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Seizures-neonatal, infants, febrile

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CNS Infections

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COMA

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STROKES in Pediatrics
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brief and subtle
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eye blinking
mouth/tongue movements
“bicycling” motion to limbs

typically sz’s can’t be provoked/consoled
autonomic changes
EEG alone less predictable-unless together
with mri.(murray,boylan,r yan-pediatrics-2009 )
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etiology
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hypoxic-ischemic encephalopathy-(30-50%)
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Presents within first day (0-24hrs)

congenital CNS anomalies
intracranial hemorrhage
electrolyte abnormalities – hypoglycemia and hypocalcemia
infections
drug withdrawal
pyrodoxine deficiency
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Drug withdrawal
CNS trauma – maternal drug toxicity
4 EPILEPTIC SYNDROMES:
1)Benign familial conv.2)fifth day fits
3)Myoclonic encephalopathy
4)epileptic encephalopathy(Ontahara
syn) 5) DE VIVO SYNDROME
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HISTORY- PHYSICAL EXAM
LAB STUDIES
RADIOLOGIC – EEG
1)ULTRASOUND- CHOICE
2)CT-LOTS OF RADIATION
BETTER,CONGENITAL, INFARCTION
3)MRI- MORE DEF OF INFARTS
AND MORE ACCURATE FOR PROGNOSIS
•

Phenobarbital-20mg/kg slowly(can go up to
40mg/kg total in intractable seizures)

•

Phenitoin-20mg/kg iv slowly over 30-45 mts

•

Lorazepan-.1mg/kg q 6-8hrs

•

Piridoxin-50-100 mg iv after previous 3 meds
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Midazolam .1-.4mg/kg/hr
Pentotal sodium-2-4mg/kg
Valproic acid- 10-25mg/kg in 3 doses
Carbamacepine- 10mg/kg/day in 3 doses
Clonacepan- .1mg/kg orally (ng)
Mysoline- 10-15mg/kg /day
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Neonatal seizure – in first 28 days of life
(typically first few days)

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Status epilepticus
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seizure lasting >30 mins
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NB rose 5-10 mins

sequential seizures without regain LOC >30min
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Febrile seizure – NIH defn. - event of
infancy/childhood, typically between age
3mo and 5yrs, with no evidence intracranial
infection or defined cause

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Epilepsy - two or more seizures not provoked
by a specific event such as fever, trauma,
infection, or chemical change
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generalized
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partial – focal onset
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LOC
tonic, clonic, tonic-clonic, myoclonic, atonic, absence
simple partial – no LOC
complex partial – LOC
partial secondarily generalized

unclassified
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infectious
metabolic
traumatic
toxic
neoplastic
epileptic
other
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syncope
breath holding
sleep disorders (eg. narcolepsy)
paroxysmal movement disorder
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tics,tremors

migraines
psychogenic seizures
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Epidemiology
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age 3mo – 5yrs
peak age 9-20 mo
2-5% children will have before age 5
25-40% will have family history
80 – 97% simple
3 - 20% complex
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< 15 mins

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no focal features

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no greater than 1 episode in 24h

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neurologically and developmentally normal
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>15 min
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febrile epilepticus >30min or recurrent without
regaining consciousness > 30min

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focal

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recurrence within 24h
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Recurrence
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risk recurrence 25-50%
risk recurrence after 2nd – 50%
most recurrences within 6-12 mo
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(20% within same febrile illness)

Risk of epilepsy
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2-3% (baseline 1%)
increased in
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family history of epilepsy
abnormal developmental status
complex febrile seizure
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definition
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seizure lasting >30 mins
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NB Rosen 5-10 mins

sequential seizures without regain LOC >30min

mortality in pediatric status epilepticus 4%
morbidity may be as high as 30%
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ABC’s
brief directed Hx and Px
glucose
antibiotics/antivirals
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if meningitis/encephalitis considered
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1st line anticonvulsants
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IV
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rectal diazepam
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lorazepam 0.1mg/kg
diazepam 0.2 mg/kg
midazolam 0.2 mg/kg
2-5 yrs – 0.5 mg/kg
6-11 yrs – 0.3 mg/kg
>12 yrs – 0.2 mg/kg

IM, intranasal, buccal midazolam
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2nd line agents
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phenytoin 20 mg/kg @ 1mg/kg/min (upto 50 mg/min)
fosphenytoin 15-20 PE/kg @ 3 mg/kg/min (upto 150
mg/min)

3rd line agents
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phenobarbital 20mg/kg @ 100mg/min
repeat prn 5-10mg/kg
maximum 40 mg/kg or 1 gram
•

consider midazolam
–
–

•

induce barbiturate coma
–
–

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0.2 mg/kg bolus
then 1-10 mcg/kg/min infusion
pentobarbital 5-15 mg/kg @ 25 mg/min
then 1-5 mg/kg/hour

others
–
–
–
–

valproic acid
paraldehyde, chloral hydrate
propofol, inhalational anesthesia, paralysis
lidocaine
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history
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pre-seizure
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seizure
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what was child doing when attack occurred
precipitants – fever, trauma, poisoning, drug/med use
aura
what movements – incl. eyes
how long
LOC?
consequences – resp distress, incontinence, injury

post seizure
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Post-ictal
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physical directed towards
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systemic disease
infection
toxic exposure
focal neuro signs
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blood glucose?
electrolytes?
magnesium, calcium?
anything at all?
what about first time seizures? recurrent?
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septic work-up (CBC, BC, urine C+S, CXR, LP)
–

as indicated
•
•

sick child
< 12 - 18 mo

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therapeutic drug levels

•

other
–
–
–
–

ABG
toxicologic screen
TORCH, ammonia, amino acids in neonate
CPK, lactate, prolactin – ?confirm seizure?
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patients at greatest risk for meningitis
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other indications
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under 18 months of age
seizure in the ED
focal or prolonged seizure
seen a physician within the past 48 hours
concern about follow-up
prior treatment with antibiotics

The American Academy of Pediatrics
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“strongly consider” in infants under 12 months of age with a first
febrile seizure
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WHO? which patients?

