This document discusses radiological imaging techniques for diagnosing various neurodegenerative diseases and dementias. It provides an overview of different neurodegenerative diseases categorized by their underlying pathological processes including synucleinopathies, tauopathies, cerebral amyloidosis, spinocerebellar ataxias, and prion diseases. It then focuses on Alzheimer's disease, providing details on structural changes seen on MRI, patterns of hypometabolism on FDG-PET and amyloid deposition on amyloid PET. Imaging patterns of other diseases like vascular dementia, frontotemporal dementia, dementia with Lewy bodies, and corticobasal degeneration are also summarized.

1. Radiological Imaging of Neurodegenerative
Diseases And Dementia of Adults.
Dr/ ABD ALLAH NAZEER. MD.

2. Neurodegenerative diseases
Neurodegenerative diseases are legion and their classification just as
protean. A useful approach is to divide them according to underlying
pathological process, although even using this schema, there is much
overlap and thus resulting confusion.
Neurodegenerative diseases.
Synucleinopathies
Diseases with Lewy bodies[+]
Multiple systemic atrophy(MSA) [+]
Tauopathies:
Alzheimer disease [+]
Chronic traumatic encephalopathy(CTE)
Corticobasal degeneration
Front-temporal lobar degeneration (FTLD) (not all are tau) [+]
Pick disease
Progressive supra-nuclear palsy(PSP)

3. Cerebral amyloidosis
cerebral amyloid angiopathy (CAA)[+]
transthyretine-associated cerebral amyloidosis
neuronal intranuclear hyaline inclusion disease (NIHID)
Spinocerebellar ataxias.
Huntington disease
Hereditary spastic paraplegia. Amyotrophic lateral sclerosis(ALS)
Clinically unclassifiable parkinsonism(CUP)
Unverricht-Lundborg disease
Prion diseases (not always included as neurodegenerative)
Creutzfeldt-Jakob disease (sporadic, variant, familial, and
iatrogenic)
Fatal familial insomnia
Gerstmann-Straussler-Scheinker disease
kuru
Variably protease sensitive prionopathy

6. Alzheimer Disease (AD) represents the underlying cause of
approximately 50–80% of all cases of dementia. The incidence of AD
doubles every 5 years after the age of 60 years old. Clinically, this
disease progresses with decline in episodic memory with or without
language or visual difficulties. The prodromal stage of MCI has been
defined as cognitive decline greater than expected for age but not
interfering with activities of daily living. Progression to AD has been
reported in approximately 10–15% of patients with MCI annually.
It is difficult to differentiate MCI and AD from cortical atrophy
related to normal aging using MRI. Typical structural changes seen
in AD occur late in the disease process and include disproportionate
hippocampal, amygdala, and temporoparietal volume loss with
sparing of the primary sensorimotor cortex. Volumetric software for
quantifying hippocampal volumes can be helpful. Visible change
within a 12- to 18-month time period on serial imaging has been
reported to increase the sensitivity for the diagnosis of AD.

7. Brain volume measurements, assessed with segmentation, demonstrate that patients with
Alzheimer disease have accelerated rates of brain volume loss, typically around twice normal
(1% vs. ~0.5% per year). This is even more marked in the hippocampi, with affected individuals
exhibiting three times the volume loss per year (~4.5% vs. ~1.5% per year).
Nuclear medicine
SPECT and PET are able to detect regional hypoperfusion/hypometabolism in a biparietal and
bitemporal distribution.
FDG PET
18F-fluorodeoxyglucose (FDG) PET typically shows bilateral temporoparietal, precuneus and
posterior cingulate hypometabolism which is usually symmetric. Uptake may be asymmetric in
the early stages. The anterior cingulate, visual cortex (eyes should be kept open while scanning
to avoid the pitfall of hypometabolism in the visual cortex), basal ganglia, thalami, occipital
lobes and cerebellum are usually spared. Frontal lobes may be involved in late stage.
Amyloid PET
11C-Pittsburgh compound B, as well as newer compounds such as 18F-florbetapir, 18F-
flutemetamol, and 18F- florbetaben, are PET tracers that bind preferentially to beta-amyloid
fibrils and thus may be able to improve the specificity of antemortem diagnosis, although there
is considerable overlap with normal controls. With increased cerebral amyloid-β (Aβ) deposition,
increased activity is demonstrated in the cortex. It is particularly useful in excluding Alzheimer
disease as the cause of dementia, as a negative amyloid PET scan renders the diagnosis unlikely.
Tau PET
Newer PET agents that bind tau proteins are being investigated, which result in increased
activity in the expected locations (hippocampus, entorhinal cortex and temporal and parietal
cortex).

