events are seemingly less frequent


Neurology_Adams

Neurology_Adams. were left with persistent sensorineural hearing loss; for meningococcal and H. influenzae meningitis, the figures were 10.5 and 6 percent, respectively. These events are seemingly less frequent now, specifically in developed countries, but still reflect the seriousness of these sequealae in less advantaged regions of the world.


Neurology_Adams

Neurology_Adams. Cranial nerve palsies other than deafness, if they occur, tend to disappear after a few weeks or months. Deafness in these infections is a result of suppurative cochlear destruction or, less often now, of the ototoxic effects of aminoglycoside antibiotics. Bacteria reach the cochlea mainly via the cochlear aqueduct, which connects the subarachnoid space to the scala tympani. This occurs quite early in the course of infection, hearing loss being evident within a day of onset of the meningitis; in about half or most of such cases, the acute deafness resolves. Hydrocephalus is an infrequent complication that may become manifest months after treatment and then requires shunting if gait or mentation is affected. It may be difficult to determine on clinical grounds whether a residual state of imbalance is the result of hydrocephalus or of eighth nerve damage. The acute complications of bacterial meningitis, the intermediate and late neurologic sequelae, and the pathologic basis of these


Neurology_Adams

Neurology_Adams. imbalance is the result of hydrocephalus or of eighth nerve damage. The acute complications of bacterial meningitis, the intermediate and late neurologic sequelae, and the pathologic basis of these effects are summarized in Table 31-1.


Neurology_Adams

Neurology_Adams. Quite apart from acute and subacute bacterial endocarditis, which may give rise to cerebral embolism and characteristic inflammatory reactions in the brain (see further on), there are several systemic bacterial infections that are complicated by a special type of encephalitis or meningoencephalitis. Three common ones are Mycoplasma pneumoniae infections, L. monocytogenes meningoencephalitis, and Legionnaire disease. Probably Lyme borreliosis should be included in this category but it is more chronic and is described further on in this chapter with the spirochetal infections. The rickettsial encephalitides (particularly Q fever), which mimic bacterial meningoencephalitis, are also addressed later in the chapter. Catscratch disease is another rare cause of bacterial meningoencephalitis. Meningoencephalitis caused by brucellosis occurs very rarely in the United States. Whipple disease, discussed later, which appears to be a focal invasion of the brain by an unusual intracellular


Neurology_Adams

Neurology_Adams. Meningoencephalitis caused by brucellosis occurs very rarely in the United States. Whipple disease, discussed later, which appears to be a focal invasion of the brain by an unusual intracellular bacterium, is an oddity but also belongs in this category.


Neurology_Adams

Neurology_Adams. This organism, which causes 10 to 20 percent of community acquired pneumonias, is associated with a number of neurologic syndromes. Guillain-Barré polyneuritis, cranial neuritis, acute myositis, aseptic meningitis, transverse myelitis, global encephalitis, seizures, cerebellitis, acute disseminated (postinfectious) encephalomyelitis, and acute hemorrhagic leukoencephalitis (Hurst disease) have all been reported in association with mycoplasmal pneumonias or with serologic evidence of a recent infection (Westenfelder et al; Fisher et al; Rothstein and Kenny). We have observed several patients with striking cerebral, cerebellar, brainstem, or spinal cord syndromes incurred during or soon after a mycoplasmal pneumonia or tracheobronchitis. In addition to the cerebellitis, which is clinically similar to the illness that follows varicella, unusual encephalitic syndromes of choreoathetosis, seizures, delirium, hemiparesis, and acute brain swelling (Reye syndrome) have each been reported in a


Neurology_Adams

Neurology_Adams. to the illness that follows varicella, unusual encephalitic syndromes of choreoathetosis, seizures, delirium, hemiparesis, and acute brain swelling (Reye syndrome) have each been reported in a few cases. The incidence of these complications has been estimated as 1 in 1,000 mycoplasmal infections, but it may approach 5 percent when more careful surveillance is carried out during epidemics. A severe prodromal headache has occurred in most of the cases we have observed. At the time of onset of the neurologic symptoms, there may be scant signs of pneumonia, and in some patients, only an upper respiratory syndrome occurs.


Neurology_Adams

Neurology_Adams. The mechanism of cerebral damage that complicates mycoplasmal infections has not been established, but evidence suggests that the organism may be present in the CNS during the acute illness. To our knowledge, the organism has been cultured from the brain in only one fatal case, but PCR techniques have detected fragments of mycoplasmal DNA in the spinal fluid from several patients (Narita et al). In other instances, the nature of the neurologic complications and their temporal relationship to the mycoplasmal infection clearly suggest that secondary autoimmune factors are operative, that is, that these are instances of postinfectious encephalomyelitis (a type of acute disseminated encephalomyelitis as described in Chap. 35). This is almost certainly the mechanism of postmycoplasmal Guillain-Barrè syndrome. Most of the patients with the infectious variety have recovered with few or no sequelae, but rare fatalities are reported.


Neurology_Adams

Neurology_Adams. The CSF usually contains small numbers of lymphocytes and other mononuclear cells and increased protein content. The diagnosis can be established by culture of the organism from the respiratory tract (which is difficult), by rising serum titers of complement-fixing IgG and IgM antibodies, and by cold agglutinin antibodies in the blood and CSF, or by DNA detection techniques from the CSF. Treatment Macrolide antibiotics such as azithromicin and clarithromicin but also erythromycin and tetracycline derivatives reduce morbidity, mainly by eradicating the pulmonary infection, but the effects of antibiotics on the nervous system complications are not known.


