Cirosis Es Neuro Tunetek PDF

The Nervous Liver: Neurological complications associated
with Cirrhosis & Liver Transplantation

Poster No.:
C-1397
Congress:
ECR 2014
Type:
Educational Exhibit
Authors:
A. Arora, A. Mukund, S. Rajesh, Y. Patidar, S. K. Sarin; New Delhi/

IN
Keywords:
Transplantation, Metabolic disorders, Education and training,

Education, MR-Diffusion/Perfusion, MR, CT, CNS
DOI:
10.1594/ecr2014/C-1397
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Page 1 of 110
Learning objectives
That there is a relationship between the brain and the liver has been known for many
years, and patients with chronic liver disease frequently experience a wide spectrum of
neurological problems that can adversely affect patient's neurocognitive functioning [1-3].
These neurological problems range from neurological complications such as hepatic
myelopathy, acquired hepatocerebral degeneration, cognitive and mental status changes
such as hepatic encephalopathy to metabolic, infective and hemorrhagic complications
of liver cirrhosis; and, can severely restrict the patient's functioning and also result in
significant morbidity and mortality [3-6].
Fig. 1: The Nervous Liver!

References: RADIODIAGNOSIS, INSTITUTE OF LIVER & BILIARY SCIENCES,
INSTITUTE OF LIVER & BILIARY SCIENCES - New Delhi/IN
Page 2 of 110
The present exhibit aims:

1. To appraise the wide array of neurological syndromes and disorderes that can
be associated with liver cirrhosis, highlighting their most pertinent neuroimaging
manifestations and providing an up-to-date information on these relatively understudied
entities.
2. To study and illustrate perioperative neurological complications which may originate
before, during or after orthotopic liver transplantation.
Background
LIVER-BRAIN AXIS
Normal brain functioning depends on several aspects of normal liver functioning. For
example, the liver supplies certain nutrients to the brain that the brain itself cannot
produce. The liver also cleanses the blood of substances that could damage brain cells
(i.e., neurotoxins, for e.g. ammonia, manganese, and other chemicals).
In chronic liver disease and cirrhosis, the liver loses its capacity to remove toxic
substances from the blood due to loss of functional liver cells (i.e., hepatocytes).
Moreover, some of the blood that normally flows through the portal vein into the liver for
cleansing is diverted directly into the general circulation without first passing through the
liver, a phenomenon known as portal-systemic shunting. As a result, the shunted blood is
not detoxified and blood levels of toxic substances rise. Persistently elevated neurotoxin
levels can damage brain cells and cause a wide spectrum of neurocognitive decline.
NEUROLOGY OF LIVER CIRRHOSIS

A neurological syndrome associated with a liver disease may affect the CNS, the
peripheral nervous system, or both; and, could represent a direct complication of the
disease, or part of spectrum of pathologies that affect the brain and liver concurrently
[1-6].
Boradly, neurological disorders in cirrhosis can be attributed to:
Page 3 of 110
(A) Direct effects of cirrhosis on the nervous system:
Neuroimaging alterations with/without clinical symptoms

Hepatic encephalopathy
Cirrhotic or hepatic myelopathy
Acquired hepatocerebral degeneration
Cirrhosis-related Parkinsonism
Cirrhosis related intracerebral hemorrhage
Infective comlpications of cirrhosis
Raised intracranial pressure (acute-on-chronic liver failure)
(B) Neurological complications related to chronic alcohol use:
Osmotic demyelination syndromes

Wernicke encephalopathy
Marchiafava-Bignami disease
Alcohol withdrawal syndrome
Cerebral atrophy and cognitive dysfunction
Alcoholic cerebellar degeneration
(C) Induced by a factor that also contributes to the (hepatic) disease:
Wilson disease
Hepatitis C virus infection
(D) De#cits unrelated to liver disease, such as:
Residual de#cits of prior strokes
LIVER TRANSPLANTATION-RELATED COMPLICATIONS

Among solid organ transplant recipients, recipients of liver transplantation have the
highest incidence of neurological complications. Neurological complications following
liver transplantation have an overall incidence of 13 - 47%.
These complications can be broadly classified into:
(1) Immunosuppressive neurotoxicity

(2) Opportunistic infections
Page 4 of 110
(3) Osmotic demyelination

(4) Cerebrovascular complications
(5) Post transplant encephalopathy
(6) Hepatic encephalopathy
(7) Seizures
(8) Post transplant lymphoproliferative disorder
Findings and procedure details
NEUROLOGY OF LIVER CIRRHOSIS
NEUROIMAGING CHANGES IN CHRONIC LIVER DISEASE
Cirrhotic patients frequently display changes on neuroimaging studies;

although, these patients may or may not develop neurological symptoms
[1-7].
The most striking neuroimaging manifestation includes high symmetrical and

bilateral signal intensities of various extents involving the basal ganglia and
the hypothalamus on T1WI [1, 7, 8].
Hyperintense signals in the basal ganglia, namely the globus pallidus, can
be seen in as many as 70-100% of patients with liver cirrhosis (Fig 2) [1, 7].
Page 5 of 110
Fig. 2: Symmetrical T1-hyperintensity involving the bilateral globus pallidus (arrows) in

an asymptomatic 54-year old male with hepatitis-B related liver cirrhosis.
Other sites of involvement include the pituitary gland, contiguous internal

capsule of the hypothalamus, putamen, caudate, substantia nigra, and
mesencephalic tegmentum (Fig 3) [8].
Page 6 of 110
Fig. 3: Axial T1-weighted MR images showing hyperintense signal of the caudate

nucleus (black arrows) in addition to the involvement of the globos pallidi (white
arrows).
The exact causes and mechanisms of the increased signal intensity remain
indefinite, however several hypotheses have been proposed. Deposition of
paramagnetic substances, particularly manganese (Mn), is speculated to be
responsible for the signal alteration [1, 7, 8].
Manganese (Mn) deposition has been attributed to liver dysfunction

(hepatocellular failure) and/or portosystemic shunting [7-9]. In addition,
pallidal deposition of manganese also reflects the presence of an adaptive
process designed to improve the efficacy of ammonia detoxification by
astrocytes [10, 11].
Although the mechanisms of manganese neurotoxicity are poorly

understood, there is evidence to suggest that manganese deposition in the
pallidum may lead to dopaminergic dysfunction [12, 13].
The pituitary gland is another commonly affected site shown on the MR

images; and when involved appears homogeneously bright on spin echo
T1-weighted images. The hyperintense signal of the pituitary gland makes
it impossible to distinguish between the normal isointense anterior pituitary
signal and the posterior pituitary hyperintensity [8].
Abnormalities on T2-WI within the globi pallidi have been reported to

accompany the T1-WI findings, but these findings may be masked by T1
shortening (Fig 4) [7].
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Fig. 4: (A) Axial T2-WI and (B) FLAIR sequence delineating subtle symmetrical
hyperintensity involving the bilateral lentiform nuclei in a young 26-year old lady with
liver cirrhosis.
Asymptomatic symmetric high-signal intensity in the hemispheric white

matter on fast-FLAIR MR images is present in cirrhosis. Normalization of
this finding after successful liver transplantation and its correlation with MTR
values suggest that this signal abnormality reflects mild edema (Fig 5) [8].
Page 8 of 110
Fig. 5: A 40-year old male with alcoholic liver cirrhosis and grade-I hepatic
encephalopathy. Fast-FLAIR MR images reveal diffuse high-signal intensity in the
hemispheric white matter on either sides.
DWI (and ADC maps) has also identified abnormalities within the
periventricular white, thalami, and basal ganglia in studies of patients with
cirrhosis with hepatic encephalopathy [9, 10].
Although no significant relationship has been demonstrated between

the presence of these signal intensity changes and the patients'
neuropsychiatric status, nevertheless, their presence has been shown to
relate to both the severity of the liver disease and the presence and degree
of portal-systemic shunting of blood [10].
Another common neuroimaging manifestation in cirrhotic patients is the

presence of cerebral atrophy. Zeneroli et al reported brain atrophy in 87.5%
of alcoholic and in 50% of nonalcoholic liver cirrhosis patients (Fig 6) [14].
Page 9 of 110
Fig. 6: Cerebral atrophy accompanying typical intracranial signal intensity changes

in a 36-year old patient with long standing cryptogenic cirrhosis. Axial T1-WI shows
symmetrical T1-prolongation of the basal ganglia (asterisk) representing manganese
deposition. Attendant widening of the sylvian fissures (thick arrows) and ventricular
enlargement (thin arrows) suggest cerebral parenchymal atrophy.
Computerized (CT or MR) morphometric studies of liver-disease brains have

revealed ventricular enlargement, cisternal and sulcal prominence, selective
loss of subcortical white matter, and prominent subarachnoid CSF spaces.
Brain atrophy in alcoholic patients can be attributed at least in part to the

toxic effect of alcohol, whereas, brain atrophy in nonalcoholic liver cirrhosis
seems to indicate that the chronic exposure to toxins leads to neuronal
alterations and cortical loss (Fig 7) [14-16].
Page 10 of 110
Fig. 7: Ventricular enlargement (white arrow) and subarachnoid CSF-space (sylvian

fissure) widening represent cerebral involutional changes in a 30-year old male with
alcohol induced liver cirrhosis.
Amodio et al has shown that brain atrophy in liver cirrhosis is associated

with a poor psychometric performance and both brain atrophy and EEG
alterations independently predict cognitive dysfunction in cirrhotic patients
[16].
Classical, MR spectroscopy (MRS) findings include elevated glutamine/

glutamate peak coupled with decreased myo-inositol and choline signals on
proton MRS [17].
HEPATIC ENCEPHALOPATHY
Hepatic encephalopathy (HE) is the most frequent cause of altered mental

status and coma in cirrhotic patients.
Patients suspected of acute HE are typically subjected to CT or MR imaging

