2. ANATOMY AND PHYSIOLOGY
Physiologic Considerations -
By weight and volume, the brain is a small structure. However, relative to its
size, the brain is one of the most metabolically active of all organs.
It normally receives ∼ 15% of total cardiac output, consumes ∼ 20% of blood
oxygen and metabolizes up to 20% of blood glucose.
Because of its high intrinsic metabolic demands, the brain is sensitive to
processes that decrease delivery or utilization of blood, oxygen and glucose.
3. Two areas of the brain are especially susceptible to toxic and metabolic
damage:-
(1). The deep gray nuclei.
(2). The cerebral white matter(WM).
The basal ganglia (BG) are highly vascular, rich in mitochondria and loaded
with neurotransmitter.
The BG—especially the putamen and globus pallidus are particularly
susceptible to hypoxia or anoxia and are also commonly affected by toxins
and metabolic derangements.
The cerebral WM is particularly vulnerable to lipophilic toxic substances.
4. Normal Gross Anatomy -
The BG are symmetric paired subcortical (deep gray
matter) nuclei that form the core of the
extrapyramidal system and control motor activity.
The BG consist of (1) the caudate nucleus (CNuc),
(2) the putamen and (3) the GP.
The thalami are the largest and most prominent of
the deep gray matter nuclei but are generally not
included in the term “basal ganglia.”
Normal Imaging Anatomy-
NCCT-
The BG and thalami are symmetrically hyperdense
compared to normal WM. Physiologic calcifications in
the globi pallidi are common in adults.
5. T1WI -
The Caudate nucleus, putamina and
thalami are isointense with cortex on T1
scans.
As the site of both physiologic calcification
and age-related iron deposition, the GP
segments vary in signal intensity.
Calcification may cause T1 shortening
and mild hyperintensity in the medial
segment.
6. T2WI -
The Caudate nucleus, putamina and
thalami are isointense with cortical gray
matter on T2 scans.
The myelin content in the GP is higher
relative to the putamen, so it appears
relatively more hypointense on T2WI
Increasing iron deposition occurs with
aging, and the putamen becomes
progressively more hypointense. A “dark”
putamen is normal by the seventh or
eighth decade of life.
T2* The GP is hypointense relative to cortex
on GRE or SWI imaging. By the seventh or
eighth decade of life, iron deposition in the
putamen “blooms”.
T2WI, the GP are more hypointense than putamen,
caudate. Putamen reaches same hypointensity in 7th or
8th decade.
8. Axial T2WI shows innumerable variably sized CSF-like
cysts in the caudate nuclei, putamina, and GP with
relative sparing of the thalamus. These are unusually
prominent enlarged perivascular spaces (sometimes
called "état criblé" or "cribriform state")
9. TOXIC DISORDERS –
1. Alcohol and Related Disorders
2. Amphetamines and Derivatives
3. Opioids and derivatives
4. Inhaled Gases and Toxins
5. Metal Poisoning and toxicity
6. Treatment related disorders
11. Alcohol [ethanol (EtOH)] is one of the most commonly abused substances in
the world.
Ethanol easily crosses the blood-brain barrier and is a potent neurotoxin.
Excessive alcohol consumption can result in chronic brain changes as well as
acute, life-threatening neurologic disorders (cytotoxic cerebral edema and
nonconvulsive status epilepticus).
Comorbid diseases such as malnutrition with vitamin deficiencies may lead to
Wernicke encephalopathy.
Altered serum osmolarity associated with alcohol abuse can cause acute
demyelinating disorders.
12. Acute alcohol poisoning is a complication of
binge drinking and is most common in
adolescents and young adults.
A blood alcohol concentration of 0.40% typically
results in unconsciousness, and a level
exceeding 0.50% is usually lethal.
Imaging findings:-
Diffuse brain swelling and confluent
hyperintensity in the supratentorial subcortical
and deep white matter on T2/FLAIR.
Seizure-induced changes in the cortex, with
gyral hyperintensity and diffusion restriction
may also be associated.
T2WI in a comatose patient
who drank 1 gallon of vodka
or whisky daily for a full week
shows diffuse brain swelling,
hyperintense white matter,
bithalamic lesions.
1. ACUTE ALCOHOL POISONING –
13. 2. CHRONIC ALCOHOLIC ENCEPHALOPATHY -
The long-term adverse effects of ethanol on the brain are much more
common than those of acute alcohol poisoning.
Chronic alcohol-related brain damage can be divided into primary and
secondary effects.
The effects of EtOH itself on the brain and secondary effects, which are
mostly related to the sequelae of liver disease, malnutrition, malabsorption
and electrolyte disturbances.
Progressive brain volume loss is seen with chronic alcoholic
encephalopathy.
Initially, the superior vermis atrophies and the cerebellar fissures become
prominent.
14. (A)NECT in a 56y woman with chronic alcoholism and multiple falls shows severe cerebellar atrophy with grossly enlarged sulci.
B. Coronal NECT in the same case shows cerebellar volume loss . enlarged fourth ventricle The cerebral hemispheres also
appear moderately atrophic with prominent superficial sulci .