Neurology_Adams

Neurology_Adams. Meningoencephalitis from this organism is most likely to occur in immunosuppressed and debilitated individuals and is a well-known and occasionally fatal cause of meningitis in the newborn. Meningitis is the usual neurologic manifestation, but there are numerous recorded instances of isolated focal bacterial infectious encephalitis, rarely with a normal CSF, most cases showing a pleocytosis that may be initially polymorphonuclear. Between 1929, when the organism was discovered, and 1962, when Gray and Killinger collected all the reported cases, it was noted that 35 percent of patients had either meningitis or meningoencephalitis as the primary manifestation.


Neurology_Adams

Neurology_Adams. The infection may take the form of a brainstem encephalitis, or “rhombencephalitis,” specifically with several days of headache, fever, nausea, and vomiting followed by asymmetrical cranial-nerve palsies, signs of cerebellar dysfunction, hemiparesis, quadriparesis, or sensory loss. Respiratory failure has been reported. Of 62 cases of Listeria brainstem encephalitis reported 25 years ago by Armstrong and Fung 8 percent were in immunosuppressed patients, however, in the current era 20 percent or fewer of affected patients are immunocompetent. In the elderly, no additional cause of immune disorder appears to be necessary. Meningeal signs were present in the only half the patients in the above mentioned series, and the spinal fluid often showed misleadingly mild abnormalities. CSF cultures yielded Listeria in only 40 percent of cases (blood cultures were even more often normal). Consistent with our experience, the early CT scan was often normal; MRI, however, has revealed abnormal


Neurology_Adams

Neurology_Adams. yielded Listeria in only 40 percent of cases (blood cultures were even more often normal). Consistent with our experience, the early CT scan was often normal; MRI, however, has revealed abnormal signals in the parenchyma of the brainstem.


Neurology_Adams

Neurology_Adams. The monocytosis, which gives the organism part of its name, refers to the reaction in the peripheral blood in rabbits but these cells have not been prominent in the blood or CSF of patients. Judging from the clinical signs in some cases, the infection appears to affect both the brainstem parenchyma and the extraaxial portion of the lower cranial nerves. One patient described by Lechtenberg and coworkers had a proven brain abscess; other patients have had multiple small abscesses (Uldry et al) but it is not clear if this is a uniform feature of the illness that explains the rhombencephalitis. Treatment The treatment is ampicillin (2 g intravenously q4h) in combination with gentamicin (5 mg/kg intravenously in 3 divided doses daily). If the condition of the host is compromised, the outcome is often fatal, but most of our patients without serious medical disease have made a full and prompt recovery with treatment.


Neurology_Adams

Neurology_Adams. In India and Southeast Asia, particularly Cambodia and Thailand, a brainstem, cerebellar, and meningitic illness, similar to that caused by Listeria, results instead from melioidosis (Burkholderia pseudomallei). A typical presentation is of multiple small abscesses with a predilection for white matter tracts of the cerebrum and cerebellum (Fig. 31-1). It should be suspected in returning travelers from that region but the disease is, of course, well known to physicians in areas endemic for the organism. Diabetics are particularly prone to this infection. The CSF shows one to several dozen white blood cells and raised protein but glucose may be normal. There is usually an associated pulmonary infection but this may be minor and the degree of temperature elevation varies. The diagnosis can be made by the culture of the organism from body sites such as CSF, pharynx, blood, urine or sputum, as it is not a normal commensal bacterium. Both blood agar and special Ashdown’s medium containing


Neurology_Adams

Neurology_Adams. be made by the culture of the organism from body sites such as CSF, pharynx, blood, urine or sputum, as it is not a normal commensal bacterium. Both blood agar and special Ashdown’s medium containing gentamicin are required for culture. There is a commercial serologic test but there are high background rates of positivity in endemic regions.


Neurology_Adams

Neurology_Adams. Treatment This is in two phases, an intesive eradication component with high intravenous doses of ceftazidime (or several equivalent regimens) for 10 to 14 days, followed by an eradication phase that is necessary to prevent relapse, using trimethoprim/sulfamethoxazole alone or accompanied by doxycycline.


Neurology_Adams

Neurology_Adams. This potentially fatal respiratory disease caused by the gram-negative bacillus Legionella pneumophila, first came to medical notice in July 1976, when a large number of members of the American Legion fell ill at their annual convention in Philadelphia. The fatality rate was high. In addition to the obvious pulmonary infection, manifestations referable to the CNS and other organs were observed regularly. Lees and Tyrrell described patients with severe and diffuse cerebral involvement, and Baker and associates and Shetty and colleagues described others with cerebellar and brainstem syndromes. The clinical details have varied. One constellation consisted of headache, obtundation, acute confusion or delirium with high fever, and evidence of pulmonary distress; another took the form of tremor, nystagmus, cerebellar ataxia, extraocular muscle and gaze palsies, and dysarthria.


Neurology_Adams

Neurology_Adams. Other neurologic abnormalities have been observed, such as inappropriate ADH secretion, or a syndrome of more diffuse encephalomyelitis or transverse myelitis, similar to that observed with Mycoplasma infections. The CSF is usually normal and CT scans of the brain are negative, a circumstance that makes diagnosis difficult. Suspicion of the disease, based on exposure or on the presence of an atypical pneumonia, should prompt urine antigen and culture of blood and CSF. Serologic tests are available but require paired sera and have little impact on clinical decision making. In most patients the signs of CNS disorder resolve rapidly and completely, although residual impairment of memory and a cerebellar ataxia have been recorded. To date, the Legionella bacillus has only rarely been isolated from the brain or spinal fluid.


