clinical neuroimaging: toxic‐metabolic disorders toxins

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Clinical Neuroimaging: Toxic‐Metabolic Disorders

Dara G. Jamieson, M.D.Associate Professor of Clinical Neurology

Headache CenterStroke Center

Toxic Metabolic Disorders Affecting the CNS

• Hypoxic/ischemic injury,

• Hypoglycemia

• Hypertensive disorders (PRES/RCVS)

• Osmotic demylination

• Organ failure: Liver, Renal

• Poisoning: ethanol, methanol, alcohol, CO, ethylene glycol

• Illicit drugs

• Toxic effects of therapies/medications

Characteristic areas of involvement in toxic metabolic disorders

• Areas of increased cellular respiratory metabolism

– Basal ganglia

– Hippocampus

– Cerebellum

• Cerebral white matter (leukoencephalopathy), corpus callosum

• Midbrain, pons

Toxins & brain areas of high‐oxygen demand

• Areas of increased cellular respiratory metabolism

– basal ganglia, cerebellum, hippocampus

• Basal ganglia lesions

– carbon monoxide, methanol, cyanide

– liver dysfunction

– hypoxic‐ischemic brain damage

– severe glucose abnormalities

– mitochondrial disorders

Bilateral Basal Ganglia Lesions

• Normal: dilated perivascular spaces

• Vascular: hypoxic/ischemic encephalopathy, infarcts (arterial, venous)

• Toxicity: CO, methanol, cyanide, hydrogen sulfide, Mg, toluene, disulfram

• Metabolic: hypo/hyperglycemia, osmotic demylination, hemolytic‐uremia syndrome, hepatic disease

• Inherited disorders: Leigh’s, Wilson’s, Huntington’s, methylmalonic acidemia, Alexander’s, Canavan, MLD

• Infection: toxoplasmosis, cryptococcosis, post‐infectious acute striatal necrosis, CJD

Acute unknown toxicity – basal ganglia lesions

43 year‐old healthy woman blamed acute GI complaints, along with headache and generalized aching, on shrimp from a street cart. A week into her symptoms, she developed hand tremors and unsteady walking. On examination she had sustention/intention tremor and cogwheel rigidity. She recently stopped smoking and urine was positive for cannabinoids. Blood testing and CSF analysis was negative. She recovered with supportive care, without neurological abnormality.

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Acute unknown toxicity – basal ganglia lesions

DWI FLAIR

T1C T2

Leukoencephalopathy

• Hypertension

• Environmental toxins

– Organic solvents

• Substances of abuse

– Cocaine, heroin, toluene, alcohol, methadone

• CNS irradiation

• Chemotherapeutic/immunosuppressive agents

– Methotrexate (IT), BCNU, Ara‐C, cisplatin, thiotepa, fludarabine

– Cyclosporine, tacrolimus (PRES)

Targets of Toxins in Cerebral White Matter

Filley & Kleinschmidt-DeMasters. N Engl J Med2001; 345:425-431

Acute unknown toxicity ‐ leukoencephalopathy

26 year old man with depression, anxiety and insomnia was found unconscious by his room-mate after presumably taking medications (including an antidepressant, sleep aid, opioids) and smoking marijuana. His recreational drug use was unknown by his family who brought him to the hospital. He had multiple seizures and was intubated for 6 weeks, with fevers and autonomic instability. He recovered with bilateral foot drop, thought to be peripheral nerve related.

Midbrain Lesions• Symmetric midbrain lesions: +/‐ diencephalon, basal ganglia.

• Ethylene glycol, methanol, chronic alcohol abuse (Wernicke’s encephalopathy)

• Kearn‐Sayers syndrome,

• Adult onset X‐linked adrenoleukodystrophy

• Hepatic disease, Wilson’s disease

Known Causes of a Toxic‐Metabolic Disorder

• A woman with new onset renal disease and a headache

• Seizing child with leukemia

• A confused woman with terminal cancer

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Nephrotic syndrome & blurred vision69 year old woman with post‐infectious glomerulonephritis, treatedwith high dose steroids, was admitted with a headache, blurred vision,confusion and difficulty walking. Her BP was 186/95. She had LEedema. On examination paraphasic errors and dysnomia, with a RHH,were noted. A HCT was obtained. After aggressive BP control anddiuresis, her neurological examination normalized.