8. Brain With Alzheimer's Disease

9. How the Brain and Nerve Cells Change During Alzheimer's Disease
Medical illustration showing how the brain and nerve cells change during Alzheimer's

10. Substantia Nigra: substantia nigra appear darker than neighboring areas due to high levels
of melanin in dopaminergic neurons and Parkinson's disease is characterized by the death of
dopaminergic neurons in the substantia nigra.
Brain With Parkinson's Disease

12. A, Axial T2-weighted FLAIR images at varying intracranial levels (left image, middle left image, middle right image), and coronal T1-
weighted volumetric acquisition image (right image) show mild diffuse cerebral and cerebellar atrophy and normal hippocampi for age.
B, FDG PET images (B), 3D stereotactic surface projection maps (C), and Z-score maps (D) show mild
temporoparietal lobe hypometabolism, right worse than left, and mildly diminished activity in
posterior cingulate gyrus (arrows, D); these findings are suggestive of early Alzheimer disease.

13. C, FDG PET images (B), 3D stereotactic surface projection maps (C), and Z-score maps (D) show mild temporoparietal lobe hypometabolism, right
worse than left, and mildly diminished activity in posterior cingulate gyrus (arrows, D); these findings are suggestive of early Alzheimer disease.
D, FDG PET images (B), 3D stereotactic surface projection maps (C), and Z-score maps (D) show mild temporoparietal lobe hypometabolism, right
worse than left, and mildly diminished activity in posterior cingulate gyrus (arrows, D); these findings are suggestive of early Alzheimer disease.
E, Amyloid PET images reveal abnormal diffuse activity in gray matter (arrows) similar to white matter.

14. A, Axial T2-weighted FLAIR images at varying intracranial levels (left image, middle left
image, middle right image) and coronal T1-weighted image at hippocampal level (right
image) show generalized cerebral volume loss that is most notable in perisylvian regions
and commensurate volume loss of both hippocampal formations (arrows).
B, FDG PET images show marked right and moderate left temporoparietal
hypometabolism. Prominent right frontal lobe hypometabolism is also
noted. There is motor and visual cortex sparing.

15. C, Three-dimensional stereotactic surface projection maps (C) and Z-score maps (D) show significant temporoparietal
lobe hypometabolism, right greater than left (> 6 SD) and bilateral posterior cingulate gyri hypometabolism (arrows, D).
D, Three-dimensional stereotactic surface projection maps (C) and Z-score maps (D) show significant temporoparietal lobe
hypometabolism, right greater than left (> 6 SD) and bilateral posterior cingulate gyri hypometabolism (arrows, D).
E, Amyloid PET images reveal intense activity in gray matter (arrows) similar to activity in
white matter indicating positive study.

16. Comparison of arterial spin
labeling (ASL) and
fluorodeoxyglucose (FDG) images.
Representative images from
control subjects (top row) and AD
patients (bottom row) comparing
structural magnetic resonance
imaging images (T1 and fluid-
attenuated inversion recovery),
arterial spin labeling magnetic
resonance imaging (ASL-MRI),
and fluorodeoxyglucose positron
emission tomography (FDG-PET).
All four patients were diagnosed
correctly by both readers using
both modalities. White arrows
highlight areas of concordant
hypometabolism on FDG-PET and
hypoperfusion on ASL-MRI.

17. Alzheimer’s
disease.

18. Vascular dementia may present with sudden onset of dysfunction or
stepwise deterioration in patients with risk factors for stroke, systemic
vascular disease, or a history of stroke. Because white matter disease
increases with age, there remains uncertainty about the severity of disease
needed to diagnose vascular dementia. Some sources suggest that
approximately 25% of white matter needs to be affected; however, this
imaging pattern alone does not imply clinical findings of dementia. Vascular
dementia is most commonly sporadic because of underlying pathologic
conditions such as atherosclerosis or cerebral amyloid angiopathy (CAA).
More rarely, vascular dementia may be heritable, such as in cerebral
autosomal-dominant arteriopathy with subcortical infarcts and
leukoencephalopathy (CADASIL). Complicating matters is the fact that the
coexistence of vascular dementia and AD is common given the shared risk
factors in an aging population
Large-vessel disease may result in a typical cerebral vascular distribution
of cortical or subcortical infarcts. However, small-vessel disease is more
common, resulting in focal or confluent regions of subcortical and
periventricular increased signal intensity on T2-weighted FLAIR imaging,
sparing of the subcortical U fibers, and small lacunar infarcts.

