Histoplasmosis of the nervous system
Histoplasmosis is an infection caused by the fungus Histoplasma capsulatum. Infection is endemic to certain areas of the United States, including the
Jun. 09, 2021
At vero eos et accusamus et iusto odio dignissimos ducimus qui blanditiis praesentium voluptatum deleniti atque corrupti quos dolores et quas.
Streptococcus pneumoniae is the leading cause of bacterial meningitis in the United States and accounts for significant morbidity and mortality in essentially all age groups. Prompt recognition and treatment can improve outcomes. Treatment guidelines recommend that dexamethasone should be added to initial empiric antibiotic therapy. In this article, the author reviews the clinical manifestations of S pneumoniae infection, with emphasis on neurologic symptoms and key features that can help avoid pitfalls leading to missed or late diagnosis. A report indicated that after pneumococcal meningitis adults are at increased risk of neurologic and neuropsychologic deficits, impaired daily activities, and poor quality of life. Current diagnostic laboratory techniques are evaluated, and up-to-date treatment recommendations based on the most recent research and expert opinion are incorporated. Research regarding the importance of endocarditis and bacteremia to neuropathogenesis, as well as the effect of bacterial meningitis on neurogenesis, is presented.
• Globally, community-acquired bacterial meningitis is most frequently caused by Streptococcus pneumoniae.
• Patients with a basilar skull or cribriform fracture with a CSF leak are at increased risk of acquiring pneumococcal meningitis.
• Streptococcus pneumoniae often leads to a severe degree of meningeal inflammation.
• Pneumococcal meningitis is treated intravenously with a combination of a third-generation cephalosporin and vancomycin.
• Corticosteroids reduce mortality.
• Corticosteroids treatment leads to lower rates of hearing loss.
In 1881, Streptococcus pneumoniae was identified simultaneously by Pasteur in France, who named it Microbe septice mique du salive, and by Sternberg in the United States, who called it Micrococcus pasteuri. By the late 1880s, the term pneumococcus had come into general use because of the association between this organism and lobar pneumonia. In 1926, the term Diplococcus was assigned because of the organism’s appearance in gram-stained sputum. Finally, in 1974, the organism was renamed, Streptococcus pneumoniae because of its morphology during growth in liquid medium (93; 54).
Streptococcus pneumoniae infections are more common in children and persons over 65 years of age. S pneumoniae is a causative agent for many serious systemic infections, including pneumonia, septicemia, sinusitis, and otitis media (15; 48). The most frequent predisposing and associated conditions for pneumococcal meningitis are pneumonia, sinusitis, or otitis media. Invasive pneumococcal disease is defined as a bacteriologically confirmed S pneumoniae infection following isolation of bacteria from a normally sterile body site (blood or cerebrospinal fluid but not sputum) (12).
Pneumococcal meningitis symptoms typically include fever, headache, nausea, vomiting, irritability, and lethargy proceeding to further clouding of consciousness. Fever may be 103°F or higher. Clinical signs include evidence of meningeal irritation, though this can be lacking in children, the elderly, and the deeply comatose. Focal signs may also appear. The course is frequently fulminant, with rapid neurologic deterioration leading to respiratory arrest and death (18; 89).
Lobar pneumonia and meningitis are the 2 most serious forms of S pneumoniae infection. Lobar pneumonia affects more people and, therefore, causes more morbidity and mortality, whereas meningitis has a higher mortality rate. S pneumoniae is the most common cause of bacterial meningitis in adults worldwide, and, in many countries, it is most common in children above the newborn period (69; 54). S pneumoniae is also a frequent cause of recurrent bacterial meningitis, which should prompt evaluation for a dural defect. In recurrent disease, the organism uses such an opening to directly enter the central nervous system.
Finally, as a respiratory pathogen, the most typical coexisting complications will affect the upper or lower airways. Concomitant pneumonia is frequent in patients with S pneumoniae meningitis. Not infrequently, it is possible to obtain a history of productive cough, dyspnea, and constitutional symptoms in the days prior to onset of meningitis-like symptoms. Bacteria and inflammatory exudate accumulate in the alveoli of the lung, allowing a diagnosis of pneumonia to be made when a consolidated area appears on chest x-ray (54). The more severe cases of pneumonia are more likely to be associated with bacteremia (60; 92) and, therefore, with meningitis. Meningitis occurs in approximately 8% of patients who become bacteremic with this organism (72).