Nephrotic syndrome & blurred vision

FLAIR GRE DWIInitial

10 dayslater

Nephrotic syndrome & blurred vision

What is the cause of this woman’s blurred vision?

1. Lymphoma

2. Posterior Reversible Encephalopathy Syndrome (PRES)

3. Acute Disseminated Encephalomyelitis (ADEM)

4. Osmotic Demyelination Syndrome (ODS)

5. Renal Cell Carcinoma

9 year old girl with headaches, and elevated BP.FLAIR DWI

A 9 year old girl with autoimmune hemolytic anemia s/p splenectomy developed fever, severe anemia and low back pain. She was treated with ceftriaxone, valgancyclovir, methylprednisolone and cyclosporine. Her blood pressure, 100/60 on admission, gradually elevated to the 140/90’s over the next week and she developed headaches. She had two generalized seizures about 10 days after admission. An initial MRI scan showed both abnormal FLAIR signal and bright signal on DWI.

Seizures & encephalopathy in a girlOn nicardipine, her BPs decreased to the levels present on

admission. A follow‐up MRI scan 2 days later showed almost normalization in the DWI signal, but persistent FLAIR signal abnormality.

Posterior Reversible Encephalopathy Syndrome (PRES)

• Nomenclature– Not exclusively posterior ; not always reversible

– “Reversible Posterior Leukoencephalopathy (RPLE)”

– Hypertensive encephalopathy

– Pre‐eclampsia; eclampsia

• Vasogenic cerebral edema (cortical, subcortical, spinal cord)– Vasoconstriction

– Hyperperfusion

• Diverse clinical & radiographic presentations– Headache, seizures, visual symptoms, mental status changes

– Parietal‐occipital white matter; holohemispheric pattern; superior frontal region; brainstem; spinal cord

– Untreated: intracerebral hemorrhage, coma, death

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PRES

• Theory 1: Hypertension/Hyperperfusion

– Severe HTN exceeds autoregulatory capacity of brain, failed auto‐regulation, hyperperfusion, endothelial injury, vasogenic edema

• Theory 2: Vasoconstriction/Hypoperfusion

– Evolving HTN leads to vasoconstriction, decreased perfusion, ischemia, edema

Diseases underlying PRES

• Acute hypertension

• Preeclampsia/eclampsia, HELLP

• TTP, hemolytic uremic syndrome, porphyria, DKA

• Liver disease; renal disease

• Chemotherapy (tacrolimus, cyclosporine, CHOP)

• Organ/marrow transplantation

• IVIG, steroids

• Severe electrolyte imbalance

• Elevated Ca++; hyperparathyroidism

• Sepsis

Typical appearance of PRES on MRI

Appearance on MRI

– Multifocal T2‐FLAIR hyperintensities (c/w vasogenic edema)

– Favors parietal and occipital white matter but can involve other areas: cortex, thalamus, basal ganglia, cerebellum, brainstem and spinal cord.

– Usually not apparent on DWI. • DWI changes maybe related to accompanying seizures .

• Ischemic changes on DWI/ADC are associated with worse prognosis.

– Can hemorrhage with GRE lesions

– Can exhibit subcortical “gyral” enhancement secondary to breakdown of the blood‐brain barrier.

– Can show mass effect associated with vasogenic evolving to cytotoxic edema.

Deterioration in a woman with metastatic cervical cancer

57 year-old female with cervical cancer, metastatic to bladder &

liver, had status epilepticus. She had a history of progressive

cognitive decline, with inability to walk. She was intubated in the

ICU and seizures were successfully treated. Klebsiella

pneumoniae sepsis was treated with multiple antibiotics. She

had episodes of ileus with vomiting. She was maintained on

anti-epileptics with fluctuations in mental status from

unresponsive to minimally conversant. Responsiveness

decreased; she became hypotensive; and she died 36 days after

admission.

Confusion in woman with metastatic cancer

T2-FLAIR

Woman with metastatic cervical cancer

FLAIR

DWI

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Deterioration in a woman with metastatic cervical cancer

57 year-old female with cervical cancer, metastatic to bladder &

liver, had status epilepticus. She had a history of progressive

cognitive decline, with inability to walk. She was intubated in the

ICU and seizures were successfully treated. Klebsiella

pneumoniae sepsis was treated with multiple antibiotics. She

had episodes of ileus with vomiting. She was maintained on

anti-epileptics with fluctuations in mental status from

unresponsive to minimally conversant. Responsiveness

decreased; she became hypotensive; and she died 36 days after

admission.

