MD3-CNS INFECTIONS MAKATU.pptx1234556778

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1. CNS Infections and Associated Complications Makatu Conrad

2. Introduction Infection of the central nervous system is a life-threatening condition in the pediatric population. Almost all agents can cause infection within the central nervous system and the extent of infection ranges from diffuse involvement of the meninges, brain, or the spinal cord to localized involvement presenting as a space-occupying lesion Sahu , et al.: Infection in pediatric population 2009

3. Introduction Infections of the central nervous system (CNS) can be divided into 2 broad categories: Those primarily involving the meninges (meningitis) Those primarily confined to the parenchyma (encephalitis) However, these anatomic boundaries may be indistinct during infection. Terms such as meningoencephalitis may better describe diffuse infections of the CNS by pathogens such as viruses

4. Meningitis Meningitis is an inflammatory process involving the meninges. The differential diagnosis is broad . Aseptic meningitis is the most common form. Aseptic is differentiated from bacterial meningitis if there is meningeal inflammation without signs of bacterial growth in cultures. Mount, H. R., & Boyle, S. D. (2017). Aseptic and Bacterial Meningitis: Evaluation, Treatment, and Prevention. American Family Physician, 96(5), 314–322 .

5. Acute Bacterial Meningitis Bacterial meningitis is a severe, life-threatening infection of the central nervous system that requires immediate medical attention. Even with appropriate treatment morbidity and mortality can be substantial. Acute bacterial meningitis has a relatively rapid onset of symptoms, and routine laboratory techniques can usually identify the pathogen. The most common causes have been Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae type b (Hib), group B Streptococcus (GBS), and Listeria monocytogenes. Swanson, D. (2021). Meningitis .

6. Acute Bacterial Meningitis In addition, rates of pneumococcal meningitis from non-PCV7–serotype strains began to increase, including cases of meningitis due to drug-resistant strains, such as serotype 19A. In 2010, PCV13 was introduced to respond to the emerging invasive strains of pneumococcus. Currently, S pneumoniae remains the most common cause of acute bacterial meningitis for children older than 1 month Swanson, D. (2021). Meningitis .

7. Aseptic Meningitis Aseptic meningitis is characterized by clinical signs and symptoms of meningitis without evidence of a bacterial cause by usual laboratory testing methods. Some bacteria that do not grow in routine culture, such as Mycobacterium tuberculosis and Borrelia burgdorferi, can cause aseptic meningitis. Aseptic meningitis has many infectious and noninfectious causes.

8. Aseptic Meningitis The incidence is uncertain because aseptic meningitis is not a reportable disease. A birth cohort study from Finland found the annual incidence to be 28 per 100,000 persons, with the highest rates in children younger than 4 years of age. Enteroviruses and parechoviruses account for most of all known cases. In temperate climates, infections with these viruses typically occur in the summer and fall seasons. Arboviruses encompass a vast number of viruses from different biologic families that are transmitted by arthropods, especially mosquitoes. The most commonly reported arboviruses causing aseptic meningitis infections in the United States are West Nile virus and La Crosse virus.

9. Chronic Meningitis Chronic meningitis involves ongoing signs and symptoms of meningitis for 4 or more weeks without clinical improvement. It has many infectious and noninfectious causes each with its own epidemiology. The overall incidence of chronic meningitis is unknown due to limitations in data collection. The epidemiology differs according to the causative agent Swanson, D. (2021). Meningitis .

10. Epidemiology In all age groups, S. pneumoniae and N. meningitidis were the predominant pathogens in all regions, accounting for 25.1-41.2% and 9.1-36.2% of bacterial meningitis cases, respectively. S. pneumoniae infection was the most common cause of bacterial meningitis in the `all children’ group, ranging from 22.5% (Europe) to 41.1% (Africa), and in all adults ranging from 9.6% (Western Pacific) to 75.2% (Africa). E. coli and S. pneumoniae were the most common pathogens that caused bacterial meningitis in neonates in Africa (17.7% and 20.4%, respectively). N. meningitidis was the most common in children aged ±1±5 years in Europe (47.0%). Oordt-speets, A. M., Bolijn, R., Hoorn, R. C. Van, Bhavsar, A., & Kyaw, H. (2018). Global etiology of bacterial meningitis : A systematic review and meta-analysis. 1–16.

11. Pathogenesis Meningitis usually follows invasion of the bloodstream by organisms that have colonized mucosal surfaces. In the neonatal period, vertical transmissions from the mother. Neonates with longer nursery stays can also be exposed to multiple nosocomial pathogens In infants and children, meningitis usually develops after encapsulated bacteria that have colonized the nasopharynx are disseminated in the blood. Sáez-Llorens , X., & McCracken, G. H. (2003). Bacterial meningitis in children. Lancet, 361(9375), 2139–2148. https://doi.org/10.1016/S0140-6736(03)13693-8

12. Pathogenesis Viral infections of the upper respiratory tract commonly precede invasion of the bloodstream. Subsequently, organisms penetrate vulnerable sites of the blood-brain barrier ( eg , choroid plexus and cerebral capillaries) and reach the subarachnoid space. Meningitis can also develop by direct extension of infection from a paranasal sinus or from the middle ear through the mastoid to the meninges.

13. Pathogenesis Severe head trauma with a skull fracture, cerebrospinal fluid (CSF) rhinorrhea, or both, can lead to meningitis, usually caused by S pneumoniae. Bacteria can be directly inoculated into the CSF by congenital dural defects (dermal sinus or meningomyelocele), neurosurgical procedures (such as CSF diversion shunts), penetrating wounds, or extension from a suppurative parameningeal focus Sáez-Llorens , X., & McCracken, G. H. (2003). Bacterial meningitis in children. Lancet, 361(9375), 2139–2148. https://doi.org/10.1016/S0140-6736(03)13693-8

14. Clinical Manifestations-Neonates and Infants The clinical manifestations of neonatal bacterial meningitis are generally nonspecific and usually comprise a constellation of signs and symptoms. Temperature instability is a common feature, with either fever or hypothermia occurring in about 60% of newborns who have bacterial meningitis, normothermia is not unusual. There is often a report of vomiting and poor feeding. Parents frequently state that their infant is fussy, inconsolable, sleepy, weak, or jittery.

15. Clinical Manifestations-Neonates and Infants Seizures occur in 20% to 50% of infants with the presentation of illness. Neck stiffness is uncommon in neonates. Parents may report that the baby has a “knot on its head” to describe the presence of a bulging fontanelle.

16. Clinical Manifestations-Older Child The clinical presentation of meningitis in older children often occurs over a few days and may include: Progressive history of fever Headache Lethargy, Irritability, Confusion, Photophobia Nausea, vomiting back pain, Stiff neck

17. Clinical Manifestations-Older Child Sometimes the presenting signs and symptoms are severe and sudden, occurring within a period of hours. About 20% of affected children have a seizure before diagnosis, and about 25% have a seizure during the first few days of hospitalization The seizures are frequently complex and more common with meningitis due to Hib or S pneumoniae than N meningitidis.

18. Physical Examination-Neonate and Infants Vital signs and general appearance should be assessed. Neurologic features of meningitis in infants include inconsolable irritability, lethargy, poor tone, and seizures. Nuchal rigidity is uncommon. The anterior fontanelle is usually full but not often bulging. Poor capillary refill and respiratory difficulty with grunting, tachypnea, and nasal flaring are frequent findings. The infant is less active and often seems apathetic and disinterested in its surroundings. Head circumference should be measured daily to monitor for increased intracranial pressure

19. Physical Examination-Older Child The child with meningitis is usually irritable or lethargic on physical examination. Vital signs, including pulse oximetry, should be obtained promptly to help evaluate for hypovolemia, shock, and increased intracranial pressure(ICP). Cushing triad (hypertension, bradycardia, and respiratory depression) is a late finding of increased ICP. Although the following signs of ICP are uncommon, patients should screened for papilledema, diplopia, and cranial nerve paralysis. The pediatric GCS can be a useful tool to monitor the patient’s level of consciousness. Children who are obtunded or comatose upon admission have worse outcomes than those who are not.

20. Diagnostic Evaluation

21. Management

22. Fluid Management Careful management of fluid and electrolyte balance is an important aspect of supportive therapy. Both over- and underhydration are associated with adverse outcomes. Hypotonic fluids should be avoided because they deliver too much free water, which contributes to hyponatremia and can exacerbate cerebral edema

23. Fluid Management Shock Children who are in shock should receive sufficient quantities of isotonic fluid to maintain blood pressure and cerebral perfusion. Hypovolemia without shock Children who are volume depleted, but not in shock, should receive volume repletion with isotonic fluids with careful and frequent attention to fluid status. Daily weight, urine output, and serum electrolytes should be monitored.

24. Fluid Management- Hyponatremia and SIADH Hyponatremia is defined as a serum sodium decrease of <135 mEq /L. The commonest electrolyte abnormality occurring in 3–35% of hospitalized patients, 50% of neurological admissions, and one-third of patients in intensive care units.

25. Fluid Management- Hyponatremia, SIADH, CSW Hyponatremia in a patient may be due to a number of causes such as: Poor intake of sodium, drugs, vomiting, diarrhea, liver, kidney or heart failure, endocrine disorders. Syndrome of inappropriate section of antidiuretic hormone (SIADH) and cerebral salt wasting (CSW). Stroke, subarachnoid hemorrhage, head injury, neurosurgical operations and central nervous system (CNS) infections Misra , U. K., & Kalita , J. (2020). Mechanism , spectrum , consequences and management of hyponatremia in tuberculous meningitis [ version 1 ; peer review : 2 approved ].

26. Dexamethasone The best evidence supports the use of dexamethasone 10 to 20 minutes before or concomitantly with antibiotic administration in the following groups: infants and children with H. influenzae type B, adults with S. pneumoniae patients with Mycobacterium tuberculosis without concomitant human immunodeficiency virus infection. Some evidence also shows a benefit with corticosteroids in children older than six weeks with pneumococcal meningitis. Mount, H. R., & Boyle, S. D. (2017). Aseptic and Bacterial Meningitis: Evaluation, Treatment, and Prevention. American Family Physician, 96(5), 314–322.

27. Dexamethasone Because the etiology is not known at presentation, dexamethasone should be given before or at the time of initial antibiotics while awaiting the final culture results in all patients older than six weeks with suspected bacterial meningitis. Dexamethasone can be discontinued after four days or earlier if the pathogen is not H. influenzae or S. pneumoniae, or if CSF findings are more consistent with aseptic meningitis. Mount, H. R., & Boyle, S. D. (2017). Aseptic and Bacterial Meningitis: Evaluation, Treatment, and Prevention. American Family Physician, 96(5), 314–322 .

28. Prognosis Prognosis varies by age and etiology of meningitis. In a large analysis of patients from 1998 to 2007, the overall mortality rate in those with bacterial meningitis was 14.8%. Worse outcomes occurred in those with: Low Glasgow Coma Scale scores Systemic compromise (e.g., low CSF white blood cell count, tachycardia, positive blood cultures, abnormal neurologic examination, fever) Pneumococcal infection

29. Complications Complications from bacterial meningitis also vary by age. Neurologic sequelae such as hearing loss occur in approximately 6% to 31% of children and can resolve within 48 hours, but may be permanent in 2% to 7% of children. An audiology assessment should be considered in children before discharge. Mount, H. R., & Boyle, S. D. (2017). Aseptic and Bacterial Meningitis: Evaluation, Treatment, and Prevention. American Family Physician, 96(5), 314–322 .

30. Viral Meningitis Aseptic meningitis is the clinical syndrome of meningeal inflammation with negative cultures for routine bacterial pathogens in a patient who did not receive antibiotics before lumbar puncture. Aseptic meningitis has a number of infectious and noninfectious causes . Viruses (usually enteroviruses[EVs]) are the most common cause. Because viruses are the most common cause of aseptic meningitis, the terms aseptic meningitis and viral meningitis are sometimes used synonymously

31. Viral Meningitis Viral causes of meningitis have become more common as the prevalence of bacterial meningitis has decreased due to vaccinations, and viral meningitis is the most common form of meningitis in many countries. Viral meningitis typically presents with the acute onset of fever, headache, photophobia, neck stiffness, and often nausea and vomiting, although younger children may not show signs of meningeal irritation. Viral meningitis is usually a self-limiting illness with a good prognosis Cantu, R. M., & Das, J. M. (2021). Viral Meningitis. (Lcmv), 1–7 .

32. Epidemiology Viral meningitis most commonly occurs in young children, with the incidence decreasing with age. In countries with high rates of immunization coverage, viral meningitis is more common than bacterial meningitis, with an estimated 3 to18% of childhood meningitis being bacterial in origin Vaccinations for Haemophilus influenza type B, Streptococcus pneumoniae and Neisseria meningitidis have significantly decreased cases of bacterial meningitis. The incidence of viral meningitis has been estimated to range from 0.26 to 17 cases per 100000 people. In the United States, there are up to 75000 cases of enteroviral meningitis annually.

33. Etiology Enteroviruses (Coxsackie or Echovirus groups) are the most common cause of viral meningitis across all age groups; parechoviruses are also common in children. Herpesviruses that cause meningitis include herpes simplex virus(HSV) 1 and 2, varicella-zoster virus (VZV), cytomegalovirus, Epstein-Barr virus, and human herpesvirus 6. Other viral causes include adenovirus, lymphocytic choriomeningitis virus (LCMV), influenza, parainfluenza, and mumps. Arboviruses that can cause viral meningitis include West Nile virus (WNV), Zika, chikungunya, dengue, LaCross , Saint Louise encephalitis, Powassan, and eastern equine encephalitis virus

34. Evaluation LP as in bacterial meningitis Polymerase chain reaction (PCR) tests can be used to diagnose some causes of viral meningitis, such as enterovirus, VZV, and HSV. Serum white blood cell count and C-reactive protein do not reliably distinguish viral and bacterial meningitis. CSF C-reactive protein and procalcitonin have not been shown to differentiate viral vs. bacterial meningitis compared to serum levels

35. Treatment Most viruses causing meningitis have no specific treatment other than supportive care. Fluid and electrolyte management and pain control are the mainstays of management of viral meningitis. Patients should undergo observation for neurological and neuroendocrine complications, including seizures, cerebral edema, and SIADH. Because of the difficulty in differentiating viral from bacterial meningitis initially, empiric antibiotic therapy is usually indicated until bacterial meningitis is ruled out.

36. Treatment In patients aged one month and older, empiric therapy for bacterial meningitis can be provided with vancomycin in combination with either ceftriaxone or cefotaxime while culture results are pending. If encephalitis is suspected, empiric antiviral treatment with intravenous acyclovir should be a consideration. Acyclovir should be the choice for suspected or proven HSV or VZV infections, although it has been shown to provide benefits in HSV encephalitis, not meningitis.

37. Prognosis The prognosis of viral meningitis without associated encephalitis is generally good. Viral meningitis typically has a spontaneous recovery, compared to bacterial meningitis in which progressive mental status deterioration may occur. Older infants and children are often ill for greater than a week but usually, have a full recovery. While viral meningitis is usually self-limiting, there can be morbidity

38. Complications Enterovirus meningitis typically has a benign course, while enterovirus encephalitis can result in long-term neurological sequelae. Significant morbidity and mortality follow enteroviral meningitis in neonates and immunocompromised patients. Some subtypes of enterovirus, such as EV71 and EV68, are associated with more severe neurological disease and worse outcomes.

39. Complications The most common severe complications of enteroviral meningitis are meningoencephalitis, myocarditis, and pericarditis. In children, neurologic complications of enteroviral infection can include acute flaccid paralysis and rhombencephalitis. Neuropsychological impairments after viral meningitis are measurable but typically not as severe as those sustained after bacterial meningitis. Some studies have noted impaired sleep as a long-term sequela of meningitis.

40. Central nervous system tuberculosis Forms of central nervous system (CNS) infection due to Mycobacterium tuberculosis include meningitis, tuberculoma, and spinal arachnoiditis. Among patients with tuberculosis, approximately 1 to 5 percent are complicated by CNS TB. In regions where the prevalence of TB is high and the prevalence of post-primary dissemination is common among children and young adults, all three forms of CNS TB (tuberculous meningitis, intracranial tuberculoma, and spinal tuberculous arachnoiditis) are encountered relatively frequently

41. Pathogenesis During the bacillaemia that follows primary infection or late reactivation TB, scattered tuberculous foci(tubercles) are established in the brain, meninges, or adjacent cranial bone. The establishment of a cortical or meningeal tubercle (Rich focus), with subsequent rupture into the subarachnoid space, is the critical event in the development of TB meningitis. The widespread and dense distribution of foci seen in association with progressive miliary TB greatly increases the chance that juxta-ependymal tubercles will be established.

42. Pathogenesis The spillage of tubercular bacilli and tubercular protein into the subarachnoid space produces an intense hypersensitivity reaction, giving rise to inflammatory changes that are most marked at the base of the brain. Three features dominate the pathology and explain the clinical manifestations:

43. Pathogenesis Thick gelatinous exudate, most marked at the basal part of the brain, eventually produces a fibrous mass that encases adjacent cranial nerves and vessels of Circle of Willis, leading to cranial nerve palsies and periventricular infarcts, respectively. Tuberculous vasculitis with resultant inflammatory vascular changes leads to spasm, constriction, thrombosis, and occlusion of intracerebral vessels. Occlusion of cerebral arteries results in infarction of the brain parenchyma.

44. Pathogenesis Hydrocephalus eventually develops in the majority of patients with tuberculous meningitis. Communicating hydrocephalus results from extension of the inflammatory process to the basilar cisterns and impedance of cerebrospinal fluid circulation and resorption.

45. Tuberculous Meningitis Tuberculous meningitis develops most commonly as a complication of progressive primary infection in infants and young children. Patients with tuberculous meningitis commonly present with stiff neck, headache, fever, and vomiting; these symptoms are also frequently observed with bacterial meningitis Seizures are more common in children and tend to occur early in illness

46. Phases of TB Meningitis The early prodromal phase , lasting one to three weeks, is characterized by the insidious onset of malaise, lassitude, headache, low-grade fever, and personality change. The meningitic phase follows with more pronounced neurologic features, such as meningismus, protracted headache, vomiting, lethargy, confusion, and varying degrees of cranial nerve and long-tract signs. The paralytic phase supervenes as the pace of illness accelerates rapidly; confusion gives way to stupor and coma, seizures, and often hemiparesis. For the majority of untreated patients, death ensues within five to eight weeks of the onset of illness

47. Disease Stages Stage I – Alert and oriented with no focal neurologic signs. Stage II – Conscious but with inattention, confusion, lethargy; they may have mild focal signs such as cranial nerve palsies or hemiparesis (Glasgow coma score 11 to 15) Stage III – Advanced illness with delirium, stupor, coma, seizures, multiple cranial nerve palsies, and/or dense hemiplegia (Glasgow coma score ≤10)

48. Examination Findings Routine blood counts and chemistries are relatively nonspecific; mild anemia is common. Hyponatremia may be observed in the context of inappropriate antidiuretic hormone or cerebral salt wasting Central diabetes insipidus resulting in hypernatremia has also been described. Chest radiograph abnormalities may be seen in up to half of patients with CNS TB, ranging from focal lesions to a miliary pattern

49. Examination Findings CT of the chest is an important diagnostic modality to evaluate for concomitant pulmonary tuberculosis. The tuberculin skin test (TST) or an interferon-gamma release assay (IGRA) is frequently positive however, a negative result does not exclude TB.

50. Diagnosis The diagnosis of tuberculous meningitis should be suspected inpatients with relevant clinical manifestations (subacute presentation of stiff neck, headache, fever, and vomiting) Relevant epidemiologic factors (history of prior tuberculosis [TB] infection or disease, known or possible TB exposure, and/or past or present residence in or travel to an area where TB is endemic). The diagnosis may be definitively established in the setting of cerebrospinal fluid (CSF) with positive smear for acid-fast bacilli (AFB), CSF culture positive for M. tuberculosis or CSF with positive nucleic acid amplification test (NAAT)

51. Diagnosis However, definitive diagnosis can be challenging, given suboptimal sensitivity and specificity of diagnostic tests A presumptive diagnosis of tuberculous meningitis may be made in the setting of relevant clinical and epidemiologic factors and typical CSF findings(lymphocytic pleocytosis, elevated protein concentration, and low glucose concentration).

52. Differential Diagnosis Fungal meningitis (cryptococcosis, histoplasmosis, blastomycosis, coccidioidomycosis) Neurobrucellosis – Brucellosis typically presents with insidious onset of fever, malaise, night sweats, and arthralgias. Neurosyphilis – Meningitis and meningovascular disease are manifestations of early neurosyphilis. Bacterial meningitis , Viral Meningitis Focal parameningeal infection (brain abscess, spinal epidural abscess, sphenoid sinusitis) – Clinical manifestations of parameningeal infection may be subacute and nonspecific.

53. Management Treatment of tuberculous meningitis consists of prompt administration of antituberculous therapy, together with glucocorticoids.

54. Complications Hydrocephalus occurs in up to 80 percent of patients with tuberculous meningitis, and is often accompanied by signs of raised intracranial pressure. Hyponatremia is a potentially serious complication of tuberculous meningitis. Hyponatremia may develop at any point of time during course of tuberculous meningitis. Vision loss, a severely disabling complication of tuberculous meningitis, occurs in approximately one-quarter of patients Many survivors of tuberculous meningitis have permanent blindness