A unique case report of pneumococcal meningitis complicated by diffuse vasculitis and severe neurologic debility. Child displayed remarkable recovery with steroid therapy despite prolonged severe disease course!
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Complicated Pediatric Pneumococcal Meningitis - Case Presentation
1. Complicated Pneumococcal Meningitis - A Unique
Case Presentation
Presenter: Fatima Farid Pediatric - Resident Year II
Supervised by Pediatric Hematology Team
2. Patient was managed by a multidisciplinary team with general
pediatrics, pediatric neurology and anesthesiology.
4. Case
◦ Five-year-old previously healthy boy.
◦ Presented with two- day history of fever and headache, followed by one day of
vomiting.
4
5. Two days prior to presentation
◦ Child was apparently well and attended school.
◦ While running during school hours, he sustained trauma to right parietal region of
head after fall to ground.
◦ After trauma, child first developed severe localized headache.
◦ No active interventions were made at the time, and child continued his day.
◦ Upon return home, mother first checked temperature and found fever at 39C.
◦ Adol suppositories were given as needed, but fever and headache persisted.
5
6. One day prior to presentation
◦ Fever spiked every 6- 8 hours between 38- 39C with only temporary response to Adol.
◦ Patient was taken to a private clinic, and subsequently a private hospital where only
antipyretics were given, and child was discharged home.
◦ Fever and headache continued, and child vomited once after dinner. Emesis was non-
projectile, of food contents only, non- bilious/ non- bloody.
◦ Child was brought to ED the next morning with fever, headache, increasing
somnolence and decreased appetite.
6
7. Systemic Review
◦ No loss of consciousness, seizures/ abnormal movements or drowsiness immediately
after fall.
◦ No history of runny nose, cough, ear pain/ discharge or throat pain.
◦ No skin rash.
◦ No change in bladder or bowel habits.
◦ No weight loss.
◦ No recent sick contacts or travel abroad.
7
8. Additional History
◦ No past medical or surgical history.
◦ Not on regular medications.
◦ Fully immunized as per schedule.
◦ Development appropriate for age, attending KG- II.
◦ Born at term via elective LSCS with uneventful antenatal/ post- natal period. Birth weight
3.5 kg.
◦ On regular family diet.
◦ No known allergies to food or drugs.
◦ Second child to non- consanguineous parents. Unremarkable family history.
8
10. Physical Examination
◦ General: Conscious, oriented but irritable. Well- hydrated. Capillary refill less than 2
seconds. Comfortable on room air.
◦ ENT: Normal. No palpable cervical lymph nodes.
◦ Chest: Bilateral equal air entry with no added sounds. Normal heart sounds with no
murmur. Peripheral pulses well- felt bilaterally.
◦ Abdomen: Soft, non- tender with no palpable organomegaly.
◦ CNS:
◦ GCS 15/ 15
◦ Neck stiffness present. Brudzinski and Kernig signs unable to elicit as child irritable and
uncooperative.
◦ Tone, power, reflexes and cranial nerves intact.
◦ Skin: No rash present.
10
11. What is the differential diagnosis and next step in care?
13. Management in ED
13
Labs were collected and child was sent for
CT brain without contrast.
By the time child returned, both lab results
and image reports were online.
Pediatric medical on- call team was then
contacted by ED physician to assess child.
14. Investigations
◦ CBG normal
◦ Full Blood Count:
◦ WBC 2.6 x10^3 /uL
◦ Absolute neutrophil count 1.2 x10^3/ uL
◦ Hemoglobin 12.7 g/dL
◦ Platelets 133 x10^3/ uL
◦ C- reactive protein: 434.8 mg/L
◦ CXR showed prominent vascular markings and parahylar haziness.
14
16. Admission
16
First dose of IV Ceftriaxone was then administered in ED, and child was admitted to
isolation ward.
In view of high-grade fever, headache, neck stiffness and raised inflammatory markers
the picture is in favor of bacterial meningitis rather than intra- cranial bleed.
17. Emergency
management of
suspected
meningitis
◦ Suspected bacterial meningitis is a medical
emergency, and immediate diagnostic steps must
be established to determine the specific cause so
that appropriate antimicrobial therapy can be
initiated.
◦ Antibiotic therapy should be initiated immediately
after LP is performed if the clinical suspicion of
meningitis is high.
◦ If CT brain is to be performed before LP, antibiotic
therapy should be initiated immediately after blood
cultures are obtained, before the CT is performed.
