Pathology of Bacterial Infections
No Results
No Results
processing….
The central nervous system (CNS) is extremely resistant to infection by bacterial pathogens due to a combination of protective effects of its bony structures (skull and vertebral column), the meninges, and the blood-brain barrier. However, once infection has initiated, the CNS is generally more susceptible to infection than most other tissues. Host defense mechanisms that are normally seen in other areas of the body are inadequate in the CNS for preventing bacterial replication and progression of the disease process. The deficiency of immunologic components in the CNS is crucial, as specific antibody and complement components are essential for opsonization of encapsulated bacterial pathogens and their efficient phagocytosis and elimination.
Preexisting and/or predisposing conditions are a strong component of the severity of bacterial CNS infection. These include respiratory and systemic infections, head trauma (see the following image), previous neurosurgical procedures, malignancy, alcoholism, and other immunodeficiency states. Despite advances in diagnostic techniques and therapeutic interventions, the combination of the bacterial virulence and the patient’s immunostatus contributes to high morbidity and mortality rates associated with bacterial infections of the CNS.
Bacterial infections can involve different compartments of the CNS, leading to different clinical and pathologic manifestations. In addition, some microorganisms are more prone to involve particular regions of the nervous system. Three major infectious syndromes are defined according to the site and nature of the inflammatory reaction: meningitis, abscess, and encephalitis.
Meningitis is the inflammation of the leptomeninges and the most common central nervous system (CNS) bacterial infection. This condition may become evident over hours or days (acute) or over a longer period (subacute or chronic). Acute bacterial meningitis, or purulent meningitis, is a severe illness characterized by purulent cerebrospinal fluid (CSF); the condition is rapidly progressive and, without treatment, it is fatal. The presentation may vary depending upon the age of the patient, the presence of underlying conditions, and on the microorganism causing meningitis.
Go to Meningitis and Imaging Bacterial Meningitis for complete information on these topics.
Bacterial meningitis remains a very important disease worldwide. In the United States, the epidemiology of bacterial meningitis has changed dramatically in the last 2 decades, primarily due to the introduction of vaccination against common meningeal pathogens. In the late 1970s, the overall annual rate for bacterial meningitis was reported as 3.0 cases per 100 000 population. [1] Since then, the overall incidence of bacterial meningitis has decreased, particularly during childhood, in that bacterial meningitis has become a disease of adults. [2]
Bacterial meningitis is still a major problem in many areas of the world, both in developing and underdeveloped countries. Data collected by the World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC) through the Pediatric Bacterial Meningitis (PBM) Surveillance Network in Sub-Saharan Africa demonstrated that between 2002 and 2008, the incidence of bacterial meningitis among children younger than 5 years was still very high, with about 75,000 reported cases. [3] Of these, 47% of cases were due to Streptococcus pneumoniae, 34% due to Haemophilus influenzae, and 19% due to Neisseria meningitidis. [3]
Bacteria invade the CNS following direct inoculation of the brain parenchyma or by spread from a focus of infection outside the CNS. Hematogenous spread is the most common route, and the upper respiratory tract is the most common source of entry of microorganisms.
Meningitis is initiated when the causative bacteria colonize the mucosa of the nasopharynx and invade the bloodstream through the epithelial cells. In the bloodstream, the bacteria has to replicate and survive the host’s defenses and gain access to the CNS directly through the microvasculature or the choroid plexus; cross the blood-brain barrier; and survive and multiply in the CSF. [4] (For a review, see Kim KS. Pathogenesis of bacterial meningitis: from bacteraemia to neuronal injury. Nat Rev Neurosci. May 2003;4(5):376-85. [4] )
The mechanisms by which most bacteria gain access to the CSF are not completely understood. Once the bacteria reside in the CSF, bacterial multiplication is facilitated, as the CSF lacks several of host defenses, including low levels of immunoglobulins and complement. The host’s immune status as well as bacterial virulence will definitively play a role in the establishment of the infection. [4]
Meningitis may also be established after direct spread of pathogens from adjacent structures to the brain, including the paranasal sinuses and middle ear and mastoid sinuses, as well as through a retrograde route via emissary veins from the face or scalp. Inoculation of pathogens may also result from direct implantation by trauma in penetrating injuries and compound skull fractures, following surgical procedures and invasive diagnostic and therapeutic interventions, and due to congenital defects such as myelomeningoceles.
The great majority of bacterial meningitis is caused by 3 main agents: N meningitides, S pneumoniae, and H influenzae. However, due to the introduction of conjugate vaccines to H influenzae type b (Hib) and S pneumoniae in many countries, there has been a shift in the causes of meningitis. Most of the recent surveillance studies in the US showed that the most common etiologic agents of bacterial meningitis were S pneumoniae (61%), N meningitides (16%), group B streptococcus (14%), H influenzae (7%), and Listeria monocytogenes (2%). [5] In fact, N meningitidis has become a leading cause of bacterial meningitis in children in the US. [6] The latest estimated average annual incidence of meningococcal disease is 0.53 cases per 100,000 population, with infants younger than 1 year having the highest incidence at 5.38 cases per 100,000 population. [7]
Specific agents of bacterial meningitis also vary according to age group and host immunostatus. In the neonatal period (newborn to 29 d), important pathogens are aerobic gram-negative bacilli, including Escherichia coli, group B-hemolytic streptococci, L monocytogenes, and Klebsiella species, among others. During childhood and adolescence, N meningitides and S pneumoniae are the most common agents in the community population.
In adults, the most important agent is S pneumoniae; especially at risk are alcoholics and people with chronic otitis, sinusitis, mastoiditis, CSF leaks, pneumococcal pneumonia, sickle cell disease, or asplenia. In the elderly population, L monocytogenes and gram-negative bacilli (most often E coli, Klebsiella spp, or Enterobacter spp) are the most common pathogens. Meningitis secondary to head trauma and following neurosurgical procedures may have different pathogens including Staphylococcus aureus, S epidermitis (particularly in patients with CSF shunts), and aerobic gram-negative bacilli (Pseudomonas aeruginosa).
The classic triad of meningitis symptoms includes fever, headache, and nuchal rigidity. Passive flexion of the neck is restricted and painful. In severe cases, attempts at neck flexion may induce flexion of the hip or knee (Brudzinski sign), and there may be resistance to passive extension of the knee while the hip is flexed (Kernig sign). Neck stiffness and Brudzinski/Kernig signs are termed meningeal signs or meningismus; they occur because tension on nerve roots passing through inflamed meninges causes irritation.