to exclude emergent phenomena such as intracranial hemorrhage or
infarction [18].
Classically, the most accepted MR imaging finding in patients with chronic

hepatic failure has been hyperintensity on T1-WI in the globi pallidi related
Page 11 of 110
to manganese, but this only variably correlates with the plasma ammonia
levels and acute HE symptoms.
Acute HE has an acute phase followed by a chronic one. Pathologically,

during the acute phase, there is acute brain edema, and in the chronic
phase, there is a thin cortex and cortical laminar necrosis [18].
The proposed cytotoxic edema mechanism in HE is hyperammonia inducing

intracerebral accumulation of glutamine, resulting in astrocyte swelling and
brain edema [18].
On MR imaging, presence of extensive cortical edema including the deep

gray matter, with symmetric involvement of the cingulate gyrus and insular
cortex on DWI or FLAIR imaging, associated with sparing of the perirolandic
and occipital cortex, appears to be a unique imaging feature of acute HE
(Fig 8) [19, 20].
Fig. 8: Typical imaging manifestations of HE. Fast FLAIR images exhibit symmetrical
cortical edema involving the insular cortex (arrow) and cingulate gyrus (arrowhead).
Note that the occipital cortex (asterisk) is characteristically spared.
Page 12 of 110
Thus, the cingulate gyrus and insular cortex appear to be particularly

vulnerable to hyperammonemic-hyperglutaminergic encephalopathy, while
the perirolandic and occipital cortex seem relatively resistant. These MR
manifestations therefore should alert the radiologist to the possibility of acute
hyperammonemic encephalopathy in appropriate clinical settings (Fig 9) [19,
20].
Fig. 9: Acute HE. DWI displaying extensive symmetrical gyral edema which
characteristically involves the insular cortex (arrow) and cingulate gyrus (arrowhead);
and, typically spares the perirolandic and occipital cortex (dotted arrow).
Page 13 of 110
Diffuse cortical involvement although can be reversible; often has a higher

potential for neurologic sequelae [21]. Concomitant subcortical white matter,
basal ganglia, thalami, and brain stem involvement suggests more severe
injury [19].
The MRI extent of cortical involvement on FLAIR and DWI has been shown
to strongly correlate with the maximal plasma ammonia level, and plasma
ammonia level correlates well with the clinical outcome. However MRI
severity correlates only moderately with the clinical outcome [21, 22].
On proton MR spectroscopy: an elevated glutamine/glutamate peak coupled

with decreased myo-inositol and choline signals, representing disturbances
in cell-volume homeostasis secondary to brain hyperammonemia, constitute
the characteristic imaging manifestations of HE.
Follow-up MR imaging may show diffuse cortical atrophy with T1 high

signals, involving both basal ganglia and temporal lobe cortex, representing
cortical laminar necrosis (chronic stage of HE) (Fig 10) [19].
Fig. 10: Chronic HE. Axial T1-WI showing cortical atrophy with gyriform T1hyperintensity representing cortical laminar necrosis in a follow-up case of liver
cirrhosis with recurrent episodes of grade-3 HE in the past.
As opposed to cortical laminar necrosis of chronic HE, cortical laminar

necrosis of hypoxic brain damage preferentially involves the watershed
Page 14 of 110
zones or the parieto-occipital regions (as opposed to the temporal lobe

cortices) [19].
It is important to note that although pallidal (T1-WI) hyperintensities are

found in approximately 90% of patients with cirrhosis, these signal-intensity
alterations are not closely linked to the presence of HE.
Patients with cirrhosis and no clinical, neuropsychological, or

neurophysiologic signs of HE can also show severe signal-intensity
alterations, whereas others with manifest HE may present only slight signalintensity alterations.
ACQUIRED HEPATOCEREBRAL DEGENERATION
Acquired (non-Wilsonian) hepatocerebral degeneration (AHD) is a rare

chronic progressive debilitating neurologic syndrome that occurs in patients
with chronic liver disease associated with multiple metabolic insults [23, 24].
The pathophysiology and the locations of the cerebral injuries

are incompletely understood and are not necessarily related to
hyperammonaemia. However, cerebral deposition of manganese may have
a pathogenetic role [25, 26].
AHD occurs in approximately 1% of patients with liver cirrhosis and seems

related to portosystemic shunts [23].
Clinically, it is characterized by a combination of parkinsonism and

cerebellar signs, with neuropsychiatric changes and movement disorders
usually being prominent clinical manifestations [23-26].
The syndrome is poorly responsive to medical (antiparkinsonism drugs)

therapy, thus being considered largely irreversible [25].
MR imaging reveals pallidal and extrapallidal lesions in most patients,

probably reflecting intracerebral deposits of manganese [23, 24].
In addition to T1-weighted hyperintensities in the globus pallidus, up to 75%

patients also exhibit extrapallidal involvement in the form of T2-weighted
hyperintensities involving the brachium pontis (middle cerebellar peduncles)
and subcortical white matter (Fig 11) [23, 24].
Page 15 of 110
Fig. 11: A 50-year old liver cirrhosis patient developed cognitive deficits, ataxia,
dysarthria, movement disorders, and features of parkinsonism. MR images reveal
symmetrical T1-hyperintensity of the basal ganglia (A) with attendant T2-hyperintense
changes involving the bilateral middle cerebellar peduncles (B). Imaging findings in the
light of the clinical details are in keeping with acquired hepatocerebral degeneration.
The increased signal intensity in the middle cerebellar peduncles or dentate

nuclei bilaterally on T2-weighted images is often indistinguishable from
Wilson disease [23-27].
Since the clinical symptoms, neuropathological features and MR imaging

appearances of AHD are almost similar to those seen in Wilson disease, so
it is also named pseudo-Wilson disease [27].
The discrimination depends on the following aspects: (1) Age: Wilson

disease is a genetic disease that rarely starts after the third decade,
whereas AHD occurs in those with severe liver disease of many causes
at different ages. (2) Copper metabolism: copper metabolism in Wilson's
disease is out of balance so that overload copper deposits in the liver, brain,
kidney, cornea, etc, while the copper metabolizes normally in patients with
AHD. (3) Wilson disease is characterized by Kayser-Fleischer ring of the
cornea which is typically absent in AHD [27].
CIRRHOSIS-RELATED PARKINSONISM
Page 16 of 110
Rapidly progressing parkinsonian symptoms, which are unresponsive to

treatment of hepatic encephalopathy, indicate cirrhosis-related Parkinsonism
[28].
Cirrhosis-related Parkinsonism was diagnosed in 9 of 214 patients (4.2%)

in a recent study by Tryc et al. In 2 patients, cirrhosis-related Parkinsonism
was associated with hepatic myelopathy [28].
The presence of significant porto-systemic shunts is considered a

precondition for the development of Parkinsonism in patients with cirrhosis.
Moreover, the observation of an increased manganese deposition in the
basal ganglia of patients with liver cirrhosis and its relationship to the degree
of porto-systemic shunting has pointed to a possible role of manganese
neurotoxicity [28-32].
The aforementioned hypothesis is supported by the observation that

cirrhosis-related Parkinsonism and dystonia could be effectively treated
with chelating agents, and by reports which have shown an improvement of
extrapyramidal symptoms after successful liver transplantation in parallel to
the disappearance of cerebral MRI signal alterations ascribed to manganese
deposition [28-32].
MR T1-weighted images show characteristic hyperintensity of the basal

ganglia including the globus pallidus, putamen, and caudate, subthalamic,
and dentate nuclei with sparing of the thalamus and ventral pons (Fig
12). When the disease is extensive, white matter and anterior pituitary
involvement can be present [32].
Page 17 of 110
Fig. 12: Symmetrical T1-hyperintensity can be seen involving the basal ganglia (A, B),
cerebral peduncles (C), and the dorsal aspect of pons (D) in a patient of liver cirrhosis
presenting with features of parkinsonism.
On T2-weighted images the changes may be appreciated, however, to a

much lesser extent. More often than not they are reported as normal on T2WI [32].
It has been shown that normalization of manganese blood levels improves

the findings on brain MRI [33].
CIRRHOTIC or HEPATIC MYELOPATHY
Page 18 of 110
Hepatic or cirrhotic myelopathy is a rare complication of chronic liver disease

that is associated with extensive portosystemic shunts [34, 35].
The main clinical feature of hepatic myelopathy is progressive spastic

paraparesis in the absence of sensory or sphincter impairment. Typically,
a patient with underlying chronic liver disease, develops progressive pure
motor spastic paraparesis with minimal or no sensory deficit and without
bowel and bladder involvement [34].
The exact pathogenesis of HM is still unclear. However, it has been

hypothesized that the hepatocerebral dysfunction secondary to recurrent
episodes of hepatic encephalopathy, and prolonged exposure to bypassed
nitrogenous waste (ammonia, fatty acids, indoles, and mercaptans) cause
myelin damage resulting in the pathological white matter demyelination in
the brain and the spinal cord (Fig 13) [35].
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Fig. 13: A 50-year old male patient with hepatic myelopathy. MR spine failed to
depict any overt intramedullary signal alteration; however, screening of brain revealed
symmetrical hyperintensity along the bilateral corticospinal tracts.
Neuropathological studies show demyelination in the corticospinal tracts with

varying degrees of axonal loss. The selective predisposition for the motor
system has been demonstrated by involvement of the lateral corticospinal
tracts in autopsy studies [35].
Motor-evoked potential studies may be suitable for the early diagnosis of

hepatic myelopathy, even in patients with preclinical stages of the disease
[34-37].
Early and accurate diagnosis of hepatic myelopathy is important because

patients with early stages of the disease can fully recover following liver
transplantation [34-36].
Hepatic myelopathy remains a default diagnosis assigned only after the