15. In later stages, the frontal white matter becomes involved, reflected
by widened sulci and enlarged lateral ventricles.
In the final stages, global volume loss is present.
CT Findings-
NCCT scans show generalized ventricular and sulcal enlargement.
The cerebral white matter is often abnormally hypodense and
reduced in volume.
The great horizontal fissure of the cerebellum and the superior
vermian folia are unusually prominent relative to the patient's age.
16. Coronal T2WI in a 41y chronically alcoholic
man shows marked atrophy of the superior
cerebellum with striking widening of the
horizontal fissures. The supratentorial brain
is relatively spared
(B) T2WI in a 30y chronically alcoholic patient
shows generalized volume loss. Note corpus
callosum splenium lesion; This was alcohol induced
atrophy with acute toxic demyelination.
17. MR Findings –
Brain volume loss, especially in the prefrontal cortex, is common as is more
focal atrophy of the superior vermis.
Focal and confluent cerebral white matter hyperintensities on T2/FLAIR
sequences are frequently present.
Chronic liver failure secondary to cirrhosis may cause basal ganglia
hyperintensity on T1WI, probably secondary to manganese accumulation.
Increased iron deposition in the basal ganglia and dentate nuclei may occur.
18. 3. WERNICKE ENCEPHALOPATHY -
Wernicke encephalopathy (WE) is also known as Wernicke Korsakoff syndrome.
Both alcohol-related (most common cause) and non-alcohol related (thiamine
deficiency) wernicke encephalopathy can occur.
The mammillary bodies, hypothalamus, medial thalamic nuclei (adjacent to
the third ventricle), tectal plate and periaqueductal gray matter are most
commonly affected.
Demyelination and petechial hemorrhages are common in the acute stage of
Wernicke encephalopathy (WE).
Callosal necrosis, white matter rarefaction with brain volume loss and
mammillary body atrophy can be seen in chronic WE.
Clinical Issues –
Classic triad = Ocular dysfunctionn (e.g., nystagmus, conjugate gaze palsies,
ophthalmoplegia), ataxia and altered mental status.
19. Imaging –
MR is the procedure of choice in evaluating patients with possible WE.
T1WI may show hypointensity around the third ventricle and cerebral aqueduct.
T2/FLAIR hyperintensity, DWI restriction -
Common = medial thalami (85%), periaqueductal gray matter (65%), mammillary bodies
(60%), tectum (30%)
Less common = dorsal medulla (8%), cerebellum/cranial nerve nuclei (1%), corpus
callosum splenium.
SWI may show microhaemorrhages.
Enhancement varies -
More common in alcoholic WE.
Strong uniform enhancement of the mammillary bodies is seen in up to 80% of acute
cases and is considered pathognomonic of WE. With chronic WE, mammillary body
atrophy
20. (A)FLAIR scan in a patient with acute Wernicke encephalopathy shows hyperintensity in the periaqueductal gray matter and
tectum. (B) More cephalad FLAIR scan again shows the periaqueductal gray matter hyperintensity . Both mammillary bodies are
also hyperintense
21. FLAIR scan shows hyperintensity in the medial thalami around
the walls of the third ventricle. The hypothalamus is also
involved
DWI in the same patient shows restricted diffusion in the
mammillary bodies The periaqueductal gray matter does not
restrict, suggesting that the midbrain lesions seen on FLAIR
may be somewhat less acute.
22. Axial NECT in a 28y woman with anorexia who experienced
nystagmus after vomiting for several days appears grossly
normal. (B) Axial FLAIR in the same case shows symmetric
hyperintensities in the dorsal medulla(C) More cephalad
FLAIR shows hyperintensity in the upper dorsal pons (D)
FLAIR through the midbrain and cerebral aqueduct in the
same case shows symmetric hyperintensity surrounding the
aqueduct. (e) through the basal ganglia shows symmetric
hyperintensity in the putamina of both thalami . Note
hyperintensity along the walls of the third ventricle , focal
hyperintensity in the corpus callosum splenium (F) DWI
shows symmetric foci of restricted diffusion in the medial
thalami and corpus callosum splenium
23. Axial contrast-enhanced T1-weighted MR image shows
symmetric enhancement of the mammillary bodies (arrows)
SWI detects microbleeds in the mammillary bodies as a
hallmark of Wernicke encephalopathy (WE)
24. Differential Diagnosis –
1. The medial thalami and midbrain can be symmetrically involved in artery
of Percheron (AOP) infarct and deep cerebral vein thrombosis (CVT).
2. Infections such as influenza A and West Nile virus meningoencephalitis
cause symmetric medial thalamic and midbrain lesions that may mimic WE.
Mammillary bodies are usually not involved.
3. Neuromyelitis Optica.
25. FLAIR shows bilateral CNuc
putamina st, thalamic
hyperintensity West Nile
encephalitis.
Axial FLAIR shows bilateral but
asymmetric CNuc , putamen ,
thalamic hyperintensity. This is deep
vein occlusion.
Axial T2WI shows bilateral medial
thalamic infarcts caused by artery of
Percheron occlusion
27. 4. MARCHIAFAVA – BIGNAMI DISEASE -
Marchiafava-Bignami disease (MBD) is a rare disorder characterized by osmotic
demyelination—and later necrosis—of the corpus callosum.
