Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Medicine year 2 semester 2 > Case 22- Alzheimers and Lewy body disease > Flashcards

Case 22- Alzheimers and Lewy body disease Flashcards

1
Q

Alzheimer’s disease- two types

A
  • Sporadic age associated Alzheimer’s disease (95% of cases) with a latter age onset of 65
  • Early onset Alzheimer’s disease- affects 35-40, hereditary component
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Alzheimer’s disease- Macroscopic changes

A
  • Severe atrophy in the hippocampus, shrinkage of the grey matter and the gyri and sulci appear more pronounced.
  • Reduced brain weight around 1000g- normal 1200-1400g
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Alzheimers- changes in the anterior hippocampus

A
  • Marked enlargement of the lateral ventricle
  • Severe atrophy of the medial temporal lobe and enlargement of inferior horns of ventricle
  • Thinning of the gyri and deepening of the sulci
  • Substantial nigra of the midbrain remains fairly well pigmented
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Alzheimer’s disease- Microscopic changes

A
  • Intracellular inclusions of hyperphosphorylated tau in the cell bodies
  • Hyperphosphorylated Tau can also appear in the axons in the neurites of these neurons and these are called neuropil threads.
  • The first region of the brain affected is the hippocampus in the entorhinal cortex which explains early memory loss
  • Extracellular accumulation of amyloid-beta plaques
  • Cerebral amyloid angiopathy
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Braak stages- the particular pattern of deposition of Tau pathology:

A
  • Braak stages I and II= I NT in transentorinhal cortex, II Entorhinal cortex
  • Braak stages III and IV- III Occipito-temporal cortex, IV Middle temporal gyrus. Pre-clinical Alzheimers disease
  • Braak stages V and VI- V Peristriate (occipital), VI Striate (primary visual cortex). Alzheimer’s disease
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Alzheimers disease- extracellular accumulation of amyloid-beta (Thal phases)

A
  • Phase 1- Neocortex
  • Phase 2- Hippocampus, Amygdala, Cingulate (Limbic)
  • Phase 3- Basal ganglia, Thalamus, Motor cortex (deep grey matter)
  • Phase 4- Substantia nigra, Medulla oblongata (Brainstem)- Alzheimer’s disease
  • Phase 5- Cerebellum, Pons- Alzheimer’s disease
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Criteria for AD- AB and HPT

A

Hallmark pathologies are hyperphosphorylated tau (HPT) tangles and amyloid-beta (Aβ) plaques
Neuropathological criteria required for AD
• HPT - Braak stages V-VI AND
• Aβ Thal phases 4-5

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Symptoms of Lewy body disease

A

Clinically manifests with Parkinsonism (Parkinson’s disease). 80% then go on to develop additional psychiatric symptoms such as fluctuating cognition, REM sleep behaviour disorder, and visual hallucinations (Parkinson’s disease dementia, and dementia with Lewy bodies.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Differentiating between the different types of Parksonian diseases

A

Parkinsons disease is just associated with the physical symptoms, Parkinsons disease dementia has some of the psychiatric symptoms and Dementia with Lewy bodies has more of them. Cant differentiate between them in imaging but can clinically

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Parkinsons 1 year rule

A

If the Parkinson’s disease develops a year before the psychiatric symptoms then its Parkinson’s disease dementia. If the Psychiatric symptoms start within a year of the physical symptoms or before them then its Dementia with Lewy bodies.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Macroscopic changes in Lewy body disease

A
  • Depigmentation of the dopaminergic cells in the substantia nigra
  • Brain weight is typically normal
  • Possible cerebral atrophy in the DLB
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Microscopic changes in Lewy body dementia

A
  • Alpha-synuclein inclusions in cell bodies- Lewy bodies

* Alpha synuclein inclusions in neurites and axons- Lewy neuritis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Lewy pathology consensus criteria- where in the brain it originates

A

• Parkinsons dementia may have originated in the brainstem
• Dementia with Lewy bodies may originate in the Olfactory bulb or Amygdala
In the limbic stage they may have developed symptoms and they might not have

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Clinical symptoms of Lewy body disease

A

• Parkinsonism (PD, PDD, and DLB)
• REM sleep behaviour disorder (PDD and DLB)
• Fluctuating cognition (PDD and DLB)
• Visual hallucinations (PDD and DLB)
Hallmark pathology is α-synuclein (α-syn) positive Lewy bodies and Lewy neurites

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Neuropathological criteria required for diagnosis of LBD

A
  • Braak LB stage 3 - PD

* Braak LB stages 5 or 6 – PDD or DLB (clinical diagnosis required for final diagnosis)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Huntingtons disease

A

An autosomal dominant disorder. Abnormal expansion of CAG triplet repeat in the huntingin gene, normal 20 repeats variable penetrance of 36-39 (40+ typical).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Huntingtons disease- clinical presentation