exclusion of other causes of spastic paraparesis and partial transverse
myelopathy. Accordingly, a detailed and accurate history along with
appropriate imaging and laboratory findings remain crucial for establishing
the diagnosis [37].
Imaging features include increased signal intensity in lateral pyramidal tracts

in the cervical cord and caudally, on T2-weighted MRI. However, many a
times MR may not reveal any abnormality yet the motor-evoked potential
studies may indicate corticospinal electrophysiologic abnormalities [34-38].
Motor-evoked potential studies thus play a pivotal role for diagnosing and
monitoring disease progression and response to treatment [38].
In contrast to hepatic encephalopathy, hepatic myelopathy does not

respond to blood ammonia lowering therapies but must be considered as an
indication for urgent liver transplantation [6].
CIRRHOSIS-RELATED INTRACEREBRAL HEMORRHAGE
Spontaneous intracerebral hemorrhage (ICH) accounts for 10-15% of all

cases of stroke and systemic hypertension, elderly age group and alcohol
consumption constitute the most important risk factors [39, 40, 44].
Page 20 of 110
The risk for development of ICH in patients with liver cirrhosis is debatable;
nonetheless, various studies have proposed that liver cirrhosis is a risk
factor for ICH [39-44].
Chronic liver disease is a risk factor for ICH primarily due to impaired
coagulation. Coagulopathy in patients with liver disease results from
impairments in the clotting and fibrinolytic systems, as well as from reduced
number and function of platelets (Fig 14, 15) [41].
Fig. 14: Unenhanced CT in a liver disease patient with deranged coagulation profile
shows a large intraparenchymal hematoma (thick white arrow) in right frontal lobe with
contiguous extension into the ipsialteral ventricle (dotted arrow). In addition, there is
synchronous contralateral intracerebral bleed seen in the left frontal region (thick black
arrow). Furthermore, there is evidence of extra-axial bleed that can be seen along the
interhemispheric fissure (thin black arrow).
Page 21 of 110
Fig. 15: Infratentorial bleed in a delirious patient with decompensated liver cirrhosis.
Axial CT sections reveal a large hematoma involving the cerebellar vermis (arrow)
causing compression and effacement of the fourth ventricle with upstream obstructive
ventriculomegaly (arrowhead). The cerebral sulci are effaced and the cortico-medullary
junction indistinct (asterisk) suggesting raised intracranial pressure.
Huang et al recently reported an overall incidence of 0.8% in a retrospective

study of 4515 patients with liver cirrhosis. The incidence in the alcoholrelated group was 1.9% whereas the virus-related group had an incidence
of 0.3%. A combined group (patients with both virus- and alcohol-related
cirrhosis) had an incidence of 3% [39].
The relation between high alcohol intake and ICH may involve several
mechanisms among which alcohol-induced hypertension and coagulation
disorders are speculated to be the most likely etiological factors [41].
INFECTIVE COMPLICATIONS OF CIRRHOSIS
Cirrhosis has been characterized as the commonest acquired

immunodeficiency syndrome worldwide (exceeding even AIDS) and
infectious complications in cirrhotic patients can cause severe morbidity and
mortality [45, 46].
Page 22 of 110
Bacterial infections have been acknowledged as an important factor in

disease mortality and are estimated to cause up to 25% of deaths in cirrhotic
patients [45, 46].
The specific risk factors for infection in cirrhotic patients are low serum
albumin, gastrointestinal bleeding, repeated intensive care unit admissions
for any cause, and therapeutic endoscopy [45].
Certain infectious agents that are more virulent and more common in
patients with liver disease include Vibrio, Campylobacter, Yersinia,
Plesiomonas, Enterococcus, Aeromonas, Capnocytophaga, and Listeria
species, as well as organisms from other species [45].
Changes in gut motility, mucosal defense and microflora allow for

translocation of enteric bacteria into the blood stream (bacteremia).
Additionally, the cirrhotic liver is ineffective at clearing bacteria and
associated endotoxins from the blood thus allowing for seeding of the sterile
peritoneal fluid [47].
Compared to the general population, the mortality of infections is more than

20 times increased in cirrhosis. The incidence of bacteremia, peritonitis,
urinary tract infection, pneumonia, meningitis, and tuberculosis is increased
more than tenfold, and the mortality of each episode 3-10 times higher [48].
Liver cirrhosis patients are at increased risk of bacterial meningitis and often
have a poor prognosis (Fig 16) [49, 50].
Molle et al in a nation-wide cohort of 22,743 patients (with liver cirrhosis

in Denmark) reported an incidence rate of bacterial meningitis of 54.4 per
100,000. The highest incidence rate was found in patients with alcoholic
cirrhosis, 65.3 per 100,000 person-years. The 30-day case fatality rate
was 53.1% (95% CI 38.3-67.5), and high age and alcoholic cirrhosis were
associated with the highest case fatality rates [50].
Page 23 of 110
Fig. 16: Pyogenic meningitis and ventriculitis in a 42-year old patient with NASH
related liver cirrhosis. Post gadolinium T1-WI reveals inflammation, thickening and
abnormal enhancement of the right lateral ventricle ependyma (A, B) and choroid
plexus (C) in keeping with ventriculitis and choroid plexitis. In addition, abnormal
leptomeningeal enhancement can be seen along the right mesial temporal lobe (D) in
keeping with leptomeningitis.
The main bacterial pathogens include Streptococcus pneumoniae,

Escherichia coli, Listeria, and unspecified bacteria [49-51].
Often, nuchal rigidity may be a delayed or even absent clinical sign. Also,
the initial presentation of brain abscess may not be fever or leukocytosis, but
focal neurologic deficits [49-51].
Page 24 of 110
Mortality may reach 80% in patients with Child-Pugh stage C cirrhosis [49,
50].
Fig. 17: Miliary tuberculosis in a middle aged liver cirrhosis patient with history of
longstanding alcohol abuse. Contrast enhanced T1-WI shows multiple pinhead sized
enhancing granulomas randomly scattered in the bilateral cerebral hemispheres.
Lastly, intracranial tuberculosis should also be kept in mind when confronted

with brain space-occupying lesions in the immunocompromised or
malnutritional hosts such as liver cirrhosis (Fig 17) [52].
DIFFUSE CEREBRAL EDEMA IN ACUTE or ACUTE-ON-CHRONIC LIVER FAILURE

Page 25 of 110
Cerebral edema is very common in patients with fulminant or acute liver

failure. In severe cases, this can lead to potentially fatal herniation [53].
Whilst the primary cause of death in patients with acute liver failure (ALF) is
multi-organ failure; cerebral edema and ensuing brain herniation constitute a
major cause of mortality [54].
Brain swelling in acute liver failure is produced by a combination of

cytotoxic (cellular) and vasogenic edema [53-55]. Although cytotoxic edema
appears predominant event leading to cerebral edema, vasogenic edema
presumably represents secondary event causing intracranial hypertension
[56].
Cytotoxic brain edema is presumably secondary to astrocytic accumulation

of glutamine, whilst vasogenic edema represents an increase in cerebral
blood volume and cerebral blood flow, in part due to inflammation to
glutamine and to toxic products of the diseased liver [54-56].
Astrocyte swelling has been demonstrated to be the commonest histological

feature in patients with ALF [56].
Ranjan et al have demonstrated significantly lower apparent diffusion

coefficient in cortical and deep white and gray matter regions of interest
(on MRI performed in patients with ALF) compared to controls (p < 0.001),
suggesting cytotoxic cell swelling as the primary cause of cerebral edema
[57].
The most accurate method of diagnosing cerebral edema is intracranial

pressure monitoring [54].
CT & MR imaging is valuable not only to visualize signs of cerebral edema

which include sulcal and cisternal effacement, loss of distinction between
the grey and white matter and indistinct boundaries of the lenticular nucleus,
but, also for excluding hemorrhagic complications as most of these patients
are coagulopathic (Fig 18, 19) [53].
Page 26 of 110
Fig. 18: Diffuse cerebral edema in a patient with acute on chronic (Hepatitis-B and C
related)liver failure. Noncontrast CT shows effaced sulci with loss of cortico-medullary
differentiation and indistinct margins of the lenticular nuclei suggesting diffuse cerebral
edema and raised intracranial tension.
Page 27 of 110
Fig. 19: Fulminant hepatic failure. T2W MR imaging reveals effaced cerebral
sulci with slit-like ventricles (A, B) and diffuse gyral swelling (C, D) in keeping with
diffuse ceerbral edema. The cisternal spaces are also effaced suggesting impending
herniation (C, D).
Although CT and MR imaging have been traditionally considered unreliable

for the diagnosis of intracranial hypertension (owing to their poor correlation
with intracranial pressure); nonetheless, if interpreted carefully they can
provide pivotal information [53, 58, 59].
Also, cross sectional imaging is effective at establishing the diagnosis

of cerebral herniation, which will guide important decisions regarding
therapeutic options and prognosis (Fig 20).
Page 28 of 110
Fig. 20: (A, B) Sagittal and axial T2-WI show bilateral medial part of the temporal
lobes protruding over the tentorial edge in keeping with uncal herniation (black arrows).
In addition, there is downward cerebellar herniation (tonsillar herniation or coning) seen
in this patient of fulminant hepatic failure. The patient was subsequently declared brain
dead and succumbed to the disease.
Therapeutic measures proposed to control intracranial hypertension in liver

failure patients mainly include administration of mannitol, hypertonic saline,
indomethacin, thiopental, and hyperventilation [53-56].
ALCOHOL-RELATED NEUROLOGICAL DISORDRES
The pathogenesis of alcohol#related neurological damage has been

considered to be multifactorial and attributed to genetic predisposition,
nutritional factors, and the neurotoxic effects of ethanol or its metabolites
[60, 61].
Alcohol related neurological disorders that may complicate alcohol related

liver disease may range from Wernicke's encephalopathy, hepatocerebral
degeneration, head trauma, central pontine myelinolysis, MarchiafavaBignami syndrome to ethanol neurotoxicity [61, 62].
OSMOTIC DEMYELINATION SYNDROMES
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Adams and colleagues in 1959 described central pontine myelinolysis