Neurology_Adams

Neurology_Adams. Treatment Treatment in adults has consisted of one of levofloxacin, moxifloxacin, or azithromycin; rifampin is sometimes used. In the past, erythromycin, 0.5 to 1.0 g was used intravenously q6h for a 7 to 10 days.


Neurology_Adams

Neurology_Adams. Reports of over 100 cases of encephalitis from catscratch disease have appeared in the medical literature and several have occurred on our services over the years, for which reason we do not consider it rare. The causative organism is a gram-negative bacillus now called Bartonella henselae (formerly Rochalimaea henselae). The illness begins as unilateral axillary or cervical adenopathy occurring after a seemingly innocuous scratch (rarely a bite) from an infected cat. The cases with which we are familiar began with an encephalopathy and high fever (higher temperature than with most of the other organisms that are capable of causing bacterial encephalitis), followed by seizures or status epilepticus. The organism has also been implicated in causing a focal cerebral vasculitis in HIV patients as well as optic neuritis and neuroretinitis in both immunocompromised and immunocompetent patients. Demonstration of elevated complement-fixing titers and detection of the organism by PCR or by


Neurology_Adams

Neurology_Adams. as well as optic neuritis and neuroretinitis in both immunocompromised and immunocompetent patients. Demonstration of elevated complement-fixing titers and detection of the organism by PCR or by silver staining from an excised lymph node are diagnostic. A single high antibody titer is probably inadequate for this purpose.


Neurology_Adams

Neurology_Adams. Treatment First-line treatment is with azithromycin or doxycycline, sometimes with rifampin in recalcitrant cases. Erythromycin is used less frequently. Most patients recover completely, but one of our patients and a few reported by others have died.


Neurology_Adams

Neurology_Adams. This rare form of meningoencephalitis is included here because of the current interest in Bacillus anthracis as a bioweapon. Lanska was able to collect from the literature 70 patients with meningeal infection, most of whom were encephalopathic. He has estimated that fewer than 5 percent of infected individuals will acquire a meningoencephalitis; in a 2001 U.S. outbreak, only 1 of 11 cases with anthrax pneumonitis developed this complication. Reflecting the main site of natural infection, the majority of cases originated in cutaneous anthrax. In addition to a typically fulminating course after a prodrome of one or several days, the exceptional feature was a hemorrhagic and inflammatory spinal fluid formula. Subarachnoid hemorrhage was prominent in autopsy material, presumably reflecting necrosis of the vessel walls as a toxic effect of B. anthracis.


Neurology_Adams

Neurology_Adams. Treatment Although natural isolates are sensitive to penicillin, bioengineered strains are resistant; therefore, combined treatment with ciprofloxacin with clindamycin, rifampin, or meropenem has been recommended initially. The benefit of specific antitoxin is uncertain once meningoencephalitis has occurred. Recently, very similar overwhelming cases with meningitis and subarachnoid hemorrhage caused by Bacillus cereus have appeared in immunosuppressed patients.


Neurology_Adams

Neurology_Adams. This worldwide disease of domesticated livestock is frequently transmitted to humans in areas where the infection is enzootic. In the United States, it is distinctly rare, with 200 cases or fewer being reported annually since 1980, some in abattoir workers. During the 1950s it was a fashionable explanation for chronic fatigue. In the Middle East, infection with Brucella is still frequent, attributable to the ingestion of raw milk. In Saudi Arabia, for example, al Deeb and coworkers reported on a series of 400 cases of brucellosis, of which 13 presented with brain involvement (acute meningoencephalitis, papilledema and increased intracranial pressure, and meningovascular manifestations). The CSF showed a lymphocytic pleocytosis and increased protein content. Blood and CSF antibody titers to the organism were greater than 1:640 and 1:128, respectively. There is also a tuberculous-like osteomyelitis that may cause compression of the spinal cord.


Neurology_Adams

Neurology_Adams. Treatment Prolonged treatment with doxycycline with streptomycin or gentamicin; an alternative is doxycycline plus rifampin to suppress the infection. This is a rare but often-discussed disorder, predominantly of middle-aged men. Weight loss, fever, anemia, steatorrhea, abdominal pain and distention, arthralgia, lymphadenopathy, and hyperpigmentation are the usual systemic manifestations. Less often, infection is associated with a number of neurologic syndromes. It is caused by a gram-positive bacillus, Tropheryma whipplei, which resides predominantly in the gut. Biopsy of the jejunal mucosa, which discloses macrophages filled with the periodic acid-Schiff (PAS)-positive organisms, is diagnostic. PAS-positive histiocytes have also been identified in the CSF, as well as in periventricular regions, in the hypothalamic and tuberal nuclei, and diffusely scattered in the brain.


Neurology_Adams

Neurology_Adams. The neurologic manifestations most often take the form of a slowly progressive memory loss or dementia of subacute or early chronic evolution. Supranuclear ophthalmoplegia, ataxia, seizures, myoclonus, nystagmus, and a highly characteristic movement described as oculomasticatory myorhythmia (which looks to us like rhythmic myoclonus) have been noted less often than the dementing syndrome. The rhythmic myoclonus or spasm occurs in synchronous bursts involving several adjacent regions, mainly the eyes, jaw, and face. This movement disorder is fairly specific but insensitive for Whipple disease, occurring in only approximately 10 percent of patients. As pointed out by Matthews and colleagues, cerebellar ataxia, although obviously much less specific for Whipple disease of the brain, is more frequent, occurring in about half the documented cases. Almost always, the myorhythmias are accompanied by a supranuclear vertical gaze paresis that sometimes affects horizontal eye movements as well.