Signs of cerebral dysfunction including confusion, delirium, and lethargy to coma may also occur, depending upon the severity of the disease. Clinical symptoms may vary according to the age of the patient. For example, neonates may rarely present with signs of meningismus and most likely have clinical features of septicemia. In elderly individuals, acute meningitis may be of more insidious onset and present as lethargy and confusion rather than signs of a more acute febrile illness. Clinical symptoms also vary according to the bacterial agent. Meningococcus meningitis, for example, tend to be severe, and even when the disease is diagnosed early and adequate therapy instituted, 5-10% of patients die, typically within 24-48 hours of onset of symptoms. [6]
Neuroimaging findings of acute meningitis vary according to the stage of the disease. Imaging findings can be normal in the early phases. In the course of more established disease, diffuse meningeal enhancement is seen on magnetic resonance imaging (MRI) with occasional involvement of the perivascular Virchow-Robin spaces. Cerebral edema accompanied by communicating hydrocephalus is also seen. Hyperintensity of the cortical ribbon, mostly representing incipient infarction secondary to focal vasculitis, may be seen on T2-weighted or fluid attenuation inversion recovery (FLAIR) sequences. [8]
In the acute phase of the disease, purulent exudates are seen grossly within the subarachnoid space. Marked congestion of the leptomeningeal vessels and cerebral edema may be prominent. See the following images.
Microscopically, the meninges display abundant cellular infiltrates composed of neutrophils accompanied by fibrin exudate. Intracellular and extracellular bacteria may be seen. Once the infectious process is brought under control due to treatment, subacute or chronic phases may start with change of the cellular inflammatory infiltrates to mononuclear cells, including lymphocytes, plasma cells, and macrophages. Variable proliferation of fibroblasts may occur with a resulting leptomeningeal fibrosis. See the images below.
Inflammatory vasculitis may be seen in this phase of the disease with consequent microthrombosis and cortical infarcts. Vasculopathy and cortical infarctions seems to be most commonly associated with S pneumoniae meningitis. [9] Purulent ventriculitis may occur when the infection extends into the ventricles with formation of purulent collections that may obstruct the foramina of the ventricular system with blockage of CSF flow and obstructive hydrocephalus. Leptomeningeal fibrosis with consequent impaired reabsorption of the CSF flow may also produce communicating hydrocephalus. Small subdural collections of fluid—hygromas—may be seen primarily in small children. The infectious process may also extend to the cranial nerves, in particular the auditory nerves with consequent hearing loss, which is one of the most common sequelae of meningitis in children (see the following image). [10]
The overall mortality of community-acquired bacterial meningitis in adults has been estimated as 25% and is increased in the elderly population. [11] Mortality rates in nosocomial meningitis, however, are higher; some mortality rates have been reported to be as high as 35%. [12] Mortality rates also vary according to the bacterial agent. For example, mortality rates for S pneumoniae meningitis, considered the most frequently observed community-acquired bacterial meningitis in adults in the US, ranges from 19% to 26%. [2] In patients with an underlying disorder, the mortality rate for pneumococcus meningitis may reach 30%. The mortality ratio for meningococcal disease is 10-14%. [6]
Unfavorable prognostic factors include extremes of age, delay in diagnosis and treatment, complicating underlying illness, a low Glasgow Coma Scale score, cranial nerve palsies, and other neurologic deficits at diagnosis. Bacterial meningitis may also result in brain damage or learning disability in 10-20% of survivors. Mild to severe hearing loss is noted in as many as 20-30% of affected children with H influenzae disease. Meningococcal disease also causes substantial morbidity, with about 11-19% of survivors having significant sequelae such as neurologic dysfunction and hearing loss. [10]
A brain abscess is a focal infectious mass lesion within the brain parenchyma that has central necrosis, inflammatory neutrophilic infiltration, and capsule formation. Brain abscesses are the second most common infectious process of the central nervous system (CNS) after bacterial meningitis.
Brain abscess is a relatively rare disease in the general population, with a reported incidence of 0.3-1.3 per 100,000 hospital admissions. [13] A decrease in the incidence of brain abscesses has been attributed to improved prophylactic antibiotic treatment of congenital heart disease in children and effective treatment of otitis media and sinusitis. [14] However, the incidence of brain abscess is higher in immunocompromised patients, often caused by bacterial, fungal, or protozoan organisms. In the US, about 1500-2500 cases are reported per year. [15] In general, a peak incidence occurs in the second and third decades of life, with a median age of 30-40 years; approximately 25% of all brain abscesses occur in children (peak incidence, age 4-7 y). [13, 16] In most clinical series, there is a male preponderance. [17]
In general, brain abscesses are a secondary infection from extracerebral primary sources that involve the CNS by either hematogenous dissemination or contiguous spread from adjacent structures. Abscesses secondary to hematogenous spread from a distant focus accounts for about 20-25% of cases. [13] In adults, the most common primary sources are pulmonary infections such as bronchiectasis and lung abscesses, followed by dental infections as the second most common cause. Other sources are pelvic and abdominal infections, septicemia, and bacterial endocarditis. In children, the most common primary sources are congenital cardiac diseases with a right-to-left shunt due to paradoxical emboli. [18]
Abscesses secondary to contiguous spread of a local infection into the brain may account for about 20% of cases. [17] In children, sinusitis, acute and chronic otitis, and mastoiditis are important sources. Although a significant decrease in the incidence of these secondary abscesses has been seen due to effective treatment of local infections, brain abscesses are still seen as sequelae in 6-8% of cases of sinusitis and in 6-10% of cases of otitis media and mastoiditis. [18] In adults, sinusitis and osteomyelitis of adjacent skull bony structures are common sources.
Brain abscesses may also occur due to direct implantation of microorganisms in penetrating head trauma and postsurgical procedures. The incidence of such abscesses in these settings ranges from about 2% to 37%. [17, 19] In about 25% of brain abscesses, a source of infection is unknown; in these so-called cryptogenic abscesses, full work-up for cardiac shunts is mandatory.
The majority of brain abscesses are solitary lesions, occurring in locations close to the site of the primary source of infection. For example, abscesses related to direct spread from frontal sinuses or odontogenic foci are mostly located in the frontal lobe; abscesses secondary to ear infections are usually temporal or cerebellar. Multiple abscesses are mostly due to hematogenous spread and, although may be located in any part of the brain, are more commonly located in the distribution of the middle cerebral artery.
Bacterial agents causing abscess are various and vary according to the predisposing factors and sources of infection. Abscesses may be monomicrobial or polymicrobial, again depending on the origin of the infectious source. Table 1, below, provides some of the most commonly seen agents according to the site of infection.
Table 1. Bacterial Abscess: Source and Bacterial Agent (Open Table in a new window)
Site of Primary Infection
Bacterial Agent(s)
Hematogenous dissemination
Cyanotic Congenital Heart Disease
Haemophilus spp, S aureus, Streptococcus spp
Endocarditis and Bacteremia
S aureus, Streptococcus spp
Pulmonary Infections
Streptococcus spp, anaerobic gram-negative, Nocardia, Fusobacterium, Actinomyces
Spread of contiguous infection
Sinuses and Odontogenic Infections
Streptococcus spp, S aureus, Enterobacteriaceae, Bacteroides, Haemophilus spp
Ear and Mastoid Infections
Streptococcus spp, Pseudomonas, Enterobacteriaceae, Bacteroides spp
Penetrating Head Injury
Staphylococci, Enterobacteriaceae, Bacteroides spp, Clostridium
Post Neurosurgical Procedures
S aureus, Pseudomonas
Source: Compiled from various sources. [16, 18, 20, 21]
Clinical symptoms of patients with brain abscesses vary according to the location of the abscess and the virulence of the microorganisms. The most common symptoms include fever, headache, and changes in mental status, and their duration before diagnosis may range from several hours to months. A short duration of symptoms is mostly associated with poor outcome.