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WHAT? CT vs. MRI
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ultrasound in neonates

WHEN? emergent vs. elective
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predictors of abnormal findings of computed tomography of the head
in pediatric patients presenting with seizures

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Warden CR - Ann Emerg Med - 01-Apr-1997; 29(4): 518-23
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retrospective case series
predicts CT scan results normal if
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no underlying high-risk condition
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malignancy, NCT, recent CHI, or recent CSF shunt revision

older than 6 months
sustained a seizure of 15 minutes or less
no new-onset focal neurologic deficit

not prospectively validated
•
•
•

correct underlying pathology, if any
antipyretics ineffective in febrile seizure
anti-epileptic choice often trial and error
•
•

no anti-epileptic 100% effective
febrile seizure – diazepam, phenobarbital, valproic acid
–

•
•
•
•

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Currently AAP does not recommend

neonatal - phenobarbital
generalized TC – phenytoin, phenobarbital, carbamazepine, valproic
acid, primidone
absence – ethosuximide, valproic acid
new anti-epileptics – felbamate, gabapentin, lamotrigine,
topiramate, tiagabine, vigabatrine

in consultation with neurologist
MENINGITIS
•

Fever or hypothermia
Poor Feeding
Irritability or lethargy
Seizures
Rash
Tachypnea or apnea
Jaundice
Bulging fontanelle (late)
Vomiting or diarrhea

•

Altered Sleep Pattern

•
•
•
•
•
•
•
•

***INCREASE INTRACRANIAL PRES.3 DE CUSHING

Norris, Cecilia M.R. et al. Aseptic Meningitis in the Newborn and Young Infant. AAFP.
15 May 1999; 59.
Affects all age groups
 Male = Female
 Newborns ( 0 - 4 weeks )









Group b strep ( 50 % )
E. coli ( 25 % )
Other gram - negative rods ( 8 % )
Listeria monocytogenes ( 6 % )
S. pneumoniae ( 5 % )

Stoll BJ, Hansen NI, Sanchez PJ, et al. Early onset neonatal sepsis: the burden of group B
Streptococcal and E. Coli disease continues. Pediatrics 2011; 127: 817.


Infants ( > 1 month - < 3 months )
 Group b streptococcus ( 39 % )
 Gram-negative bacilli ( 32 % )
 S. pneumoniae ( 14 % )
 N. meningitidis ( 12 % )

Nigrovic LE, Kuppermann N, Malley R, Bacterial Meningitis Study Group of the Emergency Medicine
Collaborative Research Committee of the American Academy of Pediatrics. Children with bacterial
meningitis presenting to the emergency department during the pneumococcal conjugate vaccine era. Acad
Emerg Med 2008; 15: 522.
< 1 month old
 Amp + Aminoglycoside
 Amp + 3rd Gen Ceph
 Amp + aminoglycoside + 3rd Gen Ceph
 No Ceftriaxone in above = Kernicterus
 1 – 23 months old
 Vancomycin + 3rd Gen Ceph


Tunkel, Allan R. Practice guidelines for the management of bacterial meningitis.
Clinical Infectious Disease. 1 November 2004.
•
•

GBS + : Pen G or Amp for 14 - 21 days
E. Coli Amp Resistant: 3rd Gen Ceph plus
Aminoglycoside
•
•

•

Must repeat LP with all Gram Neg Bacilli
Min 7 - 14 days combination + total 21 days of 3rd gen
ceph or 14 days after CSF Sterility whichever is longer ( A
III )

L. Monocytogenes: Amp x 14 – 21 days

Tunkel, Allan R. Practice guidelines for the management of bacterial meningitis. Clinical Infectious
Disease. 1 November 2004.
Symptoms lasting < 24 hours ( 48 % )
 Focal Neurologic Deficit ( 33 % )
 Rash ( 26 % )
 Petechiae
 Palpable purpura
 Coma ( 14 % )
 Seizure ( 5 % )


Van de Beek D et al. Clinical features and prognostic features in adults with
bacterial meningitis. NEJM. 28 October 2004.
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Exam for signs of infection
Kernig’s Sign
Brudzinski’s sign
Glasgow Coma Scale
•

Encephalitis
•
•

•

Aseptic Meningitis
•
•
•
•
•
•
•

•

Brain Inflammation
HSV – 1 Most common cause
Viral: Enterovirus, HIV, WNV, Mumps, LCM, HSV - 2
Fungal: Coccidioidomycosis, Cryptococcus
Tuberculosis
Parasites ( Angiostrongyliasis )
Ehrlichosis, RMSF, Lyme, Syphillis
Neoplasm of the leptomeninges
Drug - Induced: NSAIDs, Septra, Pyridium, Allopurinol

Intracranial Abscess

Sadoun, Tania and Amandeep Singh. Adult Bacterial Meningitis in the United States: 2009 Update.
Emergency Medicine Practice. September 2009.Volume 11, Number 9.
LABORATORIES
Leukocytosis or leukopenia
 Possible thrombocytopenia
 Normal renal function
 + Blood cultures ( 40 – 75 % )
 CSF studies


 Gram

Stain
 Glucose
 Protein
 WBC’s ( Neutrophils, Lymphocytes )
 CULTURE – GOLD STANDARD
Pathogen

WBC’s

% Neut

Glucose

Protein

+ Gram
present

Pyogenic

>500

>80

Low

>100

~70

Listeria
Monoctyogen
es

>100

~50

Normal

>50

~30

Partial
Treated
Pyogenic

>100

~50

Normal

>70

~60

Aseptic,
Often Viral

10 –
1, 000

Early: >50
Late: <20

Normal

<200

N/A

TB

50-500 <30

Low

>100

Rare

Fungal

50-500 <30

Low

Varies

High in
Crypto

Banmberger, David, Diagnosis, Initial Management, and Prevention of Meningitis Am Fam Physician. 2010 Dec 15;82(12):
Neurological
•

•
•
•

Impaired mental status ( most irritable / lethargic
15 % comatose at admission )
Cerebral edema and increased intracranial pressure
Seizures ( 20 – 30 % )-lorazepan + dilantin
Focal Deficits
•
•

•
•
•
•

Hearing loss ( 11 % )
CN VI - most commonly affected

Cerebrovascular abnormalities
Neuropsychological impairment ( 4 % )
Subdural effusion ( 10 – 33 % )
Hydrocephalus

Kaplan, Sheldon et al. Neurologic complications of bacterial meningitis in children. UpToDate.
24 Jan 2011.
2 - 50 years of age - Empiric
 Vancomycin + 3rd gen ceph
 For Gram Stain +
 N. meningitidis / H. influenzae: 3rd gen ceph
 S. pneumoniae: Vancomycin + 3rd gen ceph