MBD is primarily associated with chronic EtOH abuse.
Imaging General Features:-
Selective involvement of the middle layers of the corpus callosum is typical.
Chronic alcoholic encephalopathy with generalized brain volume loss is
common.
Electrolyte disturbances may cause osmotic demyelination.
28. CT Findings:-
CT may be normal in the acute stage of
MBD.
Chronic MBD shows linear
hypodensity in the corpus callosum
genu that, in the setting of chronic
alcohol abuse, is highly suggestive of the
diagnosis.
CECT scan in an alcoholic patient with
Marchiafava-Bignami disease shows generalized
cerebral atrophy and striking hypodensity in the
corpus callosum genu and the adjacent white
matter.
29. MR Findings -
The initial changes of acute MBD are best seen on sagittal FLAIR.
Hyperintensity in the corpus callosum genu and frontoparietal
cortex appears first, followed by splenial lesions.
During the acute phase, the entire corpus callosum may appear
swollen and hyperintense.
DWI is initially negative, Restriction subsequently develops in the
corpus callosum splenium.
Acute white matter lesions may also enhance. Both peripheral (rim)
or solid confluent patterns have been reported.
30.
31. focal low signal intensity T1 and high FLAIR signal with
restricted diffusion in the splenium of the corpus callosum.the
corpus callosum.
32. Chronic MBD with frank callosal
necrosis is seen as thinning of the
corpus callosum on sagittal T1WI with
linear hypointensities in the middle
layers.
In patients with chronic MBD, T2*
susceptibility-weighted imaging may
demonstrate multiple microbleeds in
the cortical-subcortical regions and
corpus callosum.
sagittal T1WI in chronic alcoholic encephalopathy
and Marchiafava-Bignami disease shows
hypointensity in the entire middle corpus callosum .
Mammillary bodies and superior vermis are
atrophic.
33. (B) Sagittal T1 C+ FS scan shows
enhancing lesions in the corpus
callosum.
(A) Coronal T1 C+ shows
enhancement in the corpus
callosum.
34. 5. METHANOL INTOXICATION –
MtOH is a common component of solvents, varnishes, perfumes, paint removers,
antifreeze and gasoline mixtures.
It can be accidentally or intentionally ingested, inhaled or absorbed
transdermally.
Methanol (MtOH) is a strong CNS depressant.
Ingestion of 30 mL of pure MtOH usually results in death. As little as 4 mL can
result in blindness.
Bilateral basal ganglia necrosis is the most characteristic imaging feature of
MtOH poisoning.
Selective putamina involvement with relative sparing of the globi pallidi is
common.
35. (B) NCCT scan in a patient who
survived acute methanol poisoning
shows shrunken, hypodense putamina
and bilateral symmetric hypodensities
in the subcortical white matter.
(A) NCCT scan in a patient with
subacute methanol poisoning shows
confluent and patchy haemorrhagic
putaminal necrosis.
(B)
(A)
36. CT Findings:-
Initial NCCT scan is normal in many patients with MtOH poisoning.
Most patients who survive for more than 24 hours demonstrate bilateral
symmetric hypodense lesions in the putamina, globi pallidi and
sometimes the deep cerebral white matter.
Hemorrhagic putaminal necrosis is seen in 15-25% of cases.
Enhancement is variable, ranging from none to peripheral enhancement
of the putaminal lesions.
37. MR Findings:-
Bilateral putaminal and basal ganglia necrosis with variable white
matter involvement is present.
T2/FLAIR hyperintensity is seen with 25% exhibiting "blooming" foci on
T2*.
DWI shows restricted diffusion in the acute stage of methanol
poisoning.
MRS shows reduced NAA and markedly elevated lactate .
38. Differential Diagnosis –
Bilateral symmetric putaminal lesions are not specific for MtOH and
can be seen in Wilson disease and mitochondrial encephalopathies.
Hypoxic ischemic encephalopathy involves the caudate and other deep
gray nuclei in addition to the putamina.
Carbon monoxide poisoning generally affects the globi pallidi rather
than the putamina.
39. Axial T1WI in a patient with mitochondrial encephalopathy
(MERRF) shows multifocal hypointensities in the BG
Axial FLAIR in a patient with Wilson disease show symmetric
basal ganglia, including the caudate nuclei, putamina, as well as
the ventrolateral thalami,
40. FLAIR in a patient with HIE show increased signal in basal ganglia DWI demonstrates bilateral symmetrical hyperintensity and
restriction mainly on vulnerable cortical areas, such as perirolandic and occipital cortex. n basal ganglia
41. 6. ETHYLENE GLYCOL POISONING –
Ethylene glycol is a form of alcohol that is a common component found
in many household products such as antifreeze, deicing solutions and
windshield wiper fluids.
It may be ingested by alcoholics or, because of its sweet taste and the
ease of access, it is often accidentally ingested by children.
Imaging findings of acute ethylene glycol toxicity include edema in the
basal ganglia, thalami, midbrain and upper pons.