Depending upon the location of the abscess, focal neurologic deficits and other signs of space-occupying mass may also be present, including signs and symptoms of raised intracranial pressure. Meningismus and other signs of meningitis may also be present, because a large percentage of abscesses are accompanied by concomitant meningitis. Brain abscesses may also rupture into the ventricles, causing ventriculitis.
Neuroimaging diagnosis of brain abscess is performed by contrast-enhanced computed tomography (CT) scanning or magnetic resonance imaging (MRI) studies. Both MRI with gadolinium and contrast CT scans reveal characteristic ring-enhancing lesions with surrounding edema in mature encapsulated abscesses. However, MRI with gadolinium contrast is more sensitive and specific than CT scanning for the diagnosis of early phases of cerebritis. [22] Correlation of histologic and neuroradiologic findings has been described in animal models (see below). [23]
Gadolinium-based contrast agents (gadopentetate dimeglumine [Magnevist], gadobenate dimeglumine [MultiHance], gadodiamide [Omniscan], gadoversetamide [OptiMARK], gadoteridol [ProHance]) have been linked to the development of nephrogenic systemic fibrosis (NSF) or nephrogenic fibrosing dermopathy (NFD). For more information, see Nephrogenic Systemic Fibrosis. The disease has occurred in patients with moderate to end-stage renal disease after being given a gadolinium-based contrast agent to enhance MRI or MRA scans.
NSF/NFD is a debilitating and sometimes fatal disease. Characteristics include red or dark patches on the skin; burning, itching, swelling, hardening, and tightening of the skin; yellow spots on the whites of the eyes; joint stiffness with trouble moving or straightening the arms, hands, legs, or feet; pain deep in the hip bones or ribs; and muscle weakness.
Brain abscess initiates from direct inoculation of microorganisms into the cerebral parenchyma with focal microvascular injury. The abscesses mostly occur at the gray-white matter junction or other areas of poor blood flow/circulation, such as the deeper white matter. See the following image.
Histologic findings have been well correlated with brain CT scans in an experimental model in dogs, wherein 4 stages of formation and maturation of bacterial abscess were described. [23] The initial phase consists of a focal area of necrosis accompanied by infiltration of neutrophils, fibrinous exudate, and vascular congestion. This early cerebritis normally occurs around 1-3 days into the initial infection. The surrounding brain shows large amounts of edema and congestion. Neuroimaging shows a patchy or nonenhancing hypodensity or hypointensity on CT scan or MRI.
In the following days (days 4-9), a necrotic, purulent center develops with associated macrophage and lymphocytic infiltration. Edema and enhancement on CT scan and MRI are seen at this stage. Early capsule formation (days 10-13) with neovascular formation and infiltration of macrophages and mononuclear inflammatory cells is followed by formation of a well-vascularized, fibrocollagenous wall with circumscription of the lesion from the adjacent parenchyma after about 2 weeks of the initial process. Clear ring enhancement on neuroimaging is seen in these 2 later stages. The surrounding brain shows prominent reactive gliosis. The capsule formed by the inflammatory response tends to be thicker on the cortical surface than on the ventricular side, thus facilitating abscess rupture into the ventricular system. [24]
Spread of the abscess may develop with formation of satellite or metastatic abscesses and rupture into the subarachnoid space with the development of meningitis. Rupture into the ventricles is a serious complication of abscesses that leads to a high mortality rate. [24]
Neurologic deficits in patients who survive a brain abscess range from 20% to 70%. [16] Seizures are the most common sequelae observed in these patients. [14] In one study of 100 cases of brain abscesses, sequelae were present in 36.2% of cases, including focal neurologic deficits (24.1%), epilepsy (5.2%), hydrocephalus (5.2%), and mental disorder (1.7%). [25]
Prognostic factors that influence outcome of bacterial brain abscess appear determined by the rate of progression of the disease before hospitalization and the patient’s comatose state at presentation. [25] Underlying medical conditions also play an important role in the outcome, in particular diabetes, liver cirrhosis, intravenous drug abuse, immunosuppression secondary to malignancies, and/or chemotherapy, which are associated with higher rates of mortality. [15, 17, 26] In recent years, overall mortality of brain abscesses has ranged from 8% to 25%, [16, 17, 25] a significant improvement from past decades. [14]
Subdural empyema is a localized purulent infection that is confined to the subdural space. Although these lesions are less common than brain abscesses, they are similar in that they are serious infections of the central nervous system (CNS).
The great majority of these cases are secondary to direct spread of a contiguous focus of infection of the sinuses, middle ear, or mastoid cavity by direct involvement or secondary to venous drainage from these structures. Hematogenous spread from a distant focus, in particular the lungs, is less common. [13] Subdural empyemas may also develop after open head trauma and neurosurgical procedures.
The etiologic agents of subdural empyemas are similar to those of abscesses and meningitis that were discussed earlier (see Acute Bacterial Meningitis and Bacterial Brain Abscess). Streptococcus species are the most common pathogens isolated in these cases. [13]
Clinical features of subdural empyemas include signs and symptoms of meningitis associated with increased intracranial pressure, including headaches and altered mental status.
Subdural empyemas are associated with a 10-13% mortality rate. [19]
Actinomycetes are a large group of aerobic, Gram-positive bacteria that appear at microscopic analysis as branching, filamentous microorganisms. The most important cause of human infections is a subgroup known as “aerobic nocardiform actinomycetes” that includes the genera Mycobacteria, Corynebacteria, Nocardia, Rhodococcus, Gordona, and Tsukamurella. [27] These organisms are characterized by a thick cell wall containing, among other elements, mycolic acids that are responsible for their acid-fast properties on histochemical stains.
Mycobacterial infections, Whipple disease, actinomycosis, and nocardiosis will be discussed, respectively, in the following sections.
In this section, tuberculosis, tuberculous meningitis, tuberculomas, tuberculous abscesses, and atypical mycobacteriosis will be discussed.
CNS tuberculosis (TB) continues to be a serious public health problem due to the global increase in incidence of TB in both immunocompetent and immunocompromised individuals. Factors that have contributed to this increase are acquired immunodeficiency syndrome (AIDS) and multidrug-resistant TB. Neurotuberculosis is the most dangerous form of systemic TB, with high morbidity and mortality rates. In the central nervous system (CNS), TB may present as tuberculous meningitis, abscesses and tuberculomas, spinal meningitis, or extradural abscesses. The latter may be secondary to tuberculous vertebral osteomyelitis (Pott disease).