(CPM) as a disease affecting alcoholics and the malnourished [63].
The concept was extended from 1962 with the recognition that lesions
can occur outside the pons, so-called extrapontine myelinolysis (EPM). In
1976 a link between these disorders and the rapid correction of sodium
in hyponatraemic patients was suggested, and by 1982 substantially
established [64].
The association with alcoholism was the first to be noted and continues
to be particularly frequent (in up to 40% of cases). It has been suggested
that alcohol itself interferes with sodium/water regulation by suppression of
antidiuretic hormone, and inadequate nutrition of alcoholics is an obvious
accompaniment [64-66].
CPM is also a recognized complication of liver transplantation. In a 10 year

retrospective series of 627 transplants it occurred in 2% of cases (and
contributed to the overall neurological complication rate of 26%) [64, 65].
Clinically, whenever a patient who is gravely ill with alcoholism and

malnutrition or a systemic medical disease develops confusion, quadriplegia,
pseudobulbar palsy, and pseudo coma ('locked-in syndrome') over a period
of several days, a diagnosis of osmotic demyelination (CPM) should be
considered [64].
Radiological confirmation is necessary to exclude other diagnosis

and to determine the exact extension of the demyelination. Since CT
can underestimate the real extension MRI plays a pivotal role in the
determination of the presence, number and extension of the lesions [65].
In acute CPM, MRI shows signal alteration in the central pons with sparing
of the tegmentum, ventrolateral pons and corticospinal tracts (Fig 21, 22).
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Fig. 21: Central pontine myelinolysis. Sagittal T2-WI shows relatively bulky appearing
pons with attendant signal intensity changes (black arrow) in a 48-year old patient with
alcoholic liver cirrhosis.
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Fig. 22: (A, B) Axial Fast FLAIR and T2-WI of the aforementioned patient shows
hyperintensity involving the central pons with characteristic sparing of the periphery.
Careful evaluation suggests that there is predominant involvement of the transverse
pontine fibres - finding which is quite characteristic of CPM.
In EPM, symmetric signal alterations can be seen in the basal ganglia,

thalami, lateral geniculate body, cerebellum, and cerebral cortex (Fig 23)
[66].
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Fig. 23: Extra-pontine myelinolysis. Axial FLAIR images showing extra-pontine areas
of signal alteration (demyelination) involving the left thalamus (white arrow) and the
right cerebellar hemisphere (black arrow) in a malnourished chronic alcoholic male
patient with decompensated liver cirrhosis.
About 25-50% of patients with CPM also have EPM; this usually affects
the cerebellum but may also affect parts of the cerebrum. In up to 25% of
patients the demyelination is exclusively extrapontine [67].
WERNICKE ENCEPHALOPATHY
Wernicke encephalopathy (WE) is a neurologic emergency caused by a

thiamine deficiency. It is commonly seen in the alcoholic population but can
also be seen with malignancy, total parenteral nutrition, abdominal surgery,
hyperemesis gravidarum, hemodialysis, or any situation that predisposes an
individual to a chronically malnourished state [66].
If untreated, irreversible brain damage may ensue and could even lead to
coma, death, or Korsakoff syndrome, a permanent brain injury that results
in antegrade amnesia and confabulation. The classic triad of WE includes
ataxia, global confusion, and opthalmoplegia.
CT has been shown to have a low sensitivity for the detection of WE, and
when findings are present, they are often nonspecific areas of low density
[66].
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Fig. 24: Wernicke encephalopathy. Axial T2-WI showing confluent areas of increased
intensity surrounding the aqueduct and the third ventricle in a debilitated and
malnourished patient of alcohol induced liver cirrhosis complaining of ataxia and
opthalmoplegia.
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Fig. 25: Coronal T2-WI showing bilateral areas of increased intensity surrounding the
aqueduct and the third ventricle contiguously extending into the mamillary bodies.
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Fig. 26: Fast FLAIR images of the same patient showing symmetrical signal
alterations at characteristic sites including periventricular region of the third ventricle,
periaqueductal area, thalamus, and mamillary bodies.
On MRI, typical manifestations include symmetrical areas of increased T2and FLAIR signal intensity surrounding the aqueduct and the third ventricle,
at the floor of fourth ventricle, in the medial thalami, and in the capita of
caudate nuclei (Fig 24-26) [66].
MR spectroscopy (MRS) may depict lactate peak and low levels of Nacetylaspartate (N-NAA)/creatine (Cr) in the affected areas but does not
have a clinical prognostic impact [66].
MARCHIAFAVA-BIGNAMI DISEASE (MBD)
MBD is a rare disorder that results in progressive demyelination and

necrosis of the corpus collosum. MBD is generally associated with chronic
alcohol abuse but is occasionally seen in nonalcoholic patients. MBD is most
prevalent in men between 40 and 60 years of age [66].
The main pathologic change associated with MBD is degeneration of the

corpus callosum, which may vary from demyelination to frank necrosis.
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The disease may present in two major clinical forms: acute and chronic.
In the acute form, which often results in death, patients present with
severe impairment of consciousness, seizures, and muscle rigidity. The
chronic form of the disease may last for several months or years and is
characterized by variable degrees of mental confusion, dementia, and
impairment of gait.
CT shows diffuse periventricular low density and focal areas of low density
in the genu and splenium of the corpus callosum. On MRI, there is high
T2-and FLAIR signal intensity changes involving the body of the corpus
callosum, genu, splenium, and adjacent white matter. These appear
hypointense on T1-WI and during the acute phase, may show peripheral
contrast enhancement [66].
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Fig. 27: Sagittal T2-WI in a chronic alcoholic male showing relatively atrophic posterior
body of the corpus callosum (white arrow) with focal area of signal alteration within the
splenium (black arrow). In addition, note is made of disproportionate cerebellar atrophy
(arrowhead) - likely representing alcoholic cerebellar degeneration.
As the disease progresses, signal alterations become less evident, but

residual atrophy of the corpus callosum is usually observed (Fig 27). MBD
may be found in association with other alcohol-related diseases, including
WE, Korsakoff syndrome, and central pontine myelinolysis [66].
ALCOHOL WITHDRAWAL SYNDROME (AWS)
Alcohol withdrawal syndrome (AWS) is a constellation of symptoms

observed in a person who stops drinking alcohol after a period of continuous
and heavy alcohol consumption [66].
In AWS, disturbances in cognition, perception hallucinations, visual

impairment, nausea, and tinnitus are thought to relate to cortical dysfunction.
Tremor, sweating, depression, and anxiety are related to effects on the
limbic system. Changes in consciousness and gait disorders are associated
with brainstem involvement.
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Fig. 28: Axial FAST FLAIR image in a liver cirrhosis patient with auditory hallucinations
following alcohol withdrawal showing subtle symmetrical bi-temporal hyperintensity
(arrows).
In alcoholics with withdrawal seizures, MRI depicts cytotoxic edema in

temporal regions during the acute and subacute phases and significant
volume loss (Fig 28). It could therefore be deduced that epileptic seizures
affect alcoholic subjects similarly to temporal epilepsy, in which reversible
edema with some volume loss and consequent hippocampus atrophy is
observed [66].
Reversible vasogenic edema in the cerebellum; thalami; and cortical,

subcortical, and deep parietal white matter has also been described
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in the clinical setting of posterior reversible encephalopathy syndrome

complicating alcohol withdrawal [66].
ALCOHOLIC COGNITIVE DECLINE AND CEREBRAL ATROPHY
Approximately 50 - 70 % of alcohol abusers have cognitive deficits on

neuropsychological testing. Imaging tests, neuropathological observations,
and animal studies suggest that ethanol neurotoxicity may contribute to this
cognitive dysfunction [68-70].
Nevertheless, there is no unequivocal evidence for a brain lesion in humans

that is caused solely by chronic ethanol ingestion and that is unrelated to
coexisting nutritional deficiency, liver disease, or trauma.
CT and MRI show enlargement of the cerebral ventricles and sulci in the
majority of alcohol abusers. There is evidence for regional vulnerability
in the brains of alcohol abusers with frontal lobe changes being the most
pronounced (Fig 29).
Neuronal density in the superior frontal cortex was reduced by 22 percent

in alcohol abusers compared with nonalcoholic controls in one report.
Selective loss of neurons in frontal brain regions is mirrored by regional
hypometabolism on PET studies, and might correlate with deficits in working
memory observed in alcohol abusers [68-69].
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Fig. 29: Axial FLAIR and T2WI showing selective bi-frontal cerebral atrophy in a 36year old chronic alcoholic male patient with underlying liver cirrhosis.
Quantitative morphometry suggests that alcohol abusers, including

those with liver disease and Wernicke encephalopathy (WE), lose a
disproportionate amount of subcortical white matter compared with cortical
gray matter [68, 69].
The loss of cerebral white matter is evident across a wide range of ages,
and is of sufficient magnitude to account for the associated ventricular
enlargement. Diffusion-tensor imaging detects microstructural abnormalities
in the white matter tracts of alcohol abusers even in the absence of
macroscopic lesions.
MRI imaging of alcohol abusers shows an increase in white matter volume

following three months of abstinence, suggesting that a component of the
white matter injury is reversible.
ALCOHOLIC CEREBELLAR DEGENERATION
Besides the frequently reported effects of ethanol on supratentorial brain,

cerebellar involvement is also commonly observed in chronic alcoholics [71,
72].
Alcoholic cerebellar degeneration typically occurs after 10 or more years of