17
“Bacterial Meningitis in children older than one month: Treatment and prognosis” - UpToDate 2019
18. Emergency
management of
suspected
meningitis
◦ Although administration of antimicrobial therapy
before LP may affect the yield of CSF gram stain
and culture, pathogens other than meningococcus
usually can be identified in the CSF up to several
hours after the administration of antibiotics.
18
“Bacterial Meningitis in children older than one month: Treatment and prognosis” - UpToDate 2019
19. Admission ◦ Child was admitted to isolation room
where LP was performed.
19
22. Bacterial
meningitis
◦ Streptococcus pneumoniae is the most common
cause of bacterial meningitis in infants and children
older than one month of age.
◦ In addition, specific factors may predispose certain
hosts to bacterial meningitis with a particular
organism.
22
“Bacterial Meningitis in children older than one month: Clinical features and diagnosis” - UpToDate 2019
25. Therapy
Modification
◦ IV Vancomycin was added to IV
Ceftriaxone therapy in fear of infection
with penicillin- resistant strain of
Streptococcus pneumoniae.
25
26. Pneumococcal
antibiotic
resistance
◦ Early in the antibiotic era, pneumococci were
uniformly susceptible to penicillin.
◦ Beta-lactam resistance among pneumococci is
largely dose dependent; when non–central nervous
system infections are being treated, it can be
overcome by the doses of beta-lactams currently in
use.
26
“Resistance of Streptococcus pneumoniae to beta- lactam antibiotics” - UpToDate 2019
27. Pneumococcal
antibiotic
resistance
◦ Because of the relatively poor ability of beta-
lactams to cross the blood-brain barrier, only about
80 percent of pneumococcus isolates are fully
susceptible at concentrations achievable in the
central nervous system. Therefore, resistance is of
much greater consequence in cases of
meningitis than in cases of disease outside the
central nervous system.
27
“Resistance of Streptococcus pneumoniae to beta- lactam antibiotics” - UpToDate 2019
28. Role of
Dexamethasone
in
pneumococcal
meningitis
◦ Dexamethasone appears most beneficial in
reducing hearing loss in children with Haemophilus
influenzae meningitis.
◦ For children with suspected pneumococcal
meningitis, the benefits and harms of
dexamethasone are less certain, and the decision is
individualized.
◦ There is concern that the entry of Vancomycin into
the CSF could be reduced in patients who receive
adjunctive dexamethasone.
28
“Bacterial meningitis in children: Dexamethasone and other measures to prevent neurologic complications”- UpToDate
29. Deterioration
29
Later in the evening, blood culture reported positive for gram- positive cocci.
Fever continued, and over the next few hours child became drowsy, tachypneic and tachycardic.
He had cold mottled extremities. Capillary refill four seconds. Blood pressure maintained.
CBG: pH 7.29; PCO2 32.7; HCO3 15.1; lactic acid 7.7; glucose 99.
30. Management
◦ Two boluses of normal saline were
administered, and child was shifted to PICU
for further management.
◦ Child’s condition was re- evaluated, and
baseline investigations re- ordered.
30
31. Repeat labs
31
FBC
WBC 11.5 ( 2.6)
ANC 8.3 ( 1.2)
Hb 9.8 ( 12.7)
Platelets 20 ( 133)
Coagulation profile
PT 23.3 s
APTT 52.8 s
INR 2.08
D- dimer > 20
Fibrinogen 639
Liver function test
ALT 63
Total bilirubin 1.3
Albumin 2.3
32. Blood film showed picture of
microangiopathic hemolytic anemia:
“Platelets are severely reduced in the
smear. RBCs are normocytic with the
presence of many fragmented RBCs
(schistocytes and irregular contracted
RBCs). WBCs show left shift
neutrophils”
32
33. PICU Day 1
33
Electively intubated in view of
dropping GCS.
IV immunoglobulin given once.
IV Penicillin added to Ceftriaxone
and Vancomycin.
IV Phenobarbitone started for
neuroprotection.
34. PICU Day 1
34
Petechial rash first developed over
lower limbs.
PRBC transfusion, FFP and Vitamin
K therapy given.
37. Therapy
Modification
◦ In view of culture sensitivity and critical
condition of child, we preferred to:
◦ - discontinue Ceftriaxone,
◦ - start Meropenem and,
◦ - continue with Vancomycin
37
39. Pneumococcal
meningitis
◦ Pneumococcal conjugate vaccines are effective in
preventing invasive pneumococcal disease and
providing herd immunity.