19. A, Axial T2-weighted FLAIR images at varying intracranial levels (left image, middle left image, middle
right image), and coronal T1-weighted image at hippocampal level (right image) show moderate
periventricular leukoaraiosis and generalized cerebral atrophy, most marked in both temporal lobes
and insula. Right parafalcine occipital lobe encephalomalacia (arrows) is also present.
B, FDG PET images reveal focal hypometabolism in area of old right
posterior cerebral artery (PCA) infarct-encephalomalacia on MRI (arrow).

20. C, Three-dimensional stereotactic surface projection maps (C) and Z-score maps (D) not
only confirm hypometabolism in right PCA territory but also show multiple discrete foci
of hypometabolism throughout cortex in areas of focal gyral atrophy (arrows). This case
illustrates potential pitfall of using FDG PET/CT without anatomic imaging correlation.
D, Three-dimensional stereotactic surface projection maps (C) and Z-score maps (D) not
only confirm hypometabolism in right PCA territory but also show multiple discrete foci
of hypometabolism throughout cortex in areas of focal gyral atrophy (arrows). This case
illustrates potential pitfall of using FDG PET/CT without anatomic imaging correlation.

21. Diffusion-weighted
MRI in vascular dementia

22. Vascular dementia, no medial temporal lobe atrophy.

23. Frontotemporal Dementia: Estimated to contribute to less than 10% of all
dementia cases, FTD is the third most common type of dementia and the most
common type of dementia in patients younger than 60 years old. Clinical
symptoms include behavioral issues, affective symptoms, and language disorders.
FTD subtypes include behavioral FTD and language-predominant cognitive decline
FTD, the latter of which is referred to as primary progressive aphasia (PPA). PPA is
further classified into semantic, agrammatic or nonfluent, and logopenic PPA
variants. Compared with AD, FTD usually has an earlier onset and more rapid
progression. FTD likely represents several different types of neurodegenerative
processes, and the patterns of imaging findings can be strikingly different. Early
differentiation of FTD from AD is clinically important because symptoms caused by
FTD do not respond to traditional therapies approved for AD.
Anatomic imaging—The structural findings in patients with behavioral FTD
include symmetric or asymmetric frontal or temporal lobe atrophy with relative
sparing of the parietal and occipital lobes. Atrophy can be severe with so-called
“knife blade gyri,” but this is a late finding in the behavioral FTD process. The
following characteristic patterns of atrophy have been described for the language-
predominant cognitive decline FTD (PPA) subtypes: left anterior temporal lobe and
hippocampal atrophy in semantic PPA; left perisylvian cortex, inferior frontal gyrus
(Broca area), and superior temporal gyrus atrophy in agrammatic or nonfluent
PPA; and left posterior perisylvian or parietal atrophy in logopenic PPA.

24. Frontotemporal dementia. A, Axial T2-weighted FLAIR images at varying intracranial
levels (left image, middle left image, middle right image), and sagittal T1-weighted
(right image) show moderate diffuse parenchymal volume loss for age and
superimposed focal atrophy of the frontal and anterior temporal lobes (arrow).
B, FDG PET images show moderate to markedly decreased activity in both
Frontotemporal lobes and mildly decreased parietal lobe metabolism. Mildly
decreased basal ganglia activity. There is motor cortex preservation.

25. C, Three-dimensional stereotactic surface projection maps (C) and Z-score maps (D)
depict large areas of bilateral frontotemporal hypometabolism (3–4 SD) (arrows, D).
D, Three-dimensional stereotactic surface projection maps (C) and Z-score maps (D)
depict large areas of bilateral frontotemporal hypometabolism (3–4 SD) (arrows, D).

26. FTLD: T2WI and FLAIR with 'knife blade' atrophy of
left temporal lobe with normal right temporal lobe.

27. Brain MRI in frontotemporal dementia patients.

28. Dementia With Lewy Bodies: DLB is increasingly recognized as a
cause of dementia in patients older than 60 years old and now
possibly represents 1 in every 25 dementia cases in the community and
1 in every 12 cases in secondary care centers. Symptoms include
dementia with visual hallucinations, parkinsonism, and REM sleep
behavior disorder. In this entity, dementia symptoms occur before
parkinsonism in contrast to Parkinson disease with dementia in which
dementia occurs in the setting of well-established parkinsonism.
Approximately 70–90% of patients with DLB show Parkinsonian
symptoms at the time of cognitive symptoms. Early differentiation of
DLB from AD is critical because DLB symptoms may respond to
neuroleptic therapy, thus improving the quality of life of patients with
DLB.
Anatomic imaging—The imaging findings of DLB are nonspecific, with
varying patterns of cortical and white matter volume loss and relative
preservation of the hippocampi. Despite visual symptoms reported in
patients with DLB, occipital lobe atrophy is not typically observed.