alcohol abuse. These chronic ethanol abusers develop a chronic cerebellar
syndrome related to the degeneration of Purkinje cells in the cerebellar
cortex.
Midline cerebellar structures, especially the anterior and superior vermis are
predominantly affected [71, 72].
Symptoms, primarily related to gait disturbance, usually develop gradually

over weeks to months, but it may also evolve over years or commence
abruptly.
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Fig. 30: Alcoholic cerebellar degeneration. DIffuse cerebellar atrophy is seen in the
form of cerebellar foliar prominence, ventricular enlargement and prominence of the
infratentorial subarachnoid CSF spaces in a 44-year old male cirrhotic with history of
chronic alcohol abuse.
CT or MRI scans typically show cerebellar cortical atrophy, however, onehalf of alcoholic patients with this finding may not be ataxic on examination.
In addition, a structural imaging study is also required to exclude mass
lesions or other diagnoses (Fig 30) [71, 72].
The absence of cranial nerve abnormalities differentiates alcoholic

cerebellar degeneration from vascular disorders of the posterior circulation,
mass lesions, and demyelinative disease. The age of onset and clinical
course sets this disorder apart from some of the spinocerebellar ataxias.
Multiple systems atrophy, including olivopontocerebellar degeneration, may
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be difficult to distinguish on clinical grounds alone and require corroboratory

imaging studies.
WILSON DISEASE-RELATED NEUROIMAGING MANIFESTATIONS
Wilson disease is an uncommon, autosomal recessive, inborn defect in

copper metabolism characterized by abnormal accumulation of copper in
various tissues, particularly in the liver and the brain [73].
In Wilson disease, ceruloplasmin, the serum transport protein for copper, is

deficient. Copper accumulates in the tissues of patients primarily in the liver
and later in the brain.
Despite the ubiquitous presence of toxic copper within the brain, pathologic
findings are limited primarily to the basal ganglia, thalamus, and brain
stem. The initial neurological presentations frequently include dysarthria
and tremors, with later manifestations of neuropsychiatric problems, and
Parkinsonian tremors, ataxia, dystonia, and chorea.
The most frequently identified abnormality on MR imaging was bilateral

symmetric high signal intensity in the putamen on T2-weighted images,
followed by the caudate nucleus, globus pallidus, thalamus, midbrain (Fig
31) [73, 74].
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Fig. 31: Axial T2-WI in a patient with Wilson disease depicting symmetrical increased
signal intensity of the bilateral lentiform nuclei (ahite arrow), thalami (black arrow) and
caudate nuclei (arrowhead).
References: Image reproduced from: Arora A et al. Intracranial MR manifestations
of Wilson disease. Poster no. C-1518 on EPOS (ECR 2011). DOI: 10.1594/ecr2011/
C-1518
Diffusion-weighted images can show areas of restricted diffusion early in the

disease process due to cytotoxic edema or inflammation due to excessive
copper deposition (Fig 32). However, this restricted diffusion is not seen in
chronic cases [73].
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Fig. 32: DWI in a patient with Wilson disease depicting diffusion restriction involving
the lentiform and caudate nuclei (hepatolenticular degeneration) during the acute
phase of the disease.
C-1518
Hypointensity on T2-weighted images can be seen sometimes, secondary to

copper deposition or iron deposition (Fig 33) [73].
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Fig. 33: Axial T2WI (A) and T2*GRE (B) showing hypointense signal and blooming
reflecting heavy metal deposition in the lentiform nuclei in a patient of Wilson disease.
High-signal-intensity lesions in the basal ganglia on T1-weighted images

reflects hepatic involvement of Wilson disease-namely, chronic liver disease
or liver cirrhosis; and, is often the most common initial abnormality detected
(Fig 34).
Fig. 34: Symmetrical increased T1-signal intensity involving the lentiform nuclei in a
patient of Wilson disease.
C-1518
Diffuse brain atrophy suggests a generalized susceptibility and longstanding

effect of the central nervous system to copper intoxication.
'Face of the Giant Panda' is an uncommon intracranial manifestation of

Wilson's disease which was first described by Hitoshi et al in 1991. This
appearance is caused by a combination of signal intensity changes at
the level of midbrain on T2-WI. These include: high signal intensity in the
tegmentum, normal signals in the red nuclei and lateral portion of the pars
reticulata of the substantia nigra, and hypointensity of the superior colliculus
(Fig 35) [73, 74].
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Fig. 35: (A, B) Giant panda sign in a young patient of Wilson disease. (C) The sign
is due to a combination of high signal intensity in the tegmentum (black arrow) with
sparing of the red nuclei (dotted arrow), pars reticulate (white arrow) and the superior
colliculi (arrowhead).
C-1518
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Fig. 36: Giant panda cub. Axial T2WI in a patient of Wilson disease depicting signal
alteration in the dorsal pons simulating the face of a giant panda - popularly referred to
as 'giant panda cub' sign.
C-1518
The exact pathogenesis of this SIGN is not known, but it is postulated that
the paramagnetic effects of the deposition of heavy metals, such as iron
and copper, may be responsible. It is believed that iron is assumed to play
a more important role than copper in reducing the signal intensity of the
superior colliculi on the T2-weighted scan. At times, signal alteration may
also be encountered within the dorsal pons which has been popularly called
as 'Giant Panda Cubs' (Fig 36) [74].
HCV-RELATED CNS COMPLICATIONS
Chronic infection with hepatitis C virus (HCV), a hepatotropic and

lymphotropic agent, is a growing global health issue affecting an estimated
170 million people [75].
Neurological complications occur in a large number of patients and the

speculative pathogenetic mechanisms responsible for nervous system
dysfunction are mainly related to the upregulation of the host immune
response with production of autoantibodies, immune complexes, and
cryoglobulins [75].
HCV-related CNS complications encompass a wide spectrum of disorders

ranging from cerebrovascular events to autoimmune syndromes [75-79].
ACUTE CEREBROVASCULAR EVENTS: including ischemic stroke,

transient ischemic attacks, lacunar syndromes (Fig 37), or rarely
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hemorrhages (secondary to occlusive vasculopathy and vasculitis), have

been reported, being the initial manifestation of HCV infection in some cases
[75, 76].
Fig. 37: Transient ischemic attacks in a 39-year old patient with chronic (hepatitisC related) liver disease. DWI reveals multiple acute lacunar infarcts involving the left
pareito-temporal and right cerebellar hemisphere - possibly secondary to occlusive
vasculopathy or vasculitis.
ACUTE OR SUBACUTE ENCEPHALOPATHIC SYNDROMES: clinically

characterized by cognitive impairment, confusion, altered consciousness,
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dysarthria, dysphagia, and incontinence, have been associated with diffuse

involvement of the white matter in HCV chronically infected patients. An
ischemic pathogenesis of these rapidly evolving syndromes is supported by
MRI findings showing small lesions in subcortical regions and periventricular
white matter (Fig 38). Moreover, severe and diffuse infra- and supratentorial
white matter alterations, highly suggestive of vasculitis, are observed in
subjects with coincidental systemic vasculitis [75].
Fig. 38: A young 36-year old patient of hepatitis-C related liver cirrhosis and
progressive neurocognitive decline. Axial FAST FLAIR imaging reveals bilateral
multifocal patchy and confluent areas of subcortical white matter hyperintensities.
COGNITIVE DECLINE: slowly evolving cognitive decline, clinically

characterized by impairment of attention, executive, visual constructive,
and spatial functions, has been correlated to an increased occurrence of
periventricular white matter high intensity signals on T2-weighted MRI (Fig
39). White matter hyperinyensities likely reflect the occurrence of small
vessel disease, which leads to chronic hypoperfusion of the white matter
and local alteration of the blood-brain barrier [75].
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Fig. 39: A 45-year old male with (hepatitis-C) liver cirrhosis and rapidly progressive
dementia and neurocognitive decline. FAST FLAIR images reveal patchy and confluent
areas of signal alteration involving the periventricular as well as hemispheric white
matter.
ACUTE DISSEMINATED ENCEPHALOMYELITIS (ADEM): Sacconi and

Sim et al. have described ADEM, an autoimmune postinfectious CNS
disease, developing after HCV infection and responsive to steroid therapy,
further supporting the role of cellular immune mediated mechanisms in CNS
complications of HCV infection [77, 78].
MYELITIS: is an infrequent neurological complication in patients chronically

infected with HCV. HCV-related myelitis occurs acutely or subacutely, the
neurological presentation ranging from transverse myelitis to acute partial
transverse myelopathy, or spastic paraplegia; many patients present a
recurrent course and have a multisegmental spinal involvement at MRI,
usually at cervical and thoracic levels [75, 79].
LIVER TRANSPLANTATION-RELATED COMPLICATIONS

Neurologic complications are more common after liver transplantation than other
solid-organ transplants primarily due to the poorer clinical condition of liver disease
patients due to malnutrition, coagulopathy, electrolyte imbalance, and pre-transplant
encephalopathy. In addition, the highly complex and lengthy surgical procedure with
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major hemodynamic changes and blood/fluid shifts also predisposes these patients to
develop diverse neurological problems [80, 81].
POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME
Posterior reversible encephalopathy syndrome (PRES) is an increasingly

recognized neurological complication after transplantation with an overall
incidence of approximately 1% following liver transplantation [82, 83].
The syndrome is likely initiated by a leakage of fluid into the interstitium of

the brain tissue that is detected as vasogenic edema.
The exact pathophysiology is poorly understood but the widespread

vasoconstriction induced by calcineurin inhibitors (cyclosporine/ tacrolimus)
may lead microvascular damage with disruption of the blood-brain barrier,
increasing the risk of neurologic dysfunction posttransplant [82, 83].
Other vascular phenomena, such as hypertension with the failure of vascular

autoregulation and hyperperfusion, have also been implicated as the cause
of edema development in PRES.
Patients with a pre-liver transplant history of alcoholic liver disease are more
likely to develop PRES. Chronic alcohol presumably creates alterations in
cerebral blood flow and induce morphologic and biomechanical changes
in cerebral vessels resulting in more friability and less elasticity of blood
vessels which may influence cerebral blood flow distribution possibly
contributing to the development of PRES [82, 83].
Characteristic clinical findings include altered mental status, seizures, visual

abnormalities, and/or focal neurological deficits.
PRES is diagnosed radiologically, often by a distinguishing imaging pattern

involving the cortical or subcortical areas of the parietal or occipital lobes
(hence the name 'posterior').
CT or MR imaging typically show reversible vasogenic edema of the white

matter commonly in areas of parenchyma supplied by posterior circulation;
however, involvement of other areas such as frontal lobes, basal ganglia
and brain stem are also reported (Fig 40) [82, 83].
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Fig. 40: PRES in a post liver-transplant patient. Axial FAST FLAIR sequence
exhibiting cortico-subcortical areas of T2-hyperintensity in the parieto-occipital region.
Additionally concomitant hemorrhage can occur in up to 15% of patients with