In 2008, the World Health Organization (WHO) reported an estimated 9.4 million (8.9-9.9 million) cases of TB worldwide, of which an estimated 13-16% (1.2-1.6 million) were patients with human immunodeficiency virus (HIV) infection. [28] In the US in the same year, the incidence of TB was reported as 4.2 cases per 100,000 population [29] ; the total number of cases reported was 12,904, with 2,638 extrapulmonary cases—of which 125 (4.6%) involved the CNS (meningeal). [29]
Mycobacterium tuberculosis is the most common agent in CNS TB. The M tuberculosis complex comprises 7 species in the genus Mycobacterium with a high degree of sequence identity. (For details, see Sadek M, Yue FY, Lee EY, et al. Clinical and immunologic features of an atypical intracranial mycobacterium avium complex (MAC) infection compared with those of pulmonary MAC infections. Clin Vaccine Immunol. Oct 2008;15(10):1580-9. [30] ) Less commonly, M bovis can cause disease in humans through animal contact and consumption of unpasteurized milk.
Go to Tuberculosis for complete information on this topic.
Tuberculous meningitis is the most common presentation of neurotuberculosis. Involvement of the leptomeninges may occur by 2 main pathogenic mechanisms. The most common is due to rupture of a quiescent subarachnoid tubercle that may be reactivated because of general immunosuppression of the host. The subarachnoidal tuberculous lesion arises at initial phases of disease during early bacteremia, often due to an affected lymph node eroding and discharging into a blood vessel. These small lesions may also rupture during primary infection, particularly in children and adolescents without previous contact, mostly at the same time of active primary lung disease or miliary TB. The second pathogenic mechanism of infection is by contiguous spread of an extraneural focus of infection, such as the inner ear, mastoid, or vertebrae.
Tuberculous meningitis often presents clinically in adults as a prolonged history of intermittent headache, malaise, and low-grade fever. [31] Signs of meningism such as neck stiffness and increased intracranial pressure, including photophobia, vomiting, and confusion, may be seen. In children, the clinical presentation is more severe with severe meningitis, seizures, and altered mental status progressing to coma. In addition, due to the preferential involvement of meninges of the base of the brain, symptoms related to cranial nerve involvement may be seen in a large proportion of patients (up to 70%). [32] In a majority of the patients, concomitant extrameningeal TB is present. [31] Cerebrospinal fluid (CSF) biochemical and cytologic examination with identification of M tuberculosis is crucial for the diagnosis. [31, 33]
Common neuroradiologic findings in tuberculous meningitis include basal meningeal enhancement, hydrocephalus, and infarctions in the supratentorial brain parenchyma and brain stem. On computed tomography (CT) scans, obliteration of the basal cisterns is commonly observed; after contrast administration, diffuse meningeal enhancement of the basal cisterns and occasionally over the cerebral convexities, the sylvian fissures, and the tentorium is seen. [32]
Macroscopically, the meningeal infection is characterized by a thick, gelatinous-appearing exudate most commonly involving the base of the brain, including the brain stem, the basal cisterns, and optic chiasm. Some opacity of the meninges over the convexity may also be present. The brain shows generalized edema and vascular congestion. Depending upon the stage of the disease, hydrocephalus and cortical infarcts due to infective arteritis may be seen.
Microscopically, the meningeal inflammatory infiltrate is composed of lymphocytes, monocytes, and epithelioid granulomas. Typical granulomas contain a central caseous necrosis surrounded by mononuclear lymphoid cells, epithelioid cells, and Langhans’ giant cells (see the image below). In patients with immunodepression such as those with AIDS, the formation of granulomas may be less evident. The presence of acid-fast bacilli is variable. Meningeal, parenchymal, and subependymal small tuberculous nodules are common during the course of meningitis.
The 2 major complications of tuberculous meningitis are cortical infarcts and hydrocephalus. The infarcts are secondary to marked vascular changes with the formation of endarteritis obliterans (see the images below). The majority of the infarcts are seen in the basal ganglia and internal capsule secondary to involvement of the basal perforating arteries. With the progression of the disease and treatment, the inflammatory exudate changes to a more fibroblastic reaction which may lead to meningeal fibrosis, obstruction of the CSF flow, and communicating hydrocephalus. Obstructive hydrocephalus may also develop secondary to focal obstruction of the aqueduct or ventricular foramen due to granulomatous ependymitis.
Tuberculous meningitis may also involve the spinal cord, wherein compression of the nerve roots by the thick exudate and subsequent fibrosis may occur.
The prognosis of this condition is influenced by age, duration of symptoms, and neurologic deficits. Tuberculous meningitis is almost always fatal if left untreated. [31] Patients presenting with more advanced disease at the onset of treatment have a much worse prognosis than do those in whom treatment is initiated in the early stage. Residual neurologic sequelae rates are also high. Mortality is greatest in the extreme of ages (< 5 y, 20%; >50 y, 60%). [31]
Go to Tuberculous Meningitis for complete information on this topic.
The most common form of parenchymal involvement by TB is the tuberculous granuloma or tuberculoma. The majority of tuberculomas develop from hematogenous spread and tend to be located at the gray-white matter interface. Tuberculomas may also develop from extension of tuberculous meningitis into the adjacent parenchyma via cortical veins or perivascular Virchow-Robin spaces around small penetrating arteries.
Tuberculomas may occur at any age and are more commonly seen in patients with miliary pulmonary TB. Clinical symptoms may be more subtle than those of tuberculous meningitis, but depending upon the location and size, intracranial tuberculomas may produce space-occupying symptoms including seizures and focal neurologic deficits. Intramedullary tuberculomas are relatively rare and may present with sensory and motor deficits. [34] When associated with tuberculous meningitis, tuberculomas may be present at the time of diagnosis or appear during the course of the disease. [35]
Tuberculomas may be solitary but are most frequently multiple lesions. They are commonly located in the supratentorial compartment, followed by the cerebellum. The brain stem and spinal cord are less involved. Other locations include the subdural or epidural spaces. [13, 32] Tuberculomas associated with meningitis are commonly seen in the base of the brain. [35] Intradural extramedullary tuberculoma of the spinal cord is a rare complication of TB. [36]
The neuroimaging findings of these lesions depend on whether the tuberculoma shows a caseating central necrosis or is a more solid lesion with fibrosis and/or calcification. (For a review, see Bernaerts A, Vanhoenacker FM, Parizel PM, et al. TB of the central nervous system: overview of neuroradiological findings. Eur Radiol. Aug 2003;13(8):1876-90. [32] ) In general, the lesions are well-circumscribed, oval or lobular, with variable degrees of enhancement. Early lesions are normally surrounded by vasogenic edema. Solid lesions with caseating necrosis may have a typical ring-enhancing appearance.
Grossly, tuberculomas are relatively circumscribed lesions with a necrotic center and surrounded by a gelatinouslike, firm capsule. The necrotic, caseating center of the granuloma may have a white-grayish appearance. Most tuberculomas are located at the gray-white matter interface. The surrounding parenchyma may show firmness due to reactive gliosis.