S pneumoniae is also a frequent cause of recurrent bacterial meningitis, which should prompt evaluation for a dural defect. In recurrent disease, the organism uses such an opening to directly enter the central nervous system.
S pneumoniae is a common etiologic agent of otitis media in both children and adults (78; 21) and is either the first or second leading cause of acute sinusitis (31). These infections can provide a source of meningitis by either hematogenous spread or direct extension. It is reasonable to perform an otologic examination on any patient presenting with fever and altered consciousness (62).
The triad of pneumococcal pneumonia, meningitis, and endocarditis is a rare but serious condition known as Austrian syndrome (39). Alcoholism is the most common predisposing factor, but it is also seen with intravenous drug abuse (06), and the diagnosis of endocarditis should be considered early in every patient with pneumococcal meningitis or bacteremia (47).
Other complications of S pneumoniae include septic arthritis and osteomyelitis (24), both of which are associated with bacteremic spread, as is meningitis. Osteomyelitis also tends to involve the vertebral bones (88) and, from there, can extend directly into the central nervous system.
The prognosis of Streptococcus pneumoniae meningitis, as with most bacterial meningitis, relates directly to early diagnosis and initiation of appropriate antibiotic therapy (05). With appropriate therapy instituted early, mortality is improved. Morbidity, however, is high, even with the best possible treatment, and significant, permanent neurologic sequelae are observed in up to a third of the survivors (76; 51; 05; 81). After pneumococcal meningitis adult patients are at greater risk of neurologic and neuropsychologic deficits, impaired daily activities, and poor quality of life (42).
French data for children (5 to 15 years) with a diagnosis of pneumococcal meningitis between 2001 and 2013 were analyzed. Among the 316 children with pneumococcal meningitis, the mortality rate was approximately 10%, and additionally, 23% of cases had severe complications (abscess, coma, hemodynamic failure, cerebral thrombophlebitis, or deafness) (33). In an American retrospective study, in-patient data from 2008 to 2014 were evaluated. During the study period, there were 10,493 hospitalizations due to pneumococcal meningitis. There were 1016 deaths, with case fatality rate ranging from 8.3% to 11.2% (38).
Pneumococcal meningitis is caused by a variety of capsular serotypes (50; 61). Available vaccines do not protect against meningitis caused by all capsular serotypes (52). Acute neurologic complications, especially coma, are associated with later behavioral and developmental difficulties, mental retardation, hearing loss, motor defects, and seizures (67). Independent predictors of a poor outcome include low Glasgow coma scale score, presence of a cranial nerve palsy, elevated sedimentation rate (94), advanced age, presence of an underlying chronic illness, presence of associated pneumonia, absence of associated otitis media, seizures, requirement for assisted ventilation, high CSF protein concentration, low CSF glucose concentration, CSF white count below 500 cells/microliter (63; 43), abnormal deep tendon reflexes, and presence of stroke or hydrocephalus on imaging (81).
Complications during acute illness are similar to those seen with meningitides of any etiology and include subdural effusion, empyema, ischemic or hemorrhagic stroke, cerebritis, ventriculitis, abscess, and hydrocephalus (30; 54). Hearing loss is the most common long-term neurologic sequelae of pneumococcal meningitis, occurring in up to 35% of survivors (43). The pneumococcal toxin pneumolysin is an important factor involved in ototoxic toxicity (66). Other focal neurologic deficits, such as ataxia and paresis, occur in an additional 16% (63). Cognitive impairment, particularly psychomotor slowing, is found in approximately 30% of survivors and is stable on formal testing over time after meningitis, despite subjective perception of improvements over time (36).
A 45-year-old man with a history of alcoholism was brought by ambulance from a homeless shelter to an emergency room due to alteration in mental status. A few hours earlier, he had told the staff at the shelter that he had a bad headache. He had also vomited once. He then went to rest on his bunk. When staff checked on him, they found him to be confused. In the emergency room, he was noted to have a temperature of 39.1 degrees Celsius. He responded to his first name but was not oriented to place or time. He was given doses of ceftriaxone, vancomycin, and ampicillin. A head CT was unremarkable and a lumbar puncture was performed. CSF examination demonstrated an opening pressure of 500 mmHg, a white count of 4914 cells/ul with 91% neutrophils, a glucose concentration of 5 mg/dl, and a protein concentration of 279 mg/dl. Gram stain revealed gram positive diplococci, and a presumptive diagnosis of pneumococcal meningitis was made.