42. Sagittal T1WI shows pons and midbrain hypointensity, which is better seen as hyperintensity on
coronal FLAIR.
Patchy enhancement is seen on T1 C+ s
44. (B). AMPHETAMINES AND DERIVATIVES -
CNS stimulants include cocaine, amphetamine, methamphetamine,
methylenedioxymethamphetamine (MDMA) and methylphenidate.
Although not a classic CNS stimulant, nicotine is a prototypic drug that
is avidly self administered and has some stimulating properties.
All these drugs have a high human abuse liability.
Most addictive drugs are excitotoxic and cause two major types of
pathologies:-
(1). Vascular events (e.g., ischemia, hemorrhage)
(2). Leukoencephalopathy.
45. (1). METHAMPHETAMINE -
Methamphetamine is a highly addictive
psychostimulant drug.
Even a single acute exposure to MA can result in
profound changes in cerebral blood flow.
Both hemorrhagic and ischemic strokes occur .
MR in chronic adult MA users demonstrates lower gray
matter volumes on T1WI, especially in the frontal
lobes, and more white matter hyperintensities on
T2/FLAIR scans than are appropriate for the patient's
age.
MRS shows increased choline and myoinositol levels in
the frontal lobes.
DTI shows lower fractional anisotropy in the frontal
lobes and higher ADC values in the basal ganglia.
46. FLAIR imaging increased signal intensity of the white matter with extensive involvement of the temporal,
frontal/parietal and occipital lobe is present. DWI, lower row) shows high signal intensity
47. (2). MDMA ("Ecstasy")
3-,4-Methylenedioxymethamphetamine -
MDMA induces euphoria and sensory disturbances secondary to rapid release of
potent vasoconstrictors from serotonergic synapses.
MDMA can cause arterial constriction, vasculitis, or prolonged vasospasm with
acute ischemic infarcts.
MDMA-induced ischemia is most pronounced in serotonin-rich brain areas
such as the globus pallidus and occipital cortex, which are especially
vulnerable.
Acute hippocampal necrosis with subsequent atrophy has been reported in
chronic ecstasy users.
48. B) MRA in the same patient
shows alternating areas of
narrowing and dilatation in the
occipital, posterior parietal
arteries, consistent with drug
induced vasculitis
A) Axial FLAIR scan in a
teenager who used MDMA
shows focal left occipital lobe
hyperintensity.
50. (3). BENZODIAZEPINS -
Benzodiazepines are
psychoactive drugs used to
treat anxiety, insomnia,
seizures, muscle spasms and
alcohol withdrawal.
Benzodiazepine overdose has
been associated with hypoxic
ischemic encephalopathy ,
hemorrhagic ischemic strokes
and delayed toxic
leukoencephalopathy.
MR scans in a 45y bipolar woman with
toxicology positive for opiates and
benzodiazepines show globi pallidi and cortical
infarcts.
51. (4). COCAINE –
Cocaine can be sniffed/snorted, smoked, or injected.
Regardless of the route of administration, the adverse impact of
cocaine on the brain is largely related to its vascular effects.
Systemic hypertension can be extreme, causing spontaneous
hemorrhagic strokes.
Rupture of a preexisting aneurysm or underlying vascular
malformation accounts for nearly half of all cocaine-related
hemorrhagic strokes .
Cocaine also facilitates platelet aggregation and may lead to
thrombotic vascular occlusion.
52. Imaging –
• Strokes—both ischemic and haemorrhagic—are the major manifestations
of cocaine-induced brain damage.
• The haemorrhages can be parenchymal (secondary to hypertension or
vascular malformation) or subarachnoid (aneurysm rupture).
• Hypertensive bleeds are usually centered in the external capsule/putamen
or in the thalamus.
• Ischemic strokes can be caused by vasospasm, cocaine induced
vasoconstriction, vasculitis or thrombosis.
53. Bilateral globus pallidus infarction has also been reported as a stroke
subtype in cocaine abuse.
Acute cocaine-induced strokes are positive on DWI.
MRA, CTA, or DSA may show focal areas of arterial narrowing and
irregularity.
Acute hypertensive encephalopathy with posterior reversible encephalopathy
(PRES-like syndrome) can also occur.
Vasogenic edema in the occipital lobes is the most common finding.
D/D Embolic infarcts as well as vasculitis may appear identical to cocaine
vasculopathy.
54. (B) NECT scan in a patient with
cocaine abuse shows diffuse brain
swelling and multifocal ischemic
infarcts.
(A) NCCT shows acute
hypertensive haemorrhage
with putamen/external
capsule haemorrhage in a
patient who abused cocaine.
(A) (B)
55. Axial FLAIR scan (L) and DWI (R) in a 35y male cocaine abuser
show ischemic infarcts in the left basal ganglia.
56. Posterior reversible encephalopathy syndrome (PRES)
Also known as reversible posterior leukoencephalopathy syndrome (RPLS)
A neurotoxic state that occurs secondary to the inability of the posterior circulation to
autoregulate in response to acute changes in posterior circulation.
Hyperperfusion with resultant disruption of the blood-brain barrier results in
vasogenic edema, usually without infarction.
Most commonly in the parieto-occipital regions.
