1. Shake…Shake….Shake Neurology Module PEDIATRICS II

2. ES, 16 months old, admitted because of convulsions Five days PTA  cough and fever Two days later  grand mal seizures for 10 minutes Birth, neonatal, developmental history unremarkable First attack of febrile seizures at 6 months of age Father and cousins with febrile seizures Salient Points:

3. Pertinent Physical Examination Findings: Febrile, awake, with mild dehydration Congested pharyngeal wall, no exudates, (+) crackles on both lungs Neurological Examination Findings: Essentially normal No meningeal signs Salient Points:

4. Is there a neurologic disease? The description of event appears to be a seizure. Seizures refer to excessive neuronal discharge with change in motor activity or behavior.

5. Is there a neurologic disease? Non-neurologic Metabolic disorders Electrolyte imbalance Hypoglycemia Hypoxia Fever Systemic infections Toxins Drug-related Neurologic Tumors CNS malformation Vascular disorders Idiopathic epilepsy Causes of seizure:

6. In this patient, the seizures are ushered in by fever and respiratory infection. Benign Febrile Seizures Benign Febrile Seizures should be ruled out. The typical benign FS is characterized by: 1. Grand mal lasting for <15 min 2. Occurring once in the same illness 3. Age incidence: 3 months to 5 years 4. Occurs at temperature 38 0 C and above 5. Normal neurological examination 6. Family history (+) for FS 7. CNS infection absent What is the neurologic disease?

7. Atypical - May occur more than once in an illness, focal seizure, more than15 minutes May need investigation to rule out epilepsy With focal manifestations Complex Febrile Seizure

8. Benign febrile seizures In the presence of fever, pneumonia and seizure, a CNS infection should be considered. An infant may not show any meningeal signs even in the presence of meningitis. Diagnostic possibilities:

9. Search for cause of fever No anticonvulsants needed Antipyretics Education of parents Oral diazepam at onset of febrile episode (1 mg/kg/24 hrs) for 2-3 days Management of BFC:

10. Not necessary if clear-cut BFC Tests mainly to determine cause of fever and rule out meningitis If done, CSF examination is normal EEG - Normal and not useful in BFC Neuroimaging - No role Blood tests / chest X-ray, etc are done to diagnose the cause of fever, not the BFC Laboratory Tests:

11. Tests are usually directed towards ruling out meningitis especially in infants where meningeal signs are often lacking. Do lumbar puncture and CSF examination Diagnosis:

12. While in the hospital, he developed another seizure. Fever persisted. On examination, he was ill-looking, irritable, with some resistance on neck flexion. Patient E.S.

13. CNS Infections Differential Diagnosis: Fever with Seizures

14. Forms: Meningitis Encephalitis Brain Abscess Etiology Viral Bacterial (Acute S uppurative) Tuberculous Fungal CNS Infections

15. Acute Meningitis-Causes: Bacterial 0 - 2 months: Grp B and D strep gram-negative enteric bacilli Listeria 2 mo – 2 yrs: S. pneumoniae N. meningitis H. influenza B Older children:S. pneumoniae N. meningitides

16. Acute Route of Infection Hematogenous Contiguous focus of infection CSF leak (trauma, congenital defect) Neurosurgical procedure Bacterial Meningitis

17. Signs and symptoms Neonates Older infants and children NonspecificFever or hypothermia, abnormally sleepy or lethargic, disinterest in feeding, poor feeding, cyanosis, grunting, apneic episodes, vomiting Fever, anorexia, confusion, irritability, photophobia, nausea, vomiting, headache, seizure Meningeal inflammation +/- Neck rigidityNeck rigidity, Kernig and Brudzinski sign Increased intracranial pressure Bulging fontanel, diastasis of sutures, convulsions, opisthotonus Headache, bulging fontanel, diastasis of sutures in infants, papilledema, mental confusion, altered state of consciousness Focal neurologic signs Hemiparesis, ptosis, facial nerve palsy Hemiparesis, ptosis, deafness, facial nerve palsy, optic neuritis Clinical Features:

