Neurodegenerative Disease and Imaging - PowerPoint Presentation

Slide1

Neurodegenerative Disease and Imaging

Dr. Gene A. Ferretti

Section Chief MRI

Section Chief Neuroimaging

St. Luke’s University Hospital and Health NetworkSlide2

What is it?

A

 neurodegenerative disease

 is a blanket term encompassing a wide variety of disorders, typically slowly progressive, with variable gradual neurologic dysfunction.Slide3

Radiologist Role

Imaging of the brain in patients with suspected neurodegenerative conditions

 is common and challenging,

the

imaging findings are also subtle and equivocal. In many instances, by the time imaging findings are clear cut

,

the patient has declared themselves clinically, and the diagnosis is already established or at least strongly suggested. 

As such the true role of imaging is often to push clinicians towards or

away from a

particular differential rather than making a firm diagnosis.Slide4

Alzheimer disease (AD)

Responsible for majority of Dementias

2/3 of dementia cases aged 60-70

yo

Epidemiological risk factors have been identified, including 

:

advanced

age

female

gender

apolipoprotein

E (APOE) ε4 allele carrier

status

current

smoking

family

history of dementiaSlide5

Pathology

Alzheimer disease is

characterised

by the accumulation

of

senile (

neuritic

) plaques

, 

neuritic

(neurofibrillary) tangles

, and progressive loss of

neurons

within the brain.

The progression of pathology initially involves the

transentorhinal

region and then spreads to the hippocampal complex and mesial temporal lobe structures and eventually the temporal lobes and basal

forebrain.

The underlying reason for accumulation of senile (

neuritic

) plaques and neurofibrillary tangles remains poorly understood, as does the reason for non uniform distribution in the cortex

.Slide6

Diagnosis

Clinical diagnosis is made by identifying progressive decline in memory both with clinical examinations and

neuropsychologic

tests and has been historically based on the

the

NINCDS-ADRA criteria

, which divides patients according to the certainty of the

diagnosis different

catagories

Definite

:

clinical diagnosis and histologic confirmation

P

robable

: typical clinical syndrome without histologic confirmation

81% sensitive, 73% specific 

Possible

:

atypical clinical features without histologic confirmation but no alternative diagnosis Slide7

AD

The only definitive diagnostic test is brain biopsy which in practice is rarely obtained. As such the combination of clinical features and neuroimaging are usually considered

sufficient.

A

lthough

especially with the recognition of variants, this approach undoubtedly misdiagnoses a significant number of cases

.

A number of CSF biomarkers are being used which may further help diagnosis. They include beta-amyloid, total tau, and

hyperphosphorylated

tau  Slide8

Cat Scan

Although CT is able to demonstrate the characteristic patterns of cortical atrophy, MRI is more sensitive to these changes, and better able to exclude other causes of dementia (e.g. multi-infarct dementia) and as such is the

favored

modality. 

Case

courtesy of

A.Prof

Frank Gaillard, Radiopaedia.org,

rID

: 33753Slide9

MRI

The primary role of MRI (and CT for that matter) in the diagnosis of Alzheimer disease is the assessment of volume change in characteristic locations which can yield a diagnostic accuracy of up to 87

%

The diagnosis should be made on the basis of two features:

mesial

temporal lobe atrophy

temporoparietal

cortical atrophy Slide10

Mesial Temp. Lobe Atrophy

Mesial temporal lobe atrophy can be viewed directly by assessing for hippocampal and

parahippocampal

decrease in volume, or indirectly by examining enlargement of the

parahippocampal

fissures. The former is more sensitive and specific but ideally requires actual volumetric calculations rather than 'eye-balling' the

scan.Slide11

Case courtesy of

Dr

Bruno Di

Muzio

, Radiopaedia.org,

rID

: 42027

Case courtesy of

Dr

Bruno Di

Muzio

, Radiopaedia.org,

rID

: 42027Slide12

Case courtesy of

Dr

Bruno Di

Muzio

, Radiopaedia.org,

rID

: 37720Slide13

Coronal ImagingSlide14

NEUROQUANT

WHAT IS IT?