Neurology_Adams

Neurology_Adams. occurring in about half the documented cases. Almost always, the myorhythmias are accompanied by a supranuclear vertical gaze paresis that sometimes affects horizontal eye movements as well. Presumably, the neurologic complications are the result of infiltration of the brain by the organism, but this has not been satisfactorily established.


Neurology_Adams

Neurology_Adams. Approximately half of the patients have a mild pleocytosis and some of these have PAS-positive material in the CSF. A variety of brain imaging abnormalities have been recorded, none characteristic, but either enhancing focal lesions or a normal scan may be found. The diagnosis is made mainly from PAS staining of an intestinal (jejunal) biopsy, as already mentioned, supplemented by PCR testing of the bowel tissue or biopsy material from brain or lymph node. In cases of subacute progressive limb and gait ataxia occurring in middle-aged or older men in whom no cause is uncovered by less-invasive means, it is justifiable to perform these tests (see Chap. 5). Rarely, the neurologic symptoms may occur in the absence of gastrointestinal disease (Adams et al, 1987). In the review of 84 cases of cerebral Whipple disease by Louis and colleagues, 71 percent had cognitive changes, half with psychiatric features; 31 percent had myoclonus; 18 percent had ataxia; and 20 percent had the


Neurology_Adams

Neurology_Adams. 84 cases of cerebral Whipple disease by Louis and colleagues, 71 percent had cognitive changes, half with psychiatric features; 31 percent had myoclonus; 18 percent had ataxia; and 20 percent had the oculomasticatory and skeletal myorhythmias (Schwartz et al).


Neurology_Adams

Neurology_Adams. Treatment A course of induction by penicillin or ceftriaxone for 2 weeks followed by trimethoprim- sulfamethoxazole or doxycycline continued for 1 year are the currently recommended regimens. An alternative approach is 2 weeks of ceftriaxone followed by treatment with trimethoprim-sulfamethoxazole or a tetracycline for a year. Antibiotic-resistant cases and instances of relapse after antibiotic treatment are known. The review by Anderson may be consulted for details.


Neurology_Adams

Neurology_Adams. We are uncertain of the status of this entity but have been shown putative cases of this disorder as described by Lyon and colleagues as “acute encephalopathy of obscure origin in children,” a febrile and sometimes fatal illness that could not be ascribed to direct infection of the nervous system. The term acute toxic encephalopathy, introduced by these authors still has some utility, but a careful search for better-characterized causes of febrile coma must be undertaken. During the height of a systemic bacterial or sometimes viral infection, the child sinks into coma, seizures are infrequent, the neck is supple, and the spinal fluid shows no changes or only a few cells. This is undoubtedly an illness of diverse causes, common among them being fluid overload and electrolyte imbalance, Reye syndrome (see Chap. 29) and, possibly most commonly, the immune condition of postinfectious encephalitis (see Chap. 35). Nonetheless, cases continue to be reported, such as those by Thi and


Neurology_Adams

Neurology_Adams. Reye syndrome (see Chap. 29) and, possibly most commonly, the immune condition of postinfectious encephalitis (see Chap. 35). Nonetheless, cases continue to be reported, such as those by Thi and colleagues, which can only be classified as a noninfectious bacterial encephalopathy or encephalitis. A relationship to the “septic encephalopathy” of adults, which has been emphasized by the group from London, Ontario, is possible but unproved. The acute necrotizing encephalopathy that has been reported, particularly in Asian children after influenza, probably belongs to this category and consists of a number of diseases as discussed by Mizuguchi and coworkers.


Neurology_Adams

Neurology_Adams. Subdural empyema is an intracranial (sometimes intraspinal) purulent process between the inner surface of the dura and the outer surface of the arachnoid that occurs mainly in children and is increasingly infrequent as various bacterial infections are treated earlier in their course. The infection usually originates in the frontal or ethmoid or, less often, the sphenoid sinuses and in the middle ear and mastoid cells. In infants and children, and infrequently in adults, there may be a spread from meningitis and the collection is then often sterile. The term subdural abscess, among others, had been applied to this condition but the proper name is empyema, indicating suppuration in a preformed space. Thrombosis of the underlying cortical veins and dural sinuses is a common accompaniment.


Neurology_Adams

Neurology_Adams. Usually the history includes reference to chronic sinusitis or mastoiditis with a recent flare-up causing local pain and increase in purulent nasal or aural discharge. In sinus cases, the pain is over the brow or between the eyes; it is associated with tenderness on pressure over these parts and sometimes with orbital swelling. General malaise, fever, and headache—at first localized, then severe and generalized and associated with vomiting are the first indications of intracranial spread. They are followed in a few days by drowsiness and increasing stupor, rapidly progressing to coma. At about the same time, focal neurologic signs appear, the most important of which are unilateral motor seizures, hemiplegia, hemianesthesia, aphasia, and paralysis of lateral conjugate gaze. Fever and leukocytosis are always present and the neck is usually stiff. Cases that follow surgery may be more indolent.


Neurology_Adams

Neurology_Adams. The usual CSF findings are an increased pressure, pleocytosis in the range of 50 to 1,000/mm3, a predominance of polymorphonuclear cells, elevated protein content (75 to 300 mg/dL), and normal glucose values. The spinal fluid is often sterile, but on occasion an organism is cultured. If the patient is stuporous or comatose, there is a risk associated with performing a lumbar puncture, and one should proceed first with imaging procedures. By imaging, one can see the ear or sinus lesions or bone erosion. The meninges around the empyema enhance and the collection of pus can be visualized more dependably with MRI. Empyema that follows meningitis in children tends to localize on the undersurface of the temporal lobe and may require coronal views to be well visualized.