This condition occurs at all ages but is most common in young women .
seen in hypertension, preeclampsia, renal failure, sepsis, thrombocytopenia,
administration of cytotoxic or immunosuppressive medications
57. FLAIR fairly symmetrical high signal intensities in both subcortical regions of occipital lobes without diffusion
restriction in DWI.
59. (1). HEROIN –
Heroin is usually injected intravenously.
The most common acute complication of injected
heroin is ischemic stroke. Globus pallidus and white
matter ischemia, very similar to that seen in carbon
monoxide poisoning, is common.
The most dramatic acute effects occur with inhaled
heroin. The freebase form is heated over aluminum foil
and the vapors inhaled ("chasing the dragon").
Heroin vapor inhalation causes a striking toxic
leukoencephalopathy (cerebellum and cerebral
white matter).
61. hypodensities in the cerebellar white matter,
sometimes described as a "butterfly wing"
pattern.
MRI show symmetric hyperintensity in the
cerebellar white matter and posterior limb of
internal capsule.
62. Imaging-
CT Findings:-
Acute CNS toxicity from inhaled heroin is characterized by symmetric
hypodensities in the cerebellar white matter, sometimes described as a
"butterfly wing" pattern.
The posterior cerebral white matter, posterior limb of the internal capsule
and globi pallidi are also commonly affected.
The anterior limb of the internal capsule is typically spared.
63. MR Findings:-
T2 and FLAIR scans in patients with early heroin-related
leukoencephalopathy show symmetric hyperintensity in the cerebellar
white matter with relative sparing of the dentate nuclei.
There is often selective symmetric involvement of the posterior limb of
the internal capsule, the corticospinal tract, the medial lemniscus
and the tractus solitarius .
DWI shows acute diffusion restriction in the affected areas.
MRS shows a lactate peak in the cerebral white matter
64. "Chasing the dragon" shows hyperintensity and
restricted diffusion in periventricular WM.
65. 2. METHADONE –
The synthetic opioid methadone are used in the medication-assisted
therapy for drug abuse/dependence as well as in the management of
intractable pain.
Diffuse, symmetric, confluent hyperintensity in the cerebral white
matter on T2/FLAIR is seen.
Sparing of the subcortical U-fibers is typical.
In contrast to heroin toxicity, cerebellar and brainstem changes are
subtle or absent in adults.
Accidental ingestion of methadone has been reported to cause severe
cerebellar edema with acute obstructive hydrocephalus in children .
66. MRs in a 33y woman who overdosed on methadone
show striking symmetric confluent hyperintensity
(leukoencephalopathy) on FLAIR and restricted
diffusion on DWI.
67. Accidental methadone poisoning in a child
shows bilateral cerebellar hypodensity on
NECT, T2/FLAIR hyperintensity and restricted
diffusion.
68. (3). OXYCODONE –
Cerebellar and globus pallidus
ischemia is more common.
Toxic leukoencephalopathy is less
common.
Overdose shows restricted diffusion
in the cerebellar hemispheres and
globi pallidi.
FLAIR shows symmetric
cerebellar and white matter
lesions in oxycodone overdose.
70. (1). CARBON MONOXIDE POISONING -
The toxic effects of CO result mostly from impaired oxygen
transport. CO combines reversibly with hemoglobin (Hgb) with over
200 times higher the affinity than that of oxygen.
The globi pallidi are exquisitely sensitive to hypoxia, the hallmark of
acute CO poisoning is symmetric globus pallidi necrosis.
The cerebral white matter is the second most commonly affected
and often shows delayed demyelination and necrosis that may
appear several weeks after the initial insult.
(Subacute (“interval”) poisoning: Confluent leukoencephalopathy).
71. T1WI in a 49y man with CO poisoning shows symmetric lesions in both medial GP. showing faint hyperintense rim , thin
hypointense underlying rim, and central coagulative necrosis seen as mildly hyperintense lesions (B) FLAIR scan in the same
patient shows that the lesion is mostly hyperintense with central isointense core
72. Imaging :-
CT Findings -
Early NCCT scans may be normal. Symmetric hypodensity in both
globi pallidi develops within a few hours. Gross hemorrhage is rare.
Variable diffuse hypodensity in the hemispheric white matter can be
seen in severe cases.
MR Findings –
MR Findings T1WI shows subtle hypointensity in the globi pallidi.
A faint rim of hyperintensity caused by hemorrhage or coagulative
necrosis may be present.
T2/FLAIR shows bilateral hyperintensities in the medial globi pallidi,
with the putamina and caudate nuclei less commonly affected. A thin
hypointense rim around the lesion may be present.
73. DWI/ADC maps show restricted diffusion in the affected areas.
Bilateral globi pallidi hyperintensities as well as foci of restricted diffusion in the
subcortical white matter are typical.
T2* GRE or SWI may show hypointensity in the globi pallidi suggestive of
petechial hemorrhage.
Up to one-third of CO patients develop a delayed leukoencephalopathy with
progressive white matter demyelination, the "interval" (subacute) form of CO
poisoning. Extensive bilateral symmetric confluent areas of hyperintensity on
T2/FLAIR are characteristic findings .