29. Dementia with Lewy bodies (DLB). A, Axial T2-weighted FLAIR images at varying intracranial
levels (left image, middle left image, middle right image) and coronal T1-weighted image at
hippocampal level (right image) show mild diffuse cerebral atrophy including the hippocampi.
B, FDG PET images show parietal, occipital, posterior temporal,
and frontal lobe hypometabolism with motor strip preservation.

30. C, Three-dimensional stereotactic surface projection maps (C) and Z-score maps (D) show
significant parietooccipital hypometabolism including visual cortex (3–4 SD) (arrows, D).
D, Three-dimensional stereotactic surface projection maps (C) and Z-score maps (D) show
significant parietooccipital hypometabolism including visual cortex (3–4 SD) (arrows, D).
E, Amyloid PET images reveal abnormal diffuse activity in gray matter similar
to white matter indicating positive study (arrows).

31. Lewi body dementia: normal hippocampus.

33. Corticobasal degeneration (CBD) is characterized by cognitive decline or
behavioral disturbance that precedes the development of a movement disorder,
typically asymmetric parkinsonism or alien limb phenomenon. Specific cognitive
features include executive dysfunction, aphasia, apraxia, and visuospatial
disturbances. Similar to the parkinsonism of many other atypical degenerative
dementias, parkinsonism in CBD can be differentiated from idiopathic Parkinson
disease in that it is typically asymmetric and lacks a robust response to levodopa
therapy. Current research suggests that CBD may be further divided into FTD and
AD subtypes on the basis of the underlying histology at autopsy. Although not
robust, dopaminergic drugs may be helpful for symptom treatment. Targeted
therapy with botulinum toxin for symptomatic limb dystonia can also improve
quality of life. A relatively aggressive course is typically seen, with a mean survival
of 8 years from symptom onset.
Anatomic imaging—In the early stages of CBD, the MRI findings may be subtle.
With disease progression, asymmetric cortical atrophy involving the frontoparietal
lobes and corpus callosum may be present. There may also be atrophy of the
ipsilateral cerebellar peduncle. On T2-weighted sequences, marked hypointensity
can be seen in the putamen and globus pallidum. Volume loss does not occur in
the basal ganglia and hippocampi, which can be helpful in differentiation from AD

34. 1A —Corticobasal degeneration in 67-year-old man who presented with cognitive decline, expressive
aphasia, right upper extremity rigidity, and focal myoclonus. A, Axial (left image and middle left
image), sagittal (middle right image), and coronal (right image) T2-weighted FLAIR MR images show
asymmetric cortical atrophy in left temporal and parietal lobes (arrows).
B, Axial (left image and middle left image), sagittal (middle right image), and
coronal (right image) FDG PET images reveal marked left temporoparietal
hypometabolism with subtle decreased activity in left basal ganglia (arrows).

35. C, Three-dimensional stereotactic surface projection (SSP) maps (C) and Z-score maps (D)
confirm severe left-sided cortical hypometabolism (> 5 SD; arrows). Three-dimensional SSP
images are semi quantitative sampling of metabolism from various cortical locations. Z-
score images compare cortical metabolism with age-matched normative database; color
change is based on reduction in metabolism relative to number of SDs from mean.
D, Three-dimensional stereotactic surface projection (SSP) maps (C) and Z-score maps (D)
confirm severe left-sided cortical hypometabolism (> 5 SD; arrows). Three-dimensional
SSP images are semiquantitative sampling of metabolism from various cortical locations.
Z-score images compare cortical metabolism with age-matched normative database;
color change is based on reduction in metabolism relative to number of SDs from mean.

36. Multiple-system atrophy (MSA) is a neurodegenerative movement
disorder characterized by prominent parkinsonism. Cognitive decline
and cerebellar ataxia with early falls are characteristic of this disorder.
When dysautonomia predominates, this condition may be termed
“Shy-Drager syndrome.” This disease process is further subclassified on
the basis of the type of movement disorder: MSA with predominantly
parkinsonism symptoms is referred to as “MSA-P,” and MSA with
predominantly cerebellar ataxia symptoms is referred to as “MSA-C” .
Dopamine replacement therapy is not beneficial in patients with MSA,
unlike patients with CBD, and can potentially aggravate the
dysautonomia. As with the other atypical degenerative dementias, the
clinical course of MSA is aggressive, and death typically occurs within
10 years of diagnosis. In patients with prominent dysautonomia, the
prognosis can be even worse.
Multiple distinct patterns may be seen on conventional MRI of patients
with MSA. In MSA-P, putaminal abnormalities predominate with
atrophy and symmetric hypointensity on T2-weighted and gradient-
weighted images.

