Clinical. Toxic Encephalopathies. Toxic encephalopathy. Imaging. Exogenous Toxins

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1 Clinical Toxic Encephalopathies Sumeet Kumar National Neuroscience Institute, Duke-NUS Medical School Singapore Decreased consciousness, confusion Excitability, convulsions Motor/sensory disturbances Extrapyramidal movement disorders Disturbance of coordination Behavioral psychological change Toxic encephalopathy Disturbance of normal brain function from interaction of a chemical compound (toxin) with the brain Exogenous Endogenous Metabolic Imaging Suspect metabolic/toxic Bilateral symmetric abnormalities Deep grey nuclei, cortex, white matter FLAIR DWI T1 Potentially reversible Inborn errors of metabolism/acquired Exogenous Toxins Imaging features Selective Vulnerability o Household o Occupational o Adulterated food o Drugs of abuse o Therapeutic drugs Chemotherapy Antimicrobials o Radiation Grey matter structures: Energy depletion White matter: Accumulation of lipophilic toxins CO poisoning Pallidal necrosis

2 Imaging features Selective Vulnerability Toxins Grey matter structures: Energy depletion White matter: Accumulation of lipophilic toxins Toluene abuse CO Metronidazole Chemotherapeutic agents Alcohol Methanol Heroin, Cocaine Organic solvents Imaging features Neurovascular complications Carbon Monoxide Ischemia/ Stroke Vasospasm Vasculitis Hypotension PRES, RCVS Hemorrhage Hypertension Aneurysm Venous thrombosis Colourless, odourless gas Smoke inhalation Intentional/ Accidental Gas stove Faulty vehicle Environmental Forest fires Volcano eruptions Incomplete CO combustion Carbon containing compound Toxicology and Lab CO has 250x more affinity for Hb than O2 CO inhibits mitochondrial 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

3 Acute CO poisoning Signs and symptoms of carbon monoxide poisoning CO% Symptoms 0-10 No symptoms Headache, shortness of breath Headache, shortness of breath, nausea, dizziness Severe headache, vomiting, fatigue Confused, passing out, tachycardia, tachypnoea Syncope, seizure, coma >70 Rapidly fatal 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 Initial CT brain was normal White matter Demyelination Delayed leukoencephalopathy Long Term sequelae- Cognitive impairment, Movement disorders, Depression Day 20 Day 35 Adapted from Clinical practice of emergency medicine: Carbon Monoxide Poisoning 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 Caudate Putamen Thalamus Basal ganglia + Cortex CO poisoning- globus pallidus 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

4 Metronidazole toxicity Chemotherapeutic drugs Doses > 2gm/day Confusion Dysarthria Gait Abn Weakness Reversible Toxic effects in the CNS: Methotrexate Cytarabine Vincristine Leukoencephalopathy Neuro vascular Immune related Dentate nuclei Dorsal pons/ medulla Tectum Asparaginase Corticosteroids Periaqueduct Grey AJR 2009, P Sharma et al Metronidazole toxicity 60/M Brain abscesses Nov 2015 Treatment-induced Leukoencephalopathy Seizures Transient ischemic attacks Encephalopathy Ataxia Myelopathy Acute neurotoxic effect-methotrexate Cerebral white matter Spinal cord -acute- restricted diffusion -chronic- gliosis and encephalomalacia Feb 2016 Treated with Metronidazole Dentate signal abn Resolved 2 months after stopping Rx Risk factors for methotrexate-induced neurotoxic effects: High-dose treatment Intrathecal treatment Young age Associated cranial radiation therapy 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

5 Methotrexate induced neurotoxicity Intrathecal Methotrexate PRES Typical features Atypical features: enhancement, hemorrhage, restricted diffusion Less commonly affected regions: brainstem, basal ganglia, or cerebellum Treatment- discontinuing the offending chemotherapy agent, controlling hypertension, and administering anticonvulsive and/or antiedemic therapy Courtesy Zoran Rumboldt Chronic Methotrexate induced neurotoxicity Drugs of Abuse Courtesy Zoran Rumboldt PRES In the settings of chemotherapy, immunosuppressive therapy and sepsis- PRES may occur with normal blood pressure Alcohol- Ethanol Most commonly abused drug in the world Side Effects of Oncologic Therapies in the Pediatric Central Nervous System: Update on Neuroimaging Findings. Radiographics 2011