Microscopically, tuberculomas are caseating granulomas composed of a central zone of necrosis surrounded by a capsule of collagenous tissue, epithelioid cells, multinucleated giant cells, and mononuclear inflammatory cells. M tuberculosis forms are only rarely seen by acid-fast stains. The surrounding parenchyma may show variable degree of edema and astrocytic proliferation. Tuberculomas may become fibrotic and calcified with small degree of inflammatory reaction.
Tuberculomas may be curable with anti-tuberculous chemotherapy and corticosteroids. [33] A diagnosis by histopathology and mycobacterial culture is recommended for adequate treatment. [33]
Tuberculous abscess formation is a rare complication even in TB endemic areas. [37] This lesion mostly occurs in patients with abnormal cell-mediated immunity, particularly in patients with AIDS or other immunodeficiencies that preclude a granulomatous inflammatory response. Patients with tuberculous abscess tend to have a more severe clinical presentation than those with tuberculomas, with a shorter duration of symptoms similar to pyogenic abscesses. Likewise, neuroradiologic findings are very similar to other abscesses.
Histologically, tuberculous abscesses are composed of a necrotic, purulent center surrounded by a loose capsule without an epithelioid granulomatous reaction. In contrast to tuberculomas, which contain few bacilli, tuberculous abscesses contain abundant M tuberculosis bacilli. See the image below.
Atypical mycobacteriosis rarely involves the CNS even in patients with disseminated disease. The M avium complex (MAC), including M avium and M intracellulare, are the most common agents of human atypical mycobacteriosis. [38] The incidence of MAC increased rapidly in past decades with the emergence of AIDS, but this disease has declined subsequently with the introduction of effective antiretroviral therapy. [38] Involvement of the CNS by infection is rare, even in patients with widely disseminated disease. Isolated CNS infection in the absence of HIV infection is extremely rare, with only a few reported cases. (For a review, see Sadek M, Yue FY, Lee EY, et al. Clinical and immunologic features of an atypical intracranial mycobacterium avium complex (MAC) infection compared with those of pulmonary MAC infections. Clin Vaccine Immunol. Oct 2008;15(10):1580-9. [30] ) An association with sarcoidosis has been suggested. [30]
Atypical mycobacteriosis may be associated with meningitis, abscesses, and rarely, meningoencephalitis. Lesions mimicking tumors have been described in immunocompetent patients. [39, 40] Histopathologically, the lesions consisted of small aggregates of lymphocytes and macrophages that contain acid-fast microorganisms without caseating necrosis or multinucleated giant cells and present in a predominantly perivascular location.
Whipple disease is a multisystem infectious disease caused by Tropheryma whipplei, a ubiquitous gram-positive actinomycete . [41] The disease is commonly diagnosed by small-bowel biopsy, with demonstration of characteristic periodic acid-Schiff (PAS)–positive inclusions in macrophages of the lamina propria. Typical clinical manifestations of classic Whipple disease are arthralgia, weight loss, diarrhea, and abdominal pain. [42, 43] Neurologic involvement has been reported in 10-40% of patients with Whipple disease. [43]
Clinically, the disease tends to occur in white males (male-to-female ratio, about 8:1) aged between the fourth and seventh decades, [44] although a slight increase in female rates has been reported in recent years. [43] Although there has been no definitive association of the disease with specific genetic factors, a genetic risk linkage has been suggested by the predominance of men and the higher frequency of the human leukocyte antigen (HLA)-B27 among those with Whipple disease. [42] Patients with neurologic abnormalities as the initial manifestation have been reported to be younger (average age, 42 y) and without a sex predilection (male-to-female ratio, 1:1). [45] CNS Whipple disease has been rarely reported in association with acquired immunodeficiency syndrome (AIDS). [46]
Neurologic disease has been described in 3 clinical scenarios: neurologic involvement in classic Whipple disease, neurologic relapse of previously treated Whipple disease, and isolated neurologic manifestation without evidence of intestinal involvement. [42, 43] A recent review of the literature revealed 24 cases of cerebral Whipple disease without systemic involvement. [47] Clinical manifestations are varied and may mimic any major neurologic condition; the most common are cognitive dysfunctions, including memory impairment, confusion, or dementia. Visual disturbances that include supranuclear ophthalmoplegia in combination with oculofacioskeletal myorhythmia are considered highly suggestive of Whipple disease.
Disturbances of the hypothalamic-pituitary axis are also described. In patients with isolated central nervous system (CNS) involvement or those in whom neurologic involvement is the initial manifestation of the disease, focal neurologic symptoms secondary to a solitary mass lesion, such as seizures, headache, and ataxia, or symptoms secondary to meningitis may be seen. [43, 46] Even in the absence of neurologic symptoms, a high percentage of patients with Whipple disease shows cerebrospinal fluid (CSF) positivity for microorganisms by polymerase chain reaction (PCR) analysis before treatment. [48]
Neuroimaging findings are nonspecific and may resemble other CNS infectious syndromes, such as focal or multiple masses, cerebritis, and meningitis. Cerebral magnetic resonance imaging (MRI) appears to be the best imaging modality for Whipple disease and may most often show hyperintense lesions on T2-weighted sequences with diffuse enhancement. [45] Ring-enhancing lesions have also been documented. [46]
Gross pathologic findings of the CNS include generalized atrophy, scattered granulomalike lesions in the gray matter of the cerebral and cerebellar cortex, the basal ganglia, the hypothalamus, the periventricular and periaqueductal gray matter, and the cerebellum. [45] Involvement of the spinal cord is rare. The lesions may become confluent and produce large, necroticlike lesions, similar to abscesses. [46] Leptomeningeal involvement may be complicated by superficial, small infarcts and clinical features of brain infarction or strokelike syndromes. [13, 49]
Microscopically, numerous perivascular foamy histiocytes accompanied by variable chronic inflammation are present. The foamy histiocytes show characteristic periodic acid-Schiff (PAS)–positive intracellular bacilli that are also Gram positive and methenamine-silver stain positive. Bacteria may also be seen free in the parenchyma. Detection of the bacilli has been shown to be improved by immunohistochemical stains using specific antibodies against T whipplei. [50] Ultrastructural analysis characteristically shows bacillary structures within phagosomes of the foamy histiocytes, astrocytes and pericytes. [13]
The prognosis for patients with CNS Whipple infection remains poor, particularly in patients with recurrent disease. [45, 51] Long-term follow-up of patients with CNS disease have shown a mortality rate of 25%, and the same proportion of patients have major sequelae. [52]
Actinomycosis is a rare, chronic disease caused by anaerobic gram-positive bacteria, primarily of the genus Actinomyces, which normally colonize the mouth, gastrointestinal, and urogenital tract. The most common location of actinomycosis infection is the perimandibular region, followed by the pelvic and thoracic regions. [53]
Actinomycosis is endemic and has a worldwide distribution [53] ; there is no age, race, seasonal, or occupational predilection. Although it is not considered an opportunistic infection, actinomycosis has been described in patients with human immunodeficiency virus (HIV) infection, leukemia, and other causes of immunodeficiency. [54]
The majority of human actinomycosis disease is produced by Actinomyces israeli and A bovis. The infections are acquired by disruption of the mucosal barrier and entry of the bacteria into tissues. Therefore, most of infections are secondary to conditions that result in loss of mucosal integrity, including dental procedures, oral surgeries, head and neck radiotherapy, pulmonary and abdominal infections, gastrointestinal surgeries, and infections such as diverticulitis. Lesions of the central nervous system (CNS) are usually due to a focus elsewhere in the body, with spread to the nervous system either by direct extension or via bloodstream. However, brain abscesses have been reported without a recognized primary infection elsewhere. [55]
Involvement of the CNS by actinomycosis is rare, with a reported incidence ranging from 1% to 15% of patients with disease. [55] In a large series of pyogenic abscesses, Actinomyces abscesses represented less than 2% of cases. [56] Brain abscess is the most common CNS manifestation of actinomycosis; therefore, clinical symptoms and signs are secondary to mass-effect, including focal neurologic deficits and headache. The infections may also present as chronic meningitis secondary to spread of a parameningeal infection, most commonly the middle ear and paranasal sinuses. Less commonly, actinomycosis may present as meningoencephalitis, subdural empyema, and epidural abscess.