What is the pathological diagnosis in this woman with metastatic cervical cancer?

1. Posterior Reversible Encephalopathy Syndrome (PRES)

2. Acute Disseminated Encephalomyelitis (ADEM)

3. Osmotic Demyelination Syndrome (ODS)

4. Paraneoplastic encephalitis

5. Viral encephalitis

Pathological FindingsMyelin loss, Gliosis, Edema, Vacuolization• Pons• Occipital cortex, parietal lobe, frontal lobe• Cerebellum• Spinal cord

Differential Dx:• Osmotic demyelination syndrome

– Cerebellum, thalamus, basal ganglia, subcortical white matter

• Inflammatory demyelinating disorders (ADEM, MS)– Lesions not inflammatory

• B12 deficiency (subacute combined degeneration)– Not pontine

Osmotic myelinolysis (or demyelination) syndrome

Associated with:– Hyponatremia

– Hypernatremia

– Rapid correction

– Slow correction

– No correction

– Severe hyperglycemia

Hypernatremia from a hunger strike as a cause of osmotic myelinolysis.van der Helm-van Mil AH, van Vugt JP, Lammers GJ, Harinck HI.Neurology. 2005 Feb 8;64(3):574-5. Extrapontine myelinolysis with involvement of the hippocampus in three children with severe hypernatremia.Brown WD, Caruso JM.J Child Neurol. 1999 Jul;14(7):428-33

CNS Toxicity of Alcohol

ACUTE CNS EFFECTS OF ALCOHOLBAL Effect

< 0.04% Mild euphoria

0.05 ‐ 0.09% Disinhibition, increased self confidence, alteration of judgment

0.10 ‐ 0.14% Confusion, loss of critical judgment, memory impairment, sleepiness

0.15 ‐ 0.29% Ataxia, analgesia, disorientation, exaggeration of emotions

0.30 ‐ 0.39% Stupor, marked incordination

>0.4% Anesthesia, deep coma, death

BAL – Blood Alcohol Level

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Alcohol & Trauma

A 50 year old man with a history of alcohol abuse fell down the stairs while drunk. On examination he was inattentive but without motor deficits.

Chronic CNS Effects of Alcohol

• Atrophy – cortical, cerebellar

• Wernicke – Korsakoff Syndrome

• Marchiafava – Bignami disease / Morel's Laminar Sclerosis

• Pellagra

• Fetal Alcohol Syndrome

• Osmotic Demyelination Syndrome / Central Pontine Myelinolysis

Alcohol & Atrophy

Surgeon (not practicing) with alcoholism since age 30 years, currently drinking 2 pints of vodka a day. HCTs at age 63 years and age 67 years.

Alcohol‐related brain injury

Atrophy out of proportion to age– Enlarged ventricles/sulci, anterior superior vermis

– May reverse with abstinence

– Not well correlated with cognitive loss

Marchiafava‐Bignami Syndrome– Demyelination/necrosis of corpus callosum,

periventricular white matter

– Malnourishment (alcoholics, non‐alcoholics)

– Dementia, spasticity, dysarthria, gait disorder

Alcohol/Nutrition‐related brain injury

• Wernicke’s encephalopathy– Ataxia, ophthalmoplegia, nystagmus, encephalopathy

– Thiamine deficiency

– MRI: can be normal, but generally mamillary body lesions

– Dorsomedial thalamus, locus ceruleus, periaqeductal grey, ocular/vestibular nuclei

– Petechial hemorrhage

Figure. (A) Gadolinium-enhanced T1-weighted axial MRI shows symmetric enhancement of the mamillary bodies (paired arrowheads). (B) Enlarged axial view of the region of the hypothalamus showing mamillary body enhancement (paired arrowheads). (C) Enlarged coronal view of the mamillary body enhancement (paired arrowheads). (D) FLAIR hyperintensity of the hypothalamus is seen in an axial view (arrows). (E) FLAIR hyperintensity of the periaqueductal gray (arrows). (F) FLAIR hyperintensity of the dorsomedian thalamus (arrows). (G) FLAIR hyperintensity of the floor of the fourth ventricle (arrows). (H) FLAIR hyperintensity is seen throughout the low medulla (arrows).