37. 2A —Multiple-system atrophy (MSA-C) in 56-year-old man who presented with mild
parkinsonism, cerebellar ataxia, and autonomic dysfunction.
A, Axial T2-weighted FLAIR images (images from left to right: skull base to vertex) show
marked focal atrophy of midbrain and both middle cerebral peduncles, exvacuo dilatation of
fourth ventricle, and “hot cross bun” sign with cruciform T2 hyperintensity in pons (arrows).
B, Axial FDG PET images (images from left to right [B]: skull base to vertex), 3D
stereotactic surface projection maps (C), and Z-score projection maps (D) show dominant
cerebellar and mild pontine hypometabolism (arrows) typical of subtype of MSA with
predominantly cerebellar ataxia symptoms.

38. C, Axial FDG PET images (images from left to right [B]: skull base to vertex), 3D
stereotactic surface projection maps (C), and Z-score projection maps (D) show
dominant cerebellar and mild pontine hypometabolism (arrows) typical of
subtype of MSA with predominantly cerebellar ataxia symptoms.
D, Axial FDG PET images (images from left to right [B]: skull base to vertex),
3D stereotactic surface projection maps (C), and Z-score projection maps (D)
show dominant cerebellar and mild pontine hypometabolism (arrows) typical
of subtype of MSA with predominantly cerebellar ataxia symptoms.

39. 'Hot cross bun sign' in MSA

40. Progressive Supranuclear Palsy: PSP is clinically characterized by
parkinsonism, postural instability, and vertical gaze palsy. PSP is the second
most common cause of parkinsonism after idiopathic Parkinson disease. PSP is
characterized by early falls within the first year of disease onset, and there is
typically symmetric involvement at presentation with central (i.e., trunk and
neck) involvement greater than limb involvement. Although supranuclear
ophthalmoplegia is the most striking cranial nerve finding, other cranial nerves
can also be involved, producing pseudobulbar palsy and cervical dystonia.
Concomitant cognitive impairment is typically characterized by personality
change, memory impairment, and depression or apathy. Disease progression is
usually aggressive, with death occurring within 6–10 years of diagnosis.
Misdiagnosis as idiopathic Parkinson disease is not rare, and this misdiagnosis
may lead to unnecessary trials of dopamine replacement therapy, to which PSP
is typically unresponsive.
Conventional MRI. These abnormalities include the following: first, atrophy of
the mid-brain tegmentum with relative preservation of the pons, which is
termed the “hummingbird” sign, on midline sagittal images; second, atrophy of
the midbrain, preservation of the tectum, and widening of the interpeduncular
cistern, which is termed the “Mickey Mouse” sign, on axial images; and
putaminal T2 hypointensity, which is likely caused by iron deposition

41. Progressive supranuclear palsy: A, Axial T2-weighted FLAIR images (first three images from
left to right: skull base to vertex) and sagittal T1-weighted image (right image) show
generalized cerebral atrophy is more prominent in frontotemporal lobes including hippocampi
and perisylvian regions. Selective atrophy of midbrain tegmentum with relative preservation
of pons (arrow), which is termed “hummingbird” sign, is seen on sagittal image.
B, Axial FDG PET images (first three images from left to right, B), sagittal FDG
PET image (right image, B), and sagittal 3D stereotactic surface projection
maps (C) show subtle posterior frontal cortex hypometabolism.

42. C, Axial FDG PET images (first three images from left to right, B), sagittal
FDG PET image (right image, B), and sagittal 3D stereotactic surface
projection maps (C) show subtle posterior frontal cortex hypometabolism.
D, Posterior frontal cortex hypometabolism (arrows)
is better delineated on sagittal Z-score maps.