The patient was admitted to the neurologic intensive care unit. Triple antibiotic coverage was continued pending definitive speciation and antibiotic sensitivity determination. Intravenous dexamethasone was also added to the regimen. The patient’s condition continued to deteriorate and he required ventilatory support. A repeat head CT demonstrated worsening cerebral edema. The patient developed signs of cerebral herniation and a brain code was initiated. He was temporarily stabilized, but then required pressor support. He became increasingly bradycardic, and eventually died, 30 hours after initial presentation.
CSF and blood cultures both confirmed the diagnosis of infection with Streptococcus pneumoniae, sensitive to all tested antibiotics.
Streptococcus pneumoniae is the prototypic extracellular bacterial pathogens. In the absence of antibody, they resist phagocytosis and grow extracellularly. They are gram-positive cocci that tend to grow in chains. They are catalase negative and grow better with a source of catalase, such as red blood cells. S pneumoniae produce pneumolysin, which degrades hemoglobin to a green pigment; they are, therefore, surrounded by a green zone on blood-agar growth media, a process termed alpha-hemolysis. Currently, at least 94 distinct serotypes have been identified based on the structure and antigenicity of their polysaccharide capsules. Of these, a limited number of capsular serotypes account for the majority of invasive pneumococcal disease (25; 29; 10; 54; 91). Invasive disease caused by different serotypes may result in different degrees of host response (77), leading to different pathogenic mechanisms, clinical courses, and outcomes.
Streptococcus pneumoniae causes infection of the upper and lower respiratory tracts by spread from the nasopharynx, which is normally colonized; it causes infection elsewhere, including the central nervous system, via hematogenous spread. In fact, an autopsy study of children who died from bacterial meningitis showed no evidence for direct extension, suggesting that even in cases of otitis media, meningitis may be due to bacteremia (22). The bacteremia may actually contribute to the neurologic injury by affecting cerebral blood flow regulation, blood-brain barrier permeability, and cerebral edema (08; 65).
A key bacterial factor enabling S pneumoniae to cause disease is its capsular polysaccharide. The capsule allows the organism to escape immune surveillance and ingestion by phagocytes. The capsule may have electrochemical forces that repel phagocytes and may mask cell wall constituents, which would otherwise be immunogenic (54). Pneumococcal bacterial genetic variation has been found a determinant of invasive pneumococcal disease phenotype. Variations in S pneumoniae genome also contribute in determining the clinical phenotype of invasive pneumococcal disease. For example, the presence of pneumococcal gene slaA along with sequence cluster 9 were independent predictors of meningitis. In addition, a set of 4 pneumococcal genes co-located on a prophage independently predicted 30-day increased mortality (17).
Various bacterial and host factors contribute to pathogenicity of the organism within the central nervous system. In its attempt to fight the infection, the host inflammatory response probably causes most of the pathological damage. The role of bacterial factors is to stimulate this response. Bacterial cell wall constituents, such as peptidoglycan, are critically important (87). Pneumolysin destroys phagocytic cells, activates complement and other cytokines, and induces apoptosis-like programmed cell death in neurons and brain-derived endothelial cells (49). Host inflammatory mediators include complement (75), tumor necrosis factor, interleukin-1, interleukin-6, and C-reactive protein (68; 95; 54). An altered balance of matrix metalloproteinase (MMP-9) and its tissue inhibitor (TIMP-1) may play a role in disruption of the blood-brain barrier and extent of cortical damage in a rat model of pneumococcal meningitis (79). Additionally, upregulation of aquaporin-4 may contribute to increased water permeability across the blood-brain barrier, accounting for the brain edema seen in pneumococcal meningitis (64).
In response to bacterial infection of the central nervous system, neural progenitor cells proliferate and differentiate, although bacterial factors, like cell wall constituents, may trigger immunoreactivity, which can hamper this neurogenesis (34). Work in a murine model of pneumococcal meningitis has demonstrated upregulated expression of brain derived neurotrophic factor (BDNF) and its receptor (TrkB), associated with increased density of dentate granule cells in the hippocampal formation (84) as well as the possibility that BDNF prevents neuronal cell loss (46).
Brain histopathology of 31 patients who died of pneumococcal meningitis was assessed. Common pathological observations were inflammation of medium-large arteries, cerebral hemorrhage, cerebritis, thrombosis, infarction, and ventriculitis. Inflammation of arteries leading to obstruction of the vascular lumen was associated with cerebral infarction (23).