Flint A C et al. Neurology 2006;67:2015-2015

©2006 by Lippincott Williams & Wilkins

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Alcohol abuse & nutritional deficiency

32 yr. old woman was admitted to the psychiatry service with a history of alcohol abuse (admitting to a 6 pack a day) and binging and purging. Her urine was + benzodiazepines. She was a thin women, who was confabulatory and incoherent, with difficulty following directions. She had nystagmus. She did not cooperate with strength testing (moving all extremities) but she was unable to walk. Reflexes were decreased distally. An MRI was obtained. With high dose intravenous thiamine, cognition improved. She had a residual foot drop.

Alcohol abuse & nutritional deficiencyWernicke‐Korsakoff encephalopathy in a 32 year old woman

March 11On admission

April 4After high dose thiamine

Alcohol withdrawal in a 44 year old man

He stopped drinking a bottle of vodka aday 4 days before presenting to the ED foragitation and tremulousness. His BP was221/200 with a HR of 122. While receivingIV diazepam, he seized and was intubatedfor airway protection. With high doses ofbenzodiazepines and thiamine his vitalsigns and agitation were managed but hehallucinated when extubated.

Alcohol withdrawal67 year male with HIV (last CD4 201, VL undetectable), HTN, and decades of 12 oz of vodka a day was evaluated for a seizure, presumed to be due to alcohol withdrawal, in the setting of hospitalization for diarrhea. No specific laboratory abnormality was noted. On neurological examination, he was sedated on benzodiazepines but his neurological examination was without focality. A CT scan of the head and MRI were obtained.

Alcohol withdrawal

DWI

FLAIR

FLAIR

BRAVO

T2

CNS Toxicity of Substances of Abuse

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Chasing the Dragon (Heroin Leukoencephalopathy)

• Toxic spongiform leukoencephalopathy with mortality rate of 25%.

• inhaled vapors from heroin that has been heated on a piece of foil aka "chasing the dragon."

• Cerebellar ataxia, agitation, focal neurologic symptoms, coma

• Often a latent period between exposure and clinical presentation.

• MRI: cerebellar white matter, cerebellar peduncles, brainstem, posterior cerebral white matter, posterior limbs of the internal capsules; reduced NAA and increased lactate peaks

• DDx: PRES

AJNR 2011;36

MRI, T2 hyperintensity of centrum semiovale

Biopsy showing delayed demyelination, luxol fast blue

Heroin Associated Leukoencephalopathy

Alcohol and cocaine toxicity

50 year old man was admitted with slurred speech, diplopia and difficulty walking. Chronic alcohol use had recently increased to 24 drinks a week and he used cocaine every other day. He had a 30 pack year smoking history. He abused benzodiazepines. On examination he was alert and oriented with slurred speech. He had bilateral abduction deficits but no nystagmus. He had no motor deficit but reflexes were brisk. Gait was markedly ataxic.

Alcohol and cocaine toxicity

Acute cranial nerve abnormality in a depressed man.

A 50 year old man was depressed about losing a job. He was found unconscious and taken to OSH, where he was intubated and hemodialysis was initiated for acute renal failure. After gradual improvement, he was transferred to a psychiatric hospital two weeks later. Two days after admission a stroke code was called when he was noted to have mild left facial weakness (NIHSS 1). HCT was normal. An MRI was obtained.


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Why does this man have cranial nerve abnormalities on MRI?

1. Hypoglycemia

2. Toluene poisoning

3. Cyanide poisoning

4. Ethylene glycol ingestion


Enhancement of CN V, VIIPossible enhancement of IX, X, XIRestricted diffusion of bilateral CN V

Ethylene Glycol C2H4(OH)2Odorless, colorless liquid with bittersweet taste

Metabolites – glycoaldehyde, glycolic acid, oxalic acid

Ingestion – metabolic acidosis, ARF, delayed neurological damage.

1‐12 hrs: inebriation, ataxia, coma, seizures

12‐24 hrs: cardiac, pulmonary complications

24‐72 hrs: metabolic acidosis, ARF, crystal oxaluria

5‐20 days: lower motor dysfunction of lower cranial nerves

(facial weakness, bulbar dysfunction), basal ganglia disease

Etiology of delayed CN disease: Inflammatory response to local oxalate microcrystal deposition?