Tunkel, Allan R. et al. Practice guidelines for the management of bacterial meningitis. Clin Infect
Dis. 1 November 2004.
Inpatient ( often ICU )
 Appropriate Antibiotic Therapy
Supportive Care(hemo-dinamic ,respiratory,
renal & electrolytes, myocardial support)
 Treat coexisting conditions(seizures ,brain
edema)
 Prevent hypothermia and dehydration


Tunkel, Allan R. et al. Practice guidelines for the management of bacterial meningitis.
Clin Infect Dis. 1 November 2004.
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CSF positive Gram staining
Seizure
Presence of purpura
Toxic appearance
CSF protein > 50 mg / dl
Serum Procalcitonin > 0.5 ng / ml

Dubos, Francois et al. Clinical decision rules for evaluating meningitis in children. Current Opinion in
Neurology 2009, 22:288–293.
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Etiology: more with pneumococcal

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Seizure after 72 hours

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CSF sugar < 20 mg per dl at admission

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Delayed sterilization of CSF : > 24 hours
The End









Estado patologico caracterizado por
1)inconciencia profunda-perdida de via
area , broncoaspiracion.
2)ojos cerrados
3)resistencia a estimulos externos
4)DISFUNCION de ARAS
5)Bien en tronco o hemisferios cer.
6)requiere minimo una hora para
distingirlo de contusion,sincope u otras entidades
de aparicion transitoria.







Management of ABC ,S comes first
Airway clearing comes first
If hx. Of trauma or not CSPINE stabilization
Respiratory effort evaluation + 02 supp or
providing airway
May need assist control respiration plus
volume support
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Evaluation of “DERM”
D- depth of coma or response to stimuli
E- pupils equal ,reactive ,dilated ,constricted
R- respiration altered?taquipnea,distress ?
M- paralysis? Motor response? How is the
response ? Decorticate? Decerabrate?
VITAL-SIGNS:SHOCK?ARRYTMIA??FEVER?
CUSHING TRIAD(icp high)







Injuries causing coma?-injuries caused by fall?
What do witness referred?
Causes: not enough 02? Low sugar?
Decreased brain perfusion with decrease 02
and sugar.
Structural causes: trauma plus consequences
Metabolic, toxins, infection, fever?
Pediatric neurologic emergencies
Pediatric neurologic emergencies
Pediatric neurologic emergencies
Pediatric neurologic emergencies
Pediatric neurologic emergencies

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Pediatric neurologic emergencies

