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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
Tweet @drmankad
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
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