Reddy et al. Clinical Toxicology 2010;48:967‐973

Ethylene Glycol Brain Toxicity

Perivascular Birefringent Calcium Oxalate Crystals

—25-year-old man with decreased level of consciousness after suicide attempt by ingesting ethylene glycol.

Sharma P et al. AJR 2009;193:879-886

©2009 by American Roentgen Ray Society

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—25-year-old man with decreased level of consciousness after suicide attempt by ingesting ethylene glycol.

Sharma P et al. AJR 2009;193:879-886


Methanol (CH₃OH) Toxicity• Bilateral necrosis of

the basal ganglia (putamen)

• Cerebral edema/necrosis

• Cerebellar lesions• SAH • Bilateral ICH • Bilateral tegmental

necrosisGadodia A, Singhal B, Sharma R. Methanol intoxication causing putaminal necrosis. J Emerg Trauma Shock 2011;4:300-1

Weakness and swallowing difficulties• 49 year old man awoke with R arm and leg weakness and

diplopia, a few days prior to admission. He had transient diplopia3 months prior to admission. His weakness worsened, withslurred speech, and he was brought to hospital.

• PMH/PSH – denied toxic habits but his sister said he used drugs

• ROS – sore throat

• Tongue with black plaque

• Pulmonary congestion

• Decreased speech volume and difficulty with secretions.

• Mental status: intact but evasive

• CN: bilateral VI paresis; cough with water

• Motor/sensory: spastic R hemiparesis, decreased sensation in R leg

Weakness and swallowing difficulties



• Clival cultures grew methicillin‐resistant Staphylococcus aureus

• Intravenous antibiotics were given for 6 weeks, prior to switching to oral antibiotics.

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—32-year-old male drug abuser with loss of consciousness after cocaine overdose.

Sharma P et al. AJR 2009;193:879-886


—32-year-old male drug abuser with loss of consciousness after cocaine overdose.

Sharma P et al. AJR 2009;193:879-886


CNS Effects of Metabolic Perturbations

CNS Effects of Metabolic Perturbations

Hypoxia

Hypoglycemia

Electrolyte imbalance

Dysmyelination

Disorders of oxygenation

Disorders of cerebral autoregulation

Organ failure (liver, renal)

Hypoxic – Ischemic Injury ‐ Imaging

1‐2 days after event

CT: • Diffuse swelling: effacement of the basal cisterns, ventricles and

sulci, attenuation of the grey–white matter interface

• Hypodensity of the cortex, basal ganglia (cytotoxic edema)

• Hypodensity of the white matter (distension of the deep medullary veins, obstruction of the cerebral venous drainage)

• Focal areas of infarction (basal ganglia. cortical boundary zone territories)

Howard et al. Practical Neurology 2011;11:4‐18

Early Profound HIE

Cerebral edemabilateral cerebral hemisphere sulcal effacementloss of gray-white differentiationprobable decreased size of ventricles and cisterns

A 43 year old woman suffered an out of hospital cardio-pulmonary arrest with CPR started within minutes, with EMSarriving in about 15 minutes. Coarse v-fib was converted to sinusrhythm. In the ED she was unresponsive, with sluggishlyresponsive pupils, absent corneals, weak gag. Her arms flexedto painful stimulation and she was without movement in her legs.A HCT was obtained.

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Polysubstance abuse & hypoxia32 year old woman with poly‐substance abuse, HCV, HTN wasadmitted for 2nd and 3rd degree burns over her scapula. After takingclonezapam, trazodone, and intravenous heroin, patient fell asleepleaning on a heating pipe. A week into the admission for excision andgrafting of her burns, she developed hypoxia, lethargy, tachypnea, andpinpoint pupils, so was intubated for airway protection. During Foleyinsertion, a bottle of clonezapam was found in her vagina/perineum. Ahead CT scan showed bilateral basal ganglia infarcts.

Polysubstance abuse & hypoxiaOn examination a week later, when extubated, she was alert, oriented and inappropriately cheerful. STM was poor (1/3). Language was normal. Motor/sensory/coordination/reflex testing was unremarkable. An MRI scan showed subacute basal ganglia infarcts.