  • 1.
  • 2.  Seizures-neonatal, infants, febrile  CNS Infections  COMA  STROKES in Pediatrics
  • 3.  brief and subtle       eye blinking mouth/tongue movements “bicycling” motion to limbs typically sz’s can’t be provoked/consoled autonomic changes EEG alone less predictable-unless together with mri.(murray,boylan,r yan-pediatrics-2009 )
  • 4.  etiology  hypoxic-ischemic encephalopathy-(30-50%)        Presents within first day (0-24hrs) congenital CNS anomalies intracranial hemorrhage electrolyte abnormalities – hypoglycemia and hypocalcemia infections drug withdrawal pyrodoxine deficiency
  • 5.
  • 6.
  • 7.        Drug withdrawal CNS trauma – maternal drug toxicity 4 EPILEPTIC SYNDROMES: 1)Benign familial conv.2)fifth day fits 3)Myoclonic encephalopathy 4)epileptic encephalopathy(Ontahara syn) 5) DE VIVO SYNDROME
  • 8.       HISTORY- PHYSICAL EXAM LAB STUDIES RADIOLOGIC – EEG 1)ULTRASOUND- CHOICE 2)CT-LOTS OF RADIATION BETTER,CONGENITAL, INFARCTION 3)MRI- MORE DEF OF INFARTS AND MORE ACCURATE FOR PROGNOSIS
  • 9. • Phenobarbital-20mg/kg slowly(can go up to 40mg/kg total in intractable seizures) • Phenitoin-20mg/kg iv slowly over 30-45 mts • Lorazepan-.1mg/kg q 6-8hrs • Piridoxin-50-100 mg iv after previous 3 meds
  • 10.       Midazolam .1-.4mg/kg/hr Pentotal sodium-2-4mg/kg Valproic acid- 10-25mg/kg in 3 doses Carbamacepine- 10mg/kg/day in 3 doses Clonacepan- .1mg/kg orally (ng) Mysoline- 10-15mg/kg /day
  • 11.  Neonatal seizure – in first 28 days of life (typically first few days)  Status epilepticus  seizure lasting >30 mins   NB rose 5-10 mins sequential seizures without regain LOC >30min
  • 12.  Febrile seizure – NIH defn. - event of infancy/childhood, typically between age 3mo and 5yrs, with no evidence intracranial infection or defined cause  Epilepsy - two or more seizures not provoked by a specific event such as fever, trauma, infection, or chemical change
  • 13.  generalized    partial – focal onset     LOC tonic, clonic, tonic-clonic, myoclonic, atonic, absence simple partial – no LOC complex partial – LOC partial secondarily generalized unclassified
  • 15.     syncope breath holding sleep disorders (eg. narcolepsy) paroxysmal movement disorder    tics,tremors migraines psychogenic seizures
  • 16.
  • 17.  Epidemiology       age 3mo – 5yrs peak age 9-20 mo 2-5% children will have before age 5 25-40% will have family history 80 – 97% simple 3 - 20% complex
  • 18.  < 15 mins  no focal features  no greater than 1 episode in 24h  neurologically and developmentally normal
  • 19.  >15 min  febrile epilepticus >30min or recurrent without regaining consciousness > 30min  focal  recurrence within 24h
  • 20.  Recurrence    risk recurrence 25-50% risk recurrence after 2nd – 50% most recurrences within 6-12 mo   (20% within same febrile illness) Risk of epilepsy   2-3% (baseline 1%) increased in    family history of epilepsy abnormal developmental status complex febrile seizure
  • 21.  definition  seizure lasting >30 mins     NB Rosen 5-10 mins sequential seizures without regain LOC >30min mortality in pediatric status epilepticus 4% morbidity may be as high as 30%
  • 22.     ABC’s brief directed Hx and Px glucose antibiotics/antivirals  if meningitis/encephalitis considered
  • 23.  1st line anticonvulsants  IV     rectal diazepam     lorazepam 0.1mg/kg diazepam 0.2 mg/kg midazolam 0.2 mg/kg 2-5 yrs – 0.5 mg/kg 6-11 yrs – 0.3 mg/kg >12 yrs – 0.2 mg/kg IM, intranasal, buccal midazolam
  • 24.  2nd line agents    phenytoin 20 mg/kg @ 1mg/kg/min (upto 50 mg/min) fosphenytoin 15-20 PE/kg @ 3 mg/kg/min (upto 150 mg/min) 3rd line agents    phenobarbital 20mg/kg @ 100mg/min repeat prn 5-10mg/kg maximum 40 mg/kg or 1 gram
  • 25. • consider midazolam – – • induce barbiturate coma – – • 0.2 mg/kg bolus then 1-10 mcg/kg/min infusion pentobarbital 5-15 mg/kg @ 25 mg/min then 1-5 mg/kg/hour others – – – – valproic acid paraldehyde, chloral hydrate propofol, inhalational anesthesia, paralysis lidocaine
  • 26.  history  pre-seizure     seizure      what was child doing when attack occurred precipitants – fever, trauma, poisoning, drug/med use aura what movements – incl. eyes how long LOC? consequences – resp distress, incontinence, injury post seizure  Post-ictal
  • 27.  physical directed towards     systemic disease infection toxic exposure focal neuro signs
  • 28.      blood glucose? electrolytes? magnesium, calcium? anything at all? what about first time seizures? recurrent?
  • 29. • septic work-up (CBC, BC, urine C+S, CXR, LP) – as indicated • • sick child < 12 - 18 mo • therapeutic drug levels • other – – – – ABG toxicologic screen TORCH, ammonia, amino acids in neonate CPK, lactate, prolactin – ?confirm seizure?
  • 30.  patients at greatest risk for meningitis      other indications    under 18 months of age seizure in the ED focal or prolonged seizure seen a physician within the past 48 hours concern about follow-up prior treatment with antibiotics The American Academy of Pediatrics  “strongly consider” in infants under 12 months of age with a first febrile seizure
  • 31.  WHO? which patients?  WHAT? CT vs. MRI   ultrasound in neonates WHEN? emergent vs. elective
  • 32.  predictors of abnormal findings of computed tomography of the head in pediatric patients presenting with seizures  Warden CR - Ann Emerg Med - 01-Apr-1997; 29(4): 518-23   retrospective case series predicts CT scan results normal if  no underlying high-risk condition      malignancy, NCT, recent CHI, or recent CSF shunt revision older than 6 months sustained a seizure of 15 minutes or less no new-onset focal neurologic deficit not prospectively validated
  • 33. • • • correct underlying pathology, if any antipyretics ineffective in febrile seizure anti-epileptic choice often trial and error • • no anti-epileptic 100% effective febrile seizure – diazepam, phenobarbital, valproic acid – • • • • • Currently AAP does not recommend neonatal - phenobarbital generalized TC – phenytoin, phenobarbital, carbamazepine, valproic acid, primidone absence – ethosuximide, valproic acid new anti-epileptics – felbamate, gabapentin, lamotrigine, topiramate, tiagabine, vigabatrine in consultation with neurologist
