Transcript Lewy Body Dementia - Royal United Hospital

Dementia with Lewy
Bodies
Leonard Griffiths
Thursday 22nd Nov 07
Case: Mrs ME
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86♀
Admitted 2/10/07 with 2/12 Hx worsening
mobility
• Leg weakness
• No altered sensation of pain
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Fall noted 6/52 prior to admission
• ‘mechanical sounding’
• No LOC/HI/CP/palpitations/SOB
• Recalled incident
Case: Mrs ME
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Intermittent confusion for 5/52 prior to
admission
• Treated for UTI (although no urinary signs or
symptoms)
Case: Mrs ME
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PMH
• ‘Registered blind’
• Osteoporosis
• Angina
• Hypertension
• Asthma
• Episode of jaundice 40 yrs ago
PTWR
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Diagnosed ‘weakness of legs’
• ?musuloskeletal
• ?UTI
Abnormal results
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WBC 11.5; Neut 8.2
Na+ 128
• U Osmo 566
• U Na+ <20
• P Osmo 282
• P Na+ 132
•  not SIADH
Abnormal results
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Urine dip
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Lab +ve for nitrites and leukocytes
• Blood +
• Leuk +++
• Protein +
• Nitrites +
• Culture  ‘mixed growth suggesting contam.’
Abnormal results
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AMSE
• 8/10
• MMSE 20/28
• GDS 3/15
• i.e. not depressed
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CT brain
• Moderate small vessel disease
• Small L occipital infarct
SHO WR 6/10/07
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Thought pt had low mood  d/w
consultant  ref to Ψ liaison
• Felt that ‘new environment and poor eyesight
a significant factor in agitation’
Consultant WR 9/10/07
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Cogwheeling
Tremor
Short shuffling gait
‘Leans backwards’
• Impression: Parkinsonism
• 1/52 domperidone commenced
• Ref. to PD consultant
SHO WR 11/10/07
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Hallucinating
• “Horse woman of the year”
• Believed someone gave her eye drops (not
prescribed)
PD consultant review
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“Tricky mixed picture which is difficult to
disentangle”
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Hallucinations
• Although ?Charles Bonnet in relation to reduced
eyesight
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Some reduced memory
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Parkinsonism – but not typical PD
• ?DLB but has cerebrovascular disease
• ‘tremor rather fine’
• ‘balance  back’
Try madopar, ‘but suspect little to be gained
from medication’
SHO WR 15/10/07
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Hallucinating
• Relatives
• Monkey
Progress…
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18/10/07 madopar commenced
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22/10/07 more confused and
hallucinations worsening  madopar
stopped & rivastigmine commenced
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30/10/07 – paranoia and aggressive
Progress…
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6/11/07 – hallucinations worse at night 
quetiapine added
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16/11/07 – mood even lower 
venlafaxine added
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Now awaiting community hospital bed
Diagnosis
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Clinical features reflect anatomical
distribution of pathology rather than its
nature
Therefore subtle clinical features not
helpful
What is Dementia?
ICD-10 definition
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1. A decline in memory to an extent that it interferes with everyday
activities, or makes independent living either difficult or impossible.
2. A decline in thinking, planning and organizing day-to-day things, again
to the above extent.
3. Initially, preserved awareness of the environment, including orientation
in space and time.
4. A decline in emotional control or motivation, or a change in social
behaviour, as shown in one or more of the following: emotional lability,
irritability, apathy or coarsening of social behaviour, as in eating, dressing
and interacting with others.
• Maj, M.. 2002., Dementia, Second Edition [online]. 2nd Edition. Wiley.
Available from:
http://mil.ingramdigital.com/Browse/open.asp?ID=10147&loc=Cover
15 November 2007
Wikipedia definition
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Dementia is the progressive decline in
cognitive function due to damage or
disease in the brain beyond what might be
expected from normal ageing.