A
  • Triad- motor, behaviour and cognitive defects. Can progress to dementia
  • Chorea 50-70%
  • Hypokinetic disorder
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Huntington’s- Macroscopic changes

A
  • Cerebral atrophy (30% volume)
  • Enlargement of lateral ventricles
  • Gyral shrinkage
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Key hallmarks of Huntington’s disease

A

Key hallmarks is atrophy of the neostriatum (caudate and putamen). 60-64% of volume is lost happens in a caudal to rostral direction. There is atrophy of the globus pallidus, thalamus, brain stem (s.nigra) and the cerebellum

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Huntingtons disease- Microscopic changes (focus on the striatum)

A
  • Loss of neurons
  • Remaining neurons are shrunken and dysfunctional. Called Neostriatal dark neurones due to the condensed chromatin in the middle
  • Astrocytosis and microgliosis- may be due to inflammation
  • Intranuclear inclusions of huntington proteins for differentiation from huntington mimics
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Huntingtons disease- Vonsattel grading (0-4)- the 3 sections

A

Takes into account macro and microscopic descriptions- you need 3 coronal sections:
• Level of the nucleus accumbens (striatum)
• Caudate edge of the anterior commissure: Globus Pallidus
• Lateral geniculate nucleus: Thalamus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Vonsattel grading= Grade 0 and 1 (Huntingtons disease)

A
  • Macroscopically normal brain
  • Neuronal loss <50% in striatum (quantitative)
  • None - moderate astrocytosis in striatum
  • Nuclear inclusions present
  • 4% of Huntingtons cases
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Vonsattel grading= Grade 2 (Huntington’s disease)

A
  • Visible atrophy of caudate head (convex) and putamen.
  • G.Pallidus and nucleus accumbens normal
  • Neuronal loss and moderate astrocytosis evident (qualitative) in striatum
  • 16% of Huntington cases
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Vonsattel grading= grade 3 (Huntingtons disease)

A
  • Severe atrophy of caudate (flat) and putamen.
  • Moderate atrophy of G.Pallidus. N accumbens spared
  • Severe neuronal loss and astrocytosis in G. Pallidus
  • 52% of Huntingtons cases
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Vonsattel grading= grade 4 (Huntingtons disease)

A
  • Very severe atrophy of caudate (concave) and putamen.
  • G.Pallidus severely atrophic. Yellow brown discolouration
  • Neuronal loss >90% and severe astrocytosis in striatum and G. Pallidus. Mild neuronal loss in N.accumbens
  • 28% of Huntingtons cases
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Hallmarks of Huntingtons

A

Macroscopically the key hallmark observation is atrophy of the neostriatum (caudate and putamen)
Hallmark pathology is intranuclear inclusions of huntingtin and astrogliosis in the caudate and putamen)

27
Q

Movement disorders

A

Diseases characterised by abnormal or excessive movements occurring in conscious patients. They are disorders of basal ganglia function but there is poor correlation between movement disorders and basal ganglia lesions

28
Q

The Basal ganglia

A

1) The Basal ganglia are nuclei deep in the brain that are responsible for involuntary movements such as tremors, athetosis, and chorea.
2) Close to the thalamus and ventricles.
3) The globus pallidus is divided into an internal and external portion.
4) The basal ganglia is comprised of the striatum, which consists of the caudate nucleus and the putamen, the globus pallidus, the subthalamic nucleus, and the substantia nigra.

29
Q

The systems the Basal ganglia is involved in

A

Its involved in motor, associative (cognitive) and limbic system (processing of information)

30
Q

The subdivisions of movement disorders

A
  • Akinetic-rigid disorders i.e. Parkinson’s disease, slowness and reduced movement (though there is a tremor in Parkinsons)
  • Hyperkinetic disorders i.e. Huntington’s disease- excessive movement
31
Q

Hyperkinetic symptoms

A
  • Tremor- an involuntary, rhythmic, oscillatory movement of a body part
  • Dystonia- sustained muscle contractions, which frequently cause twisting and repetitive movements or abnormal postures
  • Chorea- irregular, unpredictable, brief, jerky movements that flit from one body part to another in a random sequence
  • Ballism- large amplitude, violent flinging or flailing. Can involve the subthalamic nucleus, seen in Parkinsons
  • Tic- an abrupt, jerky, repetitive movement involving discrete muscle groups. Can be repetitive. Can be vocal or motor
  • Myoclonus- a sudden, brief, shock like involuntary movement. Can be cortical or spinal
32
Q

Types of tremor

A

You can have an action or rest tremor. Types of action tremor- postural, kinetic (simple and intentional movement), task specific i.e. writing. Isometric tremors which occur when you exert pressure i.e. pushing your hands against a wall