WHY USE IT?Slide15

NEUROQUANT

NeuroQuant

provides automatic computation of volumes of 11 key neuro structures.

Results

are reported in a General

Morphometry

Report with volumes by hemisphere with

an

asymmetry index

Age

Related Atrophy report for hippocampal and inferior left ventricular volumes plotted against an age related normative database.Slide16

ADNI

Alzheimer’s Disease Neuroimaging Initiative

800 total pts

200 controls

4

00 pts with Prodromal AD or MCI

200 pts early stage AD

Developed scanning parameters to allow volumetric imaging over multiple platforms

3D T1 weighted data sets with high quality G-W diff.

Approved by FDASlide17

Flow of DataSlide18

Neurologist Feedback

vMRI

provides information

that is not otherwise available and

that

is

complementary to the history, neurological

exam, neuropsychological

testing,

biofluid

tests, and

nuclear medicine

imaging currently available for

evaluating cognitive

impairment. In addition, the report

provides a

visual aid for educating patients and their families.Slide19

Conversion of MCI to AD

Behavioral, CSF and

vMRI

biomarkers each predict risk of conversion

Combinations of these substantially improve predictions

Goal of CSF markers to increase certainty that a pt. with MCI has or does not have the underlying AD pathophysiology

Medial T. lobe atrophy alone or in combination was associated with the most rapid rate of conversion, (15 month median survival times)Slide20

Atrophy

i

s the pathological event that immediately precedes and underlies, functional decline to dementia

AB develops years or decades prior to cog. imp. But when its

assoc

with memory impairment it has a sig. higher risk of conversion

Pts. With MCI who test +for AB were likely to convert to AD when hippocampal atrophy was present

Neurology 2011;77:1619-1628Slide21

Tech. Factors

Must say

Neuroquant

on the Rx

Pts. Scanned at certain sites. (B,AL,AN,Q,W,P)

Pt. motion

during scan.

Artifacts affecting overall image quality.

Brains showing gross amount of structural abnormality.

Surgical resections must not be larger than 30 cc.

Tumors must not be larger than 15 cc. No contrast agents are applied.Slide22

Age Related Atrophy ReportSlide23

General Morphometry ReportSlide24

Chronic Traumatic

Encehalopathy

Chronic traumatic encephalopathy

 (

CTE

) is a 

neurodegenerative

tauopathy

 that is thought to result from mild repetitive head trauma

.

M

ost

commonly seen in amateur and professional

athletes

where head contact is common (e.g. boxing

, football, rugby, ice hockey), as well as in military personnel exposed to explosive

blasts.

 Slide25

CTE

Symptoms have an insidious onset, most often years after the initial injuries, with loss of normal attention, concentration and memory. This can progress, in some cases in 2-3 years, to include motor symptoms such impaired gait, impaired, executive function, lack of insight and poor judgementSlide26

CTE

There is

generalized

cerebral atrophy with more pronounced atrophy of the frontal and temporal lobes (including 

mesial temporal lobe

) as well as the 

thalamus

, 

hypothalamus

and

mammillary bodies

. 

CTE is

characterized

by the presence of 

neurofibrillary

 tangles and TDP-43 binding protein in subcortical and perivascular regions, often with reactive astrocytes and microglia Slide27

MRI

Imaging

features of CTE are nonspecific but the following may be seen 

generalized

cortical atrophy

hippocampal atrophy

vermian

atrophy

cavum septum

pellucidum

features of 

diffuse axonal injury

 (e.g.

microhaemorrhagesSlide28

PET IMAGING with [F-18]

FDDNP

attaches to Tau proteinsSlide29

Vascular Dementia

Vascular dementia

, also known as

 vascular cognitive impairment

, is the second most common cause of

dementia.

It

is primarily seen in patients with 

atherosclerosis

and chronic

htn

 and results from the accumulation of multiple white matter or cortical infarcts, although cerebral

haemorrhages

can be variably includedSlide30

Vascular Dementia

Incidence has been variably reported, but is strongly correlated with age, seen in only 1% of patients over the age of 55 years of age, but in over 4% of patients over 71 years of age 

.

To

add to the confusion, given the prevalence of Alzheimer's disease, the two are commonly seen

together.