18. 1.Lumbar Puncture Contraindications Skin infection over site Increased ICP with papilledema Focal neurologic deficits Suspected mass lesion Hematologic problems Significant cardiopulmonary compromise and shock Laboratory Diagnosis:

19. CSF Findings Pressure (mm H 2 0) Cell Count (white blood cells/mm 3 ) Glucose (mg/100 ml) Protein (mg/100 ml) Normal values90-1800-5 lymphocytes50-75 (at least 50% of simultaneous serum glucose) 15-40 Bacterial meningitis200-300100-5,000; neutrophils usually >80% Reduced, < 40100-1,000 Tuberculous meningitis180-300Usually < 500 lymphocytes Reduced, < 40100-200, but up to 1,000 if CSF block is present Cryptococcal meningitis180-30010-200 lymphocytesReduced, <4050-200 Viral meningitis90-20010-300 lymphocytes; may be >1,000 in echoviral and mumps meningitis and in lymphocytic choriomeningitis; early echoviral meningitis may show up to 80% neutrophilic predominance Normal; occasionally slightly reduced in mumps meningitis and LCM 50-100 Viral encephalitis180-3000-500 lymphocytesNormal50-100

20. Contrast enhanced CT image of a 3-month-old baby brain show brain edema and subdural empyema Subdural effusion, cerebritis and developing abscess formation in a patient with bacterial meningitis 2. Neuroimaging Laboratory Diagnosis:

21. CSF Analysis: Clear, colorless fluid OP 130 WBC = 320/cumm, all neutrophils RBC = 0 Protein = 90 Sugar = 40% of blood sugar Gram stain = (+) gram-negative coccobacilli Culture (-) CBC: Hgb 11, RBC 4.3, WBC 12,000 with lymphocytic predominance Patient’s laboratory results:

22. Acute Bacterial Meningitis (Hemophilus) Pneumonia Diagnosis:

23. Bacterial meningitis is a medical emergency; delay in treatment may lead to increased sequelae or death Drug of choice must be bactericidal for pathogen involved Must achieve adequate levels in the CSF Initial regimen should cover most likely pathogens for specific age groups, and reach bactericidal levels in the CSF Treatment:

24. Knowledge of local susceptibility patterns is essential Antibiotics should be guided by the bacteriologic results Duration of treatment: 10 -14 days Treatment:

25. Patient groupLikely etiologyAntimicrobial choice PrimaryAlternative 0-2 mosE. coli Gram (-) bacilli S. pneumoniae Ampicillin or Penicillin + Aminoglycoside Ampicillin + Cefotaxime or Ceftriaxone 2mos – 5 yrsH. influenzae S. pneumoniae N. meningitidis Ampicillin or Chloramphenicol Cefotaxime or Ceftriaxone >5 yrsS. pneumoniae N. meningitidis Penicillin GChloramphenicol Task Force on Meningitis Philippine Society of Microbiology and Infectious Diseases Empiric Therapy for Bacterial Meningitis:

26. Subacute to chronic Staging of symptoms Stage I: early nonspecific Stage II: altered consciousness, minor focal signs, meningism, abnormal involuntary movements Stage III: stupor or coma, seizures, severe neurologic deficits and/or abnormal movements Prognosis is related directly to the clinical stage of diagnosis Tuberculous Meningitis