Neurology_Adams

Neurology_Adams. Pathogenesis Infection gains entry to the subdural space by direct extension through bone and dura or by spread from septic thrombosis of the venous sinuses, particularly the superior longitudinal sinus. Rarely, the subdural infection is the result of hematogenous spread from lung infection. Occasionally it extends from a brain abscess. It is currently predominantly the result of surgical procedures on the sinuses and cranium. In cases originating after cranial surgery, staphylococcus is involved. Streptococci (nonhemolytic and viridans) are the most common organisms if the sinuses are the origin of infection, followed by facultative anaerobic streptococci (often Streptococcus milleri) or Bacteroides. Less often S. aureus, E. coli, Proteus, and Pseudomonas are causative. In about half the cases unrelated to surgery, no organisms can be cultured or seen on Gram stain.


Neurology_Adams

Neurology_Adams. Pathology A collection of subdural pus ranging from a few milliliters to 100 to 200 mL lies over the cerebral hemispheres. Pus may spread into the interhemispheric fissure or be confined there; occasionally it is found in the posterior fossa, covering the cerebellum. The arachnoid, when cleared of exudate, is cloudy, and thrombosis of meningeal veins may be seen. The underlying cerebral hemisphere is compressed, and in fatal cases there is often an ipsilateral temporal lobe herniation. Microscopic examination discloses various degrees of organization of the exudate on the inner surface of the dura and infiltration of the underlying arachnoid with small numbers of neutrophilic leukocytes, lymphocytes, and mononuclear cells. Thrombi in cerebral veins seem to begin on the sides of the veins nearest the subdural exudate. The superficial layers of the cerebral cortex undergo ischemic necrosis, which probably accounts for focal seizures and other signs of disordered cerebral function (Kubik


Neurology_Adams

Neurology_Adams. the subdural exudate. The superficial layers of the cerebral cortex undergo ischemic necrosis, which probably accounts for focal seizures and other signs of disordered cerebral function (Kubik and Adams).


Neurology_Adams

Neurology_Adams. Several conditions must be distinguished clinically from subdural empyema: a treated subacute bacterial meningitis, cerebral thrombophlebitis, brain abscess (see in the following text), herpes simplex encephalitis (see Chap. 32), acute disseminated encephalomyelitis and necrotizing hemorrhagic leukoencephalitis (see Chap. 35), and septic embolism because of bacterial endocarditis (see further on in this chapter).


Neurology_Adams

Neurology_Adams. Treatment Most subdural empyemas, by the time they are recognized clinically, require drainage through multiple burr holes, or through a craniotomy in cases with an interhemispheric, subtemporal, or posterior fossa location. The surgical procedure should be coupled with appropriate antibiotic therapy, generally a third- generation cephalosporin and metronidazole. Bacteriologic findings or an unusual presumed source may dictate a change to different drugs, particularly to later-generation cephalosporins. Without such antimicrobial therapy and surgery, some patients will die, usually within 7 to 14 days. On the other hand, patients who are treated promptly may make a surprisingly good recovery, including full or partial resolution of their focal neurologic deficits.


Neurology_Adams

Neurology_Adams. As with certain small brain abscesses, small subdural collections of pus that are recognized by CT or MRI before stupor and coma have supervened may respond to treatment with antibiotics alone. The resolution (or lack thereof) of the empyema can be readily followed by repeated imaging of the brain (Leys et al). This condition is usually associated with osteomyelitis in a cranial bone and originates from an infection in the ear or paranasal sinuses, or it is from a surgical procedure, particularly if the frontal sinus or mastoid had been opened or a foreign device inserted. Rarely, the infection is from a remote source or spreads outward from a dural sinus thrombophlebitis. Pus and granulation tissue accumulate on the outer surface of the dura, separating it from the cranial bone.


Neurology_Adams

Neurology_Adams. The symptoms are those of a local inflammatory process: frontal or auricular pain, purulent discharge from sinuses or ear, and fever and local tenderness. Sometimes the neck is slightly stiff. Localizing neurologic signs are usually absent. Rarely, a focal seizure may occur, or the fifth and sixth cranial nerves may be involved with infections of the petrous part of the temporal bone. The CSF is usually clear and under normal pressure but may contain a few lymphocytes and neutrophils (20 to 100 per mL; fewer than in subdural empyema) and a slightly increased amount of protein. Treatment consists of antibiotics, usually vancomycin and cephalosporin, aimed at the appropriate pathogen(s)—often S. aureus. Later, the diseased bone in the frontal sinus or the mastoid, from which the extradural infection had arisen, may have to be removed. Results of treatment are usually good. (See Chap. 42)


Neurology_Adams

Neurology_Adams. (See Chap. 42) These types of abscesses possess unique clinical features and constitute important neurologic and neurosurgical emergencies. They are discussed in Chap. 42 with other diseases of the spinal column and spinal cord. INTRACRANIAL SEPTIC THROMBOPHLEBITIS (SEE ALSO CHAP. 33) The dural sinuses drain blood from all of the brain into the jugular veins. The largest and most important of these, and the ones usually involved by infection, are the lateral (transverse), cavernous, petrous, and, less frequently, the longitudinal (sagittal) sinuses. A complex system of lesser sinuses and cerebral veins connects these large sinuses to one another as well as to the diploic and meningeal veins and veins of the face and scalp. The basilar venous sinuses are contiguous to several of the paranasal sinuses and mastoid cells.