43. Progressive supranuclear palsy (PSP): PSP is also one of the atypical
parkinsonian syndromes. In PSP there is pronounced atrophy of the midbrain
(mesencephalon), which accounts for the typical upward gaze paralysis.
PSP with midbrain atrophy. PSP: 'humming bird sign' due to
midbrain atrophy

44. Pseudodementia has been described as a reversible dementia syndrome
secondary to a primary psychiatric disorder, classically major depressive disorder.
This diagnosis should be considered in the differential diagnosis of any patient
with a long-standing psychiatric history. Clinically, the only major differentiating
factor is the complete reversibility of the symptoms after treatment. In the
population with treatment-resistant major depressive disorder, cognitive
symptom improvement may be achieved only after electroconvulsive therapy
(ECT). Significant morbidity and mortality can be associated with this condition,
which stresses the importance of early and accurate diagnosis.
Anatomic imaging—No structural or morphologic abnormalities are seen on
conventional MRI in pseudodementia. However, this lack of structural
abnormalities may be indistinguishable from other early-stage dementia
processes.
Metabolic imaging—A broad spectrum of presentations may be seen on FDG
PET/CT; most commonly, FDG PET/CT of these patients will show normal
metabolism. However, diffuse hypometabolism has also been described, and
there have been several cases reported of severe depressive pseudodementia
with diffuse cerebral hypometabolism showing varying degrees of metabolic
change after ECT

45. Pseudodementia in 57-year-old woman who presented with progressive cognitive decline
and history of depression. A, Axial FLAIR MR images (images from left to right [A]: base to
vertex), axial FDG PET images (B), 3D stereotactic surface projection maps (C), and sagittal
Z-score maps (D) show normal findings. Both MRI and PET studies show normal findings.
Nonspecific pattern of diffuse cortical hypometabolism can be seen with pseudodementia.
B, Axial FLAIR MR images (images from left to right [A]: base to vertex), axial FDG PET
images (B), 3D stereotactic surface projection maps (C), and sagittal Z-score maps (D)
show normal findings. Both MRI and PET studies show normal findings. Nonspecific
pattern of diffuse cortical hypometabolism can be seen with pseudodementia.

46. C, Axial FLAIR MR images (images from left to right [A]: base to vertex), axial FDG PET
images (B), 3D stereotactic surface projection maps (C), and sagittal Z-score maps (D) show
normal findings. Both MRI and PET studies show normal findings. Nonspecific pattern of
diffuse cortical hypometabolism can be seen with pseudodementia.
D, Axial FLAIR MR images (images from left to right [A]: base to vertex), axial FDG PET
images (B), 3D stereotactic surface projection maps (C), and sagittal Z-score maps (D)
show normal findings. Both MRI and PET studies show normal findings. Nonspecific
pattern of diffuse cortical hypometabolism can be seen with pseudodementia.

47. Paraneoplastic neurological syndromes (PNS) are a rare group of disorders that result from
neuronal dysfunction in the setting of malignancy that is likely because of immune-mediated
direct damage rather than because of metastasis, infection, metabolic deficits, or treatment.
This phenomenon is most frequently encountered in breast, lung, and ovarian cancer and is
estimated to occur in less than 0.01% of patients with cancer. Most often, the symptoms of PNS
develop before the detection of the primary malignancy. There are multiple syndromes included
in the PNS that may present clinically with cognitive symptoms; two of the more common
entities include paraneoplastic limbic encephalitis and subacute cerebellar degeneration.
Patients with paraneoplastic limbic encephalitis, the most common clinical paraneoplastic
syndrome, present with cognitive decline, confusion, and possibly seizures. Patients with sub-
acute cerebellar degeneration typically present with profound axial and appendicular ataxia,
dysarthria, and nystagmus. Accurate diagnosis can help to initiate treatment with immune-
modulating therapies and elicit a search for occult malignancy in these patients.
Anatomic imaging—Conventional MRI findings may range from grossly normal to abnormal in
PNS. Paraneoplastic limbic encephalitis can mimic herpes encephalitis on imaging with relatively
symmetric T2 hyperintensity in the medial temporal lobes. The cingulate gyrus, insula, inferior
frontal cortex, and white matter may be involved as well. Minimal mass effect and patchy
contrast enhancement can be present, which may confuse the imaging appearance. In acute
cases in which herpes cannot be excluded, treatment with antiviral agents is advised until
herpes encephalitis can be excluded by spinal fluid examination. In paraneoplastic cerebellar
degeneration, focal atrophy of the cerebellum is noted. This disorder can be difficult to
accurately diagnose in patients with more widespread cerebral atrophy, but there is progressive
volume loss on serial examinations. The cerebellar atrophy is often more obvious on sagittal
images than on axial images.