74. Axial T2WI in a patient with CO poisoning shows characteristic
bilateral hyperintensities in globi pallidi .Confluent
hyperintensity now involves virtually all of the cerebral WM
except the subcortical U-fibers
More cephalad T2WI shows that the hyperintensity involves
most of the corona radiata mostly spares subcortical WM. This
was "interval" (subacute) form of CO poisoning with toxic
demyelination.
75. (2). NITROUS OXIDE -
Nitrous oxide (N₂O), commonly known as
"laughing gas“.
N₂O is extremely soluble in fatty compounds.
Excess N₂O irreversibly oxidizes the cobalt ion
of vitamin B12, which is necessary for
methylation of myelin sheath phospholipids.
Long-term nitrous oxide abuse causes
progressive myelopathy and a peripheral
polyneuropathy.
The end result is subacute combined
degeneration of the spinal cord. The dorsal
columns and corticospinal tracts are
preferentially affected.
Axial T2WI in a patient with nitrous oxide
abuse shows selective symmetric
demyelination of the posterior columns ,
characteristic of subacute combined
degeneration Inverted "V" sign/
INVERTED RABBIT EAR sign
76. Differential Diagnosis subacute combined degeneration
Nutritional/metabolic deficiency or toxicity:
Copper deficiency
vitamin E deficiency
Methotrexate-induced myelopathy
• Demyelinating myelopathy:
Transverse myelitis : Not preferentially involve dorsal columns and is limited to one or
two spinal segments.
Multiple sclerosis : spinal cord involvement is asymmetric and affects fewer segments.
• Infectious myelopathy:
HIV Vacuolar myelopathy
Tabes dorsalis (neurosyphilis)
• Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation:
Symmetrically involves the posterolateral columns
This condition affects the entire spinal cord and can extend to involve the medulla.
77. (3). TOLUENE ABUSE –
Toluene is lipid-soluble and rapidly absorbed by the CNS.
Prolonged exposure causes multifocal neurologic defects and optic neuropathy.
Toluene poisoning results in chronic solvent encephalopathy.
The common methods of solvent abuse are "sniffing" (direct inhalation from a
container), "huffing" (inhalation from a soaked rag held over the nose and
mouth), and "bagging" (inhalation from a plastic bag).
78. Axial T2-weighted MR image symmetric hypointensities involving the globi pallidi and thalami. (b) Coronal T2-weighted MR
image shows symmetric hypointensities involving the thalami and substantiae nigrae.
79. T2 hypointensity involving the thalami, basal ganglia, and
substantiae nigrae . The cause for such hypointensity is still not known.
It has been hypothesized to be secondary to excessive iron deposition.
Diffuse white matter lesions are seen in nearly half of all patients, initially seen
as T2/FLAIR hyperintensity in the deep periventricular white matter with
subsequent spread into the centrum semiovale and subcortical areas.
The internal capsule, cerebellum and pons are often affected.
Chronic prolonged toluene exposure also causes generalized atrophy with
ventricular dilatation and enlarged subarachnoid spaces.
80. sagittal T1WI shows thinned corpus callosum , and T2/FLAIR demonstrates confluent white matter
hyperintensity. This was toluene toxicity due to chronic glue sniffing.
81. (4). ORGANOPHOSPHATE POISONING -
Organophosphates (OPs) are common ingredients in pesticides.
OPs are potential sources of accidental or suicidal exposure.
Acute OP poisoning causes hemorrhagic basal ganglia necrosis with the "eye
of the tiger" sign.
On T2WI, a ring of marked hypointensity caused by excess iron
accumulation surrounds a central hyperintense focus in the medial globus
pallidus.
The differential diagnosis of OP poisoning includes other drug-induced causes
of pallidal necrosis such as carbon monoxide poisoning. HIE and metabolic
encephalopathies such as Leigh and Wilson diseases also affect the basal
ganglia.
82. T2WI shows classic "eye of the tiger" with medial GP
hyperintensities ſt surrounded by well-defined hypointensity
Pantothenate kinase-associated
neurodegeneration (PKAN), also known
as Hallervorden-Spatz syndrome
83. (5). CYANIDE POISONING –
Cyanide (CN) is one of the most potent and deadly of all poisons.
CN poisoning can occur by inhalation, ingestion or transdermal absorption.
CN inactivates cytochrome oxidase, a key enzyme in the mitochondrial
respiratory chain. Therefore, acute CN poisoning typically affects structures with
high metabolic requirements.
The basal ganglia and cortex are most commonly involve.
Hemorrhagic basal ganglia necrosis and laminar cortical necrosis are the
pathologic hallmarks of CN poisoning.
84. Imaging-
MR show symmetric hyperintensity in the
basal ganglia and linear cortical
hyperintensity on T2WI and FLAIR.
CN poisoning usually spares the
hippocampi.
T1 C+ scans typically show intense
enhancement in the affected areas.
In the subacute and chronic stages,
hemorrhagic necrosis causes T1
hyperintensity in the basal ganglia.
Differential diagnosis of CN poisoning is
hypoxic-ischemic encephalopathy.