Neurology_Adams

Neurology_Adams. Usually there is evidence that septic thrombophlebitis of the large dural sinuses has extended from an infection of the middle ear and mastoid cells, the paranasal sinuses, or skin around the upper lip, nose, and eyes. Other forms of intracranial infection frequently complicate these cases, including meningitis, epidural abscess, subdural empyema, and brain abscess. Occasionally, infection may be introduced by direct trauma to large veins or dural sinuses. A variety of organisms, including all the ones that ordinarily inhabit the paranasal sinuses and skin of the nose and face, may give rise to intracranial thrombophlebitis. Streptococci and staphylococci are the ones most often incriminated. With the exception of fever and poorer outcome, the syndromes associated with septic phlebitis discussed below are similar to those produced by noninfectious thrombosis of the veins, as discussed in Chap. 33, on cerebrovascular diseases. Some of the subtle differences between syndromes involving


Neurology_Adams

Neurology_Adams. below are similar to those produced by noninfectious thrombosis of the veins, as discussed in Chap. 33, on cerebrovascular diseases. Some of the subtle differences between syndromes involving each of the major venous sinuses are detailed in the following text.


Neurology_Adams

Neurology_Adams. In lateral (transverse) sinus thrombophlebitis, which usually follows chronic infection of the middle ear, mastoid, or petrous bone, earache and mastoid tenderness are succeeded, after a period of a few days to weeks by generalized headache and in some instances, papilledema. If the thrombophlebitis remains confined to the transverse sinus, there are no other neurologic signs. Spread to the jugular bulb may give rise to the syndrome of the jugular foramen (see Table 44-1) and involvement of the torcula, leading to increased intracranial pressure. One lateral sinus, usually the right, is normally larger than the other, which may account for greatly elevated pressure when it is occluded. However, contiguous involvement of the superior sagittal sinus and cortical veins emanating from it causes seizures and focal cerebral signs (see in the following text).


Neurology_Adams

Neurology_Adams. Fever, as in all forms of septic intracranial thrombophlebitis tends to be present but intermittent, and other signs of the septic state may be prominent. The CSF has increased pressure but the formula is usually normal but may show a small number of cells and a modest elevation of protein content. The term “otitic hydrocephalus” was introduced for this condition by Sir Charles Symonds, giving the erroneous impression that hydrocephalus was the cause of raised intracranial pressure. It is mentioned here because his clinical description, as for many other conditions, remains an outstanding source.


Neurology_Adams

Neurology_Adams. Imaging by MR and CT are the main means of confirming the diagnosis of venous sinus thrombosis. MRI or CT are also able to detect the local source of infection in the bone or soft tissue and other secondary changes such as venous infarction, cerebral edema, abscess, and hydrocephalus. The distinction between septic and sterile venous sinus thrombosis is difficult to make unless there is adjacent infection. Certain characteristics such as intense contrast enhancement are suggestive of infection. Prolonged administration of high doses of antibiotics is the mainstay of treatment. Anticoagulation, shown to be beneficial in small series of aseptic venous occlusion, is of uncertain value, but it is usually administered as well.


Neurology_Adams

Neurology_Adams. This condition is usually secondary to infections of the ethmoid, sphenoid, or maxillary sinuses or the skin around the eyes and nose, sometimes originating in a seemingly innocuous lesion. In addition to headache, high fluctuating fever, and signs of systemic toxicity, there are characteristic local effects. Obstruction of the ophthalmic veins leads to chemosis, proptosis, and edema of the ipsilateral eyelids, forehead, and nose. The retinal veins become engorged, which may be followed by retinal hemorrhages and papilledema. More often, however, vision in the affected eye is lost by a retrobulbar optic neuropathy as noted below, without visible alterations in the fundus. Involvement of the third, fourth, sixth, and ophthalmic and maxillary divisions of the fifth cranial nerves, which lie in the lateral wall of the cavernous sinus (see Chap. 33), leads to ptosis, varying degrees of ocular palsy, pain around the eye, and sensory loss over the maxilla and forehead. Within a few days,


Neurology_Adams

Neurology_Adams. in the lateral wall of the cavernous sinus (see Chap. 33), leads to ptosis, varying degrees of ocular palsy, pain around the eye, and sensory loss over the maxilla and forehead. Within a few days, spread through the circular sinus to the opposite cavernous sinus results in bilateral symptoms. The posterior part of the cavernous sinus may become infected via the superior and inferior petrosal veins without the occurrence of orbital edema or ophthalmoplegia but usually with abducens and facial paralysis. The CSF is usually normal unless there is an associated meningitis or subdural empyema.


Neurology_Adams

Neurology_Adams. The only effective therapy in the fulminant variety, associated with thrombosis of the anterior portion of the sinus, is the administration of high doses of antibiotics aimed at coagulase-positive staphylococci, and probably gram-negative pathogens and at anaerobes if there has been sinusitis. As with septic lateral sinus phlebitis, anticoagulants have been used, but their value has not been proved. In cases under our observation, the cranial-nerve palsies have resolved to a large extent, but visual loss, if it occurs, has tended to remain, with findings suggestive of infarction of the retroorbital part of the optic nerve. Cavernous sinus thrombosis must be differentiated from mucormycosis infection of the sinuses and from orbital cellulitis, which usually occur in patients with uncontrolled diabetes, and from other fungus infections (notably Aspergillus), Tolosa-Hunt syndrome (see Chap. 44), cavernous-carotid fistula, Wegener granulomatosis, and sphenoid wing meningioma.