  • 35. • Fever or hypothermia Poor Feeding Irritability or lethargy Seizures Rash Tachypnea or apnea Jaundice Bulging fontanelle (late) Vomiting or diarrhea • Altered Sleep Pattern • • • • • • • • ***INCREASE INTRACRANIAL PRES.3 DE CUSHING Norris, Cecilia M.R. et al. Aseptic Meningitis in the Newborn and Young Infant. AAFP. 15 May 1999; 59.
  • 36. Affects all age groups  Male = Female  Newborns ( 0 - 4 weeks )       Group b strep ( 50 % ) E. coli ( 25 % ) Other gram - negative rods ( 8 % ) Listeria monocytogenes ( 6 % ) S. pneumoniae ( 5 % ) Stoll BJ, Hansen NI, Sanchez PJ, et al. Early onset neonatal sepsis: the burden of group B Streptococcal and E. Coli disease continues. Pediatrics 2011; 127: 817.
  • 37.  Infants ( > 1 month - < 3 months )  Group b streptococcus ( 39 % )  Gram-negative bacilli ( 32 % )  S. pneumoniae ( 14 % )  N. meningitidis ( 12 % ) Nigrovic LE, Kuppermann N, Malley R, Bacterial Meningitis Study Group of the Emergency Medicine Collaborative Research Committee of the American Academy of Pediatrics. Children with bacterial meningitis presenting to the emergency department during the pneumococcal conjugate vaccine era. Acad Emerg Med 2008; 15: 522.
  • 38.
  • 39. < 1 month old  Amp + Aminoglycoside  Amp + 3rd Gen Ceph  Amp + aminoglycoside + 3rd Gen Ceph  No Ceftriaxone in above = Kernicterus  1 – 23 months old  Vancomycin + 3rd Gen Ceph  Tunkel, Allan R. Practice guidelines for the management of bacterial meningitis. Clinical Infectious Disease. 1 November 2004.
  • 40. • • GBS + : Pen G or Amp for 14 - 21 days E. Coli Amp Resistant: 3rd Gen Ceph plus Aminoglycoside • • • Must repeat LP with all Gram Neg Bacilli Min 7 - 14 days combination + total 21 days of 3rd gen ceph or 14 days after CSF Sterility whichever is longer ( A III ) L. Monocytogenes: Amp x 14 – 21 days Tunkel, Allan R. Practice guidelines for the management of bacterial meningitis. Clinical Infectious Disease. 1 November 2004.
  • 41. Symptoms lasting < 24 hours ( 48 % )  Focal Neurologic Deficit ( 33 % )  Rash ( 26 % )  Petechiae  Palpable purpura  Coma ( 14 % )  Seizure ( 5 % )  Van de Beek D et al. Clinical features and prognostic features in adults with bacterial meningitis. NEJM. 28 October 2004.
  • 42.     Exam for signs of infection Kernig’s Sign Brudzinski’s sign Glasgow Coma Scale
  • 43.
  • 44. • Encephalitis • • • Aseptic Meningitis • • • • • • • • Brain Inflammation HSV – 1 Most common cause Viral: Enterovirus, HIV, WNV, Mumps, LCM, HSV - 2 Fungal: Coccidioidomycosis, Cryptococcus Tuberculosis Parasites ( Angiostrongyliasis ) Ehrlichosis, RMSF, Lyme, Syphillis Neoplasm of the leptomeninges Drug - Induced: NSAIDs, Septra, Pyridium, Allopurinol Intracranial Abscess Sadoun, Tania and Amandeep Singh. Adult Bacterial Meningitis in the United States: 2009 Update. Emergency Medicine Practice. September 2009.Volume 11, Number 9.
  • 45.
  • 46. LABORATORIES Leukocytosis or leukopenia  Possible thrombocytopenia  Normal renal function  + Blood cultures ( 40 – 75 % )  CSF studies   Gram Stain  Glucose  Protein  WBC’s ( Neutrophils, Lymphocytes )  CULTURE – GOLD STANDARD
  • 47. Pathogen WBC’s % Neut Glucose Protein + Gram present Pyogenic >500 >80 Low >100 ~70 Listeria Monoctyogen es >100 ~50 Normal >50 ~30 Partial Treated Pyogenic >100 ~50 Normal >70 ~60 Aseptic, Often Viral 10 – 1, 000 Early: >50 Late: <20 Normal <200 N/A TB 50-500 <30 Low >100 Rare Fungal 50-500 <30 Low Varies High in Crypto Banmberger, David, Diagnosis, Initial Management, and Prevention of Meningitis Am Fam Physician. 2010 Dec 15;82(12):
  • 48. Neurological • • • • Impaired mental status ( most irritable / lethargic 15 % comatose at admission ) Cerebral edema and increased intracranial pressure Seizures ( 20 – 30 % )-lorazepan + dilantin Focal Deficits • • • • • • Hearing loss ( 11 % ) CN VI - most commonly affected Cerebrovascular abnormalities Neuropsychological impairment ( 4 % ) Subdural effusion ( 10 – 33 % ) Hydrocephalus Kaplan, Sheldon et al. Neurologic complications of bacterial meningitis in children. UpToDate. 24 Jan 2011.
  • 49. 2 - 50 years of age - Empiric  Vancomycin + 3rd gen ceph  For Gram Stain +  N. meningitidis / H. influenzae: 3rd gen ceph  S. pneumoniae: Vancomycin + 3rd gen ceph  Tunkel, Allan R. et al. Practice guidelines for the management of bacterial meningitis. Clin Infect Dis. 1 November 2004.
  • 50. Inpatient ( often ICU )  Appropriate Antibiotic Therapy Supportive Care(hemo-dinamic ,respiratory, renal & electrolytes, myocardial support)  Treat coexisting conditions(seizures ,brain edema)  Prevent hypothermia and dehydration  Tunkel, Allan R. et al. Practice guidelines for the management of bacterial meningitis. Clin Infect Dis. 1 November 2004.
  • 51.       CSF positive Gram staining Seizure Presence of purpura Toxic appearance CSF protein > 50 mg / dl Serum Procalcitonin > 0.5 ng / ml Dubos, Francois et al. Clinical decision rules for evaluating meningitis in children. Current Opinion in Neurology 2009, 22:288–293.
  • 52.  Etiology: more with pneumococcal  Seizure after 72 hours  CSF sugar < 20 mg per dl at admission  Delayed sterilization of CSF : > 24 hours
  • 54.        Estado patologico caracterizado por 1)inconciencia profunda-perdida de via area , broncoaspiracion. 2)ojos cerrados 3)resistencia a estimulos externos 4)DISFUNCION de ARAS 5)Bien en tronco o hemisferios cer. 6)requiere minimo una hora para distingirlo de contusion,sincope u otras entidades de aparicion transitoria.
  • 55.      Management of ABC ,S comes first Airway clearing comes first If hx. Of trauma or not CSPINE stabilization Respiratory effort evaluation + 02 supp or providing airway May need assist control respiration plus volume support
  • 56.       Evaluation of “DERM” D- depth of coma or response to stimuli E- pupils equal ,reactive ,dilated ,constricted R- respiration altered?taquipnea,distress ? M- paralysis? Motor response? How is the response ? Decorticate? Decerabrate? VITAL-SIGNS:SHOCK?ARRYTMIA??FEVER? CUSHING TRIAD(icp high)
  • 57.     Injuries causing coma?-injuries caused by fall? What do witness referred? Causes: not enough 02? Low sugar? Decreased brain perfusion with decrease 02 and sugar. Structural causes: trauma plus consequences Metabolic, toxins, infection, fever?

