ACQUIRED METABOLIC

DISORDER
Introduction
 Brain is vulnerable to damage from abnormal metabolites & toxins

Encephalopathy- Clinical situation associated with diffuse or multifocal

brain dysfunction.
 This disorder main test secondary to derangements of well
balanced environment encompassing metabolic substrates,
neurotransmitters, Electrolytes, PH level and blood flow, either by
endogenous malfunctions or exogenous toxic effect.
 Imaging helping determining the most probable diagnosis, pointing
to next step of investigations, and providing prognostic information.
Majority of cases demonstrate bilateral and symmetric
involvement of structures at imaging, affecting deep gray nuclei,
cortical gray matter and or preventricular white matter & some
shows specific imaging pattern.
IEM & hypoxia may have similar imaging features.
 Acute metabolic encephalopathy, imaging shows the presence of
vasogenic edema & Cytotoxic edema, both of which can be
reversible.
 DWI – useful in detecting early pathological alternation in
membrane & membrane related water transport proteins.
 Major cause of toxic and metabolic disorder
Most common endogenous metabolic derangements related to CNS
involvement
• Hypertensive encephalopathies
• Glucose disorders
• Parathyroid disorders
• Hepatic encephalopathy (manganese and/or ammonia levels)
• Uremic encephalopathy
• ODS Cobalamin deficiency
Major exogenous causes of toxic encephalopathy
• Alcohol-related disorders (WE, MBD)
• Industrial agents (methanol, toluen)
• Inhaled gases (carbon monoxide, pesticides)
• Illicit drug use (heroin, cocaine)
• Chemotherapeutic agents (methotrexate, fludarabine, 5-
fluorouracil) Immunosuppressive agents (TNF-α blockers,
cyclosporine)
• Other potentially neurotoxic medications (metronidazole,
vigabatrine)
Vasogenic Edema:

 Chemical insults that leads to BBB disruption, resulting in leakage

fluid from capillaries into ECF in white matter.
 Images shows T2W & FLAIR hyper intensities without restricted
diffusion.
 Can produce mass effect dislocation of structures and defacement
of cerebral sulci.
 Gray matter is maintained.
 White matter involved as fingerlike fashion

Eg: TUMOURS/ABSCESS,PRES,WE
Cytotoxic Edema:
 Water enters from extracellular space into cells,
impairing cellular metabolism and cause edema.
 Mainly affect gray matter, although white matter
also involved.
 BBB not compromised.
Types of cerebral edema

Illustration depicts the normal

relationship between brain
cells and extracellular space,
which contains water
molecules with freedom of
movement.

Illustration depicts brain tissue in a

vasogenic edema situation, with an
increased number of water
molecules occupying the
extracellular space but maintaining
freedom of movement.
Types of cerebral edema

Illustration depicts a cytotoxic brain

edema situation, represented by
the swelling of brain cells
(increased volume) without
primarily affecting the
extracellular space. Water
molecules inside the brain cells
lose their freedom of movement.

Illustration depicts intramyelinic edema,

with swelling of periaxonal space and
spaces between myelin layers, without
primarily affecting other extracellular
spaces or involving brain cells. Water
molecules inside the myelin layers cannot
move to other extracellular spaces, losing
their freedom of movement.
Imaging in Cytotoxic Edema:
Primarily,
 Changes in DWI caused by restricted diffusivity
within brain cells, without T1 or T2 W changes.
 As pathology process progresses, alterations in
T2 weighted signal intensity and contrast
enhancement occurs, secondarily.
Eg: UREMIC ENCEPHALOPATHY- Basal ganglia
type
Excitotoxic Edema:
 Commonly seen in infarction, HIE, status epilepticus,
toxic and metabolic disorder. (Glucose/sodium disorder
& Hyperammonemia)
 Due to excessive release of excitatory aminoacidemia in
synaptic cleft, Mostly glutamate.
 Excessive glutamate causes cell swelling & cell death
(Cytotoxic edema).
Intra Myelinic Edema:

 Edema between myelin layer and periaxonal space.

 Non - Neurotoxic edema
 Characteristic by RESTRICTED DIFFUSION and REVERSIBLITY
(without cell death)
 Reversible DWI
 When cellular edema is present – irreversible or partially irreversible.