Neurology_Adams

Neurology_Adams. Septic Thrombosis of the Superior Sagittal Sinus


Neurology_Adams

Neurology_Adams. This entity is now less common than at a time when septic transverse sinus thrombosis from uncontrolled ear and sinus infections were frequent. The disorder manifests as fever, headache, unilateral convulsions (most frequent or prominent in the leg), and weakness, first on one side of the body, then on the other, as a result of extension of the thrombophlebitis into the cortical veins that drain into the sinus. Papilledema and increased intracranial pressure often accompany these signs. Severe generalized and vertex headache is a typical but not invariable complaint. Because of the localization of function in the cortex that is drained by the sinus, the weakness may take the form of a crural (lower limb) monoplegia or, less often, of paraplegia. Sensory loss may occur in the same distribution. Homonymous hemianopia or quadrantanopia, aphasia, paralysis of conjugate gaze, and urinary incontinence (in bilateral cases) have also been observed.


Neurology_Adams

Neurology_Adams. As in the case of aseptic thrombosis, loss of the flow void in the superior sagittal sinus in the MRI demonstrates the clot. A similar change can be seen on axial images of the contrast-enhanced CT scan by altering the viewing windows so as to show the clot within the posterior portion of the sagittal sinus. The CT scan performed early in the illness without contrast infusion usually shows the high-density clot within cortical veins as well, but only if carefully studied by altering the viewing window.


Neurology_Adams

Neurology_Adams. Treatment consists of high doses of antibiotics and temporization until the thrombus recanalizes. Although not of proven benefit (as it is in bland cerebral vein thrombosis), we have used heparin in these circumstances unless there are very large biparietal hemorrhagic infarctions. Because of the highly epileptogenic nature of the attendant venous infarction, we have also administered antiepileptic drugs prophylactically, but there is no clinical study to guide the clinician in this regard. Recovery from paralysis may be complete, or the patient may be left with seizures and varying degrees of spasticity in the lower limbs.


Neurology_Adams

Neurology_Adams. All types of thrombophlebitis, especially those related to infections of the ear and paranasal sinuses, may be simultaneously associated with other forms of intracranial purulent infection, namely bacterial meningitis, subdural empyema, or brain abscess. Therapy in these complicated forms of infection must be individualized. As a rule, the best plan is to institute antibiotic treatment of the intracranial disease and to decide, after it has been brought under control, whether surgery on the offending ear or sinus is necessary. To operate on the primary focus before medical treatment has been discouraged. In cases complicated by bacterial meningitis, treatment of the latter usually takes precedence over the surgical treatment of complications, such as brain abscess and subdural empyema.


Neurology_Adams

Neurology_Adams. Aseptic thrombosis of intracranial venous sinuses and cerebral veins is discussed in Chap. 33 on cerebrovascular disease; aspects related to intracranial pressure are discussed in Chap. 29, on CSF circulation.


Neurology_Adams

Neurology_Adams. With the exception of a small proportion of cases (approximately 10 percent) in which infection is introduced from the outside (compound fractures of the skull, intracranial operation, bullet wounds), brain abscess is secondary to bacteremia and a bacterial focus elsewhere in the body. Purulent pulmonary infections (abscess, bronchiectasis) and bacterial endocarditis account for the largest number of brain abscesses in the modern era. A decreasing proportion of brain abscesses in the current era is related to disease of the paranasal sinuses, middle ear, and mastoid cells. Of abscesses originating in the ear, about one-third lie in the anterolateral part of the cerebellar hemisphere; the remainder occurs in the middle and inferior parts of the temporal lobe. The sinuses most frequently implicated are the frontal and sphenoid, and the abscesses derived from them are in the frontal and temporal lobes, respectively.


Neurology_Adams

Neurology_Adams. Otogenic and rhinogenic abscesses reach the nervous system by direct extension, in which the bone of the middle ear or nasal sinuses becomes the seat of an osteomyelitis, with penetration of the dura and leptomeninges, infection may spread along the major intracranial veins. Thrombophlebitis of the pial veins and dural sinuses, by infarcting brain tissue, renders the latter more vulnerable to invasion by infectious material. The close anatomic relationship of the lateral (transverse) sinus to the cerebellum explains the frequency with which this portion of the brain is infected via the venous route. The spread along venous channels also explains how an abscess may sometimes form at a considerable distance from the primary focus in the middle ear or paranasal sinuses.


Neurology_Adams

Neurology_Adams. As mentioned, the majority of brain abscesses is metastatic, that is, hematogenous. These are usually traceable to bacterial endocarditis or to a primary septic focus in the lungs or pleura, as indicated earlier. Occasional cases are associated with infected pelvic organs, skin, tonsils, abscessed teeth, and osteomyelitis of noncranial bones. Individuals with a congenital cardiac defect with right-to-left shunt or pulmonary arteriovenous malformation (including Osler-Weber-Rendu malformations) that permits infected emboli to bypass the pulmonary circulation and reach the brain, are particularly vulnerable to brain abscess. In approximately 20 percent of cases, the source cannot be ascertained.


Neurology_Adams

Neurology_Adams. Metastatic abscesses from hematogenous spread are usually situated in the distal territory of the middle cerebral arteries (Fig. 31-2), and they sometimes may be multiple, in contrast to otogenic and rhinogenic abscesses. Also, almost all deep cerebral abscesses have a systemic source. It should also be noted that the clinical and radiologic features of a solitary abscess mimic those of a brain tumor. Small and miliary abscesses may progress to large ones.