Additionally

some patients develop accelerated vascular changes due to specific underlying disease (e.g. 

CADASIL

 and 

Fabry

disease

), and thus their demographics will be quite separate from the general population. Slide31

Vascular Dementia

Case

courtesy of

A.Prof

Frank Gaillard, Radiopaedia.org,

rID

: 10674Slide32

Cerebral microhaemorrhage

Overlap of CMH and Dementias.

Seen in Chronic HTN, AA, CTE, Vascular Dem.

CMH

,

or

microbleeds

,

are usually defined as <5 mm in size, and have a number of underlying causes

.

Best seen on Gradient imaging and esp. SWI imaging.Slide33

Types of Microhemmorhages

Chronic Hypertensive

Amyloid

A

ngiopathySlide34

Etiology

chronic hypertensive encephalopathy

 (common)

typically involve the basal ganglia, thalami as well as brain stem, cerebellum and corona

radiata

cerebral amyloid

angiopathy

 (common)

typically involves the grey-white matter junction; usually spares the basal ganglia

Vascular

dementias

CTE

cavernous

malformations

multiple (familial) cavernous malformation syndrome

post cerebral radiotherapy 

septic and fat emboli 

cerebral vasculitis

 (primary or secondary): 

microhaemorrhages

usually located at the

corticomedullary

junction

haemorrhagic

diffuse axonal injury (DAI)

: typically involves the grey–white matter junction, splenium of the corpus callosum, and

dorso

-lateral brainstem 

haemorrhagic

micrometastases

 (rare): melanoma or renal cell carcinoma 

CADASIL

 (rare): 

microhaemorrhages

have been reported to occur in 25–70%of cases without a characteristic

distributionSlide35

Synucleinopathies

Synucleinopathies

 are a subgroup of 

neurodegenerative diseases

,

characterised

by impairment of alpha-

synuclein

metabolism, resulting in abnormal intracellular deposits and can further be divided into those with and those without the formation of 

Lewy bodies

:

diseases with 

Lewy bodies

Parkinson disease

 / 

Parkinson disease dementia

Lewy body disease

multiple systemic atrophy (MSA)Slide36

PD

Parkinson disease (PD)

, also known as 

idiopathic parkinsonism

, is

a

neurodegenerative

disease

 and 

movement disorder

characterised

by a resting tremor, rigidity and

hypokinesia

due to progressive degeneration of dopaminergic neurons in the

substancia

nigra. Slide37

PD

Clinical presentation

Parkinson disease is classically 

characterized

 by a triad of features: 

resting tremor

rigidity

bradykinesia

postural instability: sometimes added as a cardinal feature Slide38

MRI

Radiographic features

Initial imaging findings are subtle and only potentially seen on MRI. With advanced disease, non-specific

generalized

minor cerebral volume loss can be demonstrated.Slide39

Swallow Tail Sign

SWI Slide40

Absent Swallow Tail Sign

PD Slide41

DLB

Dementia with Lewy bodies (DLB)

, also known as 

Lewy body disease

, is

a

neurodeg

disease

related

to 

Parkinson's disease (PD

)

. It is reported as the second most common form of neurodegenerative dementia following 

Alzheimer’s disease (AD)

, accounting for 15-20% of cases at autopsy. Slide42

DLB vs. AD

Features reported

include:

generalized

decrease in cerebral volume most marked in

frontal lobes

parietotemporal

regions

enlargement of the lateral ventricles

relatively focal atrophy of  the 

midbrain

hypothalamus

substantia

innominata

Perhaps more importantly the 

hippocampi

 remain normal in size, helping to distinguish Lewy body disease from 

Alzheimer's diseaseSlide43

MSA

Multiple system atrophy (MSA)

 is a sporadic neurodegenerative disease (one of the 

synucleinopathies

)

characterised

by varying degrees of cerebellar ataxia, autonomic dysfunction, parkinsonism and corticospinal dysfunction. 