Location:
 PV white matter and splenium have higher metabolism more susceptible
to intramyelinic edema.
 ALT acute toxic leukoencepalopathy
 Relates to cerebral white matter alterations secondary to various toxic
agents & great potential of reversibility if rapidly corrected.
Imaging:
 Acute diffuse white matter involvement
 B/L symmetric areas of true restricted diffusion
involving PVL and sparing of basal ganglia at DWI
signals.
 Subsequent normalization related to intramyelinic
edema.

Common Causes:
Uremia/ CO/ Metronidazole, Immunosuppressive and
chemo therapy agents, Opioids.
Imaging Patterns In Metabolic
Disorders
1. Basal ganglia and/or thalami involvement. The periventricular white matter
and the cortical gray matter may be also involved. This pattern is usually
related to Cytotoxic brain edema, poor outcomes, and irreversibility.

2. Dentate nuclei involvement.

3. Prominent cortical gray matter involvement. Although cortical lesions can

coexist with basal ganglia- and white matter–associated

involvement, they are the most distinguishing feature.

4. Symmetric periventricular white matter involvement with gray matter

sparing. This is a pattern that includes ATL causes and is more

related to intramyelinic edema and higher possibilities

of reversibility and better outcomes.

5. Corticospinal tract region involvement.
6. Corpus callosum involvement.
7. Asymmetric white matter involvement in a demyelinating
disease pattern.
8. Parieto-occipital subcortical vasogenic edema.
9. Central pons involvement. The pattern of involvement,
damage extension, and possibility of reversion (mainly in
cases of ATL) are related primarily to the intensity and
duration of exposure to a determined agent.
 Hypertensive Encephalopathies
 If not recognized and treated, the effects of
both acutely elevated blood pressure and
chronic hypertension (HTN) on the brain can
be devastating. We begin this section with a
discussion of acute hypertensive
encephalopathy, then delve into the CNS
damage caused by chronic HTN.
Acute Hypertensive Encephalopathy
PRES with cortical/
subcortical vasogenic
edema → In the posterior
circulation with some
petechial hemorrhage
is shown.
Imaging
Diagrams show location, relative frequency of
PRES lesions. Although > 90% have lesions in
the parietooccipital subcortical WM (classic
PRES, shown in red), note that multifocality is
the rule, not the exception. Most cases of
PRES also have lesions in areas other than the
classic parietooccipital location. Both classic
PRES (red) and the superior frontal sulcus
pattern (orange) are frequently combined
with additional lesions distributed along the
hemispheric cortical (superficial) watershed
zones (depicted in the lower right image).
The cerebellum is affected in nearly 1/2 of
PRES cases, whereas about 1/3 have basal
ganglionic lesions (light blue). The pons,
medulla, cervical spinal cord, and corpus
callosum splenium are less common sites
involved by PRES, although in some cases,
only the posterior fossa is affected.
Remember: Atypical PRES is actually more
common than the classic isolated
parietooccipital involvement! (Adapted from
NECT in severe hypertension More cephalad NECT shows
shows bioccipital symmetric hypodensity in the
hypodensities in the posterior parietal and high
occipital white matter . This is
subcortical white matter
classic PRES.
 CT Findings

A 63y woman with end-stage renal MR was obtained because of suspected

disease had a seizure, then fell. Blood PRES. FLAIR MR obtained 1 hour after the
pressure on admission was 220/140. NECT shows multifocal patchy
NECT performed to evaluate for hyperintensities in the midbrain,
intracranial hemorrhage shows normal posteroinferior temporal lobes, and
findings. parietooccipital cortex→
FLAIR MR through the lateral DWI MR in the same patient
ventricles shows bilateral, shows no evidence for diffusion
relatively symmetric lesions in restriction. DWI scans are usually
(although not invariably) normal
the parietooccipital cortex
in PRES because the edema is
mostly vasogenic, not cytotoxic.
 MR
Findin
gs

Axial FLAIR MR in a 50-year-old man Additional lesions are present in

with severe hypertension (BP = the thalami , internal
200/120) shows confluent capsules , corpus callosum
hyperintensity involving the entire splenium → , and frontal WM →
medulla → . Note patchy
hyperintensities in the white matter of
both cerebellar hemispheres →
More cephalad FLAIR shows lesions
along the watershed zones →
Sagittal STIR of the cervical spine shows
confluent hyperintensity extending from the
medulla
inferiorly throughout the entire cervical
spinal cord → . This is atypical PRES.
Remember: “Atypical” PRES is more common
than “classic” PRES!
 Maligant Hypertension

