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Special acknowledgements Dr Prasad Hanagandi, KSA Prof Manu Shroff, SickKids Dr Ramesh Konani, India Dr Sunila Jaggi, India Dr Kling Chong, London

Acute Neurotoxicity

Dr Kshitij (Kish) Mankad Great Ormond Street Hospital, London

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Ha…. This is so simple!!! I have seen it on google….

I definitely need more information about the patient.

A mysterious case! 15 / boy, found on the

street comatose

The common thread….

Key Concept: Oedema

Vasogenic Disruption of

BBB

Cytotoxic Intracellular

neuronal glial

swelling

Osmolar Increased

Osmolality in the

brain

Interstitial Hydrocephalic,

Paraventricular

white matter

often an overlapping spectrum….. Intramyelinic

Disruption of

BBB

Excito-toxic Glutamate

induced

High glutamate in the receptors

Excitotoxic injury

Intramyelinic edema

Blood brain barrier (BBB)

Adapted from dams and Victor’s principles of Neurology; tenth edition

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• Intrinsic: IEM, Organ failure.

• Extrinsic: Drugs, Metal, Solvents, Radiation.

Endogenous toxins

Urea cycle defect- Hyperammonemia

20 m female, seizures, diarrhoea, dehydration, reduced urine output

Haemolytic Uraemic Syndrome

Key concept: Basic patterns

Posterior Reversible Encephalopathy Syndrome

11 / Girl post heart transplant on

FK-506

Follow-up imaging at 6/12

Transient Endothelial Dysfunction Syndrome

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Acute toxic leukoencephalopathy

Follow-up imaging after 4 months

• Manifests with transient stroke-like symptoms, encephalopathy, seizures, +/or aphasia.

• Fatal diffuse necrotizing leukoencephalopathy form is also known.

• Germline polymorphisms may contribute to MTX-induced leukoencephalopathy due to variants in GSTP1,MTHFR, & SHMT1 genes [folate pathway].

Methotrexate Toxicity

Follow-up imaging after 5 months

CAR-T

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L-asparaginase therapy

Asparaginase-induced deficiency of antithrombin III

14/Boy, Glioblastoma, H3.3 G34 mutant

Mineralizing angiopathy

Common drugs…. Uncommon manifestations….

Case 2

Vigabatrin Toxicity

DWI

6 month old infant with infantile spasms

GABA

5 year old child on Anti-Tubercular treatment

GABA

Isoniazid toxicity

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Metronidazole Toxicity

• 5/ boy, treated for febrile diarrheal illness

• Symmetrical signal abnormalities in bilateral cerebellar dentate nuclei, midbrain ,dorsal pons (vestibular, superior olivary and abducens nuclei) & dorsal medulla.

• Splenium of corpus callosum, internal capsule & anterior

commissure.

The proposed causal mechanisms include Purkinje cell damage, inhibition of protein synthesis & axonal degeneration induced by the generation of semiquinone + nitro anion radicals

Follow-up imaging 8 weeks

Acetaminophen 16 year old with liver and renal failure

MR Spectroscopy at TE 44 glutamate/glutamine peak

Key concept: maternal factors

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Cocaine, Amphetamine, Alcohol

Maternal Amphetamine Abuse

29 weeks premature baby with germinal

matrix & intraventricular

hemorrhage

Maternal Cocaine Abuse

Follow-up imaging at 2 years of age

26 weeks premature baby with isolated intraventricular hemorrhage

Accidental Cocaine consumption by kid

4 year old girl with methadone overdose

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LATERAL THINKING

• 15 year old fell from the train - had multiple injuries. Operated for the same.

• In the post-operative period, there was sudden desaturation with cardiac arrest. CPR done. Comatose since then, on ventilator.

• MRI 9 days later.

Diagnosis

Delayed White Matter Injury

(Post anoxic leukoencephalopathy)

A mysterious case! 15 / boy, found on the

street comatose

• 16 year old giddiness, diplopia, blurring of vision

followed by altered sensorium which progressed to

coma.

• No significant history available….

• Treated with steroids, gradually improved.

• After recovery, gave history of heavy consumption of

alcohol before passing out.

Toddy

• Basically a type of palm wine.

• Alcohol content increases with fermentation.

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Thank you for your attention

Expect the unexpected

LinkedIn @ drmankad