48. Paraneoplastic limbic encephalitis in 35-year-old woman who presented with subacute memory
deficits and psychiatric symptoms including paranoia and hallucinations. A, Axial T2-weighted
(first three images from left to right: base to vertex) and coronal T2-weighted FLAIR (right
image) MRI shows signal abnormalities in both mesial temporal lobes (arrows).
B, Axial FDG PET images (first three images from left to right [B]: base to vertex), coronal FDG
PET image (right image, B), and 3D stereotactic surface projection maps (C) show mild diffuse
cortical hypometabolism and intense hypermetabolism in medial temporal lobes (arrows).

49. C, Axial FDG PET images (first three images from left to right [B]: base to
vertex), coronal FDG PET image (right image, B), and 3D stereotactic
surface projection maps (C) show mild diffuse cortical hypometabolism
and intense hypermetabolism in medial temporal lobes (arrows).
D, There is no use for Z-score maps in this patient because they show areas
of cortical hypometabolism in patients with neurodegenerative disorders.

50. Creutzfeldt-Jakob disease (CJD) is a rare fatal prion neurodegenerative
disease characterized by rapidly progressive dementia with myoclonus.
Although there are classic pathologic findings on brain biopsy, noninvasive
diagnosis by a combination of electroencephalography (EEG) and imaging
findings is optimal to reduce the potential for additional potential prion
exposures. In addition to characteristic EEG periodic complexes, highly
specific features can be seen on imaging that allow accurate diagnosis of
CJD.
Anatomic imaging—The most common imaging finding is rapidly
progressive atrophy that typically involves the frontal, temporal, and
parietal lobes. Rarer subtypes can preferentially involve the occipital
(Heidenhain variant) and cerebellar (Oppenheimer-Brownell variant)
hemispheres. Aside from the progressive atrophy, more specific MRI
features can be present and include, first, T2 signal and diffusion
restriction in the pulvinar of the thalami; and, second, symmetric increased
signal intensity in the pulvinar and dorsomedial thalamus that gives a
“hockey stick” configuration. Other findings frequently encountered
include patchy gyriform T2 hyperintensity in the cerebral cortex and
increased T1 signal in the globus pallidum

51. Creutzfeldt-Jakob disease in 53-year-old
man who presented with rapidly
progressive dementia and myoclonus
B, Axial MR images obtained 3 months
after A show progressive atrophy with
increased T2 signal in caudate
(arrows, B); asymmetric gyriform pattern
of restricted diffusion in cerebral cortex
(arrows, C); involvement of caudate,
putamen, and pulvinar with increased
FLAIR signal (arrows, D); and increased
T1 signal in globus pallidum (arrow, E).
Constellation of MRI findings, short-
interval progression, and clinical scenario
obviated brain biopsy in this case.

52. Huntington disease (HD) is an uncommon autosomal-dominant
neurodegenerative disease with both juvenile and adult-onset forms that is
characterized by cytosine-adenosineguanine trinucleotide repeats in the short arm
of chromosome 4. The classic adult-onset form, accounting for approximately 90–
95% of HD cases, typically presents in patients 40–50 years old with rapidly
progressive mental deterioration and choreoathetoid movements. The less
common juvenile form typically presents in patients younger than 20 years old,
and affected patients can have prominent rigidity. Although HD is autosomal-
dominant, approximately 10–15% of cases are sporadic, which can potentially
lead to a delayed diagnosis.
Anatomic imaging—The main feature of HD is caudate atrophy with overall
decreased size, loss of the convex medial margin of the caudate heads, and an
increased intercaudate distance. Putaminal and globus pallidus volume loss with
compensatory enlargement of the anterior horns of the lateral ventricles may also
be seen. The basal ganglia atrophy can be subtle, especially in minimally
symptomatic patients or in presymptomatic patients. Therefore, volumetric
quantitation may be useful. Nonspecific T2 hypointensity in the striatum can result
from iron deposition. In the juvenile form, T2 hyperintensity in the caudate and
putamen may occur due to gliosis

53. A, Prominent bilateral caudate atrophy (arrows)
is visible on axial T2-weighted image (A) and
coronal T1-weighted image (B) of 43-year-old
man with HD who presented with choreoathetoid
movements. Axial 11C-raclopride PET images of
34-year-old control patient (E) and 32-year-old
presymptomatic HD gene carrier (F). Decreased
uptake is seen in basal ganglia of gene carrier
(arrows, F).