◦ After introduction of PCV-7, there was increase in
the proportion of invasive pneumococcal disease
(IPD) caused by non- vaccine serotypes.
◦ Even with PCV- 13 there was little change in
incidence of IPD caused by non- vaccine serotypes.
39
“Impact of universal infant immunization with pneumococcal conjugate vaccines in the United States” -
40. 40
“Impact of universal infant immunization with pneumococcal conjugate vaccines in the United States” -
41. Pneumococcal
meningitis
◦ Receiving PCV as recommended appears to be
associated with higher rates colonization with non-
vaccine serotypes.
◦ The effect of colonization with non- vaccine
serotypes depends upon the ability of the new
serotypes to cause local or invasive disease.
41
“Impact of universal infant immunization with pneumococcal conjugate vaccines in the United States” -
42. Is there any association between pneumococcal meningitis and
head trauma?
51. Two weeks into admission, there was still persistent daily fever despite
Vancomycin, Meropenem and Septrin
51
52. Two weeks into
admission
◦ Fixed flexion of upper and lower limbs with
spasticity, prominent ankle clonus, no
purposeful movements or response to voice,
no verbal output.
◦ As child was breathing spontaneously, he was
extubated after 13 days on ventilator.
52
55. MRI brain
There is evidence of multiple T1 hypointense and T2 hyperintense lesion in the frontal , temporal lobe, thalami on either side
with enhancement of the meninges along the frontal cortex on either side with minimal subdural collection along the frontal
cortices with possible early empyema along the frontal convexity on either side.
There are areas of enhancement in the region of left frontal cortex and the mid brain. There are focal areas of restricted diffusion
in the frontal lobes on either side suggest possibility of septic emboli. Lateral ventricles, 3rd and 4th ventricles appear normal in
size & contour. No dilatation or mass seen. No evidence of enhancement of the wall of ventricles. Basal cisterns are normal.
Cerebellar hemispheres appear normal in contour and signal intensity. Fluid is noted in the mastoid air cells and the middle ear
on either side. Mucosal thickening noted in the maxillary, ethmoidal and sphenoid sinuses. MRA does not reveal any significant
abnormality. MRV appears normal with small/hypoplastic left transverse sinus.
Impression: Findings are suggestive of meningoencephalitis with possible early empyema formation along the frontal
convexity on either side and the lesions seems to be mildly progressive in comparison with previous studies. No
evidence of hydrocephalous.
The lesions show symmetrical distribution bilaterally in the cerebral hemispheres and also in the thalami. The lesions show
restriction on the diffusion weighted images and a few of these show mild contrast enhancement. The distribution and the
signal pattern of the lesions in the suspicion of coexisting Wernicke’s encephalopathy.
55
57. Wernicke’s
Encephalopathy
◦ Wernicke encephalopathy (WE) and Korsakoff amnestic
syndrome (KS) are, respectively, acute and chronic brain
disorders that result from thiamine deficiency.
◦ While most often associated with chronic alcoholism, WE occurs
also in the setting of poor nutrition caused by malabsorption,
poor dietary intake, increased metabolic requirement (eg, during
systemic illnesses), or increased loss of the water-soluble
vitamin thiamine (eg, in renal dialysis).
◦ WE produces petechial hemorrhagic necrosis in midline brain
structures and corresponding deficits in mentation, oculomotor
function, and gait ataxia. All three of these classic symptoms are
present in only one-third of patients. Any one of these, most
often encephalopathy, may be seen in isolation.
57
“Wernicke’s encephalopathy” - UpToDate 2016
58. Wernicke’s
Encephalopathy
◦ WE should be considered when one or more occur in at-risk
patients.
◦ While laboratory measurements and neuroimaging are often
abnormal in WE, there is no single test with sufficiently high
diagnostic accuracy.
◦ The first imperative is to administer thiamine rather than
confirm the diagnosis, whenever WE is considered.
Untreated, WE leads to coma and death. Prognosis is
improved by prompt administration of thiamine.
58
“Wernicke’s encephalopathy” - UpToDate 2016
59. Further Measures
59
Rifampin added to Meropenem
Vancomycin as per IDU advice.
ENT advised no intervention from
their side (discharged).
Echocardiography normal.
Funduscopic assessment normal.
61. ADEM
◦ Acute disseminated encephalomyelitis (ADEM), also
known as postinfectious encephalomyelitis, is a
demyelinating disease of the central nervous
system that typically presents as a monophasic
disorder associated with multifocal neurologic
symptoms and encephalopathy.