6 Wernicke s encephalopathy Alcohol Ataxia Direct effects Cirrhosis Nutritional Acute thiamine deficiency Seizure related Osmotic myelinolysis Marchiafava Bignami disease Neurodegenerative Global confusion Ophthalmoplegia Alcohol brain injury Wernicke s encephalopathy Acute alcohol toxicity Wernicke s encephalopathy Marchiafavi Bignami disease Periqueductal grey matter Medial thalami Mamillary bodies Acute Ethanol poisoning Marchiafava Bignami Disease Rare Binge drinking Blood Eth levels above: 80mg% Reduces forebrain function Life threatening brain swelling Non convulsive status epilepticus Acute demyelination- white matter esp Splenium corpus callosum, Optic pathway esp opt nerves/ Chiasm Acute Severely impaired consciousness Seizures Muscle rigidity Death Rare complication Corpus callosum Chronic Dementia Dysarthria AbN gait

7 Marchiafava Bignami Disease Methanol Toxicity Early Hemorrhage Necrosis Corpus Callosum Methanol Formaldehyde Formic acid -Accumulates in putamen Metabolic acidosis Late Cavitations Atrophy -Optic neuritis/ Retinal damage Fatal dose: ml G Zuccoli AJR 2010 Methanol Toxicity Can be fatal, blindness Illegal liquor: Moonshine, Bootleg Very high proof-95% alcohol Ethanol laced with methanol to increase the alcohol content Methanol Toxicity T1 hyperintensity Bilateral putaminal necrosis Hemorrhage Variable enhancement AJR 2009, P Sharma et al Methanol Toxicity Methanol Toxicity Alcohol dehydrogenase Bilateral putaminal necrosis Methanol Formaldehyde Formic acid Metabolic acidosis AJR 2009, P Sharma et al Basal ganglia nuclei Subcortical wm Brainstem Cerebellum

8 Heroin Chasing the dragon Semisynthetic drug Derived from opium Inhalation Toxic leukoencephalopathy Intravenous Hypoxic Ischemic Encephalopathy Neurovascular complications Infection Seizures Case courtesy: Timo Krings, Luc van den Hauwe From Geibprasert et al. AJNR 2010 Chasing the dragon Vapour Inhalation Heroin Pyrolysate Cocaine Hallmark drug for producing both ischemic stroke and intracranial hemorrhage Highly lipophillic Spongiform leukoencephalopathy Chasing the dragon 40/M Comatose positive for opoids Symmetric Cerebellar white matter Sparing the dentate and cortex Posterior cerebral white matter Posterior limb IC Mechanism: Blocks reuptake of carrier of monoamines Vasoconstriction Increased blood pressure Tachycardia Increased cardiac output Stroke Subarachnoid hemorrhage Parenchymal hemorrhage Case courtesy of Luc van den Hauwe

9 Cocaine induced Vasospasm Cocaine induced PRES Vasospasm in a 52-year-old man with a history of recent cocaine abuse, focal stenosis of the left middle cerebral artery Cocaine-induced PRES in a 17-year-old boy. FLAIR changes in the subcortical 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 Cocaine induced Hemorrhage Chronic solvent induced Encephalopthy Cerebral white matter Posterior limb of IC Pons Cerebellar white matter Sparing dentate Atrophy Cocaine-induced aneurysm rupture with subarachnoid and parenchymal hemorrhage in a 47- year-old man with underlying aneurysm of the left middle cerebral artery 16-year-old patient who had inhaled toluene for 6 years B Tamarazi et al. Your Brain on Drugs: Imaging of Drug-related Changes in the Central Nervous System. Radiograohics by American Society of Neuroradiology Kubilay Aydin et al. AJNR Am J Neuroradiol 2002;23:

10 Take Home Messages 1. Bilateral Symmetric abn- think Metabolic/ Toxic 2. Distribution- Selective vulnerability 3. Toxicology- Lab support Thank you