Computed tomography (CT) scanning and magnetic resonance imaging (MRI) appearances are consistent with ring-enhancing, single or multiple lesions that have a thick, irregular wall with multiloculation and intense surrounding edema. [55, 56, 57]
Grossly, the lesions are usually multilocular abscesses with a necrotic center and thick wall, with a clear demarcation from the surrounding brain parenchyma (see the image below).
Histologically, the necrotic center contains dense infiltration of neutrophils, necrotic debris, and colonies of branching organisms forming sulfur granules (see the following image). The outer zone of the lesion is formed by granulation tissue containing fibroblasts, neoformed capillaries, and mononuclear inflammatory cells. Less frequently, solid nodular or mass lesions termed actinomycetomas or actinomycotic granuloma may occur. [13] Characteristically, the bacteria are gram-positive, non–acid-fast, and methenamine silver–positive filamentous organisms.
Despite advances in clinical and surgical treatments, the prognosis of CNS actinomycosis is still poor. The recommended treatment for abscesses or actinomycoma is aspiration or surgical resection, followed by a prolonged course of antibiotic therapy. [56] Complete resolution is generally achieved with this treatment; however, neurologic sequelae may be seen in large number of patients. [55, 58] In the 1980s, mortality rates were reported as 28%. [58]
Risk factors that significantly correlate with a poor outcome include disease onset longer than 2 months before diagnosis and treatment, lack of antibiotic therapy or surgery, and the performance of needle aspiration drainage rather than open drainage or excision. [59]
Nocardia species are aerobic, gram-positive, filamentous bacteria that mostly produce infection in immunocompromised patients. The most common risk factors include long-term corticosteroids and immunosuppressive therapy, malignancy, organ transplantation, human immunodeficiency virus (HIV) infection, diabetes mellitus, alcohol abuse, intravenous drug abuse, and chronic granulomatous diseases. [60, 61]
Nocardial infections are not common. In the US, about 500-1000 of new cases occur annually. [62] An estimated 10-15% of these patients also have HIV infection. Central nervous system (CNS) nocardiosis is reported in 15-44% of patients with disseminated disease and in 2% of all cerebral abscesses. [63] There is a male predominance. [63]
Nocardia most commonly infects humans through the respiratory tract by inhalation, with the lung being the main organ affected. CNS infection is predominantly secondary to hematogenous spread from a pulmonary infection or infection at other sites, including the skin or subcutaneous tissues. [63] The species most associated with infections in humans are N asteroids, N brasiliensis, N farcinica,N nova, and N pseudobrasiliensis. [27, 64, 62] N asteroides accounts for 80% of the CNS infections. [27]
In the CNS, Nocardia produces both abscesses and meningitis. Although the majority of the cases involve the supratentorial region, spinal cord involvement may also occur. [65] Most of the clinical symptoms result from mass effect of the brain abscesses, including focal deficits and seizures. [63] However, more subtle symptomatology may be seen, including psychiatric disorders. [61]
The abscesses of Nocardia may be single or multiple. Microscopically, these abscesses contain extensive suppuration with acute inflammatory infiltrates similar to those seen in pyogenic abscesses. A fibrous wall surrounds the abscess. Granulomatous inflammatory reaction is rare. The filamentous microorganisms are gram-positive, partially acid-fast positive, and strongly positive by silver impregnation, such as with Grocott methenamine-silver.
Although the overall mortality rate for cerebral nocardiosis has decreased substantially due to new neuroimaging techniques, this conditions still carries a high mortality rate of around 34%. [63] The mortality is higher in patients with immunosuppression (51%) and those with multiple lesions (41%). [63]
Schlech WF 3rd, Ward JI, Band JD, Hightower A, Fraser DW, Broome CV. Bacterial meningitis in the United States, 1978 through 1981. The National Bacterial Meningitis Surveillance Study. JAMA. 1985 Mar 22-29. 253(12):1749-54. [Medline].
Nudelman Y, Tunkel AR. Bacterial meningitis: epidemiology, pathogenesis and management update. Drugs. 2009. 69(18):2577-96. [Medline].
Pediatric bacterial meningitis surveillance – African region, 2002–2008. MMWR Morb Mortal Wkly Rep. 2009 May 15. 58(18):493-7. [Medline].
Kim KS. Pathogenesis of bacterial meningitis: from bacteraemia to neuronal injury. Nat Rev Neurosci. 2003 May. 4(5):376-85. [Medline].
Dery MA, Hasbun R. Changing epidemiology of bacterial meningitis. Curr Infect Dis Rep. 2007 Jul. 9(4):301-7. [Medline].
Bilukha OO, Rosenstein N. Prevention and control of meningococcal disease. Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2005 May 27. 54:1-21. [Medline].
Cohn AC, MacNeil JR, Harrison LH, Hatcher C, Theodore J, Schmidt M, et al. Changes in Neisseria meningitidis disease epidemiology in the United States, 1998-2007: implications for prevention of meningococcal disease. Clin Infect Dis. 2010 Jan 15. 50(2):184-91. [Medline].
Grossman RI, Yousem DM. Infectious and noninfectious inflammatory diseases of the brain. Grossman RI, Yousem DM. Neuroradiology: the Requisites. 2nd ed. Philadelphia, Pa: Mosby; 2003. Chapter 6.
Katchanov J, Heuschmann PU, Endres M, Weber JR. Cerebral infarction in bacterial meningitis: predictive factors and outcome. J Neurol. 2010 May. 257(5):716-20. [Medline].
Edwards MS, Baker CJ. Complications and sequelae of meningococcal infections in children. J Pediatr. 1981 Oct. 99(4):540-5. [Medline].
Tunkel AR, Van de Beek D, Scheld WM. Acute meningitis. Mandell GL, Bennett JE, Dolin R, eds. Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases. 7th ed. Philadelphia, Pa: Churchill Livingstone-Elsevier; 2010. Chapter 84.