PRES (Fig 41).
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Fig. 41: Axial T2*GRE image of the hitherto discussed patient with PRES showing
punctate areas of blooming in keeping with petechial hemorrhages in the left occipital
lobe.
If timely diagnosed, the patients experience a good recovery without

sequelae. Nevertheless, when unrecognized, PRES can progress to
ischemia or massive infarction with significant morbidity and mortality [82,
83].
IMMUNOSUPPRESSANT-RELATED LEUKOENCEPHALOPATHY
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A wide variety of neurologic side effects has been described with the use of
immunosuppressant drugs - most of them being minor (for e.g. headache,
tremor, paresthesia). However, immunosuppression-associated major
neurotoxicity such as leukoencephalopathy may develop in some post
transplant recipients [84-86].
Leukoencephalopathy syndrome is a neurologic complication caused

primarily by the neurotoxic effects of immunosuppressive agents on cerebral
white matter [84].
Tacrolimus and cyclosporine are lipophilic immunosuppressant agents that

cross the blood-brain barrier and are speculated to have a direct neurotoxic
effect especially on the lipid-rich white matter [85].
The reported incidence of leukoencephalopathy syndrome in liver transplant

recepients is 0.4% to 6% [84].
Time to onset of leukoencephalopathy syndrome in liver transplantation

tends to be shorter than in other organ transplantations, and in most cases,
it occurs within first three months of the transplantation [84].
Clinically, it is characterized by a reversible syndrome of headaches, sudden

onset of seizures, visual abnormalities, and hemiparesis [84-87].
The diagnosis of leukoencephalopathy requires either CT or MR imaging MR imaging indubitably has a higher sensitivity for delineating the pathology.
T2-WI MRI characteristically shows high-signal intensity involving the
occipital, parietal, and temporal white matter in a scattered fashion (Fig 42)
[84].
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Fig. 42: Immunosupressive leukoencephalopathy. A 56-year old post liver transplant

patient on tacrolimus complaining of unrelenting headaches and visual disturbances.
MR images show multifocal areas of white matter signal alteration involving the parietooccipital lobes and right fronto-parietal region appearing bright on T2WI (A) and dark
on T1WI (B).
Clinico-radiological differentiation from progressive multifocal

leukoencephalopathy (PML) can be challenging [84, 85]. A biopsy procedure
is usually not considered to be necessary to differentiate between the two
especially when after cessation or dose reduction of tacrolimus the clinical
condition improves.
PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY
Progressive multifocal leukoencephalopathy (PML), a progressive

demyelinating disease of the brain caused by JC virus (JCV), can be
seen following liver transplantation and other conditions associated with
immunosuppression [88].
Clinical course of PML is characterized by a rapid progressive neurological

decline (hemiparesis, visual field deficits, and cognitive impairment)
coinciding with the presence of white matter lesions on cross sectional
neuroimaging [89].
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In late stages of disease, patients can develop cortical blindness,

quadriparesis, severe dementia and even coma. Death usually occurs within
6 months of diagnosis [90].
MRI is undoubtedly more sensitive than CT in depicting the white matter

changes [89].
On MRI, PML lesions typically appear as hyperintense signal on T2weighted and FLAIR images (corresponding hypointense signal on T1-WI)
involving the subcortical white matter, devoid of contrast enhancement or
mass effect [88]. The lesions are multifocal albeit most commonly involve
the parieto-occipital white matter (Fig 43).
Fig. 43: Suspected PML in a 44 year old post liver transplant patient with
neurocognitive decline. Axial FLAIR images showing patchy and conflueent scattered
hyperintensities in bilateral parieto-temporal and frontal white matter.
The gold standard for the diagnosis of PML is a brain biopsy, although the
combination of a recent onset of neurological disease with white matter
lesions on MRI and a positive PCR for the JC virus in the CSF can confirm
the diagnosis in the absence of a brain biopsy [89].
PML is distinguished from immunosuppressant neurotoxicity by its rapid

radiological and clinical progression [91].
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There is no direct antiviral therapy available against the JC polyomavirus.

Restoration of the immune response achieved by tapering or terminating
the immunosuppressive regimen is the mainstay of treatment. However, the
prognosis remains extremely poor regardless of treatment [89].
CEREBROVASCULAR COMPLICATIONS
Cerebrovascular complications, including ischemic strokes and intracranial

hemorrhage, have been reported to be prevalent in 2-4% of liver transplant
recipients [92].
An increased risk of intracranial hemorrhage has been demonstrated in

patients with thrombocytopenia, old age, and overwhelming infections. That
risk is further compounded by coagulopathy associated with hepatic failure
(Fig 44) [92].
Fig. 44: Multifocal areas of bilateral intracerebral hemorrhage in a 56-year old post
liver-transplant patient.
Other less common causes of intracranial bleeding in post transplant

recipients include Aspergillus angiopathy and mycotic aneurysms.
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In addition, hypercholesterolaemia, diabetes, and hypertension secondary to

long term use of immunosuppressive therapy may also compound the risk of
cerebral bleeds.
Ischemic strokes are overall less common than intracranial hemorrhages,

and are often associated with similar risk factors as in general population,
including hypertension. Hepatic encephalopathy is also associated with
dysregulation of cerebral blood flow autoregulation (Fig 45) [92].
Fig. 45: Right middle cerebral artery (MCA) infarct. Axial T2WI (A) and DWI (B)
showing acute infarct with diffusion restriction involving the right temporal lobe in the
MCA territory.
Perioperative events, such as cerebral hypoperfusion and massive

transfusion, may also favor cerebrovascular injury.
Post anoxic cerebral ischemia is most commonly encountered following

cardiac arrest or cardiopulmonary resuscitation in which there has been
cessation of cerebral blood flow (Fig 46).
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Fig. 46: Anoxic-hypoxic ischemic encephalopathy following liver transplant (day-3).

DWI showing diffusion restriction and extensive gyral swelling involving the bilateral
cerebral hemispheres in a contiguous fashion.
Diffuse cortical (laminar) necrosis in the setting of acute anoxic insult (global
hypoperfusion) has a universally poor prognosis with most patients either
progressing to brain death or remaining in a persistent vegetative state [92].
POST-TRANSPLANT ENCEPHALOPATHY
Common causes of post-transplant encephalopathy in liver allograft

recipients include hepatic dysfunction, medication toxicity, infectious causes
(CNS infections or septic encephalopathy), complex metabolic disturbances
(uremia, CPM), cerebrovascular events or seizures.
Higher risk of encephalopathy has been reported in patients with history of

severe hepatic encephalopathy, alcohol-induced hepatic disease, metabolic
liver disease, greater severity of pre-transplant liver injury [92].
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Fig. 47: Severe hyperammonemic encephalopathy in a 35 year old post liver

transplant patient (post operative day 6). Axial FLAIR images showing extensive
cortical swelling and T2 prolongation especially along the insular cortices and cingulate
gyrus.
Delayed allograft function can precipitate hepatic encephalopathy with

clinical manifestations of ranging from subtle cognitive slowing and memory
difficulties, to somnolence, stupor and coma (Fig 47).
In addition, during early post-transplant period, a delayed arousal can

be related to persisting hepatic dysfunction, immunosuppressant related
neurotoxicity or intracerebral hemorrhage [92].
OPPORTUNISTIC INFECTIONS
Chronic immunosuppression increases the risk of opportunistic infection in

liver transplant recipients with an overall reported incidence of 5% [92].
The highest risk of developing a post transplant CNS infection is seen

between 1 - 6 months after transplantation.
Fungal and viral infections are the most common in post transplant
recipients, while bacterial and protozoic infections are less common.
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Exposure to infectious agents may stem from donor-related infections,

recipient-related infections, nosocomial infections and community infections.
Fungal CNS infections are usually associated with systemic fungal

infections, and may also extend locally following fungal sinusitis (Fig 48)
[92].
Fig. 48: Post-transplant invasive fungal sinusitis, orbital cellulitis & meningitis in a 26
year old female. Axial CT section showing destruction of the lamina papyracea (white
arrow) with extension of the fungal elements into the right orbit with attendant orbital
cellulitis (asterisk).
Candida is the most common fungal infection after liver transplantation, but
CNS infections caused by Candida species are rare.
Most common fungal CNS infections are caused by Cryptococcus

neoformans and Aspergillus species [92].
Increased risk of CNS aspergillosis has been reported after liver

retransplantation. Vasoinvasive CNS fungal infections (e.g., Aspergillus
species) are often associated with hemorrhagic strokes.
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Fig. 49: Invasive mucormycosis. Post liver-transplant patient with invasive fungal
sinusitis (asterisk) invading the left orbit (star) and ipsilateral cavernous sinus (white
arrow) with contiguous extension into the left peri-mesencephalic cistern (arrowhead).
References: Dr Rajiv Gupta, Radiology, Medanta, The Medicity, Gurgaon, India
Opportunistic bacterial CNS infections are relatively less common after liver
transplantation but the risk may be increased with environmental exposure.
Toxoplasmosis is the most common protozoal infection in transplant

recipients.
Neuroimaging, spinal tap after excluding increased intracranial pressure,

and a search for signs of systemic infection are the core of diagnosis. Brain
biopsy may be warranted in selected cases [92, 93].
OSMOTIC DEMYELINATION
Up to 1-2% of liver transplant recipients may develop osmotic demyelination