Streptococcus pneumoniae is the leading cause of bacterial meningitis in the United States and other parts of world. In an American retrospective study from 2008 to 2014 there were 10,493 hospitalizations due to pneumococcal meningitis. Overall, pneumococcal meningitis incidence decreased from 0.62 to 0.38 cases per 100,000 over this time (39% decrease). Among children less than 2 years of age, the average annualized pneumococcal meningitis rate decreased by 45% from 2.19 to 1.20 per 100,000. Annual pneumococcal meningitis rates decreased in those 18 to 39 years of age (0.25 to 0.15 cases per 100,000) and 40 to 64 years of age (0.95 to 0.54 cases per 100,000) (38). In Europe, a decrease in incidence of adult bacterial meningitis has been noted. Authors assessed 1412 episodes of community-acquired bacterial meningitis. Incidence declined from 1.72 cases per 100,000 adults per year in 2007 to 2008 to 0.94 per 100,000 per year in 2013 to 2014. S pneumoniae caused 1017 (72%) of 1412 episodes (07). A much higher incidence has been reported in Africa. The pooled incidence of invasive pneumococcal disease (including meningitis) in children in Africa was 62.6 per 100,000 person-years. Pneumococcal meningitis had a pooled African incidence of 24.7 per 100,000 person-years (37).
Patients with various underlying conditions, such as asplenic states, cancer, alcoholism, malnutrition, diabetes mellitus, HIV, and other chronic diseases, may be at increased risk for developing pneumococcal infection, including meningitis (26; 27; 02). Certain ethnic groups, including Native Americans, Alaskans, and Australian Aboriginals, may have an incidence as much as 10-fold greater than the general population (19; 85; 40). The reasons for this remain unclear. Infants (but not neonates) up to 2 years of age and adults over 65 years are also at increased risk (09).
Transmission can occur due to close contact, such as in daycare centers, military camps, prisons, homeless shelters, and nursing homes (53; 35; 55; 80). Despite media reports to the contrary, contact in schools or at work has not been associated with spread of this disease, except by a few case reports. The rate of invasive pneumococcal disease is highest in the elderly, and manifestations are influenced by advancing age (37).
Pneumococcal vaccine led to a significant decline in invasive pneumococcal disease-related deaths. The invasive pneumococcal disease-related deaths declined after the introduction of the 7-valent pneumococcal conjugate vaccine from 1.25 out of 100,000 children in 2006 to 2007 to 0.60 out of 100,000 in 2009 to 2010, with a further reduction following 13-valent pneumococcal conjugate vaccine introduction from 2010 to 0.39 out of 100,000 in 2013 to 2014 (58). Immunization with 13-valent pneumococcal conjugate vaccine has further reduced the rate of pneumococcal meningitis in children (less than 15 years of age) with a near-elimination of cefotaxime-resistant isolates (74).
The Centers for Disease Control and Prevention recommends routine pneumococcal vaccine for the following types of patients: immunocompetent but at increased risk of acquiring pneumococcal infection or having a serious complication, such as patients with chronic pulmonary disease, cardiovascular disease, diabetes, alcoholism, liver and renal disease, CSF leak, and those older than 65 years of age; and immunocompromised patients, including those with functional or anatomic asplenia (sickle cell disease), malignancy, HIV infection, or organ transplantation. Vaccine may also be reasonable for other populations at risk by virtue of ethnicity (Native Americans) or crowded living conditions (11; 54).
Pneumococcal conjugate vaccines are now part of national immunization programs of many countries (15). There are 2 types of pneumococcal vaccines currently available—pneumococcal conjugate vaccine (PCV13) and pneumococcal polysaccharide vaccine. The polysaccharide vaccine consists of purified capsular polysaccharides from the 23 serotypes responsible for 90% of invasive pneumococcal infection. Pneumococcal conjugate vaccines contain polysaccharides from 7 serotypes covering 65% to 80% of serotypes associated with invasive pneumococcal disease among young children in Western industrialized countries. The polysaccharides are conjugated to a carrier protein, which makes them more immunogenic and effective in protecting against infection, particularly in young children less than 2 years of age. Furthermore, the vaccine protects against both systemic and mucosal infection and prevents nasopharyngeal colonization, thereby reducing transmission in the community.