•
http://en.wikipedia.org/wiki/Dementia
Dementia
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Alzheimer's
Vascular
Lewy body
Alcohol
Pure vascular
Frontotemporal lobar degenerations
Creutzfeldt-Jakob disease
Dementia pugilistica
Moyamoya disease
Nomenclature
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Diffuse Lewy body Disease
Cortical Lewy body Disease
Lewy Body Dementia
Senile Dementia Of Lewy Type
Lewy Body Variant of Alzheimer's
Disease
Dementia with Lewy Bodies (preferred)
Dementia with Lewy Bodies
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Describes several common disorders causing
dementia
The main features of these conditions are:
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development of dementia with features overlapping
with those of Alzheimer's disease
development of features of Parkinson's disease
fluctuation in severity of condition on a day-to-day
basis
early development of hallucinations
Neuropathology
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Degeneration of substantia nigra
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Degeneration of the cortical areas of the
brain with many or all of the features
seen in Alzheimer's disease
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Remaining nerve cells contain abnormal
structures called ‘Lewy bodies’
Lewy Bodies
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Abnormal aggregation of proteins, including
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alpha-synuclein, neurofilament and ubiquitin
• PD
• Dementia with Lewy bodies
• MSA
• Amyotrophic lateral sclerosis
• Hallervorden-Spatz syndrome
Core, body, halo
Variations in shape
Synucleopathies
www.saigata-nh.go.jp/.../SN295LEWYSYNUCLX100.JPG
www.saigata-nh.go.jp/.../SN295LEWYSYNUCLX100.JPG
Tonus und Bewegund (Muscle
Tone and Movement)
Frederich Heinrich Lewy
opm.phar.umich.edu/images/proteins/1xq8.gif
Alpha-synuclein
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Abundant CNS protein
Composed of 140 amino acids
Alpha form of synuclein is the only form
capable of aggregating into fibrillar structures
in vitro
Beta-synuclein is not localized in Lewy
bodies, it may have a role in regulating
alpha-synuclein metabolism or aggregation
faculty.uncfsu.edu/shan/0728%2020c%20006a.gif
Normal role of alpha-synuclein
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Synaptic plasticity
Negative regulation of dopamine
neurotransmission
Protection at nerve terminals during
injury
Trafficking of cargo in the ER/Golgi
complex
Alpha-synuclein in disease
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‘Ubiquitinated’ with no loss of
proteasome function, suggesting there is
an excessive accumulation of alphasynuclein that overwhelms the
proteolytic machinery (Tofaris, et al.
2003). This may promote the formation
of Lewy bodies
Presenting Features DLB
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Dementia normally presenting feature
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Minority present with parkinsonism
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Some with psychiatric disorder without dementia
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Others with orthostatic hypotension, falls or transient
disturbances of consciousness
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Sporadic (rarely familial)
Common Features
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Fluctuation in cognitive performance and
functional ability
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Variations in attention and level of
consciousness
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Visual hallucinations in two-thirds
Gelder, Michael G.; Lopez-Ibor, Juan Jose; Andreasen, Nancy C..
2003., New Oxford Textbook of Psychiatry, Volume 1 [online]. New
Edition. Oxford University Press. Available from:
http://www.myilibrary.com/Browse/open.asp?ID=14714&loc=416 15
November 2007
Sensitive signs for ‘bedside’
diagnosis
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Psychiatric vs. cognitive symptoms
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Fluctuant cognitive state
• Hallucinations
• Delusions
Hallucinations
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Repeated visual hallucinations are
present in about two-thirds of patients
• vivid, colourful, and sometimes fragmented
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figures of people and animals
often complex, detailed and rapidly moving
can involve scenes and bizarre situations
can start with misinterpretations and are usually
short
often occur at night
usually not distressing to the patient
Treatment
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No cure
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Cognitive symptoms 
acetylcholinesterase inhibitors, such as
donepezil and rivastigmine
• May reduce psychiatric and motor symptoms
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Rigidity  levodopa
Summary
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Third most common dementia
Central feature is progressive cognitive
decline
• Pronounced fluctuations
• Recurrent visual hallucinations
• Parkinsonism
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Symptoms caused by Lewy Bodies
comprised of bits of alpha-synuclein