(pontine or extrapontine) [66, 92].
Relatively high prevalence of central pontine (CPM) or extrapontine

myelinolysis (EPM) in the early period after liver transplantation is
probably attributable to large fluid shifts, similarly as in rapid correction of
hyponatremia [92].
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Fig. 50: Central pontine myelinolysis in a post liver transplant patient. Axial FLAIR
image showing predominant involvement of the transverse pontine fibres (white arrow)
with characteristic sparing of the descending corticospinal tracts (asterisk). Note
the peripheral pontine fibers (black arrow) are also spared - hence the term 'central'
pontine myelinolysis.
Due to massive fluid shifts in early posttransplant period, the risk of CPM/
EPM is also higher in first 48 h after transplantation (Fig 49).
In addition, higher risk of has been reported in patients with preoperative

hyponatremia and worse liver dysfunction [92, 93].
POSTTRANSPLANTATION LYMPHOPROLIFERATIVE DISORDER
Lymphoma is the commonest cerebral brain tumor seen in transplant

recipients; and, the CNS may be the primary site of involvement or
associated with systemic posttransplantation lymphoproliferative disorder
(PTLD) [94].
Majority of the PTLD cases are associated with Epstein-Barr virus (EBV)
infection and occur a few years following solid organ transplantation.
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Intracranial involvement is more often parenchymal than leptomeningeal

[94].
On imaging, the lesions tend to be multiple (often periventricular) and often

show avid enhancement.
Differentiation from toxoplasmosis may be challenging. However, an

increased uptake on single-photon emission CT (SPECT) may be useful to
differentiate the two entities [94].
Images for this section:
Fig. 2: Symmetrical T1-hyperintensity involving the bilateral globus pallidus (arrows) in

an asymptomatic 54-year old male with hepatitis-B related liver cirrhosis.
Page 65 of 110
Fig. 3: Axial T1-weighted MR images showing hyperintense signal of the caudate nucleus
(black arrows) in addition to the involvement of the globos pallidi (white arrows).
Fig. 4: (A) Axial T2-WI and (B) FLAIR sequence delineating subtle symmetrical
hyperintensity involving the bilateral lentiform nuclei in a young 26-year old lady with liver
cirrhosis.
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Fig. 5: A 40-year old male with alcoholic liver cirrhosis and grade-I hepatic
encephalopathy. Fast-FLAIR MR images reveal diffuse high-signal intensity in the
hemispheric white matter on either sides.
Fig. 6: Cerebral atrophy accompanying typical intracranial signal intensity changes

in a 36-year old patient with long standing cryptogenic cirrhosis. Axial T1-WI shows
symmetrical T1-prolongation of the basal ganglia (asterisk) representing manganese
deposition. Attendant widening of the sylvian fissures (thick arrows) and ventricular
enlargement (thin arrows) suggest cerebral parenchymal atrophy.
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Fig. 7: Ventricular enlargement (white arrow) and subarachnoid CSF-space (sylvian

fissure) widening represent cerebral involutional changes in a 30-year old male with
alcohol induced liver cirrhosis.
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Fig. 8: Typical imaging manifestations of HE. Fast FLAIR images exhibit symmetrical
cortical edema involving the insular cortex (arrow) and cingulate gyrus (arrowhead). Note
that the occipital cortex (asterisk) is characteristically spared.
Fig. 9: Acute HE. DWI displaying extensive symmetrical gyral edema which
characteristically involves the insular cortex (arrow) and cingulate gyrus (arrowhead);
and, typically spares the perirolandic and occipital cortex (dotted arrow).
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Fig. 10: Chronic HE. Axial T1-WI showing cortical atrophy with gyriform T1-hyperintensity
representing cortical laminar necrosis in a follow-up case of liver cirrhosis with recurrent
episodes of grade-3 HE in the past.
Fig. 11: A 50-year old liver cirrhosis patient developed cognitive deficits, ataxia,
dysarthria, movement disorders, and features of parkinsonism. MR images reveal
symmetrical T1-hyperintensity of the basal ganglia (A) with attendant T2-hyperintense
changes involving the bilateral middle cerebellar peduncles (B). Imaging findings in the
light of the clinical details are in keeping with acquired hepatocerebral degeneration.
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Fig. 12: Symmetrical T1-hyperintensity can be seen involving the basal ganglia (A, B),
cerebral peduncles (C), and the dorsal aspect of pons (D) in a patient of liver cirrhosis
presenting with features of parkinsonism.
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Fig. 13: A 50-year old male patient with hepatic myelopathy. MR spine failed to depict any
overt intramedullary signal alteration; however, screening of brain revealed symmetrical
hyperintensity along the bilateral corticospinal tracts.
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Fig. 14: Unenhanced CT in a liver disease patient with deranged coagulation profile
shows a large intraparenchymal hematoma (thick white arrow) in right frontal lobe with
contiguous extension into the ipsialteral ventricle (dotted arrow). In addition, there is
synchronous contralateral intracerebral bleed seen in the left frontal region (thick black
arrow). Furthermore, there is evidence of extra-axial bleed that can be seen along the
interhemispheric fissure (thin black arrow).
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Fig. 15: Infratentorial bleed in a delirious patient with decompensated liver cirrhosis.
Axial CT sections reveal a large hematoma involving the cerebellar vermis (arrow)
causing compression and effacement of the fourth ventricle with upstream obstructive
ventriculomegaly (arrowhead). The cerebral sulci are effaced and the cortico-medullary
junction indistinct (asterisk) suggesting raised intracranial pressure.
Fig. 16: Pyogenic meningitis and ventriculitis in a 42-year old patient with NASH related
liver cirrhosis. Post gadolinium T1-WI reveals inflammation, thickening and abnormal
enhancement of the right lateral ventricle ependyma (A, B) and choroid plexus (C)
in keeping with ventriculitis and choroid plexitis. In addition, abnormal leptomeningeal
enhancement can be seen along the right mesial temporal lobe (D) in keeping with
leptomeningitis.
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Fig. 17: Miliary tuberculosis in a middle aged liver cirrhosis patient with history of
longstanding alcohol abuse. Contrast enhanced T1-WI shows multiple pinhead sized
enhancing granulomas randomly scattered in the bilateral cerebral hemispheres.
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Fig. 18: Diffuse cerebral edema in a patient with acute on chronic (Hepatitis-B and C
related)liver failure. Noncontrast CT shows effaced sulci with loss of cortico-medullary
differentiation and indistinct margins of the lenticular nuclei suggesting diffuse cerebral
edema and raised intracranial tension.
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Fig. 19: Fulminant hepatic failure. T2W MR imaging reveals effaced cerebral sulci with
slit-like ventricles (A, B) and diffuse gyral swelling (C, D) in keeping with diffuse ceerbral
edema. The cisternal spaces are also effaced suggesting impending herniation (C, D).
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Fig. 20: (A, B) Sagittal and axial T2-WI show bilateral medial part of the temporal lobes
protruding over the tentorial edge in keeping with uncal herniation (black arrows). In
addition, there is downward cerebellar herniation (tonsillar herniation or coning) seen
in this patient of fulminant hepatic failure. The patient was subsequently declared brain
dead and succumbed to the disease.
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Fig. 21: Central pontine myelinolysis. Sagittal T2-WI shows relatively bulky appearing
pons with attendant signal intensity changes (black arrow) in a 48-year old patient with
alcoholic liver cirrhosis.
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Fig. 22: (A, B) Axial Fast FLAIR and T2-WI of the aforementioned patient shows
hyperintensity involving the central pons with characteristic sparing of the periphery.
Careful evaluation suggests that there is predominant involvement of the transverse
pontine fibres - finding which is quite characteristic of CPM.
Fig. 23: Extra-pontine myelinolysis. Axial FLAIR images showing extra-pontine areas of
signal alteration (demyelination) involving the left thalamus (white arrow) and the right
cerebellar hemisphere (black arrow) in a malnourished chronic alcoholic male patient
with decompensated liver cirrhosis.
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Fig. 24: Wernicke encephalopathy. Axial T2-WI showing confluent areas of increased
intensity surrounding the aqueduct and the third ventricle in a debilitated and
malnourished patient of alcohol induced liver cirrhosis complaining of ataxia and
opthalmoplegia.
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Fig. 25: Coronal T2-WI showing bilateral areas of increased intensity surrounding the
aqueduct and the third ventricle contiguously extending into the mamillary bodies.
Page 82 of 110
Fig. 26: Fast FLAIR images of the same patient showing symmetrical signal alterations
at characteristic sites including periventricular region of the third ventricle, periaqueductal
area, thalamus, and mamillary bodies.
Page 83 of 110
Fig. 27: Sagittal T2-WI in a chronic alcoholic male showing relatively atrophic posterior
body of the corpus callosum (white arrow) with focal area of signal alteration within the
splenium (black arrow). In addition, note is made of disproportionate cerebellar atrophy
(arrowhead) - likely representing alcoholic cerebellar degeneration.
Page 84 of 110
Fig. 28: Axial FAST FLAIR image in a liver cirrhosis patient with auditory hallucinations
following alcohol withdrawal showing subtle symmetrical bi-temporal hyperintensity
(arrows).
Page 85 of 110
Fig. 29: Axial FLAIR and T2WI showing selective bi-frontal cerebral atrophy in a 36-year
old chronic alcoholic male patient with underlying liver cirrhosis.
Page 86 of 110
Fig. 30: Alcoholic cerebellar degeneration. DIffuse cerebellar atrophy is seen in the
form of cerebellar foliar prominence, ventricular enlargement and prominence of the
infratentorial subarachnoid CSF spaces in a 44-year old male cirrhotic with history of
chronic alcohol abuse.
Page 87 of 110
Fig. 31: Axial T2-WI in a patient with Wilson disease depicting symmetrical increased
signal intensity of the bilateral lentiform nuclei (ahite arrow), thalami (black arrow) and
caudate nuclei (arrowhead).
Page 88 of 110
Fig. 32: DWI in a patient with Wilson disease depicting diffusion restriction involving the
lentiform and caudate nuclei (hepatolenticular degeneration) during the acute phase of
the disease.
Fig. 33: Axial T2WI (A) and T2*GRE (B) showing hypointense signal and blooming
reflecting heavy metal deposition in the lentiform nuclei in a patient of Wilson disease.
Page 89 of 110
Fig. 34: Symmetrical increased T1-signal intensity involving the lentiform nuclei in a
patient of Wilson disease.
Page 90 of 110
Fig. 35: (A, B) Giant panda sign in a young patient of Wilson disease. (C) The sign is
due to a combination of high signal intensity in the tegmentum (black arrow) with sparing
of the red nuclei (dotted arrow), pars reticulate (white arrow) and the superior colliculi
(arrowhead).
Page 91 of 110
Fig. 36: Giant panda cub. Axial T2WI in a patient of Wilson disease depicting signal
alteration in the dorsal pons simulating the face of a giant panda - popularly referred to
as 'giant panda cub' sign.
Page 92 of 110
Fig. 37: Transient ischemic attacks in a 39-year old patient with chronic (hepatitisC related) liver disease. DWI reveals multiple acute lacunar infarcts involving the left
pareito-temporal and right cerebellar hemisphere - possibly secondary to occlusive
vasculopathy or vasculitis.
Page 93 of 110
Fig. 38: A young 36-year old patient of hepatitis-C related liver cirrhosis and progressive
neurocognitive decline. Axial FAST FLAIR imaging reveals bilateral multifocal patchy and
confluent areas of subcortical white matter hyperintensities.
Fig. 39: A 45-year old male with (hepatitis-C) liver cirrhosis and rapidly progressive
dementia and neurocognitive decline. FAST FLAIR images reveal patchy and confluent
areas of signal alteration involving the periventricular as well as hemispheric white matter.
Page 94 of 110
Fig. 40: PRES in a post liver-transplant patient. Axial FAST FLAIR sequence exhibiting
cortico-subcortical areas of T2-hyperintensity in the parieto-occipital region.
Page 95 of 110
Fig. 41: Axial T2*GRE image of the hitherto discussed patient with PRES showing
punctate areas of blooming in keeping with petechial hemorrhages in the left occipital
lobe.
Page 96 of 110
Fig. 42: Immunosupressive leukoencephalopathy. A 56-year old post liver transplant