Since 2010, pneumococcal conjugate vaccine 13 has been recommended for infants and children in place of pneumococcal conjugate vaccine 7. The Centers for Disease Control and Prevention and the American Academy of Pediatrics recommend the expanded use of PCV13 in children 6 through 18 years of age with increased risk of invasive pneumococcal disease. The 23-valent pneumococcal polysaccharide vaccine has been recommended for all adults 65 years of age or older and in younger patients who have a condition that increases risk for invasive pneumococcal disease (04). Both vaccines are well tolerated and highly effective, and they can be administered at the same time as other vaccines (03). In England and Wales introduction of 3-valent (PCV13) pneumococcal conjugate vaccines in 2010 has led to a substantial (48%) reduction in pneumococcal meningitis incidence by 2015 to 2016 (57).
The history and examination data obtained from any given case of acute bacterial meningitis can be quite variable. Some findings are typically present, whereas others may be absent. Additionally, the signs and symptoms frequently seen with acute bacterial meningitis, including fever, behavioral or personality changes, and mental status changes can be nonspecific and suggest other diagnoses, including systemic infection or sepsis, viral encephalitis or meningitis, fungal or tuberculous meningitis, trauma or closed head injury or child abuse, multiple metabolic abnormalities (hypoglycemia, ketoacidosis, electrolyte imbalance, uremia, toxic exposure), seizure, and brain tumor. Even meningismus does not exclude alternative diagnoses such as subarachnoid hemorrhage, intracranial hemorrhage, and epidural abscess. In order to prevent morbidity and mortality from missed diagnoses, it is important to keep a high index of suspicion for acute bacterial meningitis and err on the side of starting treatment early and potentially unnecessarily (05).
Streptococcus pneumoniae and Neisseria meningitidis are the most common etiologic agents of bacterial meningitis at all ages after 1 year of age. In children less than 1 year of age, Group B streptococci and gram-negative enteric bacilli, particularly Escherichia coli, are the leading etiologic agents, presumably because of exposure to these agents during birth. Due to passive transfer of maternal antibodies, these neonates do not typically develop Haemophilus influenzae or pneumococcal or meningococcal meningitis (59).
In the setting of a preceding sinusitis, otitis media, head trauma, neurosurgical procedure, or cerebrospinal fluid leak, S pneumoniae and nontypeable H. influenzae are both common etiologic agents of recurrent meningitis (41; 01) because both are a common part of “normal” skin and nasopharyngeal colonization. One study provides good evidence that surgical repair of CSF leak of various origins effectively prevents recurrent bacterial meningitis (82).
In patients over 50 years of age, the most common causes of bacterial meningitis include S pneumoniae and gram-negative bacilli (28; 71). H influenzae is included in the gram-negative group, along with E coli, Enterobacter, and Pseudomonas. S pneumoniae is more likely in association with pneumonia, Pseudomonas in association with chronic lung disease, E coli, or Enterobacter in the setting of chronic urinary tract infection, and S pneumoniae or H. influenzae in the setting of sinusitis, otitis media, head trauma, or a neurosurgical procedure. Listeria monocytogenes can also be seen, especially in the immunosuppressed elderly, and Staphylococcus aureus is seen in neurosurgical patients.
Bacterial meningitis, including that caused by Streptococcus pneumoniae, should be considered and promptly treated in any patient with a compatible presentation, keeping in mind that the presentation may be atypical in some patients, especially young children and the elderly. CSF examination showing a predominantly neutrophilic pleocytosis and a decreased glucose concentration is strongly suggestive of bacterial meningitis (05). Empiric therapy is initiated with a third- or fourth-generation cephalosporin and vancomycin along with dexamethasone if CSF values are consistent with bacterial meningitis (16).
If imaging is performed before CSF examination, images should be evaluated for contraindications for lumbar puncture. In such a scenario, empirical treatment should be initiated before the patient is sent for neuroimaging (16).
No tests are currently available that are rapid enough to confirm S pneumoniae as the causative organism in time to base initial treatment on that finding. The main value of these tests, therefore, is to confirm the correct initial clinical diagnosis.
With S pneumoniae meningitis, as well as most other etiologic agents, both blood and CSF cultures will usually be positive. However, again, treatment should be initiated without delay, even prior to obtaining culture samples. Multiplex PCR platforms for simultaneous detection of multiple bacterial pathogens causing meningitis are now commercially available. A probe to detect unique S pneumoniae RNA sequences is also available. Methods for detecting antibody to capsular polysaccharide have proven neither sensitive nor specific enough to be clinically useful.