FLAIR in 54y woman T2* SWI shows More cephalad T2* SWI
with chronic renal multiple “blooming” demonstrates more
failure, TTP, confusion foci → throughout the blooming WM
shows bifrontal white matter. The hypointensities →.
confluent and cortex is spared.
scattered WM →
hyperintensities.
 Chronic Hypertensive
Encephalopathy

T2* GRE in a 37y woman Numerous

with longstanding, poorly Scattered foci of
hypointensities in the gradient susceptibility
treated hypertensions basal ganglia and
shows multiple in the cortex→ ,
thalami and a extensive
“blooming” foci in the single lesion in the left
pons → periventricular WM
insular cortex → are hyperintensities are
present present. Chronic HTN.
✔ The brain is a glucose glutton, consuming > ½ of the body’s total glucose.
Because the brain does not store excess energy as glycogen, CNS function is
highly dependent on a steady, continuous supply of blood glucose.

✔ Blood glucose levels are tightly regulated and are normally maintained within a
narrow physiologic range. Disorders of glucose metabolism— both
hypoglycemia and hyperglycemia—can injure the CNS.

✔ The neurologic manifestations of deranged glucose metabolism range from

mild, reversible focal deficits to status epilepticus, coma, and death. Because the
clinical and imaging manifestations differ in neonates from those of older
children and adults, hypoglycemia in these two age groups is discussed
separately.
Pediatric / Adult Hypoglycemic
Encephalopathy

Autopsy of severe
hypoglycemia shows
bilateral symmetric
parietooccipital, frontal
cortical necrosis → .
 CT Finding MR Finding

NECT shows typical changes of DWI MR in the same case of typical

hypoglycemia with AHE shows restricted diffusion in
parietooccipital gyral swelling parietooccipital cortex, putamina
→, putamen hypodensity , with thalamic and WM sparing
spared thalami .
 Neonatal/Infantile Hypoglycemia

T2 MR in 5-day-old T2 MR at 1 year shows

ADC shows profound shrunken, hyperintense
hypoglycemic infant shows
restricted diffusion in the parietooccipital lobes with
edematous, hyperintense
parietal and occipital lobes  cortical loss and
parietooccipital lobes ,
and corpus callosum splenium encephalomalacicappearing
corpus callosum splenium  .
. .. WM .
 PARATHYROID AND RELATED DISORDERS
Hyperparathyroidism

Axial bone CT in a patient NECT in a 31-year-old

with 2° HPTH shows
leontiasis ossea with
marked calvarial thickening,
focal sclerotic “brown
tumors” 
Coronal bone CT in the man with ESRD shows
same patient demonstrates markedly thickened,
the striking calvarial plaque-like deposits along
thickening. the tentorium .
 Hypoparathyroid Disorders

NECT in 7y with Axial T1 MR in 34y woman T2* SWI shows symmetric

hypoparathyroidism shows
calcifications in the globi
pallidi with smaller
calcific foci at the GM-WM
interfaces
with PPHP on calcitriol hypointensity in both caudate
shows symmetric T1 nucle  , putamina , and the
shortening in both caudate globi pallidi (Courtesy P.
nuclei and putamina . Hildenbrand, MD.)
 NECT in a 54-year-old man with Coronal NECT in the same
NECT of the skull in a case shows how symmetric
hyperparathyroidism shows
patient with HPTH shows the basal Ca⁺⁺ is. Note
extensive symmetric Ca⁺⁺ in
the characteristic alternating GM-WM interface
basal ganglia , thalami ,
salt and pepper foci of
cortex 🡪. calcifications 🡪.
resorption and sclerosis.
 THYROID DISORDERS
Acquired Hypothyroid Disorders
Hashimoto Encephalopathy – MR Images

T2 MR of acute Hashimoto FLAIR MR through corona

More cephalad T2 MR shows
encephalopathy shows the frontoparietal dominance
confluent, symmetric
of WM edema. Occipital
hyperintense ity in the lobes are largely spared
subcortical, deep WM .
radiata shows frontal
subcortical/deep WM
edemawith marked
sparing of the occipital
lobes .
 MISCELLANEOUS DISORDERS
Hepatic Encephalopathy
Chronic Hepatic Encephalopathy

T1 MR in chronic liver failure with

acute onset of encephalopathy
shows striking, symmetric T1
shortening in the globi pallidi .
Acute-on-Chronic Liver Failure

Axial FLAIR MR in the same case Hyperintensity in periaqueductal gray

shows symmetric hyperintensity  in , tectum , both mammillary bodies .
the medial thalami around the 3rd Acute WE superimposed on chronic
ventricle. liver failure.
 Hyperthermic Encephalopathy