27. CSF Findings Pressure (mm H 2 0) Cell Count (white blood cells/mm 3 ) Glucose (mg/100 ml) Protein (mg/100 ml) Normal values90-1800-5 lymphocytes50-75 (at least 50% of simultaneous serum glucose) 15-40 Bacterial meningitis200-300100-5,000; neutrophils usually >80% Reduced, < 40100-1,000 Tuberculous meningitis180-300Usually < 500 lymphocytes Reduced, < 40100-200, but up to 1,000 if CSF block is present Cryptococcal meningitis 180-30010-200 lymphocytesReduced, <4050-200 Viral meningitis90-20010-300 lymphocytes; may be >1,000 in echoviral and mumps meningitis and in lymphocytic choriomeningitis; early echoviral meningitis may show up to 80% neutrophilic predominance Normal; occasionally slightly reduced in mumps meningitis and LCM 50-100 Viral encephalitis180-3000-500 lymphocytesNormal50-100

28. Visual impairment Strabismus Hearing loss or impairment Locomotion/neuromotor deficits Epilepsy Mental or psychomotor retardation Hydrocephalus Microcephaly Late Neurologic Sequelae:

29. Hydrocephalus

30. Cerebral Atrophy Microcephaly

31. Majority due to enteroviruses Higher incidence during summer to fall months Other viruses associated with meningitis in children: HSV types 1 and 2 Mumps Adenoviruses Polioviruses Lymphocytic choriomeningitis virus Epstein-Barr virus HIV St. Louis encephalitis virus Tick-borne encephalitis virus Viral Meningitis

32. CSF Findings Pressure (mm H 2 0) Cell Count (white blood cells/mm 3 ) Glucose (mg/100 ml) Protein (mg/100 ml) Normal values90-1800-5 lymphocytes50-75 (at least 50% of simultaneous serum glucose) 15-40 Bacterial meningitis200-300100-5,000; neutrophils usually >80% Reduced, < 40100-1,000 Tuberculous meningitis180-300Usually < 500 lymphocytes Reduced, < 40100-200, but up to 1,000 if CSF block is present Cryptococcal meningitis180-30010-200 lymphocytesReduced, <4050-200 Viral meningitis90-20010-300 lymphocytes; may be >1,000 in echoviral and mumps meningitis and in lymphocytic choriomeningitis; early echoviral meningitis may show up to 80% neutrophilic predominance Normal; occasionally slightly reduced in mumps meningitis and LCM 50-100 Viral encephalitis180-3000-500 lymphocytesNormal50-100

33. Management: 1.No specific antiviral therapy necessary 2.Treatment is supportive with IV fluids 3.Outcome is usually a full recovery Viral Meningitis

34. Distinguished from viral meningitis by the extent and severity of cerebral dysfunction Two clinical presentations: Fever and malaise without meningeal signs With meningeal signs plus cerebral dysfunction (altered consciousness, personality changes, seizures, and paresis) and cranial nerve abnormalities Viral Encephalitis

35. Causes: Epidemic Arbovirus Poliovirus Echovirus Coxsakie virus Sporadic Herpes simplex Varicella-Zoster Mumps Viral Encephalitis

36. CSF Findings Pressure (mm H 2 0) Cell Count (white blood cells/mm 3 ) Glucose (mg/100 ml) Protein (mg/100 ml) Normal values90-1800-5 lymphocytes50-75 (at least 50% of simultaneous serum glucose) 15-40 Bacterial meningitis200-300100-5,000; neutrophils usually >80% Reduced, < 40100-1,000 Tuberculous meningitis180-300Usually < 500 lymphocytes Reduced, < 40100-200, but up to 1,000 if CSF block is present Cryptococcal meningitis180-30010-200 lymphocytesReduced, <4050-200 Viral meningitis90-20010-300 lymphocytes; may be >1,000 in echoviral and mumps meningitis and in lymphocytic choriomeningitis; early echoviral meningitis may show up to 80% neutrophilic predominance Normal; occasionally slightly reduced in mumps meningitis and LCM 50-100 Viral encephalitis180-3000-500 lymphocytesNormal50-100

37. Treatment: Acyclovir 10 mg/kg IV infusion every 8 hours for at least 10 days Supportive therapy Prognosis: Mortality rate varies with etiology Permanent cerebral sequelae more likely in infants Viral Encephalitis

38. Thank you!