Notas do Editor

  1. The vital signs provide clues to volume status, presence of shock, and the presence of increased intracranial pressure. The constellation of systemic hypertension, bradycardia, and respiratory depression (Cushing triad) is a late sign of increased intracranial pressure. Head circumference should be measured at the time of admission in children younger than 18 months of age.
  2. “In prospective surveillance of nearly 400,000 neonates in the United States (2006-2009), 72 percent of those who had sepsis or meningitis within 72 hours of birth had infection caused by GBS and E. coli.”Stoll BJ, Hansen NI, Sánchez PJ, et al. Early onset neonatal sepsis: the burden of group B Streptococcal and E. coli disease continues. Pediatrics 2011; 127:817.
  3. “Nevertheless, even after institution of universal immunization with PCV7, pneumococcus remains the most common etiologic agent of bacterial meningitis in children, accounting for one-third of cases. Importantly, half of the children with pneumococcal meningitis were infected with serotypes not included in the vaccine (so-called “nonvaccine-type” strains). In our study population, many cases of pneumococcal meningitis were due to serotypes that have emerged as important causes of invasive pneumococcal disease in the post–conjugate vaccine era (such as serotypes 19A, 15C, and 33F)”. Nigrovic LE, Kuppermann N, Malley R, Bacterial Meningitis Study Group of the Pediatric Emergency Medicine Collaborative Research Committee of the American Academy of Pediatrics. Children with bacterial meningitis presenting to the emergency department during the pneumococcal conjugate vaccine era. Acad Emerg Med 2008; 15:522.
  4. “In the non-hospitalized neonate who is strongly suspected to have bacterial meningitis, but whose CSF parameters are not immediately available or not entirely consistent with bacterial meningitis (eg, negative Gram stain), ampicillin plus an aminoglycoside plus cefotaxime should be initiated. In one survey of febrile infants younger than 90 days who presented to an emergency center, nearly 80 percent of infants with meningitis had ampicillin-resistant pathogens”. Byington CL, Rittichier KK, Bassett KE, et al. Serious bacterial infections in febrile infants younger than 90 days of age: the importance of ampicillin-resistant pathogens. Pediatrics 2003; 111:964. “ The authors recommended that the initial regimen contain ampicillin and gentamicin plus a third-generation cephalosporin because of the risk of GBS and L. monocytogenes infection in this age group, as well as for treatment of cefotaxime susceptible organisms. When meningitis resulting from a gram-negative organism is strongly suspected, for example when the CSF Gram stain reveals gram-negative bacilli, the empirical regimen of ampicillin and an aminoglycoside should be expanded to include cefotaxime.” Clin Microbiol Rev. 2010 July; 23(3): 467–492. doi:  Epidemiology, Diagnosis, and Antimicrobial Treatment of Acute Bacterial Meningitis Matthijs C. Brouwer,1 Allan R. Tunkel,2 and Diederik van de Beek. “Keep HSV in differential if rash, Increase liver transaminases, sepsis like syndrome: controversy over adding acyclovir: can be d/c’d once HSV PCR and cultures are negative or alternative dx is made; enteroviral PCR. Viral isolates usually grow in tissue by 4-8 days. HSV meningitis: neonatal 60mg/kg per day divided in 3 divided doses x 14-21 days.” “When meningitis resulting from a gram-negative organism is strongly suspected, for example when the CSF Gram stain reveals gram-negative bacilli, the empirical regimen of ampicillin and an aminoglycoside should be expanded to include cefotaxime.” “Late-onset sepsis without meningitis in neonates who remain hospitalized is treated with vancomycin and an aminoglycoside. When lumbar puncture suggests meningitis, cefotaxime should be added to provide an extended spectrum for gram-negative enterics and for optimal activity in the CSF against pneumococci. Ampicillin should be added to a vancomycin-aminoglycoside regimen if GBS or L. monocytogenes is suspected (eg, on the basis of the Gram stain), because vancomycin concentrations in the CSF are not bactericidal for these organisms”. Albanyan EA, Baker CJ. Is lumbar puncture necessary to exclude meningitis in neonates and young infants: lessons from the group B streptococcus cellulitis- adenitis syndrome. Pediatrics 1998; 102:985.
  5. “Repeat lumbar puncture — Lumbar puncture should be repeated routinely at 24 to 48 hours after initiation of antimicrobial therapy to document CSF sterilization. Gram-positive bacteria usually clear rapidly (within 24 to 48 hours) from the CSF after initiation of appropriate antimicrobial therapy, whereas gram-negative may persist for several days in severe cases.” “Reevaluation of the CSF 24 to 48 hours after initiation of antimicrobial therapy is important for several reasons: •Delayed sterilization of the CSF is associated with an increased risk of developing neurologic sequelae. •The persistent identification of organisms on a Gram-stained smear may be an early indication of inadequacy of antimicrobial therapy (eg, the organism is not susceptible to the concentration of antibiotic that is attained in the CSF. Persistence of viable organisms more than 48 hours after initiation of antimicrobial therapy is an indication for diagnostic neuroimaging because it can indicate a purulent focus (eg, obstructive ventriculitis, multiple small vessel thrombi) that can require additional intervention or increased duration of antimicrobial therapy. •Sterilization of the CSF is a criterion for discontinuing combination therapy for some pathogens (eg, GBS, Listeria). In uncomplicated neonatal meningitis, the CSF culture obtained 24 to 48 hours after initiation of therapy is sterile. If there is just a colony or two, it is appropriate to obtain a third CSF culture when it is known that the second is positive (ie, after an additional 24 to 48 hours). However, as indicated above, a positive culture obtained 24 to 48 hours after initiation of therapy with more than one or two colonies raises a concern for ventriculitis. The additional evaluation and management of infants with possible ventriculitis is individualized and should be undertaken in consultation with specialists in pediatric infectious diseases and pediatric neurosurgery. Treatment and outcome of bacterial meningitis in the neonate Authors Morven S Edwards, MD Carol J Baker, MD June 1, 2011. Treatment and outcome of bacterial meningitis in the neonate” Positive CSF culture — The duration of antimicrobial therapy depends upon the causative organism and the clinical course: •A 14-day course is sufficient for neonates with uncomplicated GBS meningitis and for meningitis caused by other gram-positive organisms, such as L. monocytogenes or Enterococcus. •A longer course of therapy is required for neonates with GBS meningitis who have a complicated course. •A 21-day course is the minimum for neonates with meningitis resulting from E. coli or other gram-negative pathogens. •Prolonged treatment, sometimes for as long as eight weeks, may be required for neonates with ventriculitis, abscesses, or multiple areas of infarction. “ Negative CSF culture — The duration of antibiotic therapy for neonates with negative cultures must be determined on an individual clinical basis. •For neonates with suspected but unproven bacterial meningitis, we usually suggest discontinuation of antimicrobials after 48 to 72 hours of negative CSF culture. •For neonates with CSF pleocytosis and bacteremia, but a negative CSF culture, we usually continue meningeal doses of antimicrobial therapy