More cephalad T2 MR
NECT of heatstroke 6 days T2 MR shows diffuse
shows diffuse cortical
after admission shows swelling and hyperintensity
hyperintensity . This
swollen temporal lobes  , of both temporal lobes .
is heat stroke.
cerebellum , The cerebellar white matter
(Courtesy P. Hudgins,
compressed 4th ventricle . is also hyperintense 
MD.)
 Osmotic Encephalopathy

Graphic shows acute osmotic Autopsied remote CPM shows

central pontine demyelination  . triangular shape of brown discolored
Note sparing of peripheral WM, demyelination in the central
traversing corticospinal tracts . pons. (From Agamanolis DP, op cit.)
CT Findings

NECT in a 37-year-old woman

with osmotic demyelination
syndrome shows a triangular
central pontine hypodensity .

T2 MR shows CPM . The
peripheral pons is spared
as are the corticospinal tracts
and transverse pontine fibers
.
MR Findings
T1 MR shows that the lesion is
hypointense . Transverse
pontine fibers are spared, seen
here as lines of preserved brain .
T2 MR through the upper
pons shows the lesion
with “stripes” of preserved
myelinated transverse
pontine tracts .
A variant case of ODS is illustrated by
DWI MR shows that the cortex is also diffusely
this axial FLAIR MR in a 56-year-old
but somewhat asymmetrically affected.
man with confusion after rapid
Cortical laminar necrosis can sometimes be
correction of hyponatremia. Note
seen in ODS.
hyperintensity in the basal
gangliaand both thalami .
Wernicke Encephalopathy
 Thiamine is important is maintaining osmotic gradients across the cell
membrane, ensuring its integrity.
 Thiamine deficiency: More than 3 weeks results in cerebral lactic acidosis
failure to maintain cellular electrolytes homeostasis impairment of glial cells
and neurons due to excessive glutamate.
 Cerebral atrophy and micro hemorrhages can manifest in chronic alcohol
intake.
 Memory and cognitive impairment due to involvement of thalamus and
mammillary bodies
 Ataxia due to involvement of periaqueductal gray matter (cerebella vermis).
Wernicke Encephalopathy

 MRI is much more sensitive than CT in WE evaluation.

 DWI superior to T2WI & FLAIR
 Structures surroundings the third ventricle are mainly involved (Medial
Thalamus, Pontine tegmentum, Mammillary body, Tectal plate of midbrain)
 Strong uniform postcontrast enhancement of the mammillary bodies is
observed in upto 80% of cases – Pathognomonic finding for WE.
 In chronic phase, the mammillary bodies are atrophied.
 High signal intensity on DWI and low ADC value do not always corresponds to
irreversible tissue damage.
 Since signal abnormalities or normalized within 2 weeks when adequate
thiamine is supplied.
 This indicates reversible Cytotoxic edema before the cell enters necrotic
state.
 Ophmalmic symptoms improve within
hours, Ataxia requires longer time.
 Follow-up MRI: Complete disappearance of
signal abnormalities
 D/D: thalamic infarction, cmv encephalitis,
Cerebral lymphoma, mitochondrial
disorders.
Basal Ganglia and/or Thalami
Involvement
 WE in a patient
Wernicke Encephalopathy with diplopia and
impaired mental
status after long-
term parenteral
nutrition. (a–d)
Axial FLAIR MR
images show
bilateral and
symmetric
hyperintensities
involving the
medial thalamus
(arrow in a),
hypothalamus
(arrow in b),
periaqueductal
gray matter (arrow
in c), tectum
(arrowhead in c),
and dorsal pons
(arrows in d).
Basal Ganglia and/or Thalami
Involvement
(e) Axial contrast-
enhanced T1-
weighted MR
image shows
symmetric
enhancement of
the mammillary
bodies (arrows).
(f) Axial FLAIR MR
image shows
perirolandic
cortical
involvement
(arrows).
Wernicke Encephalopathy
Corticospinal Tract Involvement
Cobalamin deficiency
with combined
subacute
degeneration of the
spinal cord.
(a) Axial T2-weighted
MR image of the
cervical spine shows
involvement of the
dorsal and lateral
columns (arrow) in an
inverted V shape.
(b) Axial FLAIR MR
image of the head
shows bilateral
hyperintensities
(arrows) involving the
Cobalamin Deficiency region of the
corticospinal tract.