◦ Uncommon illness with no ethnic predisposition.
May be slightly more common among males.
61
“Acute disseminated encephalomyelitis in children: Pathogenesis, clinical features, and diagnosis” - UpToDate
62. ADEM
◦ ADEM is often preceded by a viral or bacterial
infection, usually in the form of a nonspecific upper
respiratory infection. May also occur post-
vaccination.
◦ In general, patients will present within one month
of their illness.
◦ It is an autoimmune disorder of the CNS that is
triggered by an environmental stimulus in
genetically susceptible individuals.
62
“Acute disseminated encephalomyelitis in children: Pathogenesis, clinical features, and diagnosis” - UpToDate
63. ADEM
◦ A febrile illness occurs in 50 to 75 percent of children
in the four weeks prior to the onset of typical
neurologic symptoms.
◦ Fever, headache, vomiting, and meningismus are often
present at the time of initial presentation and may
persist during the hospitalization.
◦ Encephalopathy is a characteristic feature and usually
develops rapidly in association with multifocal
neurologic deficits.
◦ New clinical symptoms may develop during
hospitalization.
63
“Acute disseminated encephalomyelitis in children: Pathogenesis, clinical features, and diagnosis” - UpToDate
65. ADEM
◦ The mainstay of treatment for ADEM is high-dose
intravenous glucocorticoids.
◦ Most children with ADEM make a full recovery,
usually slowly over four to six weeks. At follow-up,
approximately 60 to 90 percent have minimal or no
neurologic deficits.
65
“Acute disseminated encephalomyelitis in children: Treatment and prognosis” - UpToDate 2019
68. Discussion
◦ After MRI brain was performed, discussion began
around the possibility of ADEM secondary to
infection.
◦ This raised the question of starting steroid therapy
for the child.
◦ However after discussion with neuroradiologist in
RH, Wernicke’s could be a possible differential, and
lesions on MRI were atypical for ADEM, hence
steroids were not started at that point.
68
69. Worsening condition
69
Daily fever continued despite
therapy with Vancomycin,
Meropenem and Rifampin.
A new fine erythematous rash
developed over entire body.
Patient began to display lip
smacking and tongue
thrusting.
71. Do you have any ideas about the next step in care?
71
72. Dermatology consult
72
Proposed either
drug- induced
allergic reaction or
a sequelae of
underlying
infection.
Advised to
continue
supportive therapy
with oral
antihistamines and
topical emollients.
Rash persisted
despite regular
therapy.
74. On Day 21 of
admission
◦ Father requested for second opinion from a
private neurosurgeon.
74
75. Second opinion
75
Also not keen on surgical
intervention as fluid collection had
no contrast enhancement or
secondary midline shift.
Advised to repeat lumbar puncture
after CT brain to assess response to
antibiotic therapy.
77. Therapy
77
IV Rifampin stopped after
finishing 10 days therapy.
10- day course of IV Thiamine
also completed.
Meropenem and Vancomycin
were still ongoing.
78. Further worsening
78
Neurological condition remained static.
Fever and rash continued at same pace.
Joint swelling of knees and hips was super- added (USS revealed minimal effusion only).
80. Work- up
80
Repeat FBC and CRP still improving.
Blood, urine and respiratory cultures all sterile.
Immune status screen, immunoglobulins and complement levels were all normal.
81. Consultations
81
Infectious disease consultation once again raised possibility of immune- mediated
vasculitis secondary to Streptococcus pneumoniae meningitis.
Investigations were done to rule out collagen vascular disease/ Macrophage
Activation Syndrome, and labs were not suggestive of the same.
82. Out of PICU
◦ Child’s condition was stable enough to be
shifted down.
◦ Shifted to isolation ward on after 22 days in
PICU.
82
83. Course in Ward
83
Fever, rash and neurological condition remained unresponsive to all
therapies.
Further investigations like T- spot testing was negative.
84. ◦ After extensive discussion with pediatric
neurology team, it was decided to repeat
brain MRI to assess extent of brain damage.
84
86. MRI Brain
86
Changes of Meningitis. Multiple acute / subacute infarcts noted
in both basal ganglia and anterior limb of internal capsule could
be sequelae of vasculitis secondary to meningitis. Mild to
moderate hydrocephalic changes with minimal periventricular
CSF seepage. Multiple areas of diffusion restriction noted in both
thalami and subcortical white matter have resolved in the
present scan.
95. ◦ In conjunction with pediatric neurology
team, it was decided to initiate IV
Methylprednisolone therapy for five days,
followed by prolonged oral Prednisolone
tapering course.