for 10 days for gram-positive bacteremia (ie, GBS) and 14 days for gram-negative bacteremia. “ E. Coli Ampicillin Resistant: 3rd Generation Cephalosporin plus Aminoglycoside Minimum 7 - 14 days combination plus total 21 days of 3rd generation cephalosporin or 14 days after CSF Sterility whichever is longer ( A III ) “Duration of therapy depends on individual patient response, though generalized guidelines according to the responsible pathogen are as follows: Neisseria meningitidis or H. influenzae, seven days; S. pneumoniae, 10 to 14 days; Streptococcus agalactiae, 14 to 21 days; aerobic gram-negative bacilli, 21 days (two weeks beyond the first sterile CSF culture in neonates); Listeria monocytogenes, 21 days or longer. Intravenous therapy is recommended throughout to maintain sufficient CSF concentrations. In neonates with meningitis caused by gram-negative bacilli, the duration of therapy should be determined in part by repeated lumbar punctures documenting CSF sterilization (A-III). Patients who have not responded clinically after 48 hours of appropriate therapy also should be monitored with repeated CSF analysis (A-III), particularly those with meningitis caused by resistant strains and those who have received adjunctive dexamethasone.” After Discharge: check audiology screen (also prior to d/c), consider earlier cochlear implant. Hearing test after 4-6 weeks. Check the following: hearing loss, orthopedic complication, skin complication, psychosocial problems, neurological and developmental problems, renal failure. Do Immune testing if more than 1 episode of meningococcal dz, if serotypes other than ACY W135, plus menigococcal dz plus other bacterial meningitis. Coagulase-negative staphylococci — Vancomycin is the antimicrobial of choice for proven meningitis caused by coagulase-negative staphylococci. These organisms rarely invade the meninges except as a complication of bacteremia accompanying intraventricular hemorrhage in very LBW infants (birth weight &lt;1500 g) or as a result of surgical manipulations or placement of a ventriculoperitoneal shunt. Such infections invariably are of late onset.
  6. Van de Beek D et al. Clinical features and prognostic features in adults with bacterial meningitis. NEJM. 28 October 2004. “Sixty-three percent of patients with meningococcal meningitis present with a rash that is usually petechial. Petechial rash may also be caused by Haemophilus influenzae or Streptococcus pneumoniae infection. Pneumococcal meningitis is more likely than meningococcal meningitis to be associated with seizures, focal neurologic findings, and altered consciousness. Clinical or laboratory feature Sensitivity (%) Two of the following features: fever, neck stiffness, altered mental status, and headache 95 Cerebrospinal fluid white blood cell count ≥ 100 per μL (0.10 × 109 per L) 93 Headache 87 Neck stiffness 83 Fever ≥ 100.4°F (38°C)77 Nausea74 Altered mental status (Glasgow Coma Scale score &lt; 14)69 Growth of organism in blood culture 66 Triad of fever, neck stiffness, and altered mental status 44 Focal neurologic signs33 Seizure 5 Papilledema 3”
  7. “5% sensitivity and 95% specificity for kernigs and brudzinski’s signs; 30% sensitivity for Nuchal rigidity-late presentation in children. Meningeal signs — Although meningeal signs are present at the time of admission in the majority of patients, they are not invariably present. In one review of 1064 cases of acute bacterial meningitis in children older than one month, 16 (1.5 percent) had no meningeal signs during their entire period of hospitalization. Nuchal rigidity may not be elicited in comatose patients or those with focal or diffuse neurologic deficits. In addition, nuchal rigidity may occur late in the course, particularly in young children. When meningitis was defined as ≥6 white cells/microL of CSF, the sensitivity was extremely low (5 percent for each sign and 30 percent for nuchal rigidity); the specificity was 95 percent for each sign and 68 percent for nuchal rigidity. Neither Kernig&apos;s nor Brudzinski&apos;s sign performed much better among the 29 patients with moderate or the four patients with severe meningeal inflammation, defined as ≥100 and ≥1000 white cells/microL, respectively. Nuchal rigidity was present in all four patients with severe meningeal irritation but had a specificity of only 70 percent”: Clinical Features of Bacterial Meningitis UpToDate.
  8. Sadoun, Tania and Amandeep Singh. Adult Bacterial Meningitis in the United States: 2009 Update. Emergency Medicine Practice. September 2009.Volume 11, Number 9. OBTAIN an extensive travel and exposure history. --exposure to rodents (LCM), ticks (lyme), TB --Sexual activity (HSV-2, HIV, Syphillis) --Contacts with patients with viral exanthems (enterovirus) --Use of meds Physical exam: Rash: maculopauluar exanthem; enterovirus, HIV, syphillis, meningococcal, RMSF --parotitis ---severe vesicular/ulcerative genital lesions HSV-2 ---oropharyngeal thrush and cervical lymphadenopathy—HIV ---asymmetric flaccid paralysis: WNV. Meningitis: uncomfortable, lethargic, ha, cerebral function mostly normal can have seizure Encephalitis: AMS, as above, motor or sensory deficits, altered behavior, personality changes, speech or movement d/o. May present with meningoencephalitis a combo of both. Meds as cuase: A delayed hypersensitivity type reaction or 2 direct meningeal irritation. CSF with CSF RBC &gt;2000 in nontraumatic tab: HSV Encephalatis: 0-27,000 RBCs also ct with frontal and temporal edema. RESOLVES WITHOUT SPECIFIC THERAPY. PCR for CSF Enterovirus: confirms diagnosis, decreases cost of unnecessary antibiotics, shorten stays in hospital. LCM: lymphocytic Choriomeningitis Virus. Human Zoonosis—Rodent borne areanovirus. Common in winter: excreted in feces of mice, rats,. HSV-2: Sexualy Activity: think of HSV- 2, HIV, Syphillis. IF GENITAL LESION present current OR week prior to meningeal symtpoms: Strong suggestion of HSV -2: 85% genital lesion present or preceded by about 1 week. USE ACYCLOVIR 10mg/kg q 8 hour oral agent at D/C x 10-14 days. PCR for HSVDNA in the CSF. IF recurrent HSV2 meningitis: a form of recurrent benign lymphocytic meningitis (RBLSM) : &gt;3 episodes of fever and mengismus lasting 2-5 days caused by HSV2: Recurrent Mollaret’s Meningitis. “Successful management of intracranial abscess involves the administration of parenteral antibiotics and neurosurgical consultation. The combination of a third-generation cephalosporin (cefotaxime 50 mg/kg IV every 4 hours, with a maximum dose of 2 gm; or ceftriaxone 50 mg/kg IV every 12 hours, with a maximum dose of 2 gm), metronidazole (15 mg/kg IV every 12 hours), and vancomycin (15 mg/kg IV every 6 hours with a maximum dose of 500 mg) can be used in most patients who are presumed to have a contiguous source of infection (eg, an ear, sinus, or dental infection). Although some experimental evidence suggests that corticosteroids (dexamethasone 10 mg IV followed by 4 mg every 6 hours) reduce edema surrounding brain abscesses,36,37 no quality trials in humans have demonstrated clinical benefits from corticosteroid therapy. Emergent neurosurgical drainage should be considered in patients with signs of increased ICP; otherwise, patients may be observed for clinical response to parenteral antibiotics.”