Durand ML, Calderwood SB, Weber DJ, Miller SI, Southwick FS, Caviness VS Jr, et al. Acute bacterial meningitis in adults. A review of 493 episodes. N Engl J Med. 1993 Jan 7. 328(1):21-8. [Medline].
Brown E, Gray F. Greenfield’s Neuropathology. Love S, Louis DN, Ellison DW, eds. Bacterial infections. 8th ed. London, UK: Hodder Arnold; 2009. Chapter 18.
Sharma R, Mohandas K, Cooke RP. Intracranial abscesses: changes in epidemiology and management over five decades in Merseyside. Infection. 2009 Feb. 37(1):39-43. [Medline].
Mamelak AN, Mampalam TJ, Obana WG, Rosenblum ML. Improved management of multiple brain abscesses: a combined surgical and medical approach. Neurosurgery. 1995 Jan. 36(1):76-85; discussion 85-6. [Medline].
Tunkel AR. Brain abscess. Mandell GL, Bennett JE, Dolin R, eds. Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases. 7th ed. Philadelphia, Pa: Churchill Livingstone-Elsevier; 2010. Chapter 88.
Carpenter J, Stapleton S, Holliman R. Retrospective analysis of 49 cases of brain abscess and review of the literature. Eur J Clin Microbiol Infect Dis. 2007 Jan. 26(1):1-11. [Medline].
Frazier JL, Ahn ES, Jallo GI. Management of brain abscesses in children. Neurosurg Focus. 2008. 24(6):E8. [Medline].
Honda H, Warren DK. Central nervous system infections: meningitis and brain abscess. Infect Dis Clin North Am. 2009 Sep. 23(3):609-23. [Medline].
Dashti SR, Baharvahdat H, Spetzler RF, Sauvageau E, Chang SW, Stiefel MF, et al. Operative intracranial infection following craniotomy. Neurosurg Focus. 2008. 24(6):E10. [Medline].
Cavusoglu H, Kaya RA, Türkmenoglu ON, Colak I, Aydin Y. Brain abscess: analysis of results in a series of 51 patients with a combined surgical and medical approach during an 11-year period. Neurosurg Focus. 2008. 24(6):E9. [Medline].
Bernardini GL. Diagnosis and management of brain abscess and subdural empyema. Curr Neurol Neurosci Rep. 2004 Nov. 4(6):448-56. [Medline].
Britt RH, Enzmann DR, Placone RC Jr, Obana WG, Yeager AS. Experimental anaerobic brain abscess. Computerized tomographic and neuropathological correlations. J Neurosurg. 1984 Jun. 60(6):1148-59. [Medline].
Lee TH, Chang WN, Su TM, Chang HW, Lui CC, Ho JT, et al. Clinical features and predictive factors of intraventricular rupture in patients who have bacterial brain abscesses. J Neurol Neurosurg Psychiatry. 2007 Mar. 78(3):303-9. [Medline]. [Full Text].
Tonon E, Scotton PG, Gallucci M, Vaglia A. Brain abscess: clinical aspects of 100 patients. Int J Infect Dis. 2006 Mar. 10(2):103-9. [Medline].
Kao PT, Tseng HK, Liu CP, Su SC, Lee CM. Brain abscess: clinical analysis of 53 cases. J Microbiol Immunol Infect. 2003 Jun. 36(2):129-36. [Medline].
Sorrell TC, Mitchell DH, Iredell JR, Chen SC-A. Chapter 254. Mandell GL, Bennett JE, Dolin R, eds. Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases. 7th ed. Philadelphia, Pa: Churchill Livingstone-Elsevier; 2010.
World Health Organization (WHO). Global tuberculosis control: a short update to the 2009 report. Available at http://at http://www.who.int/tb/publications/global_report/en/. Accessed: February 8, 2011.
Centers for Disease Control and Prevention. Reported Tuberculosis in the United States, 2008. Atlanta Ga: CDC; September 2009.
Sadek M, Yue FY, Lee EY, Gyenes G, Jones RB, Hoffstein V, et al. Clinical and immunologic features of an atypical intracranial mycobacterium avium complex (MAC) infection compared with those of pulmonary MAC infections. Clin Vaccine Immunol. 2008 Oct. 15(10):1580-9. [Medline]. [Full Text].
Fizgerald DW, Sterling TR, Haas DW. Mycobacterium tuberculosis. Mandell GL, Bennett JE, Dolin R, eds. Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases. 7th ed. Philadelphia, Pa: Churchill Livingstone-Elsevier; 2010. Chapter 250.
Bernaerts A, Vanhoenacker FM, Parizel PM, Van Goethem JW, Van Altena R, Laridon A, et al. Tuberculosis of the central nervous system: overview of neuroradiological findings. Eur Radiol. 2003 Aug. 13(8):1876-90. [Medline].
Thwaites G, Fisher M, Hemingway C, Scott G, Solomon T, Innes J. British Infection Society guidelines for the diagnosis and treatment of tuberculosis of the central nervous system in adults and children. J Infect. 2009 Sep. 59(3):167-87. [Medline].
Ramdurg SR, Gupta DK, Suri A, Sharma BS, Mahapatra AK. Spinal intramedullary tuberculosis: a series of 15 cases. Clin Neurol Neurosurg. 2009 Feb. 111(2):115-8. [Medline].
Ravenscroft A, Schoeman JF, Donald PR. Tuberculous granulomas in childhood tuberculous meningitis: radiological features and course. J Trop Pediatr. 2001 Feb. 47(1):5-12. [Medline].
Muthukumar N, Sureshkumar V, Ramesh VG. En plaque intradural extramedullary spinal tuberculoma and concurrent intracranial tuberculomas: paradoxical response to antituberculous therapy. Case report. J Neurosurg Spine. 2007 Feb. 6(2):169-73. [Medline].
Kumar R, Pandey CK, Bose N, Sahay S. Tuberculous brain abscess: clinical presentation, pathophysiology and treatment (in children). Childs Nerv Syst. 2002 Apr. 18(3-4):118-23. [Medline].
Gordin FM, Horsburgh CR Jr. Mycobacterium avium complex. Mandell GL, Bennett JE, Dolin R, eds. Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases. 7th ed. Philadelphia, Pa: Churchill Livingstone-Elsevier; 2010. Chapter 252.
Di Patre PL, Radziszewski W, Martin NA, Brooks A, Vinters HV. A meningioma-mimicking tumor caused by Mycobacterium avium complex in an immunocompromised patient. Am J Surg Pathol. 2000 Jan. 24(1):136-9. [Medline].
Dickerman RD, Stevens QE, Rak R, Dorman SE, Holland SM, Nguyen TT. Isolated intracranial infection with Mycobacterium avium complex. J Neurosurg Sci. 2003 Jun. 47(2):101-5; discussion 105. [Medline].
La Scola B, Fenollar F, Fournier PE, Altwegg M, Mallet MN, Raoult D. Description of Tropheryma whipplei gen. nov., sp. nov., the Whipple’s disease bacillus. Int J Syst Evol Microbiol. 2001 Jul. 51:1471-9. [Medline].