Neurology_Adams

Neurology_Adams. A distinction had in the past been made between the neuropathologic effects of endocarditis caused by different organisms. What had been divided into acute bacterial endocarditis (ABE) and subacute bacterial endocarditis (SBE) are now instead characterized by the virulence of the causative organism. For example, endocarditis from the implantation in the brain of streptococci of low virulence (alpha and gamma streptococci) or similar organisms on heart valves previously damaged by rheumatic fever seldom gives rise to a brain abscess. In contrast, organisms such as S. aureus and gram-negative bacteria have a propensity to cause abscesses. The cerebral lesions in all forms of endocarditis are a result of embolic occlusion of vessels by fragments of vegetations and bacteria, which cause infarction of brain tissue and a restricted inflammatory response around the involved blood vessels and the overlying meninges (cerebritis). It is the subsequent evolution of the process that is dependent


Neurology_Adams

Neurology_Adams. of brain tissue and a restricted inflammatory response around the involved blood vessels and the overlying meninges (cerebritis). It is the subsequent evolution of the process that is dependent on the inherent tendency of the organism to be invasive. Therefore, the former distinction between acute and subacute bacterial endocarditis has become less useful. The cerebral symptoms of a stroke may be the first clinical manifestations of the disease. Over time, sometimes within days but usually longer, the inflamed artery may form an aneurysm (mycotic aneurysm) that later gives rise to parenchymal or subarachnoid hemorrhage (see Chap. 33). Bacterial meningitis rarely develops with abscess and most often the CSF is sterile but there are exceptions.


Neurology_Adams

Neurology_Adams. Rapidly evolving cerebral signs in patients with acute endocarditis are usually caused by septic embolic infarction or hemorrhage and not by an abscess. Anticoagulation has not been shown to reduce the incidence of embolization from endocarditis; the risk of inducing hemorrhage is uncertain but the rate of hemorrhage may have been overestimated in the past. In patients with endocarditis on a prosthetic heart valve, anticoagulation may be continued, but this treatment is suspended if there is a hemorrhagic brain infarction. Existing anticoagulation need not be reversed unless a cerebral hemorrhage evolves.


Neurology_Adams

Neurology_Adams. It has been estimated that 5 percent of cases of congenital heart disease are complicated by brain abscess (Cohen; Newton). Viewed from another perspective, in children, more than 60 percent of cerebral abscesses are associated with congenital heart disease. The abscess is usually solitary; this fact, coupled with the potentially correctable underlying cardiac abnormality, makes the recognition of brain abscess in congenital heart disease a matter of considerable practical importance. For some unknown reason, brain abscess associated with congenital heart disease is rarely seen before the third year of life. The tetralogy of Fallot is the most common anomaly implicated, but the abscesses may occur with any right-to-left intracardiac or pulmonary shunt that allows venous blood returning to the heart to enter the systemic circulation without first passing through the lungs. Pulmonary emboli, by increasing the back pressure in the right heart, may open (make patent) an occult foramen


Neurology_Adams

Neurology_Adams. to the heart to enter the systemic circulation without first passing through the lungs. Pulmonary emboli, by increasing the back pressure in the right heart, may open (make patent) an occult foramen ovale. A pulmonary arteriovenous malformation has a similar effect. Nearly half of the reported cases of pulmonary arteriovenous fistulas have hereditary hemorrhage (Osler-Weber-Rendu) telangiectasia. When the filtering effect of the lungs is thus circumvented, pyogenic bacteria or infected emboli from a variety of sources may gain access to the brain, where, aided by the effects of venous stasis and perhaps of infarction, an abscess is established.


Neurology_Adams

Neurology_Adams. The most common organisms causing bacterial cerebral abscess are virulent streptococci, many of which are anaerobic or microaerophilic. These organisms are often found in combination with other anaerobes (polymicrobial), notably Bacteroides, Fusobacterium, and Prevotella and less often, Propionibacterium (diphtheroids), and may be combined with Hemophilus species, Enterobacteriaceae, such as E. coli and Proteus. Staphylococci also commonly cause brain abscess, but pneumococci, meningococci, and H. influenzae rarely do. In addition, the gram-positive higher bacteria Actinomyces and Nocardia and certain fungi discussed later, notably Candida, Mucor, and Aspergillus, are isolated in some cases.


Neurology_Adams

Neurology_Adams. The type of organism tends to vary with the source of the abscess; staphylococcal abscesses are usually a consequence of accidental or surgical trauma, sometimes of endocarditis, especially in intravenous drug abusers; abscesses originating from otitic infections usually contain oropharyngeal flora including anaerobes and enteric organisms; and anaerobic streptococci are commonly metastatic from the lung and paranasal sinuses. Predisposing to nocardial brain abscess is pulmonary nocardial infection, often in immunosuppressed patients; this diagnosis is doubtful without a pneumonic infiltrate. In immunosuppressed patients, brain abscess is usually from a nonbacterial organism; fungi and parasites (toxoplasmosis) prevail although Mycobacteria are common and Listeria and melioidosis occurs but constitute special cases of an encephalitic disorder with small abscesses. Thus knowledge of the antecedent history enables one to institute appropriate therapy while awaiting the results of


Neurology_Adams

Neurology_Adams. but constitute special cases of an encephalitic disorder with small abscesses. Thus knowledge of the antecedent history enables one to institute appropriate therapy while awaiting the results of bacterial and fungal cultures.