MSA-C: 

 predominance of cerebellar symptoms (

olivopontocerebellar

atrophy

)

MSA-P: 

 predominance of parkinsonian signs and symptoms (

striatonigral

degeneration

)Slide44

MSA

MRI

T2: 

hyperintensities

 typically present in the pontocerebellar tracts

pons: 

hot cross bun sign

 (MSA-C)

middle cerebellar peduncles

cerebellum

putaminal

findings in

(MSA-P

)

:

reduced volume

reduced GRE and T2 signal relative to

globus

pallidus

reduced GRE and T2 signal relative to red nucleus

abnormally high T2 linear rim surrounding the putamen ("

putaminal

rim sign

"), seen at 1.5T (this is normal at 3T) Slide45

Hot Cross Bun Sign

MSA-C

Case courtesy of

A.Prof

Frank Gaillard, Radiopaedia.org,

rID

: 5465

Case courtesy of

A.Prof

Frank Gaillard, Radiopaedia.org,

rID

: 28472Slide46

Putaminal Rim Sign

MSA-PSlide47

NPH

Normal pressure hydrocephalus (NPH)

 remains a controversial entity with often ambiguous imaging findings. It is classically

characterized

by the triad of gait apraxia, urinary incontinence and dementia, although not all patients with NPH have all three. Slide48

Epidemiology

In a large study in Norway found a striking increasing incidence with increasing

age:

3.3 per 100,000 for people 50 to 59 years of age

49.3 per 100,000 for people 60 to 69 years of age

181.7 per 100,000 for people 70 to 79 years of ageSlide49

NPH

The classical clinical findings of normal pressure hydrocephalus

are:

urinary incontinence

deterioration in cognition (dementia)

gait disturbances

These can be remembered with the unkind mnemonic 

Wet, Wacky and Wobbly

. 

As the name suggests mean CSF opening pressure in patients with NPH is within the normal range  (<18

cmH

2

O).

 Slide50

NPH

Morphological changes

ventriculomegaly

frontal and temporal horns of the 

lateral ventricles

 most affected

upward bowing of the 

corpus

callosum

periventricular high signal on T2 weighted sequences

narrow 

callosal

angle

changes in

sulcal

size

crowding of the gyri at the vertex (with small sulci)

cingulate sulcus sign

: posterior part of cingulate sulcus is narrower than the anterior part, the divider between the two being a line drawn parallel to the floor of the 4th

ventricle

sylvian

fissures

 out of proportion to

sulcal

enlargement (which is minimal) and hippocampus and mesial temporal lobe volumes (which are near normal)Slide51

NPH

Case courtesy of

Dr

Bruno Di

Muzio

, Radiopaedia.org,

rID

: 41180

Case courtesy of

Dr

Ruslan

Esedov

, Radiopaedia.org,

rID

: 8401Slide52

Narrow Callosal

Angle

50-80 degreesSlide53

Cingulate Sulcus Sign

narrower post than antSlide54

NPH

CSF flow studies

increased

aqueductal

stroke volume

aqueductal

stroke volume is the average volume of CSF moving through the cerebral aqueduct

calculated by summing the absolute values of stroke volume in systole and diastole and dividing by 2

(forward stroke volume + reverse stroke volume)/2

increased

aqueductal

peak velocity

various publications have set various normal and abnormal ranges

flow rate of > 24.5mL/min 95% specific for NPH 

9,11

stroke volume of > 42

microL

shown on one paper to predict good response from shunting Slide55

Clinical History

A good clinical history is

a must

if the importance of subtle findings is be appreciated. Unfortunately all too often requests contain only vague details such as "dementia?". If possible further history should be obtained including: 

patient demographics

age, gender, ethnicity, occupation

main presenting complaint

characterization

of cognitive symptoms

attentional problems

memory problems (e.g. short term / long term / ante-grade / retrograde)

language problems (e.g. receptive, expressive) 

visual/constructional problems

apraxia

personality change (e.g. disinhibition, aggression) 

characterization

of physical symptoms

Tremor, Rigidity,

Hyperkinesis

, Falls, Dysphagia, Incontinence, eye

signs

time course

onset, duration, progression

any relevant family

history

any risk factors for differential diagnosis

e.g. smoking, hypertension, diabetes, stroke

clearly

stated differential

diagnosis.