FLAIR scan in smoke inhalation with CN poisoning
shows symmetric hyperintensity in caudate nuclei and
putamina , more subtle lesions in posteromedial
thalami , and curvilinear cortical hyperintensities
86. Manganese Poisoning
Mn toxicity commonly results from
occupational exposure in welders and
smelters, contaminated water, and chronic
TPN.
Inhaled Mn may be transported via specialized
olfactory neurons into the brain, the main
pathologic target of Mn toxicity.
Mn excretion is primarily via the hepatobiliary
system.
Impaired hepatobiliary excretion in the setting
of chronic liver disease may lead to rapid Mn
accumulation
T1 hyperintensity in the globus pallidus.
87. LEAD POISONING –
Lead (Pb) is a potent and pervasive environmental
neurotoxicant that is especially harmful during
childhood development.
Chronic Pb poisoning occurs in three forms:-
(1) Gastrointestinal form (anorexia, vomiting,
lead "colic").
(2) Neuromuscular form (muscle weakness,
myalgias, peripheral neuritis).
(3) Cerebral or neuropsychiatric form
(irritability, headache, encephalopathy, seizure).
The cerebral form is common in children.
CT or MR may reveal volume loss, especially in
the frontal cortex and subcortical WM.
NCCT scan shows volume
loss in the frontal and
temporal lobes attributable
to lead poisoning.
88. GADOLINIUM -
Gadolinium is a rare earth heavy metal in the lanthanide series.
Its seven unpaired electrons induce a strong paramagnetic effect, reflected in its
widespread use for contrast-enhanced MR sequences.
Free gadolinium is extremely toxic so various chelating ligands are used to avoid
the adverse effects of free gadolinium.
Gadolinium in the blood must remain in chelated form until it is excreted by the
kidneys.
Gadolinium based contrast agents (GBCAs) are drained from the CSF through
olfactory nerves via the “glymphatic” system.
GBCAs are divided into two categories: Linear and macrocyclic.
89. Gadolinium retention from linear GBCAs is 10x higher than with macrocyclic
GBCAs.
MR Images shows high T1 signal intensity in the dentate nucleus and globi
pallidi.
91. (1). RADIATION INJURY –
Radiation-induced injury divided into three phases:-
1. Acute radiation injury:- (days to weeks)
T2/FLAIR may show white matter edema.
TSPO-PET(translocator protein) may show neuroinflammation.
2. Early delayed injury (at least 6 months)
Necrotizing leukoencephalopathy
Confluent hyperintensity.
3. Long-term sequelae:-
Necrotizing leukoencephalopathy
Vasculopathy, mineralizing microangiopathy
Vascular malformations (T2* "black dots")
Radiation-induced neoplasms
92. FLAIR in a patient with cognitive decline 3 years after whole-
brain XRT for leukemia shows confluent WM hyperintensity .
T2* scan shows multiple foci of gradient blooming
necrotizing leukoencephalopathy with XRT-induced vascular
malformations
93. MRA in a case with right MCA stroke years after XRT shows postradiation vasculopathy. Stenosis of both
supraclinoid ICAs is present; right MCA is occluded. NECT shows 20y man with XRT and chemo at age 8 for
medulloblastoma. BG , subcortical WM calcifications are characteristic of mineralizing microangiopathy
94. (2). CHEMOTHERAPY EFFECTS -
The most common chemotherapy agents in CNS toxicity are methotrexate, cytarabine,
vincristine, asparaginase and corticosteroids.
The two most frequent abnormalities are:-
1. Posterior reversible encephalopathy syndrome (PRES):-
In chemotherapy-related PRES(cyclosporine and tacrolimus)., imaging findings are
often atypical.
The occipital lobes are frequently spared whereas the cerebellum, brainstem and basal
ganglia are frequently involved.
Hemorrhage, contrast enhancement and diffusion restriction common.
2. Acute leukoencephalopathy:-
Reflects acute neurotoxicity.
Transient T2/FLAIR periventricular hyperintensity.
95. a Axial images with T2/FLAIR sequence vasogenic edema in the occipital lobes and splenium of the corpus
callosum . b Vasogenic edema may also involve the thalamus, basal ganglia (c) and brainstem-midbrain (d), with
partial/asymmetric (e) or absent (f) involvement of the parietal and occipital lobes. DWI and T2*-weighted gradient-
echo sequences demonstrate complications of PRES such as ischemic areas
96. Methotrexate leukoencephalopathy
Three main pattern
(a) toxic leukoencephalopathy,
(b) disseminated necrotizing encephalopathy,(rare)
(c) subacute combined degeneration.
Toxic leukoencephalopathy is the most common manifestation
MC seen between 2 and 14 days after methotrexate administration, but manifestation can
occur on a delay, even years after use
Imaging finding
True diffusion restriction, bilaterally asymmetric across multiple vascular territories,
affecting the centrum semiovale and sparing the subcortical U fibers.
The same regions appear on T2-weighted and FLAIR images as hyperintensities and can
disappear or persist after symptom resolution
97. B) More cephalad scan in the same
patient shows the confluent WM
hyperintensity and spared
subcortical WM. This is
methotrexate induced
leukoencephalopathy.