33
Q

Tremors in Parkinsons

A
  • Rest tremor- a tremor in a fully resting limb. In Parkinsons it usually starts as a pill-rolling motion in the fingers and thumb of one hand then becomes bilateral.
  • Postural tremor- occurs whilst voluntarily maintaining a position against gravity. For example, holding your hand out
  • Intention tremor- occurs during voluntary movement, becomes worse when you get nearer the object i.e. to pick up an orange
  • Orthostatic tremor- 13 to 18 Hz tremor which predominantly affects the weight bearing limbs i.e. when standing. High coherence between antagonistic and contralateral muscle groups. Sensation of unsteadiness and imbalance while standing. Tends to disappear when the person starts walking
34
Q

Dystonia

A

Sustained muscle contractions which frequently cause twisting and repetitive movements or abnormal postures. Jerky movement in one direction. Cervical dystonia affects the head and neck

35
Q

Chorea

A

Choreic movements. Irregular, unpredictable, brief, jerky movements that flit from one body part to another in a random sequence. Irregular rhythmic oscillation of the body part.

36
Q

Hypokinetic phenomena- Parkinsons

A
  • Bradykinesia- slowness and poverty of movements, seen in Parkinsons
  • Rigidity- an increase in muscle tone, elicited during passive movement. In Parkinsons its more prominent in flexor muscles, causes the stooped posture. A big increase in muscle tone of the neck is a red flag for Parkinsonian syndrome such as progressive supranuclear palsy or multiple system atrophy
  • Postural disturbances- i.e. stooped posture in Parkinsons disease, flexion in knees and elbow. The tone in the flexor muscles are more prominent then in the extensor muscles
37
Q

How does Bradykinesia usually manifest as

A
  • Hypomimia- reduction in visual expression
  • Micrographia- reduction in size of hand writing
  • Monotonous speech or slurred
  • Reduced blink rate
  • Generalised motor slowness
  • Reduction in arm swing when walking
37
Q

How does Bradykinesia usually manifest as

A
  • Hypomimia- reduction in visual expression
  • Micrographia- reduction in size of hand writing
  • Monotonous speech or slurred
  • Reduced blink rate
  • Generalised motor slowness
  • Reduction in arm swing when walking
38
Q

Parkinsons epidemiology

A

Parkinsons is a progressive neurodegenerative disease which affects 1-2% of >60. Incidence increases with age and men are more frequently affected then women. Risk may be related to ethnicity or geography. Most common movement disorder. Patients who get Parkinsons under 50 are more likely to have the gene mutations

39
Q

Causes of PD is multifactorial with contributions from:

A
  • Ageing
  • Genetic predisposition
  • Exposure to toxins/viruses
  • Head injuries- especially if it causes damage in the Basal ganglia
  • Impaired oxidative mechanisms
40
Q

The cardinal pathological features of PD are

A

• Formation of proteinaceous intraneuronal inclusions (Lewy bodies and Lewy neuritis)
• Progressive neuronal loss particularly targeting the substantia nigra pars compacta in the midbrain
• There is loss of the neuromelanin in the substantia nigra
The major component of Lewy bodies and Lewy neurites in an aggregated form of alpha-synuclein. You also get decreased dopamine content in the substantia nigra and neostratum in PD.

41
Q

Parkinsons- Nigrostriatal pathway

A

Starts in the substantia nigra, the dopaminergic neurones project the the basal ganglia and the striatum (mostly putamen) into the caudate. This is the pathway affected in Parkinsons. Reduces dopamine in the putamen, caudate and striatum. Results in rigidity, tremor and bradykinesia

42
Q

Motor symptoms in PD

A
  • Tremor
  • Increased muscle tone- rigidity, stiffness
  • Bradykinesia- reduced or slow movement
  • Postural instability
43
Q

Non-motor symptoms of PD

A
  • Sleep disorders
  • Depression
  • Dementia
  • Fatigue
  • Hyposmia
  • Pathological gambling
44
Q

Time scale of symptoms in Parkinsons

A

Hyposmia, fatigue and sleep disorders can occur before the physical symptoms. Related to the Lewy bodies being in the lower brainstem. REM sleep disorder is the prodromal stage of Parkinsons and Lewy body dementia.

45
Q

Parkinsons- scans

A

DAT scan can be used to diagnose Parkinsons, the dopamine terminal takes up the tracer and is dyed. In PD the dye is not taken up and its less bright. There is reduced signal from the substantia nigra, loss is normally in the posterior part of the putamen. Cant differentiate between the different types of Parkinsonism in a scan.