Fenollar F, Puéchal X, Raoult D. Whipple’s disease. N Engl J Med. 2007 Jan 4. 356(1):55-66. [Medline].
Schneider T, Moos V, Loddenkemper C, Marth T, Fenollar F, Raoult D. Whipple’s disease: new aspects of pathogenesis and treatment. Lancet Infect Dis. 2008 Mar. 8(3):179-90. [Medline].
Marth T, Raoult D. Whipple’s disease. Lancet. 2003 Jan 18. 361(9353):239-46. [Medline].
Gerard A, Sarrot-Reynauld F, Liozon E, Cathebras P, Besson G, Robin C, et al. Neurologic presentation of Whipple disease: report of 12 cases and review of the literature. Medicine (Baltimore). 2002 Nov. 81(6):443-57. [Medline].
Guthikonda B, Rouah E, Krishnan B, Powell SZ, Goodman JC, Gopinath SP, et al. Whipple disease of the central nervous system: an unusual occurrence in association with acquired immune deficiency syndrome. J Neurosurg. 2010 May. 112(5):983-9. [Medline].
Mohamed W, Neil E, Kupsky WJ, Juhász C, Mittal S, Santhakumar S. Isolated intracranial Whipple’s disease–report of a rare case and review of the literature. J Neurol Sci. 2011 Sep 15. 308(1-2):1-8. [Medline].
von Herbay A, Ditton HJ, Schuhmacher F, Maiwald M. Whipple’s disease: staging and monitoring by cytology and polymerase chain reaction analysis of cerebrospinal fluid. Gastroenterology. 1997 Aug. 113(2):434-41. [Medline].
Famularo G, Minisola G, De Simone C. A patient with cerebral Whipple’s disease and a stroke-like syndrome. Scand J Gastroenterol. 2005 May. 40(5):607-9. [Medline].
Baisden BL, Lepidi H, Raoult D, Argani P, Yardley JH, Dumler JS. Diagnosis of Wihipple disease by immunohistochemical analysis: a sensitive and specific method for the detection of Tropheryma whipplei (the Whipple bacillus) in paraffin-embedded tissue. Am J Clin Pathol. 2002 Nov. 118(5):742-8. [Medline].
Marth T. New insights into Whipple’s disease – a rare intestinal inflammatory disorder. Dig Dis. 2009. 27(4):494-501. [Medline].
Schnider PJ, Reisinger EC, Gerschlager W, Müller C, Berger T, Krejs GJ, et al. Long-term follow-up in cerebral Whipple’s disease. Eur J Gastroenterol Hepatol. 1996 Sep. 8(9):899-903. [Medline].
Russo TA. Agents of actinomycosis. Mandell GL, Bennett JE, Dolin R, eds. . Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases. 7th ed. Philadelphia, Pa: Churchill Livingstone-Elsevier; 2010. Chapter 255.
Chaudhry SI, Greenspan JS. Actinomycosis in HIV infection: a review of a rare complication. Int J STD AIDS. 2000 Jun. 11(6):349-55. [Medline].
Sharma BS, Banerjee AK, Sobti MK, Kak VK. Actinomycotic brain abscess. Clin Neurol Neurosurg. 1990. 92(4):373-6. [Medline].
Dailey AT, LeRoux PD, Grady MS. Resolution of an actinomycotic abscess with nonsurgical treatment: case report. Neurosurgery. 1993 Jan. 32(1):134-6; discussion 136-7. [Medline].
Wang S, Wolf RL, Woo JH, Wang J, O’Rourke DM, Roy S, et al. Actinomycotic brain infection: registered diffusion, perfusion MR imaging and MR spectroscopy. Neuroradiology. 2006 May. 48(5):346-50. [Medline].
Smego RA Jr. Actinomycosis of the central nervous system. Rev Infect Dis. 1987 Sep-Oct. 9(5):855-65. [Medline].
Smego RA Jr, Foglia G. Actinomycosis. Clin Infect Dis. 1998 Jun. 26(6):1255-61; quiz 1262-3. [Medline].
Lerner PI. Nocardiosis. Clin Infect Dis. 1996 Jun. 22(6):891-903; quiz 904-5. [Medline].
Corti ME, Villafañe-Fioti MF. Nocardiosis: a review. Int J Infect Dis. 2003 Dec. 7(4):243-50. [Medline].
Centers for Disease Control and Prevention. Nocardiosis: technical information. Available at http://www.cdc.gov/nczved/divisions/dfbmd/diseases/nocardiosis/technical.html. Accessed: February 8, 2011.
Mamelak AN, Obana WG, Flaherty JF, Rosenblum ML. Nocardial brain abscess: treatment strategies and factors influencing outcome. Neurosurgery. 1994 Oct. 35(4):622-31. [Medline].
Chedid MB, Chedid MF, Porto NS, Severo CB, Severo LC. Nocardial infections: report of 22 cases. Rev Inst Med Trop Sao Paulo. 2007 Jul-Aug. 49(4):239-46. [Medline].
Zakaria A, Elwatidy S, Elgamal E. Nocardia brain abscess: severe CNS infection that needs aggressive management; case report. Acta Neurochir (Wien). 2008 Oct. 150(10):1097-101; discussion 1101. [Medline].
Site of Primary Infection
Bacterial Agent(s)
Hematogenous dissemination
Cyanotic Congenital Heart Disease
Haemophilus spp, S aureus, Streptococcus spp
Endocarditis and Bacteremia
S aureus, Streptococcus spp
Pulmonary Infections
Streptococcus spp, anaerobic gram-negative, Nocardia, Fusobacterium, Actinomyces
Spread of contiguous infection
Sinuses and Odontogenic Infections
Streptococcus spp, S aureus, Enterobacteriaceae, Bacteroides, Haemophilus spp
Ear and Mastoid Infections
Streptococcus spp, Pseudomonas, Enterobacteriaceae, Bacteroides spp
Penetrating Head Injury
Staphylococci, Enterobacteriaceae, Bacteroides spp, Clostridium
Post Neurosurgical Procedures
S aureus, Pseudomonas
Source: Compiled from various sources. [16, 18, 20, 21]
M Beatriz S Lopes, MD, PhD Professor of Pathology and Neurological Surgery, University of Virginia School of Medicine
M Beatriz S Lopes, MD, PhD is a member of the following medical societies: American Association of Neuropathologists, American Society for Investigative Pathology
Disclosure: Nothing to disclose.
Adekunle M Adesina, MD, PhD Professor, Medical Director, Section of Neuropathology, Director, Molecular Neuropathology Laboratory, Texas Children’s Hospital, Department of Pathology and Immunology, Baylor College of Medicine
Adekunle M Adesina, MD, PhD is a member of the following medical societies: American Association for the Advancement of Science, American Association of Neuropathologists, College of American Pathologists, United States and Canadian Academy of Pathology
Disclosure: Nothing to disclose.
Pathology of Bacterial Infections
Research & References of Pathology of Bacterial Infections|A&C Accounting And Tax Services
Source
0 Comments