DWI FLAIR T2

Hypoxic–ischemic brain injury – MRI

MRI• Acute:

– Logistically difficult early after cardiopulmonary event– DWI/FLAIR: hyperintensity in basal ganglia, caudate, striatum, thalamus– Cortex, subcortical white matter, cerebellum, hippocampus

• Subacute: – resolution of DWI signal abnormality with decreased edema– FLAIR/T2: changes in basal ganglia, cortex, subcortical white matter, hippocampus

• Chronic:– Diffuse atrophy– Cortical laminar necrosis (cell death in layers III, IV of cortical mantle– Infarction in boundary zone territories between ACA, MCA, PCA – Cerebellar infarcts– Delayed leukoencephalopathy


Acute hypoxic‐ ischemic injuryA 52 year old woman with vascular risk factors had an in-hospital asthma attack. She was quickly intubated, then wentinto a PEA arrest. Resuscitation was successful within 2-3mins; but, she had only brainstem reflexes. A CT scan hourslater was negative. An MRI scan 2 days later showed extensiverestricted diffusion in the cortical grey matter, periventricular

white matterand centralpons.

Hypoxic–ischemic brain injury – MRIMRI• Acute:

– Logistically difficult early after cardiopulmonary event– DWI/FLAIR: hyperintensity in basal ganglia, caudate, striatum, thalamus– Cortex, subcortical white matter, cerebellum, hippocampus

• Subacute: – resolution of DWI signal abnormality with decreased edema– FLAIR/T2: changes in basal ganglia, cortex, subcortical white matter,

hippocampus

• Chronic:– Diffuse atrophy– Cortical laminar necrosis (cell death in layers III, IV of cortical mantle– Infarction in boundary zone territories between ACA, MCA, PCA – Cerebellar infarcts– Delayed leukoencephalopathy


Cerebral air embolization• Arterial: trauma, surgery (especially cardiothoracic/neurosurgery), procedures (e.g. ERCP, arterial line, lung biopsy)

• Venous (paradoxical embolization through R‐L shunt): central venous catheter placement/removal; IV contrast injection into peripheral line

• Confusion, motor weakness, decreased consciousness, seizure and vision loss.

• Ischemic stroke; cerebral edema• CT: acute gas that is absorbed rapidly• Supportive treatment;hyperbaric oxygen therapy.

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Hypoglycemic Brain Injury

• Insulin, medications, systemic diseases,

• Lesions

• Cerebral cortex, hippocampus, insula, dentate nucleus

• Subcortical white matter

• Basal ganglia, substantia nigra

• Non‐hemorrhage, may enhance

• Rare: splenium of corpus callosum, corona radiata, internal capsule

• Sparing: cerebellar hemispheres, brain stem, thalamus

G. Bathla, et al AJNR 35:833; 2014

Young diabetic man with hypoglycemiaA 21 year old man with type 1 DM on an insulin pump had two days of memory loss and confusion. His fasting glucose was reported to be 44 and a history was given of intermittent hypoglycemia. He was amnestic for events of the past week. An MRI was obtained. He was given glucose and his pump was discontinued. Memory improved over several weeks. He was brought in by his mother two years later because of anger, anxiety and poor grades in graduate school. A follow‐up MRI was obtained.

Acute hypoglycemia

2009

2011

—43-year-old man with hypoglycemic coma who was found to have serum glucose level of 1.2 mmol/L (normal reference range, 4–6 mmol/L).

Sharma P et al. AJR 2009;193:879-886


—43-year-old man with hypoglycemic coma who was found to have serum glucose level of 1.2 mmol/L (normal reference range, 4–6 mmol/L).

Sharma P et al. AJR 2009;193:879-886


Acute on chronic confusion in a middle‐aged woman

• 45 year old woman was found by her husband in her pajamas, sleepy and confused at 5 pm. She vomited and complained of a headache. Her husband noted that she seemed more forgetful recently.

• PSH: – getting MA in history – just finished her examination

– living in temporary shelter as home burned down a year ago

• PMH: – chronic depression with postpartum acetaminophen OD suicide attempt

• Exam: not oriented to date or day, 1/3 with repeated trials, unable to recall events of the day.

• At hospital: HCT negative, CSF – bland; EEG – L temporal slowing

• An MRI scan was obtained.

