Clinical
• Decreased consciousness, confusion • Excitability, convulsions • Motor/sensory disturbances • Extrapyramidal movement disorders Toxic Encephalopathies • Disturbance of coordination • Behavioral psychological change Sumeet Kumar National Neuroscience Institute, Duke-NUS Medical School Singapore
Toxic encephalopathy Imaging
• Disturbance of normal brain function from • Suspect metabolic/toxic interaction of a chemical compound (toxin) – Bilateral symmetric abnormalities with the brain – Deep grey nuclei, cortex, white matter – FLAIR Endogenous Exogenous – DWI – T1 Metabolic – Potentially reversible
Inborn errors of metabolism/acquired
Imaging features Exogenous Toxins Selective Vulnerability
• Grey matter structures: – Energy depletion o Household o Occupational o Adulterated food • White matter: o Drugs of abuse – Accumulation of lipophilic o Therapeutic drugs toxins • Chemotherapy CO poisoning Pallidal necrosis • Antimicrobials o Radiation Imaging features Selective Vulnerability Toxins
• Grey matter structures: • CO – Energy depletion • Metronidazole • Chemotherapeutic agents • White matter: • Alcohol – Accumulation of lipophilic • Methanol toxins • Heroin, Cocaine Toluene abuse • Organic solvents
Imaging features Neurovascular complications Carbon Monoxide
• Colourless, odourless gas CO • Smoke inhalation Ischemia/ Stroke PRES, RCVS Hemorrhage • Intentional/ Accidental – Gas stove – Faulty vehicle • Environmental Incomplete combustion Hypertension Vasospasm – Forest fires Aneurysm Vasculitis – Volcano eruptions Carbon containing Hypotension Venous thrombosis compound
Toxicology and Lab CO has 250x more affinity for Hb CO inhibits mitochondrial than O2 function
Brain lipid peroxidation
Oxygen free radical formation Cellular damage
Reduces O2 carrying capacity of Hb Hypoxia
Dries et al. "Inhalation injury: epidemiology, pathology, treatment strategies." Scand J Trauma Resusc Emerg Med Acute CO poisoning CO poisoning A 67 year old gentleman with a history of depression was found unconscious by his son in an enclosed room with a stove of burning charcoal Signs and symptoms of carbon monoxide poisoning Initial CT brain was normal CO% Symptoms 0-10 No symptoms 10-20 Headache, shortness of breath White matter 20-30 Headache, shortness of breath, nausea, dizziness Demyelination 30-40 Severe headache, vomiting, fatigue 40-50 Confused, passing out, tachycardia, tachypnoea Delayed 50-60 Syncope, seizure, coma leukoencephalopathy >70 Rapidly fatal
• Long Term sequelae- Cognitive impairment, Movement disorders, Depression Day 20 Day 35
Adapted from Clinical practice of emergency medicine: Carbon Monoxide Poisoning
CO poisoning Basal ganglia + Cortex A 40 year old lady with a history of depression was found by a friend unresponsive in a room with burning charcoal and dense noxious fumes • CO poisoning- globus pallidus Caudate Putamen Thalamus • Methanol poisoning- putamen • Cyanide- putamen
Bilateral symmetric necrosis of globus pallidus
CO poisoning A 40 year old lady with a history of depression was found by a friend unresponsive in a room with burning charcoal and dense noxious fumes
Hypoxic ischemic injury
Focal cortical injury Temporal lobes hippocampi
Infarct Edema
Hegde et al. Differential Diagnosis for Bilateral Abnormalities of the Basal Ganglia and Thalamus Radiographics 2011 Metronidazole toxicity Chemotherapeutic drugs
Doses > 2gm/day Reversible Toxic effects in the CNS: Confusion • Methotrexate Dysarthria Leukoencephalopathy Gait Abn • Cytarabine Neuro vascular Weakness • Vincristine Immune related Dentate nuclei • Asparaginase Dorsal pons/ • Corticosteroids medulla Tectum Periaqueduct Grey AJR 2009, P Sharma et al
Metronidazole toxicity 60/M Brain Treatment-induced abscesses Nov 2015 Leukoencephalopathy
Seizures Acute neurotoxic effect-Methotrexate Transient ischemic attacks Encephalopathy Ataxia Cerebral white matter Myelopathy Spinal cord -acute- restricted diffusion -chronic- gliosis and encephalomalacia
Treated with Risk factors for methotrexate-induced Metronidazole neurotoxic effects: High-dose treatment Intrathecal treatment Dentate signal abN Young age Resolved 2 months after Associated cranial radiation therapy stopping Rx Feb 2016 Patients often recover spontaneously
Dentate nucleus Methotrexate induced neurotoxicity
Methotrexate-induced neurotoxic effects in a 12-year-old girl with acute lymphoblastic leukemia. (a) Axial FLAIR MR image shows several white matter lesions. (b) Axial diffusion-weighted image shows restricted diffusion in the lesions, which is consistent with acute methotrexate-related toxic effects.
