DIAGNOSTIC APPROACH TO ACUTE ENCEPHALOPATHY

Paediatric Update 2014Hospital Tawau

Dr. Thay Wee Ying

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 consiousness 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 DisChild. 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/ hemorrhage

Hypoxic-ischemic

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 and 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 and nature of the encephalopathy

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 and

observation

Vital signs: HR, BP, RR, Spo2, temperature

Mental state, communication, behaviour, orientation, memory etc.

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› Ammonia› 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 Necrotising Encephalopathy 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 etc.

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

Blood 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 /putamenand 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

Diffuse Intrinsic Brainstem Glioma

Gliablastoma multiformeMedulloblastoma

Acute Encephalopathy in

ChildrenCase Illustration

Case1 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

On arrival, sedated; pupils-equal & reactive; fundus-N; no focal neurological deficit

Noted hypertension but no bradycardia

Brain CT: Mild cerebral oedema

Wean off sedation but the child remained encephalopathic; Persistent hypertension

Urine ME: RBC 5+

ASOT 800

Diagnosis: Hypertensive encephalopathy secondary to post-streptococcus acute gromerulo-nephritis (AGN)

Brain MRI

Posterior Reversible Encephalopathy Syndrome

Case 211 yr old girl

Learning disability with history of recurrent stroke-like episodes & epilepsy

Diagnosed Mitochondrial Encephalomyopathy, Lactic Acidosis, Stroke-like episodes (MELAS) syndrome at 9 yr old, confirmed by gene mutation study

Able to talk & walk independently

Activities of daily living: need supervision with some assistance

On anti-epileptic drug, occasional breakthrough seizures

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

Conclusion 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