patient on tacrolimus complaining of unrelenting headaches and visual disturbances.
MR images show multifocal areas of white matter signal alteration involving the parietooccipital lobes and right fronto-parietal region appearing bright on T2WI (A) and dark on
T1WI (B).
Fig. 43: Suspected PML in a 44 year old post liver transplant patient with neurocognitive
decline. Axial FLAIR images showing patchy and conflueent scattered hyperintensities
in bilateral parieto-temporal and frontal white matter.
Page 97 of 110
Fig. 44: Multifocal areas of bilateral intracerebral hemorrhage in a 56-year old post livertransplant patient.
Fig. 45: Right middle cerebral artery (MCA) infarct. Axial T2WI (A) and DWI (B) showing
acute infarct with diffusion restriction involving the right temporal lobe in the MCA territory.
Page 98 of 110
Fig. 46: Anoxic-hypoxic ischemic encephalopathy following liver transplant (day-3). DWI
showing diffusion restriction and extensive gyral swelling involving the bilateral cerebral
hemispheres in a contiguous fashion.
Fig. 47: Severe hyperammonemic encephalopathy in a 35 year old post liver transplant
patient (post operative day 6). Axial FLAIR images showing extensive cortical swelling
and T2 prolongation especially along the insular cortices and cingulate gyrus.
Page 99 of 110
Fig. 48: Post-transplant invasive fungal sinusitis, orbital cellulitis & meningitis in a 26 year
old female. Axial CT section showing destruction of the lamina papyracea (white arrow)
with extension of the fungal elements into the right orbit with attendant orbital cellulitis
(asterisk).
Page 100 of 110
Fig. 49: Invasive mucormycosis. Post liver-transplant patient with invasive fungal sinusitis
(asterisk) invading the left orbit (star) and ipsilateral cavernous sinus (white arrow) with
contiguous extension into the left peri-mesencephalic cistern (arrowhead).
Fig. 50: Central pontine myelinolysis in a post liver transplant patient. Axial FLAIR
image showing predominant involvement of the transverse pontine fibres (white arrow)
with characteristic sparing of the descending corticospinal tracts (asterisk). Note the
peripheral pontine fibers (black arrow) are also spared - hence the term 'central' pontine
myelinolysis.
Page 101 of 110
Conclusion
Only with better understanding of the prevalence, clinical features and imaging
manifestations of different neurological complications associated with liver cirrhosis
and liver transplanatation, can we hope to aptly & promptly diagnose them and offer
appropriate therapeutic options.
Personal information
Ankur Arora, MD, DNB, FRCR, EDiR
Assistant Professor
Department of Radiology/ Interventional Radiology
Institute of Liver & Biliary Sciences
New Delhi, India
Email: aroradrankur@yahoo.com
Page 102 of 110
Fig. 51: Thank you!

References: Ankur Arora
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The Nervous Liver: Neurological complications associated

with Cirrhosis & Liver Transplantation

A. Arora, A. Mukund, S. Rajesh, Y. Patidar, S. K. Sarin; New Delhi/

Transplantation, Metabolic disorders, Education and training,

Fig. 1: The Nervous Liver!

The present exhibit aims:

NEUROLOGY OF LIVER CIRRHOSIS

(A) Direct effects of cirrhosis on the nervous system:

Neuroimaging alterations with/without clinical symptoms

(B) Neurological complications related to chronic alcohol use:

Osmotic demyelination syndromes

(C) Induced by a factor that also contributes to the (hepatic) disease:

(D) De#cits unrelated to liver disease, such as:

Residual de#cits of prior strokes

LIVER TRANSPLANTATION-RELATED COMPLICATIONS

(1) Immunosuppressive neurotoxicity

(3) Osmotic demyelination

Findings and procedure details

NEUROLOGY OF LIVER CIRRHOSIS

NEUROIMAGING CHANGES IN CHRONIC LIVER DISEASE

Cirrhotic patients frequently display changes on neuroimaging studies;

The most striking neuroimaging manifestation includes high symmetrical and

Fig. 2: Symmetrical T1-hyperintensity involving the bilateral globus pallidus (arrows) in

Other sites of involvement include the pituitary gland, contiguous internal

Fig. 3: Axial T1-weighted MR images showing hyperintense signal of the caudate

Manganese (Mn) deposition has been attributed to liver dysfunction

Although the mechanisms of manganese neurotoxicity are poorly

The pituitary gland is another commonly affected site shown on the MR

Abnormalities on T2-WI within the globi pallidi have been reported to

Asymptomatic symmetric high-signal intensity in the hemispheric white

Although no significant relationship has been demonstrated between

Another common neuroimaging manifestation in cirrhotic patients is the

Fig. 6: Cerebral atrophy accompanying typical intracranial signal intensity changes

Computerized (CT or MR) morphometric studies of liver-disease brains have

Brain atrophy in alcoholic patients can be attributed at least in part to the

Fig. 7: Ventricular enlargement (white arrow) and subarachnoid CSF-space (sylvian

Amodio et al has shown that brain atrophy in liver cirrhosis is associated

Classical, MR spectroscopy (MRS) findings include elevated glutamine/

Hepatic encephalopathy (HE) is the most frequent cause of altered mental

Patients suspected of acute HE are typically subjected to CT or MR imaging

Classically, the most accepted MR imaging finding in patients with chronic

Acute HE has an acute phase followed by a chronic one. Pathologically,

The proposed cytotoxic edema mechanism in HE is hyperammonia inducing

On MR imaging, presence of extensive cortical edema including the deep

Thus, the cingulate gyrus and insular cortex appear to be particularly

Diffuse cortical involvement although can be reversible; often has a higher

On proton MR spectroscopy: an elevated glutamine/glutamate peak coupled

Follow-up MR imaging may show diffuse cortical atrophy with T1 high

As opposed to cortical laminar necrosis of chronic HE, cortical laminar

zones or the parieto-occipital regions (as opposed to the temporal lobe

It is important to note that although pallidal (T1-WI) hyperintensities are

Patients with cirrhosis and no clinical, neuropsychological, or

ACQUIRED HEPATOCEREBRAL DEGENERATION

Acquired (non-Wilsonian) hepatocerebral degeneration (AHD) is a rare

The pathophysiology and the locations of the cerebral injuries

AHD occurs in approximately 1% of patients with liver cirrhosis and seems

Clinically, it is characterized by a combination of parkinsonism and

The syndrome is poorly responsive to medical (antiparkinsonism drugs)

MR imaging reveals pallidal and extrapallidal lesions in most patients,

In addition to T1-weighted hyperintensities in the globus pallidus, up to 75%

The increased signal intensity in the middle cerebellar peduncles or dentate

Since the clinical symptoms, neuropathological features and MR imaging

The discrimination depends on the following aspects: (1) Age: Wilson