S Khandilkar, Clin Rad 2016 Side Effects of Oncologic Therapies in the Pediatric Central Nervous System: Update on Neuroimaging Findings. Radiographics 2011 Methotrexate induced neurotoxicity PRES
Typical features Atypical features: enhancement, hemorrhage, restricted Intrathecal Methotrexate diffusion Less commonly affected regions: brainstem, basal ganglia, or cerebellum
Treatment- discontinuing the offending chemotherapy agent, controlling hypertension, and administering anticonvulsive and/or antiedemictherapy
Courtesy Zoran Rumboldt
Chronic Methotrexate induced neurotoxicity
Drugs of Abuse
Courtesy Zoran Rumboldt
PRES Alcohol- Ethanol • Most commonly abused drug in the world • In the settings of chemotherapy, immunosuppressive therapy and sepsis- PRES may occur with normal blood pressure
Side Effects of Oncologic Therapies in the Pediatric Central Nervous System: Update on Neuroimaging Findings. Radiographics 2011 Wernicke’s encephalopathy
Alcohol Ataxia
Direct Cirrhosis Nutritional Acute thiamine effects deficiency
Osmotic Marchiafava Seizure related Neurodegenerative myelinolysis Bignami disease Global confusion Ophthalmoplegia
Alcohol brain injury Wernicke’s encephalopathy
• Acute alcohol toxicity • Wernicke’s encephalopathy • Marchiafavi Bignami disease
Periqueductal Mamillary Medial thalami grey matter bodies
Acute Ethanol poisoning Marchiafava Bignami Disease
• Rare Rare complication • Binge drinking • Blood Eth levels above: 80mg% Acute Chronic Severely • Reduces forebrain function impaired • Life threatening brain swelling consciousness Corpus callosum Dementia Seizures • Non convulsive status epilepticus Dysarthria • Acute demyelination- white matter esp Splenium Muscle rigidity corpus callosum, Optic pathway esp opt nerves/ Death AbN gait Chiasm Marchiafava Bignami Disease Methanol Toxicity
Early Hemorrhage Formic acid Necrosis -Accumulates in
Metabolic Corpus Callosum Methanol Formaldehyde putamen acidosis Late Cavitations -Optic neuritis/ Atrophy Retinal damage
Fatal dose: 60-120 ml G Zuccoli AJR 2010
Methanol Toxicity Methanol Toxicity
• Can be fatal, blindness Bilateral • putaminal Illegal liquor: necrosis Moonshine, Bootleg • Very high proof-95% alcohol Hemorrhage • Ethanol laced with methanol to increase the Variable alcohol content T1 hyperintensity enhancement
AJR 2009, P Sharma et al
Methanol Toxicity Methanol Toxicity
Bilateral putaminal necrosis Alcohol dehydrogenase
Metabolic Methanol Formaldehyde Formic acid acidosis
Basal ganglia nuclei Subcortical wm Brainstem
AJR 2009, P Sharma et al Cerebellum Chasing the dragon Heroin
Semisynthetic drug Inhalation Derived from opium Toxic leukoencephalopathy
Neurovascular complications Intravenous Infection Hypoxic Ischemic Encephalopathy Seizures
Case courtesy: Timo Krings, Luc van den Hauwe From Geibprasert et al. AJNR 2010
Chasing the dragon Cocaine
Vapour Inhalation Hallmark drug for producing both ischemic stroke and intracranial hemorrhage Heroin Pyrolysate
Highly lipophillic
Spongiform leukoencephalopathy
Chasing the dragon 40/M Comatose positive for opoids
Symmetric Mechanism: Blocks reuptake of carrier of monoamines Cerebellar white matter Sparing the dentate and cortex • Vasoconstriction • Increased blood pressure • Tachycardia Posterior cerebral white • Increased cardiac output matter Stroke Subarachnoid hemorrhage Posterior limb IC Parenchymal hemorrhage
Case courtesy of Luc van den Hauwe https://americanaddictioncenters.org/cocaine-treatment/ Cocaine induced Vasospasm Cocaine induced PRES
Vasospasm in a 52-year-old man with a history of recent cocaine abuse, focal stenosis Cocaine-induced PRES in a 17-year-old boy. FLAIR changes in the subcortical of the left middle cerebral artery white matter involving the posterior frontal and parietal lobes
B Tamarazi et al. Your Brain on Drugs: Imaging of Drug-related Changes in the Central Nervous System. Radiograohics 2012 B Tamarazi et al. Your Brain on Drugs: Imaging of Drug-related Changes in the Central Nervous System. Radiograohics 2012
Cocaine-induced ischemia. Organic solvents
• Occupational/ Substance abuse – Liquid thinner, spray paint, glue, varnish, gasoline – Toluene, trichloroethane, nitrous oxide
• Lipophilic • Chronic Encephalopathy
B Tamarazi et al. Your Brain on Drugs: Imaging of Drug-related Changes in the Central Nervous System. Radiograohics 2012
Chronic solvent induced Cocaine induced Hemorrhage Encephalopthy
Cerebral white matter
Posterior limb of IC Pons Cerebellar white matter Sparing dentate
Atrophy
16-year-old patient who had inhaled toluene for 6 years Cocaine-induced aneurysm rupture with subarachnoid and parenchymal hemorrhage in a 47- year-old man with underlying aneurysm of the left middle cerebral artery
Kubilay Aydin et al. AJNR Am J Neuroradiol B Tamarazi et al. Your Brain on Drugs: Imaging of Drug-related Changes in the Central Nervous System. Radiograohics 2012 2002;23:1173-1179 ©2002 by American Society of Neuroradiology Take Home Messages
1. Bilateral Symmetric abn- think Metabolic/ Toxic
2. Distribution- Selective vulnerability
3. Toxicology- Lab support
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