Historically, pneumococci have been identified in culture by the following characteristics: alpha-hemolysis of blood agar, catalase negativity, susceptibility to optochin, and solubility in bile salts (54). With the modern techniques of molecular biology, reliance on these bacterial properties may be less important, but cultures remain vital to determine antibiotic sensitivity.
When bacterial meningitis is suspected, emergent antibiotic treatment must be initiated without waiting for speciation to be made (05). In persons older than the neonatal period, empiric treatment is directed primarily against S pneumoniae and N meningitidis. Current recommendations for treatment of community-acquired meningitis for ages 3 months to 50 years is vancomycin 15 mg/kg IV every 8 to 12 hours and up to 2 g/day (maintain serum trough concentration of 15 to 20 ug/ml) plus either cefotaxime 50 mg/kg IV every 4 to 6 hours (maximum 2 g IV every 4 hours) or ceftriaxone 50 to 100 mg/kg IV every 12 hours (maximum 2 g IV every 12 hours) (86). For patients over age 50 years, addition of ampicillin 2 g IV every 4 hours is recommended. For patients with severe penicillin or cephalosporin allergy, the recommended treatment includes vancomycin and moxifloxacin.
In patients with pneumococcal meningitis caused by penicillin- or cephalosporin-resistant strains, rifampicin or vancomycin can be added to the ceftriaxone regimen if the isolate demonstrates good response on sensitivity testing. Fluoroquinolone with in vitro activity against Streptococcus pneumoniae can also be considered in case treatment response is poor. Fluoroquinolone should always be combined with a third-generation cephalosporin or vancomycin (32).
Dexamethasone should be added to empirical therapy before or at the same time as the first antibiotic dose. Dexamethasone needs to be continued for 4 days in those with pneumococcal meningitis (96). Dexamethasone 0.15 mg/kg every 6 hours is given 15 to 20 minutes prior to antibiotics administration (20; 90; 86). There has been some concern that dexamethasone could decrease the penetration of vancomycin into the CSF. However, 1 study demonstrated that appropriate levels of vancomycin are reached in the CSF of patients with pneumococcal meningitis receiving dexamethasone as long as proper serum levels of vancomycin are maintained (73). Dexamethasone 0.15 mg/kg every 6 hours, initiated prior to the first dose of antibiotic and continued for the first 2 to 4 days of treatment, decreases the risk of neurologic sequelae from community-acquired bacterial meningitis in children (45; 56; 83).
In addition to medication therapies, it is imperative that appropriate supportive care be instituted. Advancements in intensive care techniques offer significant benefit for patients with bacterial meningitis, including S pneumoniae meningitis.
Vaccination of pregnant women against Streptococcus pneumoniae is not recommended because it is not known whether these vaccines can cause fetal harm (03; 44; 70). A Cochrane Systematic Review also does not suggest that administration of pneumococcal vaccine during pregnancy is efficacious in reducing infant infections during pregnancy (14). As per the Centers for Disease Control and Prevention, the safety of pneumococcal polysaccharide vaccine during pregnancy has not been evaluated. However, no adverse consequences have been reported among newborns whose mothers were inadvertently vaccinated during pregnancy (13).
Ravindra Kumar Garg MD
Dr. Garg of King George's Medical University in Lucknow, India, has no relevant financial relationships to disclose.See Profile
Christina M Marra MD
Dr. Marra of the University of Washington School of Medicine has no relevant financial relationships to disclose.See Profile
Nearly 3,000 illustrations, including video clips of neurologic disorders.
Every article is reviewed by our esteemed Editorial Board for accuracy and currency.
Full spectrum of neurology in 1,200 comprehensive articles.
Histoplasmosis is an infection caused by the fungus Histoplasma capsulatum. Infection is endemic to certain areas of the United States, including the
Jun. 09, 2021
May. 19, 2021
Apr. 24, 2021
Creutzfeldt-Jakob disease (CJD) is a member of the group of diseases known as prion diseases or the subacute spongiform encephalopathies. CJD is a subacute fatal disease with a clinical triad of dementia, myoclonus, and EEG abnormalities that is usually associated with other neurologic signs, along with neuropathological evidence of neuronal loss, spongiform changes, and astrocytosis.
Apr. 23, 2021
Apr. 10, 2021
Epstein-Barr virus is a ubiquitous herpes virus associated with infectious mononucleosis. Neurologic complications due to acute Epstein-Barr virus infection
Apr. 06, 2021
Apr. 03, 2021
Apr. 03, 2021