46
Q

Braak stages in the development of PD

A
  • Lewy body pathology begins in the medulla oblongata, olfactory structures, and pons (stages 1 and 2)
  • In stages 3 and 4, pathology progressively spreads to the SN, other midbrain brain nuclei, and the limbic areas. When the motor (classical) signals occur, typically after 10 years of the disease starting
  • In stages 5 to 6, inclusions appear in the association and primary neocortex. When cognitive problems occur
  • First signs of motor parkinsonism start in stage 4 and 5
47
Q

Onset of Huntingtons

A

Follows autosomal dominant inheritance, movement disorder and dementia
• Juvenile (4-19yr, Westphal variant) 10%
• Early and mid-life (20-49yr) 65%
• Late onset (25%)

48
Q

Huntingtons disease- clinical features

A
  • Neurological- chorea, Parkinsonism in juvenile onset, oculomotor impersistence
  • Psychiatric- change in personality, schizophreniform and depressive psychoses, cognitive defects then progressive dementia
  • Death 10-20 years after onset
  • In Juvenile Huntington’s the Parkinsonism with rigidity and atkinesia, whilst they may not have any Chorea
49
Q

Chorea in Huntingtons

A

Varies in severity, affects the whole body, may plateau later and be masked by rigidity. Can be minimal in juvenile onset cases, its associated with clumsiness and in-coordination.

50
Q

Huntington’s disease genetics

A
  • Mapped to the short arm of chromosome 4- its an expanded CAG repeat sequence, the normal amount is 19 in HD its 46
  • Due to a gene product called Huntingtin
  • Inverse correlation between CAGn and age of onset, the more CAG the earlier the onset
  • Anticipation- male patients with affected fathers progress the fastest
51
Q

Huntington’s pathology

A
  • Atrophy of caudate (57%) and Putamen (64%)
  • Loss of volume of the cerebral cortex
  • Neuronal loss and astrocytosis in the striatum
52
Q

Huntington’s disease management

A
  • Pharamcological= Tetrabenazine, sulpiride for chorea, they block the dopaminergic receptors. Antidepressants and mood stabilisers for psychiatric features
  • Multidisciplinary team involvement
  • Genetic testing and counselling
  • Disease modification and transplantation
53
Q

Huntington’s inheritance

A

Huntington’s disease is a neurodegenerative disease that is inherited in an autosomal dominant pattern. Children of an affected parent have a 50% chance of developing it, however, up to 10% of cases are due to a new mutation so there will be no previous family history.

54
Q

Huntington’s- triad

A

Movement disorders, behavioural problems and cognitive decline

55
Q

Huntingtons- time period

A

Symptoms tend to start at 30-50 years and they progress with time. Most early diseases start with subtle behavioural symptoms which are not initially noticed, patients tend to present with movement disorders.

56
Q

Huntington’s- movement symptoms

A
  • Chorea- classically associated with Huntington’s. Brief, irregular movements that are not rhythmic. Initially mild but can progress to cause severe uncontrollable limb movements. As the disease progresses chorea is replaced with dystonia and rigiditity
  • Dystonia- sustained or repetitive muscle contractions results in twistind and repetitive movements or abnormal fixed postures
  • Myoclonus- brief non-purposeful jerking movement of the muscle
  • Dysarthria- difficulty speaking characterised by poor articulation of words
  • Dysphagia- difficulty swallowing
  • Abnormal eye movements
57
Q

Huntington’s behavioural problems

A
  • Apathy - a lack of emotion, feeling or interest in something
  • Dysphoria - a state of unease and dissatisfaction
  • Irritability, agitation and aggression
  • Poor self-care
  • Inflexibility
58
Q

Huntingtons- cognitive decline

A

Areas of cognition that are particularly affected include:
• Planning
• Abstract thinking
• Inhibition of inappropriate actions

59
Q

Huntington’s diagnostic criteria

A

There is no agreed diagnostic criteria
• The key clinical feature for suspecting a diagnosis is the presence of specific movement disorders (e.g. chorea)
• This can then be confirmed by a diagnostic genetic test
Patients presenting with behavioural problems or cognitive decline without motor signs (even with a positive family history) should not be given a diagnostic test.

60
Q

Diagnostic genetic testing and predictive genetic testing

A

Diagnostic genetic testing is different to predictive genetic testing. Predictive genetic testing is used in patients with a family history of Huntington’s to see whether they have the gene and therefore if there are at risk of developing the disease. Although the test can tell whether the person is carrying the HD mutation, it cannot tell when the disease itself will start to develop.

61
Q

Huntington’s other investigations

A
  • MRI and CT scans can show some changes in moderate-severe disease but are unhelpful for diagnosis in early disease.
  • Testing for other causes of movement disorders e.g. thyroid disease, Wilson’s disease
  • Patients presenting with confusion should have a confusion screen
62
Q

Huntingtons- Hemiballism/Hemiballismus

A

Affects an arm and ipsilateral leg due to a stroke in the contralateral subthalamic nucleus

Medicine year 2 semester 2 (47 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions