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PEDIACTRIC CNS INFECTIONS
Terms in this set (61)
Provide information concerning the PACE of the disease.
• Acute, subacute, or Chronic
Physical and Neurological examination
localize the anatomic sight of the pathologic condition.
Three questions asked to have a neurologic diagnosis?
1. Is there a neurologic problem?
2. Where is the lesion? At what level?
3. What is the neurologic problem?
OTHER QUESTIONS FROM THE HISTORY
History of seizure/epilepsy/heart disease
Blood dyscrasias? → Leptomeningeal leukocytic infiltrates as a cause of seizure
Trauma? → subarachnoid hemorrhage
WHAT TO SEARCH FOR IN PHYSICAL EXAMINATION
o Most important
o We can palpate the anterior fontanel o Note for its fullness
o May give us an idea of how the present condition of the intracranial pressure is in our patient that is being examined
o May indicate an increased intracranial pressure §
Structural, metabolic, or infectious causes
• Skin lesions, exanthem
• Oral ulcers/enanthems
• Lymphadenopathy/parotid enlargement o In viral infections and some bacterial infections
• Ear discharges, Signs of sinusitis, and Dental abscess o Can help lead us into other focuses of infection that may particularly involve the brain
• Cardiac findings
• Dermal sinus
CASE: IS THERE NEUROLOGICAL PROBLEM
Since the patient presented with fever, seizure and altered sensorium = YES
CASE: WHERE IS THE LEVEL
Is it CNS or PNS? o Patient presented with fever and altered sensorium = problem more on cerebral cortex and subcortices of the brain rather than the PNS
CASE: WHAT IS THE NEUROLOGIC PROBLEM
Fever + Seizure/altered sensorium + Nuchal rigidity = ACUTE INFECTION OF THE CNS, MENINGITIS
INFECTIONS OF THE CENTRAL NERVOUS SYSTEM
• Most common cause of FEVER associated with signs and symptoms of CNS disease in CHILDREN
• Specific pathogens are identifiable, influenced by: o Age & immune status of host o Epidemiology of the pathogen
• Most patients with CNS infections have similar clinical manifestations
TESTS FOR MENINGEAL IRRITATION
• Nuchal rigidity •
(+) Brudzinski's neck sign o Slight flexion of neck of the neck of the patient > upward raise/flexion of lower extremities/legs
(+) Kernig's sign o Flex the knee of patient > minor/overt flexion of neck area
• Both of which would indicate a positive meningeal sign indicating meningeal irritation that is present in patients with central nervous system infection.
INFECTIONS OF CNS
• More of a diffuse condition rather than a focal Infection
o Diffuse infections include • Meningitis
o Focal Infections (Brain Abscess)
CLINICAL SYNDROMES OF CNS INFECTIONS
• MENINGITIS if: o Involves meninges
o Bacterial, TB, viral, fungal, parasitic as its primary focus or etiology of the infection
• ENCEPHALITIS if:
o Confined to the parenchyma
o Usually more diffuse
o Mainly VIRAL
• BRAIN ABSCESS if:
o Focal mass infectious mass lesion within parenchyma
o Bacterial, TB, fungal, parasitic
• Inflammation of the meninges Diffuse or nonspecific symptoms
• Meningeal irritation
o Hence the meningeal signs in your examination Signs of Increased intracranial pressure
o Changes in sensorium
• Focal neurologic signs
o CN VIII (Vestibulocochlear nerve) § Deafness/vestibular dysfunction
• Seizures in 1/3 patients
Inflammation of the brain parenchyma
Diffuse or nonspecific symptoms without meningeal signs
• Cerebral dysfunction
o Personality changes
o Altered alertness
o Cognitive dysfunction
• Both meningeal and parenchymal involvement
What is the neurologic problem or etiology?
ACRONYM: VITAMIN C and D
o History and physical examination o Onset and course of the illness
• Viral/Bacterial infection
CHRONIC & PROGRESSIVE
• TB/Fungal infection
o Congenital/developmental disorders
o Neoplasm/Nutritional deficiency
What is the neurologic problem?
Case: 3 y/o, 4 days history of fever, altered sensorium, seizure, and nuchal rigidity?
a. Benign Febrile Convulsion
b. TB Meningitis
c. Bacterial Meningitis
ANSWER: c. Bacterial Meningitis
Benign Febrile Convulsion
•Incidence: 6 months - 6 y/o
• Usually with normal neurodevelopmental status
• With a family history of febrile convulsion, usually in the 1st degree relatives
• Febrile seizures happen within the first 24 hours from the onset of fever
• Convulsion usually last for less than a minute or two and usually regains back to their usual self or consciousness usually the seizures happen during the height of the fever within the first 24 hours from the onset of the fever
• PROBABLY NOT
o Seizure on the 4th day of fever
o Did not return to his usual self
• PROBABLY NOT
o Subacute to chronic onset of CNS disorder manifestation
Pathogens are influenced by:
o Age and immune status of the host
o Epidemiology of the pathogen
ACUTE INFECTION OF THE CNS
•In Pediatrics, the etiology of the infections differs depending on the age group of the patients.
o Neonates to 2 months old
§ Gram negative enteric bacteria (*GBS)
o 3 months to <5 years old § Haemophilus influenzae
§ Streptococcus pneumoniae
If this is bacterial meningitis, what is the most likely organism? (3 year old male) a. Neisseria meningitides
b. Group B strep
c. E. coli
d. Haemophilus influenzae (Hib)
d. Haemophilus influenzae (Hib)
PATHOPHYSIOLOGY OF BACTERIAL MENINGITIS
• Usually pathogen starts to colonize in the nasopharyngeal mucosa and/or the presence of infection particularly bacterial infection in the other areas of the body. Some may have upper respiratory tract infection to start with eventually developing into pneumonia therefore bacteremia.
• Once bacteremia sets in, there is invasion of the infection in the blood vessels and the pathogen survives the host defense within the blood.
• As they continue to multiply, the bacteremia affects, crossing the Blood Brain Barrier and thereby insinuates a more diffuse infectious process as the edema and swelling of the brain continues.
• Now, there are also non-hematogenous way of invading the CSF. In this way, the integrity of the surrounding brain sub areas are surpassed.
• Conditions like Otitis Media, Mastoiditis, and Sinusitis can cause and complicate thereby causing acute bacterial CNS infections.
• Other complications from Neurosurgical procedures, spinal anesthesia, cochlear implantation,
or ventriculoperitoneal shunting may also be possible routes where the etiology of the bacterial CNS infection may occur in children.
GUIDELINES IN CNS INFECTIONS
• Way back 2014, the Child Neurology Society of the Philippines and the Philippine Infectious Disease Society come up with a Philippine Clinical Practice Guidelines (CPG) in the diagnosis and management of acute bacterial meningitis in infants and children. These are all formed by the technical working group who collected, reviewed, collated and collaborated the different proposals to come up with the clinical practice guidelines based on previous studies done locally and internationally.
• They more focus in coming up with a CPG in acute bacterial meningitis in infants and children and until now this has been used in most, if not all of the clinical practice in management of serious infections particularly acute bacterial meningitis in infants and children.
•In the clinical practice guidelines, extensive history, physical and neurologic examination is a must (these are very important in coming up with our clinical impression)
• CPG helps us determine further what tests, diagnostic and therapeutic management will be implied once we come up with a clinical impression
• Definitive Test for Bacterial Meningitis is CSF Culture
What immediate ancillary procedure will you request in the previous case?
3 y/o, 4 days Hx of fever, altered sensorium, focal seizure and nuchal rigidity.
a. Immediate lumbar tap
b. Cranial CT scan plain
c. Cranial CT scan with contrast
ANSWER: C. CRANIAL CT SCAN WITH CONTRAST Although we know that the definitive test for meningitis is CSF analysis, we should bear in mind that the patient presented with focal seizure. As such, we should make sure that there aren't any focal focus of infections or mass lesions that causes the seizures which makes it more important to rule out focal intracranial foci that would do more harm in doing lumbar puncture earlier. We must then do neuro-imaging first before considering doing lumbar tap right away.
• Used to identify the presence of complications of bacterial meningitis.
• Important Structural problems/ Complications found - HACTIVE acronym
1. Hydrocephalus - HCP
6. Ventriculitis or Vasculopathy
7. Extra-axial fluid -ex. Empyema, Hygroma
• Used to rule out contraindications in doing Lumbar tap • NOT used solely to diagnose the presence or absence of a CNS infection
Alternatively 1. Cranial ultrasound - imaging tests for children especially with open anterior fontanel
2. Cranial CT scan with contrast - older children with close fontanel
3. Cranial MRI with contrast - mass lesions and tumor
• We should overemphasize, a patient with CNS infection whether bacterial or viral still the definitive test is CSF Analysis and CSF Culture
•Along with the Philippine CTG for Acute Bacterial Meningitis, in 2006 a group of experts including our current Dean, Dr. Sosa together with other child neurologists came up with the Philippine clinical practice guideline on first Simple febrile seizure.
Strongly recommended for children < 18 months of age for a 1st Simple febrile seizure
• For those children ≥ 18 months of age, Lumbar puncture should be performed in the presence of clinical signs of meningitis (meningeal signs, sensorial changes).
• This is because before we omit the diagnosis of meningitis and commit only our impression for simple febrile seizure. We must make sure that Meningitis is really not present especially for children below 2 years of age and presenting with 1st onset Simple febrile seizure.
CONTRAINDICATIONS TO LUMBAR PUNCTURE
• Absolute contraindications
1. Signs of elevated intracranial pressure manifested by o Decreased or
fluctuating level of
consciousness, relative bradycardia and hypertension
o Presence of focal neurologic signs, posturing, unequal, dilated or poorly responsive pupils
o Presence of papilledema, abnormal Doll's eye movement
2. Local infection at desired puncture site
3. Radiologic signs of: Obstructive Hydrocephalus (HCP), cerebral edema or herniation, midline shift or mass lesion
• Relative Contraindications in doing Lumbar Puncture include the following:
o Signs of shock, sepsis or hypotension <100mmHG or DBP <60mmHG
o Coagulation defects
o (DIC, plt <50, 000/mm3 and therapeutic use of warfarin)
o Focal neurological deficit o GCS <8
o Epileptic seizures
o Respiratory insufficiency
We have been overemphasizing the importance of lumbar puncture and CSF analysis in the diagnosis of patients with acute bacterial meningitis but we should never forget that there are absolute and relative contraindications in doing the procedure
• What other tests can be requested aside from neuroimaging and lumbar puncture?
should not be used solely as a basis for starting antibiotics
we should never forget to do blood culture and it should be performed prior to staring antibiotic therapy
Serum and CSF CRP
§useful in confirming and excluding bacterial meningitis (increased in bacterial meningitis)
§Abnormal result of CRP like an increased CRP result is expected in patients with bacterial meningitis
may be utilized to amplify DNA from patients with meningitis caused by common meningeal pathogens (such as S. pneumonia, N. meningitidis, Hib) especially if CSF culture is negative
may be requested but should NOT be done routinely (sen: 0-25%)
may be used to differentiate bacterial from viral meningitis
• Empiric antibiotics or the antibiotics that is highly recommended based on studies could be effective in the management in treating acute bacterial meningitis before any CSF findings may be available to the clinician.
• Take note that CSF culture may take some time, roughly around 3-5 days before the sensitivity result may come out. We cannot wait for that such a long time. After doing the lumbar puncture, we can start with empiric antibiotic so that the treatment management may start at the soonest possible time.
What are the empiric antibiotics for acute bacterial meningitis
The Clinical Practice Guideline have the following antibiotics as part of empiric therapy suggested to be employed in the management of acute bacterial meningitis. o Neonates (0-28 days old): ampicillin
o 1 month to 18 years old: Ceftriaxone or Chloramphenicol
•*depending on local resistance pattern
• Depending on the pathogen, there are specific treatment or drug of choice that is recommended for each case. Like for Neisseria meningitides, Penicillin for 7 days is highly recommended.
VALUE OF USING STEROIDS FOR ACUTE BACTERIAL MENINGITIS
• Steroids have no role in general in neonatal meningitis.
• But in children 2 months to 5 years old wherein Hib meningitis is suspected
• Dexamethasone at a dose of 0.15 mg/kg (maximum of 10mg) every 6 hours for 4 days is recommended. o Along with or shortly before the first parenteral dose of antibiotics or if not, administer the first dose within 4 hours of starting antibiotics.
• DO NOT START dexamethasone if >12 hours after starting antibiotics o However, if antibiotics have been started already, Dexamethasone or any other steroids are not highly recommended to be given anymore.
• Reduction of edema and improvement of outcomes
RECOMMENDED DURATION OF TREATMENT FOR
ACUTE BACTERIAL MENINGITIS IN PATIENTS WHEREIN THE ORGANISM WAS NOT ISOLATED
•In terms of duration of treatment in acute bacterial meningitis wherein the organism was not isolated, or the culture turned out to be negative, what is the recommended duration of empiric treatment?
• Recommended duration of empiric treatment: 10-14 days o ≤3 months: 14 days o >3 months: 10 days (complete IV parenteral therapy)
• The duration of therapy may need to be individualized on the basis of patient's clinical response
INDICATIONS TO SHIFT TO ANOTHER ANTIBIOTIC
1. Absence of or limited improvement despite adequate antibiotic coverage (e.g persistent fever after 36 to 48 hours of adequate antibiotics)
2. Clinical deterioration
3. Drug intolerance
4. Resistant isolate based on cultures and clinically compatible with the clinical course
• *Decision is based on the clinician's clinical judgment.
APROPRIATENESS OF STEP-DOWN TO ORAL THERAPY FROM IV PARENTERAL TREATMENT
•IV → Oral Antibiotic therapy: not recommended o These considerations are not possible even if the patient remains to be clinically okay, active, or alert; switching IV therapy to Oral antibiotic therapy is not recommended.
• Chloramphenicol (100 mg/kg/day div q6): only antibiotic which could be used orally for treating community acquired CNS infections.
o Why? Because Chloramphenicol in itself has better oral absorption more than its IV preparation.
o Therefore, IV chloramphenicol can be switched to its oral form after 3 to 4 days of the initial IV therapy in children > 3 months old and are well-nourished.
o But for children less than 3 months of age, first and foremost chloramphenicol is not the first option and secondly in this group of patients, we usually continue to give IV parenteral therapy for acute bacterial meningitis treatment upon duration of 2 to 3 weeks.
• Consider antibiotic resistance patterns and drug interactions
• Give full volume of maintenance fluids unless the patient presents sign and symptoms of increase ICP or increased antidiuretic hormone secretion or what we know SIADH.
• Antiseizure medication if the patient presented with several episodes of seizure, we give anti-epileptic drugs in order for the patient not to have recurrences of seizure which may increase the patient to further brain damage, increase metabolic break in the brain, and increased ICP
INDICATIONS FOR PROPHYLAXIS AMONG CLOSE CONTACTS
•Individuals living in the same quarters as the index patient or those with body fluid exchange
o Rifampicin >1 month old: 10 mg/kg per orem q12 x 2 days
§ <15 years old, 125 mg IM single dose § >15 years old: 250 mg IM single dose
o Ciprofloxacin > 18 yo 20 mg/kg orally, single dose (max 500 mg)
•Hib (specially if with an infant <2 yo or immunocompromised person)
o Rifampicin 200 mg/kg once a day x 4 days (max 600 mg)
Q: Is bacterial Lecturer infection in the CNS
more common than viral infections in the CNS?
A: To be answered in Part 3 according to Dra. but she wasn't able to answer it. Based on Nelson's, the majority of cases of meningitis are caused by S. Pneumoniae and N. Meningitidis (page 3226, Central Nervous System Infections Chapter)
• Viral, or otherwise called aseptic meningitis
• Most frequent virus-induced neurologic disorder o Malaise, headache, vomiting, irritability o Stiff neck, neck or back pain
• Non-polio enterovirus: most frequent, are the ones most commonly affecting children o GI symptoms, evanescent, erythematous rashes or oral lesions (coxsackie, echovirus)
o Hepatomegaly and lymphadenopathy as seen in Epstein-Barr Virus (EBV)
PATHOPHYSIOLOGY OF VIRAL MENINGITIS
• Somehow is almost similar to what we discussed in the first part of this lecture. This time, the pathogen which is a virus, enters and replicate in the skin or mucosa, particularly the respiratory tract or the gastrointestinal tract +, with the poor immune response of the host, they may continue to have a hematogenous spread via the choroid plexus or the vascular endothelium, thereby breaking and passing through the blood brain barrier.
•After which, it may cause direct damage to neuronal cells or by indirect damage by stimulating an immune response or cytokine release, altering the host's immune response and function. And this have the predilection for the cerebral cortex particularly, HSV and affecting the entire brain maybe the arboviral infections, and one of the more common in the Philippines affecting the brain through the nerves are the rabies virus.
• Enteroviruses • most common cause of viral meningoencephalitis in children
o Arthropod-borne agents o In a country like the Philippines where Arthropod-borne agents are very rampant, arboviruses should never be left out as a possible cause of viral encephalitis
o Vectors: Mosquitoes and ticks are the most common vectors
o Spreading disease to humans after biting infected birds or small animals
o Dengue Virus, Japanese Encephalitis Virus
HERPES SIMPLEX VIRUS (HSV) ENCEPHALITIS
• Only effectively treatable form of encephalitis
• Focal seizures
o Temporal Lobe
§ Between the two, Temporal lobe is more commonly affected
• CSF;>100 RBC
o Micro-hemorrhage in the area of encephalitis
o Dull flat mask-like facie
§ With wide unlinking eyes
o Generalize tremor (movement disorders)
o Hypertonia, and cogwheel rigidity
•Plus/predominance of thalamic and/or basal ganglia involvement when you do CT Scan
AUTOIMMUNE ENCEPHALITIS (Non-Infectious Encephalitis)
• "N-methyl-Aspartate encephalitis
• Group of neuropsychiatric disorders, presenting acutely or sub acutely with alteration of consciousness, cognitive decline, seizure, sleep disturbances, and abnormal movements where all of which in one patient may present as a SYNDROME whenever we see patients in the clinics
DIAGNOSTICS (VIRAL ENCEPHALITIS)
• Just like bacterial causes of meningitis, viral encephalitis and its diagnosis warrants CSF examination:
o Lymphocytic pleocytosis (5 - 500 cells/mL)
o mildly elevated protein (50 - 200 mg/dL)
o Normal or slightly low glucose content
o 15% of patients with HSV: normal CSF
o Specific diagnostic studies: PCR, ELISA
o Viral culture: NOT recommended
• Herpes simplex PCR should be performed on all CSF specimens in patients with encephalitis because among all the viral encephalitis,
o Amongst the viral encephalitides, only Herpes simplex is highly detectable and highly treatable.
• For Japanese Encephalitis Virus (JEV):
o IgM and IgG capture enzyme linked immunosorbent assays (ELISA
§IgM Elisa Test detects for the acute infection IgG Elisa Test detects previous infection
§ Sensitivity and specificity of >95% • Gold standard
§ Should be repeated if initially negative (get the serum 7 days after admission)
§ *** Cross reactivity with Dengue virus (24%)
o PCR: positively 86%
o Culture: CSF rarely yields virus
• Cranial MRI more sensitive than CT scan
o HSV: medial temporal, orbitofrontal or cingulate gyrus, cortical enhancement
o JEV: thalamus and/or basal ganglia o Other encephalitis: present with normal MRI
TREATMENT (VIRAL ENCEPHALITIS)
• The Management of Encephalitis: Clinical Practice Guidelines by the Infectious Diseases Society of America
• Acyclovir should be initiated in all patients with suspected encephalitis, pending results of diagnostic studies (A-III).
• Specific therapy: (for specific viral etiologies) o HSV (Herpes Simplex Virus) and VZV (Varicella Zoster Virus): Acyclovir
o CMV (Cytomegalovirus): Ganciclovir (very well responsive)
o HHV6 (Human Herpes Virus type 6): Ganciclovir if immunocompromised)
PROGNOSIS (VIRAL ENCEPHALITIS)
• Most Viral Encephalitides are self-limiting.
• Consider treatment with Acyclovir in all patients suspected of Encephalitis, early on the course of treatment.
• Supportive and rehabilitative efforts should always be exhausted.
• Watch out for
o Motor incoordination, convulsive disorders which may add to the comorbidities of the current situation of the patient.
o Behavioral disturbances (post infectious
autoimmune encephalitis) may be seen to complicate the course of patients having NMDAR infections.
o Visual and hearing disturbances may likewise be seen as the same possible complications for those patients with bacterial meningitis.
• Overall, neurodevelopment, visual and audiologic evaluations must be emphasized especially during the follow-up period amongst patients who were treated, survived, and recovered from CNS infections
•Acute CNS infection can either be caused by bacteria or viruses
•History and physical examination are still the most important tool in the diagnosis and management
•Physicians should be aware of the most common pathogens based on the patient's age, immune system status, and epidemiology in order to give appropriate management.
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