Presentation at PNU 2014

1. DIAGNOSTIC APPROACH TO ACUTE ENCEPHALOPATHYIN CHILDREN
Dr HengHock Sin
PaediatricNeurologist
Sabah Women & Children’s Hospital
Paediatric Neurology Update 2014

2. Encephalopathy
A syndrome of global brain dysfunction
Definition [International Pediatric MS study Group 2007]:
Behavioral change: confusion, excessive irritability
Alteration in consciousness: lethargy, coma
Acute or insidious onset

3. Encephalopathy
Full consciousness Death
Restless
Agitated
Confused
Delirious
Lethargic
Drowsy
Stuporous
Comatose
*Glasgow Coma Scale

4. Causes of Acute EncephalopathyDavies E et.al. Encephalopathy in children: an approach to assessment and management. Arch DisChild. 2012 May;97(5):452-8. doi: 10.1136/adc.2011.300998. Epub 2011 Dec 27

5. Causes of Acute Encephalopathy
CNS infection /Para- infection
Autoimmune
Metabolic / Toxins
Seizure related
Hypertensive
Trauma / Haemorrhage
Hypoxic-ischaemic
Tumour / Malignancy
Hydrocephalus / Other causes of raised ICP

6. Acute Encephalopathy in Children
An important paediatric emergency
Involves children of any age
Previously normal children, or children with pre-existing neurological impairment

7. Acute Encephalopathy in Children
Associated with significant mortality & long- term morbidity in survivors
Good assessment with appropriate investigations identify treatable causes
minimize neurological impairment

8. Acute Encephalopathy
Wide range of differential diagnoses
long list of possible investigations

9. Clinical Assessment
History
Physical examination
Investigations

10. History
Timing & nature of the encepahlopathy
Associated symptoms
Fever, vomiting, loss of appetite
Headache, seizures
Current / recent febrile illness
In some cases, the cause is obvious
e.g. Acute renal / liver failure, DM, following head trauma or hypoxic event

11. History
Pre-existing medical / neurological condition
Developmental history
Travel, contact with animals / insects
Drug / toxin ingestion
Family history
Neurological / metabolic disorder; vascular / bleeding disorder
Parental consanguinity
Early / unexplained childhood deaths
Social history: Non-accidental injury

12. Examination
Opportunistic examination & observation
Vital signs: HR, BP, RR, SpO2, temperature
Mental state, communication, behaviour, orientation, memory e.t.c.

13. Examination
Neurological examination:
Focal neurological deficit
Motor & sensory
Cranial nerves & limbs
Eyes: nystagmus, ophthalmoplegia, pupils, fundoscopy
Abnormal movement
Examination of other systems

14. Investigations
Initial investigations
Blood glucose
Blood gases
Urea & electrolytes
LFT
Ammnonia
FBC & blood picture
Urine FEME
Prompt identification of treatable cause

15. Investigations
Further tests should be tailored to the differential diagnoses
Lumbar puncture: CNS infections
Neuro-imaging (Ultrasound, CT, MRI)

16. CNS infections / Para-infection
Suggestive features:
Fever , headache
Meningism
Focal neurological deficits
Seizures
Primary source of infection
Pneumonia (bacteria, mycoplasma, TB), purpuric rash (meningococcemia), mucosal herpetic lesions, cyanotic heart dis. (brain abscess)

17. CNS infection: Investigations
FBC, CRP, ESR
Blood culture
Viral study (blood, throat, urine, stool)
TB work-up
CSF: ME, sugar, protein, C&S, virology, TB, fungus

18. CNS infection: Neuro-imagingCT with contrast: Bacterial meningitis: Subdural effusion, meningealenhancement, abscess formation
CT with contrast: Brain abscess with ring enhancement

19. Neuro-imaging: TB meningitisPlain CT: Hydrocephalus
CT with contrast: Basal enhancement

20. Neuro-imaging: Herpes Encephalitis
MRI (T2): Bilateral asymmetric temporal, insular & basifrontalhyper-intensity

21. Neuro-imaging: Acute Disseminated Encephalomyelitis (ADEM) MRI, T2 (Lt), FLAIR (Rt): Multiple hyper-intense foci involving the white matter & deep grey matter

22. Neuro-imaging: Acute NecrotisingEncephalopathy of Childhood (ANEC) MRI (T2, FLAIR, DWI): Bilaterally symmetric signal change in the thalami