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Acute on chronic confusion in a middle‐aged womanMRI 4‐08

FLAIR

DWI T2

Acute on chronic confusion in a middle‐aged woman4‐08

T2 C

26 year old man with altered mental status, 13 days after extubation forinhalational injury after a kerosene truck explosion

FLAIR

DWI T1 GRE

Leg weakness and confusion

35 year old man was LKN a week prior to transfer from OSH for

stroke. Three days prior he was found by the landlord on his bathroom, lying in his waste, foaming at mouth, and lethargic. At OSH CK >20,000, BUN 77, Cr 3.2, and his right leg was weak. With hydration rhabdomyolysis improved. Unremarkable studies included CT of brain and spine, urine toxicology screen and EEG.

PMH/SH: no illnesses/toxic habits, pilot, was unpacking in new

apartment at time of incident.

Exam: oriented; knows address; mildly impaired naming, nl repetition/reading; 1/3 objects; unable to do serial 7’s;

RLE: weak, sensory loss, absent reflexes, normal temperature, intact distal pulses

MRI scan of the brain was obtained.

Leg weakness and confusion

DWI FLAIRT2 T1C

Carbon Monoxide (CO) Poisoning• Mechanisms

– CO binds to hemoglobin with more than 200x affinity of O2, forming carboxyhemoglobin

– Carboxyhemoglobin causing hypoxemia

– Decreased release of oxygen to tissues

– Direct mitochondrial toxicity of CO

• MRI Lesions– Bilateral anterior globus pallidus

– Lobar white matter, watershed cortex, hippocampus

– Thalamus, caudate, putamen, cerebellum

– Hemorrhage, necrosis

– Cortex, hippocampus, cerebellum (less common)

• Pathologic Lesions– Necrosis –bilateral globus pallidus

– Acute demyelination

– Chronic atrophy

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CNS Toxicity of Medications

CNS Toxicity of Medications

Diffuse leukoencephalopathy

Cyclosporine / FK506

Methotrexate

Cytarabine (Ara‐C)

Cisplatin

BCNU

Thiotepa

Fludarabine

Cerebellar lesions/atrophy

Lithium

Dilantin

Metronidazole

Acute onset of R weakness in 19 year old man

A week after the third injection in series of injections of IT MTX, a man with T‐cell ALL developed rapidly progressive R hemiparesis and dysarthria. A stroke code was called with NIHSS 6.

CT/CTA was normal. Treatment with tPA was considered but it not given. An MRI was obtained.

Acute onset of R weakness in man with ALL

Acute: DWI lesions

1 week later: DWI resolved; subtle FLAIR lesions

Methotrexate Toxicity• CNS (cerebral, spinal white matter) toxicity associated

with intrathecal administration

• Symptoms - Acute: headache, confusion, focal neurological deficit, seizures; Delayed: subacute encephalopathy, myelopathy, optic atrophy

• Focal lesions on DWI with restricted diffusion (cytotoxic edema)

• Focal lesions on T2, FLAIR imaging lesion common

• White matter lesions

• Non-vascular distribution of lesions

Sharma P et al. AJR 2009;193:879-886

Metronidazole Toxicity

• Neurologic symptoms at >2 g/d

• Dysarthria, gait disturbance, weakness of the extremities, and mental confusion

• MRI: Bilateral, symmetric, T2 lesions, reversible

• Dentate nuclei, the tectum, red nucleus, periaqueductal gray matter,dorsal pons

• Dorsal medulla, corpus callosum (splenium) less often affected

Sharma P et al. AJR 2009;193:879-886

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—54-year-old man who was taking metronidazole prophylactically and presented with acute onset gait ataxia and dysarthria.

Sharma P et al. AJR 2009;193:879-886


—54-year-old man who was taking metronidazole prophylactically and presented with acute onset gait ataxia and dysarthria. THREE MONTHS LATER

Sharma P et al. AJR 2009;193:879-886


51-year-old woman who developed headaches, tremors, and visual changes 4 weeks after liver transplantation and initiation of cyclosporine therapy.

ACUTE & ONE WEEK LATER

Sharma P et al. AJR 2009;193:879-886


Toxic Metabolic Disorders

• Hypoxic/ischemic injury, hypoglycemia

• Hypertensive disorders (PRES/RCVS)

• Osmotic demylination

• Liver failure

• Poisoning: ethanol, methanol, alcohol, CO, ethylene glycol

• Illicit drugs

• Toxic effects of therapies/medications

• Leukoencephalopathies

• Mitochondrial disorders

• Metabolic diseases

clinical neuroimaging: toxic‐metabolic disorders toxins

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