95
96. Within 24 hours of first dose of steroid
96
Fever and
rash resolved
completely.
FBC and
inflammator
y markers
normalized.
98. During first week of steroids
98
Rest
comfortably
in extended
position.
Independentl
y move all
limbs except
for left arm.
Actively
listening and
obeying
commands.
Smiling/
laughing
upon
stimulation.
99. During tapering course
99
Move all
limbs
freely and
purposefu
lly
Walk
independ
ently
Speak
clearly in
well-
formed
sentences
.
Name
common
objects
and
colors as
appropria
100. During tapering course
100
Color within lines
with strong grip
on pencil.
Read english and
arabic picture
books.
Feed self with
fork and spoon.
Socially interact
with both family
and strangers.
Express all needs
(i.E- toilet/ feed/
walk).
101. During tapering course
101
Gait remained
slightly weak,
but child was
improving
with
physiotherapy.
Neurological
exam was
normal, and
child had
mostly
returned to his
baseline level
of function.
102. Recovery
◦ Repeat MRI revealed static images.
◦ It was decided to repeat neuroimaging only
in case of neurological deterioration.
◦ Father continued to enhance child’s cognitive
functions through conversation, book reading
and facilitating playing with siblings.
102
103. Recovery
◦ A total of 5 weeks of Vancomycin and 7
weeks of Meropenem completed during
inpatient stay.
◦ Corticosteroid therapy was administered for a
total of 19 days as inpatient.
◦ Then our patient was finally ready to go back
home!
103
104. Discharge
◦ Discharged home on tapering course of
Prednisolone along with Vitamin D3 and
Esomeprazole.
◦ In total child received two months’ therapy of
corticosteroids for illness (combined inpatient
and outpatient).
104
105. Follow- up
◦ Follow- up 4- 5 months after discharge
revealed a thriving healthy child on no
medications, and with bilaterally passed
hearing test!
105
106. After more than month of daily fever
and neurological debilitation, by God’s
will our patient’s complete recovery
has been a marvel in medicine!
106
107. References
◦ “Pneumococcal meningitis in children” – UpToDate, August 2019.
◦ “Bacterial meningitis in children older than one month: Treatment and prognosis” - UpToDate, August 2019.
◦ “Bacterial meningitis in children older than one month: Clinical features and diagnosis” – UpToDate 2019.
◦ “Resistance of Streptococcus pneumoniae to beta- lactam antibiotics” – UpToDate 2019.
◦ “Impact of universal infant immunization with pneumococcal conjugate vaccines in the United States” – UpToDate 2019.
◦ “Wernicke’s encephalopathy” – UpToDate 2016.
◦ “Pneumococcal vaccination in children” – UpToDate, August 2019.
◦ “Acute disseminated encephalomyelitis in children: Pathogenesis, clinical features, and diagnosis” – UpToDate 2019.
◦ “Acute disseminated encephalomyelitis in children: Treatment and prognosis” – UpToDate 2019.
◦ “Bacterial meningitis in children: Dexamethasone and other measures to prevent neurologic complications” – UpToDate,
August 2019.
◦ Mukherjee D, Saha A. Cerebral Vasculitis in a Case of Meningitis. Iran J Child Neurol. Autumn 2017; 11(4):81-84.
107
108. References
◦ HK J Paedtr (New Series) 2013; 18:37-41
◦ Springerplus. 2014;3:415. Published online 2014 Aug 8. doi: 10.1186/2193-1801-3-415
◦ “Cerebral vasculitis complicating pneumococcal meningitis”- Ahmed Kheder et al.
◦ “Persisting vasculitis after pneumococcal meningitis”- Pugin D et al.
◦ “Delayed vasculitis with pneumococcal meningitis”- Dilreet Rai at al.
◦ “Pneumococcal meningitis complicated by cerebral vasculitis, abscess, hydrocephalus and hearing loss”- Abdul Razzakh Poil
et al.
◦ “Stroke in community- acquired bacterial meningitis: a Danish population- based study”- Jacob Bodilsen et al.
◦ “Pyogenic meningitis complicated with extensive central nervous system vasculitis and moyamoya vasculopathy”- Sumeet R
Dhawan et al.
◦ “Cerebrovascular complications of pediatric pneumococcal meningitis in PCV13 era”- Miya E. Bernson- Leung at al.
◦ “Cerebral vasculitis complicating pneumococcal meningitis”- Ahmed Khedher et al.
108