23. Neuro-imaging: Infantile Bilateral StriatalNecrosis (IBSN) Plain CT: Bilaterally symmetric hypodensityof the caudate nuclei & putamenwith mass effect

24. Autoimmune Encephalitis & Immune Related Encephalopathy
NMDA-receptor antibody encephalitis, limbic encephalitis, Hashimoto’s encephalopathy, CNS lupus e.t.c.
Suggestive features:
Prolonged course & fluctuating symptoms
unresponsive to anti-microbial drugs
No infectious agent identified
Specific movement disorders
Underlying immune disorder

25. Autoimmune Encephalitis & Immune Related Encephalopathy
Investigations:
Work-up for vasculitic disorders
Blood or CSF for specific neuronal antibodies:
Anti-NMDA receptor antibody
Anti-VGKC antibody e.t.c
Thyroid function, anti-thyroid antibodies

26. Intracranial Haemorrhage
Traumatic
Accidental
Non-accidental: Child abuse (Shaken baby syndrome)
Spontaneous
Vascular malformation
Bleeding disorder

27. Trauma / Intracranial Haemorrhage
Suggestive features:
History of head trauma
Sudden onset of encephalopathy ( +seizure) in a well child
Signs of acute blood loss: Pallor, tachycardia
History or family history of bleeding disorder
Non-accidental injury
Inconsistent / suspicious history, other suspicious body injuries, retinal haemorrhage, e.t.c.

28. Trauma / Intracranial Haemorrhage
Blocod count (platelet), coagulation profile
Neuro-imaging

29. Metabolic Disorders
Broad category of conditions
Suggestive features
History of development delay / regression, growth failure, epilepsy
Relapsing acute encephalopathy / septic-like episodes
Multi-organ impairment
Consanguineous parents, significant family history

30. Metabolic Disorders
Investigations
*Initial investigations
Metabolic work-up
Neuro-imaging, MR spectoscopy
MRI. Leigh syndrome: Bilateral symmetrical T2 high signal in caudate nuclei /putamenand white matter

31. Neuro-imaging: MELAS syndrome(A) CT: Basal ganglia calcification. (B & C) MRI T2: Hyperintenselesion in the left temporo-parieto-occipital regions. (D) MRS: High lactate peak

32. Tumour/ CNS Malignancy
Suggestive features
Signs & symptoms of raised ICP
Focal neurological deficit
Seizures
Extra-cranial primary malignancy
Neuro-imaging: 1stline investigation

33. Medulloblastoma
Gliablastoma multiforme
Diffuse Intrinsic Brainstem Glioma

34. Acute Encephalopathy in ChildrenCase Illustration

35. Case 1
7 year old boy, previously well
Headache & lethargic for 3 days blurred vision, confusion, followed by status epilepticus
Intubated in district hospital, seizure was aborted with iv diazepam

36. Case 1
On arrival, sedated; pupils-equal & reactive; fundus-N; no focal neuro deficit
Noted hypertension but no bradycardia
Brain CT: Mild cerebral oedema
Wean off sedation but the child remained encephalopathic; Persistent hypertension

37. Case 1
Urine ME: RBC 5+
ASOT 800
Diagnosis:
Hypertensive encephalopathy secondary to
post-streptococcus acute gromerulo- nephritis (AGN)

38. Case 1
Brain MRI
Posterior Reversible Encephalopathy Syndrome

39. Case 2
11 yr old girl
Learning disability with history of recurrent stroke-like episodes & epilepsy
Diagnosed Mitochondrial Encephalopathy Lactic Acidosis Stroke-like episodes (MELAS) syndromeat 9 yr old, confirmed by gene mutation study

40. Case 2
Able to talk & walk independently
Activities of daily living: need supervision with some assistance
On anti-epileptic drug, occasional breakthrough seizures

41. Case 2
Presented with:
More frequent seizures, 1-2 episodes / day, for 3 days
Lost her verbal skills, not interactive
Poor head control, needed assistance in walking
Drooling of saliva
Urinary incontinence
Unable to eat

42. Case 3
Video EEG: Non-convulsive status epilepticus

43. Conclusions
Acute encephalopathy in children is an emergency with wide range of differential diagnoses; significant morbidity & mortality
A systematic approach is essential for early & accurate diagnosis to ensure appropriate & timely treatment

44. Thank You