DIAGNOSTIC APPROACH TO ACUTE ENCEPHALOPATHY

IN CHILDREN

Dr Heng Hock SinPaediatric Neurologist

Sabah Women & Children’s Hospital

Paediatric Neurology Update 2014

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

Encephalopathy

Full consciousness Death

Restless

Agitated

Confused

Delirious

Lethargic

Drowsy

Stuporous

Comatose

*Glasgow Coma Scale

Causes of Acute Encephalopathy

Davies E et.al. Encephalopathy in

children: an approach to assessment and

management. Arch Dis Child. 2012

May;97(5):452-8.

doi: 10.1136/adc.2011.300998. Epub

2011 Dec 27

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

Acute Encephalopathy in Children

An important paediatric emergency

Involves children of any age

Previously normal children, or children with pre-existing neurological impairment

Acute Encephalopathy in Children

Associated with significant mortality & long-term morbidity in survivors

Good assessment with appropriate investigations identify treatable causes

minimize neurological impairment

Acute Encephalopathy

Wide range of differential diagnoses

long list of possible investigations

Clinical Assessment

History

Physical examination

Investigations

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

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

Examination

Opportunistic examination & observation

Vital signs: HR, BP, RR, SpO2, temperature

Mental state, communication, behaviour, orientation, memory e.t.c.

Examination

Neurological examination:

Focal neurological deficit

Motor & sensory

Cranial nerves & limbs

Eyes: nystagmus, ophthalmoplegia, pupils, fundoscopy

Abnormal movement

Examination of other systems

Investigations

Initial investigations

Blood glucose

Blood gases

Urea & electrolytes

LFT

Ammnonia

FBC & blood picture

Urine FEME

Prompt identification of treatable cause

Investigations

Further tests should be tailored to the differential diagnoses

Lumbar puncture: CNS infections

Neuro-imaging (Ultrasound, CT, MRI)

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)

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

CNS infection: Neuro-imaging

CT with contrast: Bacterial meningitis: Subdural effusion, meningeal enhancement, abscess formation

CT with contrast: Brain abscess with ring enhancement

Neuro-imaging: TB meningitis

Plain CT: Hydrocephalus CT with contrast: Basal enhancement

Neuro-imaging: Herpes Encephalitis

MRI (T2): Bilateral asymmetric temporal, insular & basifrontal hyper-intensity

Neuro-imaging: Acute Disseminated Encephalomyelitis (ADEM)

MRI, T2 (Lt), FLAIR (Rt): Multiple hyper-intense foci involving the white matter & deep grey matter

Neuro-imaging: Acute NecrotisingEncephalopathy of Childhood (ANEC)

MRI (T2, FLAIR, DWI):Bilaterally symmetric signal change in the thalami

Neuro-imaging: Infantile Bilateral Striatal Necrosis (IBSN)

Plain CT: Bilaterally symmetric hypodensity of the caudate nuclei & putamen with mass effect

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

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

Intracranial Haemorrhage

Traumatic

Accidental

Non-accidental: Child abuse (Shaken baby syndrome)

Spontaneous

Vascular malformation

Bleeding disorder

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.

Trauma / Intracranial Haemorrhage

Blocod count (platelet), coagulation profile

Neuro-imaging

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

Metabolic Disorders

Investigations

*Initial investigations

Metabolic work-up

Neuro-imaging, MR spectoscopy

MRI. Leigh syndrome: Bilateral symmetrical T2 high signal in caudate nuclei /putamen and white matter

Neuro-imaging: MELAS syndrome

(A) CT: Basal ganglia calcification. (B & C) MRI T2: Hyperintense lesion in the left temporo-parieto-occipital regions. (D) MRS: High lactate peak

Tumour / CNS Malignancy

Suggestive features

Signs & symptoms of raised ICP

Focal neurological deficit

Seizures

Extra-cranial primary malignancy

Neuro-imaging: 1st line investigation

Medulloblastoma Gliablastoma multiforme

Diffuse Intrinsic Brainstem Glioma

Acute Encephalopathy in Children

Case Illustration

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

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

Case 1

Urine ME: RBC 5+

ASOT 800

Diagnosis:

Hypertensive encephalopathy secondary to

post-streptococcus acute gromerulo-nephritis (AGN)

Case 1

Brain MRI

Posterior Reversible Encephalopathy Syndrome

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) syndrome at 9 yr old, confirmed by gene mutation study

Case 2

Able to talk & walk independently

Activities of daily living: need supervision with some assistance

On anti-epileptic drug, occasional breakthrough seizures

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

Case 3

Video EEG: Non-convulsive status epilepticus

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

Thank You