56. Koedam scale grade 0-1 Koedam scale grade 2-3

57. Creutzfeldt-Jakob disease (CJD): CJD is a very rare and incurable neurodegenerative
disease, caused by a unique type of infectious agent called a prion. The first symptom of
CJD is rapidly progressive dementia, leading to memory loss, personality changes and
hallucinations. The disease is characterized by spongiform changes in the cortical and
subcortical gray matter, with loss of neurons and replacement by gliosis. The
abnormalities can sometimes be detected on FLAIR, but are most conspicuous on DWI
sequences, affecting either the striatum, the neo-cortex, or a combination of both.
Changes in the neocortex as seen
on FLAIR (left) and DWI (right).

58. Pulvinar hyperintensity in new variant of CJD.

59. Typical MRI features of
Creutzfeldt-Jakob disease
(CJD). (A and B) Sporadic CJD
showing typical basal ganglia
signal return on fluid-
attenuated inversion recovery
(FLAIR) (A), which is more
obvious on diffusion-weighted
sequences (B). (C) Diffusion-
weighted imaging sequence
showing striking cortical
ribboning with normal basal
ganglia in sporadic CJD. (D)
Variant CJD showing pulvinar
sign on the FLAIR sequence.

60. Corticobasal Degeneration (CBD): CBD is a rare entity which may present with cognitive
dysfunction, usually in combination with Parkinson-like symptoms. The so-called 'Alien-
hand' syndrome is a typical manifestation. MRI shows asymmetric parietal cortical atrophy,
sometimes with associated hyperintensity of the white matter on T2W images.
Axial FLAIR image shows striking asymmetric cortical parietal atrophy in a patient with CBD.
Corticobasal degeneration.

61. Cerebral Autosomal Dominant
Arteriopathy with Subcortical Infarcts
and Leukoencephalopathy (CADASIL):
CADASIL is another hereditary disease which may present
with a progressive cognitive dysfunction. Other presenting
symptoms include migraines, stroke-like episodes and
behavioral disturbances. It affects the small vessels of the
brain. Confluent white matter hyperintensities in the frontal
and especially anterior temporal lobes in combination with
(lacunar) infarcts and microbleeds are seen on imaging. The
FLAIR images show classic findings in CADASIL - confluent
white matter hyperintensities with lacunar infarcts and
involvement of the anterior temporal lobes.

62. Cerebral
Autosomal
Dominant
Arteriopathy
with
Subcortical
Infarcts and
Leukoencepha
lopathy
(CADASIL)

63. Traumatic Brain Injury (TBI): Long term sequelae of traumatic brain injury such
as cerebral contusions and diffuse axonal injury (DAI) may include cognitive
impairment. Frontobasal/temporal parenchymal loss or T2* black dots typical for
DAI in a patient with a history of trauma must therefore be taken into
consideration when assessing MR images for dementia. The FLAIR images show
classic post-traumatic tissue loss with gliosis in both frontal lobes, the left occipital
lobe and right temporal lobe.
Traumatic brain injury.

64. Cerebral Amyloid Angiopathy (CAA)
Dementia may be the clinical presentation in CAA, a condition
in which ?-amyloid is deposited in the vessel walls of the brain.
The result is hemorrhage, usually microhemorrhages, but also
subarachnoid hemorrhage or lobar hematomas may occur.
On MR, the T2* sequence will show multiple
microhemorrhages, typically in a peripheral location (as
opposed to hypertensive microhemorrhages, which are usually
more centrally located, e.g. in the basal ganglia and thalami).
In addition, FLAIR will reveal moderate to sever white matter
hyperintensities (Fazekas grade 2 or 3) T2* images in a patient
with CAA show multiple peripherally located microbleeds.

65. Cerebral Amyloid Angiopathy

66. Cerebral Amyloid Angiopathy

67. Cerebral Amyloid Angiopathy

68. Cerebral Amyloid Angiopathy

69. Fatal familial insomnia is an extremely rare autosomal dominant inherited prion
disease 1. Unlike other prion diseases, it does not exhibit spongiform changes. The
main pathological findings are gliosis in the inferior olivary nuclei and thalami.
Cranial imaging of a FFI patient. In the MRI, there are abnormal signals in the bilateral
frontoparietal subcortical area. MRA showed smaller distal branches of cerebral arteries.

70. Familial fatal insomnia.

71. Pick disease is a neurodegenerative disease, and one of the
tauopathies characterised by the accumulation of Pick bodies.
Pick disease.

72. Primary
progressive
apraxia in
Pick's
disease.

73. Picks disease: Single-photon emission computed tomography using N-isopropyl-p-[sup 123 I]-
iodoamphetamine on June 22, 1990. Uptake decrease extends in the left perisylvian, paracentral,
and upper parietal regions. Negligible defect is observed in the right parietal region.

75. Thank You.