A) T2WI in a 5yrs child with acute
deterioration following intrathecal
methotrexate for ALL shows symmetric
confluent hyperintensity in the deep
periventricular WM. Note sparing of
subcortical U-fibers
98. Axial DWI (a) and ADC map (b) in a patient with toxic leukoencephalopathy show multiple lesions with true restricted diffusion
affecting the centrum semiovale and crossing vascular territories while sparing the subcortical U fibers.
99. Axial FLAIR MR image in case of necrotizing encephalopathy methotrexate therapy combined with whole-brain radiation
therapy shows a hypointense lesion involved by an extensive confluent area of vasogenic edema (hyperintensity). (d) Axial
contrastenhanced T1-weighted MR image in the same patient shows peripheral enhancement of the lesion (arrow) and a
circumjacent hypointense area of edema. (e) Axial contrast-enhanced T1-weighted control MR image obtained 3 months later
shows a reduction in the lesion enhancement (arrow) and surrounding edema (arrowhead).
100. Miscellaneous
1.Vigabatrin-associated Toxicity
Antiepileptic drug used for the treatment of infantile spasms.
The younger the patient, the higher the risk, with patients younger
than 1 year being the most commonly affected
Images
symmetric restricted diffusion and T2-weighted and FLAIR
hyperintensity in involved areas, subsequently normalized after
vigabatrin withdrawal.
The major affected areas are the globi pallidi, thalami, dorsal
brainstem, and dentate nuclei
101. Axial diffusion-weighted MR images show restricted diffusion symmetrically involving the globi pallidi and dorsal brainstem
(arrow in b), with normalization on the 6-month follow-up image (c).
102. 2.Metronidazole-induced Brain Toxicity
These toxic effects seen during prolonged
treatment (mean duration, 54 days)
Images
Bilateral symmetric lesions in the
cerebellum, particularly involving the
dentate nuclei also affect , vestibular
nuclei, tegmenta, and superior olivary
nuclei.
A lack of enhanced lesions with T2-
weighted and FLAIR hyperintensity is the
most common finding.
This finding also seen in treatment of
tuberculosis with isoniazid.
Axial FLAIR MR image shows a symmetric
hyperintensity involving the dentate nuclei.
103. 3.Levamisole-induced Leukoencephalopathy
This is anthelmintic with immunomodulatory properties but not use d/t side effect.
But use as a cocaine adulterant because it can induce effects similar to those of cocaine on
the CNS.
Patients are usually adolescents or young adults and present with a strokelike episode.
Images
characteristically shows lesions with a tumefactive demyelinating pattern, represented as
one or a few randomly distributed oval or round lesions in the centrum semiovale, with no
mass effect or edema, with smooth and incomplete enhancement peripherally (C-shaped
appearance, the incomplete portion is related to the cortex) and strongly restricted
diffusion.
T2-weighted and diffusion-weighted images can depict concentric layers of
hyperintensities.
Another important characteristic is that after treatment with steroids, lesions tend to
regress and even disappear.
104. (a) Axial contrast-enhanced T1-weighted MR shows hypointense lesions within the centrum semiovale with incomplete
peripheral enhancement, without edema or mass effect. (b) Axial diffusion-weighted MR image shows a lesion centered in the
centrum semiovale with strong restricted diffusion and different concentric layers of hyperintensities.
105. Acute toxic leukoencephalopathy ("CHOICES“)
C Chemotherapy
H Heroin-induced whether via intravenous or inhaled routes
O
Opioid analogue, abuse via various routes of “non-heroin”
medications
I Immunosuppressant or Imidazole medications
C “Crack” cocaine abuse
E Environmental and Ethanol-related
S
Splenial lesions (RSL), which include AEDs, chemotherapy,
immunosuppressant medication
106. Toxic LE predominately affects the cerebral WM (periventricular) and may
occur from an exposure to a variety of agents, including environmental toxins,
prescription medications, metabolic substances, and illicit drug usage
Acute toxic leukoencephalopathy (ATL) is a potentially reversible condition that may
improve after treatment or following withdrawal of the offending toxin early in the
course of disease.
MRI, ATL variably has abnormal signal on FLAIR/T2WI, but the abnormalities are
typically visible as bright on DWI and dark on accompanying ADC maps relative to
normal-appearing white matter
ATL is a less common effect of these toxins relative to another entity, posterior
reversible encephalopathy syndrome (PRES).
These two entities can be distinguished by their imaging appearances.
107. PRES ATL
Cortical and subcortical (parietal and
occipital)
Periventricular WM (corona radiata and
centrum semiovale)
DWI-positive foci are typically focal,
asymmetric, cortical-based
DWI,show reduced diffusion in a
confluent and symmetric fashion
Avid enhancement in up to 50% Rarely has contrast enhancement on
T1WI MRI (<10%)
microhemorrhages (< 1 cm) in nearly
60%, with macrohemorrhages in up to
10–20%
Microhemorrhages in 15%, but rarely
has macrohemorrhages (>1 cm)
certain degree of overlap in both etiology and pathophysiology, thought
related to toxin-induced endothelial injury with subsequent loss of