  9. “Prior administration of antimicrobial agents, particularly oral antibiotics, tends to have minimal effects on CSF cytology . However, CSF chemistry results in pretreated patients must be interpreted with caution. In a retrospective review of 231 children with bacterial meningitis in the post-Hib and pneumococcal conjugate vaccine era, 85 children received antibiotics before LP . Receipt of antibiotics for ≥12 hours before LP was associated with increased median CSF glucose concentration (48 versus 29 mg/dL [2.66 versus 1.6 mmol/L]) and decreased median CSF protein concentration (121 versus 178 mg/dL [1.21 versus 1.78 g/L]). Although the use of antimicrobial therapy before LP affects the CSF culture and perhaps the Gram stain, conventional teaching has been that a pathogen still can be identified in the CSF in the majority of patients up to several hours after the administration of antibiotics . However, a review of 128 children with bacterial meningitis specifically addressed this question and found that the time interval between antibiotic administration and negative CSF cultures may be shorter than appreciated for children who receive parenteral antibiotics : Among children with meningococcal meningitis who were treated with a parenteral dose of an extended-spectrum cephalosporin, three of nine LPs were sterile within one hour (occurring as early as 15 minutes), and all were sterile by two hours. Sterilization of the CSF was slower with pneumococcal meningitis. The first negative culture was obtained four hours after administration of antibiotics, and five of seven were negative by 10 hours. Rarely, patients with bacterial meningitis may present with normal or near-normal white blood cell counts, glucose levels, and protein levels. This has been observed in young children with neutropenia and other immunocompromised states, and very early in the course of meningococcal meningitis. Blood cultures should be obtained before antibiotic therapy is initiated in patients with suspected meningitis. Positive blood cultures are obtained in approximately two-thirds of patients with bacterial meningitis”: Van de Beek D, de Gans J, Spanjaard L, Weisfelt M, Reitsma JB, Vermeulen M. Clinical features and prognostic factors in adults with bacterial meningitis. N Engl J Med. 2004;351(18):1849-1859. (Prospective; 696 cases). “CSF culture remains the gold standard for the diagnosis of bacterial meningitis; aerobic culturing techniques are obligatory for community-acquired bacterial meningitis. Anaerobic culture may be important for postneurosurgical meningitis or for the investigation of CSF shunt meningitis. “ Clin Microbiol Rev. 2010 July; 23(3): 467–492. doi:  Epidemiology, Diagnosis, and Antimicrobial Treatment of Acute Bacterial MeningitisMatthijs C. Brouwer,1 Allan R. Tunkel,2 and Diederik van de Beek also with these same authors: Blood Culture Blood cultures are valuable to detect the causative organism and establish susceptibility patterns if CSF cultures are negative or unavailable. Blood culture positivity differs for each causative organism: 50 to 90% of H. influenzae meningitis patients, 75% of pneumococcal meningitis patients, and 40% of children and 60% of adult patients with meningococcal meningitis. The yield of blood cultures was decreased by 20% for pretreated patients in two studies.
  10. Kaplan, Sheldon et al. Neurologic complications of bacterial meningitis in children. UpToDate. 24 Jan 2011. “In one review of 235 children with bacterial meningitis, approximately 78 percent were irritable or lethargic, 7 percent were somnolent, and 15 percent semicomatose or comatose at the time of admission . Among patients with pneumococcal meningitis, 29 percent were semicomatose or comatose at the time of admission. All of the children with hearing loss had one or more of the following risk factors at presentation: Symptoms for ≥2 days before admission Absence of petechiae CSF glucose concentration ≤10.8 mg/dL (0.6 mmol/L) S. pneumoniae infection Ataxia Hearing loss is two to three times more common in children with pneumococcal meningitis than with other forms of bacterial meningitis . Ataxia is commonly associated with hearing loss in children, since both are related to bacterial labyrinthitis.” Cranial nerve palsy  The abducens (VI) nerve is the cranial nerve most commonly affected in meningitis, probably because its long intracranial segment adjacent to the brainstem is highly vulnerable to elevated intracranial pressure and the inflammatory reaction that can occur with meningitis.
  11. Tunkel, Allan R. et al. Practice guidelines for the management of bacterial meningitis. Clin Infect Dis. 1 November 2004 Empiric regimen — The empiric regimen should include coverage for penicillin-resistant S. pneumoniae and N. meningitidis, the two most common causes of bacterial meningitis in infants and children. An appropriate empiric regimen (ie, one that covers antibiotic-resistant S. pneumoniae, N. meningitidis, and Hib) includes high doses of a third-generation cephalosporin (eg, cefotaxime, ceftriaxone) and vancomycin : Cefotaxime (300 mg/kg per day intravenously [IV], maximum dose 12 g/day, in 3 or 4 divided doses), or ceftriaxone (100 mg/kg per day IV, maximum dose 4 g/day, in 1 or 2 divided doses), plus: Vancomycin (60 mg/kg per day IV, maximum dose 4 g/day, in 4 divided doses) If ceftriaxone is used, twice daily dosing to avoid the possibility of inadequate treatment in the event of dosing errors, delayed doses, or missed doses . Some experts suggest the addition of rifampin to the empiric regimen if dexamethasone is administered. Consultation with an expert in pediatric infectious diseases is recommended for children in whom cephalosporins or vancomycin are contraindicated.
  12. Prehospital: GET GCS or AVPU, Finger stick, O2, 2 largebore IV’s; universal precautions; chemoprophylaxis to those who intubate and have contact with mucous membranes as well as confirmed menigococcal meningitis.
  13. Dubos, Francois et al. Clinical decision rules for evaluating meningitis in children. Current Opinion in Neurology 2009, 22:288–293: “Refined Bacterial Meningitis Score: Introduced clinical variables and deleted less useful variables such as White count (peripheral ANC) and CSF neutrophil counts. So added purpura and added serum procalcitonin. The modified rule recommends antibiotic treatment and hospitalization for children with meningitis and presenting at least one of the following criteria: seizure, ‘toxic’ appearance (i.e.irritability, lethargy, or low capillary refill), purpura, positive CSF Gram staining, PCT of at least 0.5 ng/ml, or CSF protein at least 50 mg/dl. This modified rule, called the Meningitest, had a sensitivity of 100% in the derivation and internal validation sets (95% CI 78–100 and 65–100, respectively) and a specificity of 62 and 51%, respectively. The external validation of this Meningitest used the same European population (six hospitalbased cohort studies from five European countries) mentioned above. The sensitivity remained 100% (95%CI 96–100) but the specificity was lower [37% (95% CI 28–47)]. This would still make it possible to safely eliminate antibiotic treatments and hospital stays for 37% of the children with acute meningitis. insufficient validation for the Meningitest. Both can be used, though cautiously, bearing in mind the limitations of each rule: some rare false negative patients with the BMS and insufficient validation for the Meningitest.Large prospective multicenter studies are now needed to provide confirmation of their validity before the extensive generalization of their use. Exclusion Criteria: Neurosurgical history Immunosuppression CSF red blood cell count ≥ 0.01 × 106 per μL Antibiotic use in the previous 48 hours. 100% Sensitivity; 37-51% Specific n=365. Toxic appearance: irritability, lethargy, or low capillary refill. c The sensitivities of the rules are determined by presence of at least one criterion, and specificities by the absence of any criteria.”