Case 22- brain Flashcards
1
Q
Motor loops- Basal ganglia
A
- Role of the basal ganglia is to facilitate behaviour and movements and inhibit unwanted or inappropriate movements.
- It is the direct and indirect motor loops which allow or inhibit these movements.
- When a structure of the basal ganglia is compromised there is an inability to switch smoothly between commands that initiate and maintain a movement and those that terminate the movement.
2
Q
Nuclei of the basal ganglia
A
- Input nuclei (receive information)- caudate nucleus, Putamen
- Intrinsic nucleus (process the information)- Globus pallidus externus, Subthalamic nucleus, Substantia nigra (pars compacta)
- Output nucleus (sends out information)- Globus pallidus internus, Substantia nigra (pars reticulata)
3
Q
Direct pathway of the basal ganglia- up to Globus pallidus internus
A
- Excitatory- allows movement to occur
- Movement is initiated from the cerebral cortex causes excitation of neurones in the striatum (corticostriatal pathway)
- Glutamate is released to the Caudate and Putamen
- Excitation of striatal neurones (striatopallidal or striatonigral neurones) inhibit the activity of the globus pallidus internus and substantia nigra par reticulata through the release of GABA
4
Q
Direct pathway of the basal ganglia- after globus pallidus internus
A
- Globus pallidus internus and substantia nigra pars reticulata neurones are inhibitory therefore reducing their action on the thalamus results in increased activity of thalamic neurones due to reduced GABA release
- Increased activity of the thalamic neurones (increased Glutamic acid release) causes excitation of the cells of the cerebral cortex therefore allowing movement to occur
- Dopaminergic neurones of the substantia nigra pars compacta project to the striatum exerting an excitatory influence on the striatal neurones through the release of Dopamine
5
Q
Direct pathway- Parkinson’s disease
A
Degeneration and depigmentation of the substantia nigra pars compacta which project to the striatum. This causes akinesia/bradykinesia as it causes underactivity of the direct pathway. As there is decreased inhibition of the Globus Pallidus internus and the Substantia nigra pars reticularis, more inhibitory signals are released so less excitatory signals are released from the thalamus reducing the cortex’s activity.
6
Q
Indirect pathway of the Basal ganglia up to Globus pallidus internus
A
- Signals from the cerebral cortex activate (excitatory) neurones in the striatum through the release of Glutamic acid
- Excitation of striatal neurones (striatopallidal) inhibit the activity of the globus pallidus externus through the release of GABA
- This prevents the globus pallidus externus neurones (pallidosubthalamic fibres) from inhibiting the subthalamic nucleus neurones, less GABA is released
- Resulting in the increase of activity of the subthalamic nucleus neurones which leads to the activation of the globus pallidus internus and substantia nigra pars reticulata neurones through the release of Glutamic acid
7
Q
Indirect pathway of the Basal ganglia after the globus pallidus internus
A
- The inhibitory globus pallidus internus and substantia nigra pars reticulata inhibit the thalamic neurones from projecting to the cerebral cortex therefore stopping the stimulation of unwanted movement. No release of Glutamic acid from the Thalamus
- Dopaminergic neurones of the substantia nigra pars compacta project to the striatum (nigrostriatal pathway) and can inhibit activity of the indirect pathway. Through the release of Dopamine which is inhibitory
8
Q
Hyperdirect pathway
A
The subthalamic nucleus can also receive excitatory signals from the cerebral cortex.
9
Q
Indirect pathway- Parkinsons disease
A
- Indirect pathway - dopamine has an inhibitory effect on neurones that project to globus pallidus externus.
- Loss of striatal dopamine causes overactivity of the indirect pathway
- Causes inhibition of the globus pallidus externus neurones, disinhibition of the subthalamic nucleus and therefore excessive excitation of the internal segment of globus pallidus. Reducing activity in the Thalamus and cerebral cortex
- Induced akinesia (loss of power of voluntary movement)
10
Q
Indirect pathway- Huntington’s disease
A
- Excessive, unwanted, abnormal movements (dyskinesias) occur in Huntington’s disease.
- Degeneration of the striatum (caudate nucleus and putamen)
- In this condition there is an attrition of cells that project to the external segment of the globus pallidus.
- This leads to disinhibition of the external pallidal neurons and inhibition of the subthalamic nucleus
- The globus pallidus internus neurones therefore become abnormally underactive and involuntary movements (chorea) occur as there is reduced activity in the indirect pathway. So overexcitation of the thalamus and cerebral cortex.
11
Q
Other disorders of the motor pathway
A
Abnormal movements occur as a complication of the long-term treatment of Parkinson’s disease with levodopa – causes underactivity of the indirect pathway and overactivity of the direct pathway.
12
Q
Ballism/Hemiballism/Hemiballismus
A
- A rare condition caused by damage to the subthalamic nucleus (often by stroke).
- Characterised by gross choreic, flailing movements of the contralateral limbs due to removal of the excitatory drive upon basal ganglia output neurons.
13
Q
Alzheimer’s disease summary
A
- Commonest form of dementia- approximately 50-70% of UK cases
- Heterogeneous, caused by ageing along with a complex interaction of genetic and environmental risk factors
- Post mortem shows conglomeration of amyloid plaques and tau neurofibrillary tangles; current hypothesis is that these are degradation products rather than targetable pathology
- Insidious, gradual onset over months and years
- Early memory loss followed by later more complex and varied symptoms e.g. personality change, apraxia, apathy…
- MDT is key- refer to memory clinic! Clinical diagnosis with supporting evidence
- Pharmacological and non-pharmacological approaches should be used in conjunction
- Treatment first line = AChE inhibitors, Second line = Memantine
14
Q
Vascular dementia summary
A
- Second most common cause of dementia (10-15%)
- Risk Factors include history of stroke or TIA, AF, hypertension, diabetes, hyperlipidaemia, smoking, obesity, coronary heart disease…
- Family history of stroke or cardiovascular disease
- Presentation varies significantly, as does speed of progression. May be simply cognitive decline, may be features of weakness, visual disturbances, apathy… Depends on area of brain
- Clinically, there is often an overlap with Alzheimer’s disease
15
Q
Lewy body dementia summary
A
- Dementia characterised by eosinophilic intracytoplasmic neuronal inclusion bodies (Lewy bodies) in the brainstem and neocortex
- Spectrum of Lewy body disorders, which may overlap, that include Parkinson’s disease and Parkinson’s disease-associated dementia
- Probably third most common cause of dementia in the UK
- Diagnosis of probable LBD requires two of the three core features: Fluctuating attention and concentration, Recurrent well-formed visual hallucinations, Spontaneous Parkinsonism
- DAT scans are useful although not diagnostic- remains a clinical diagnosis
- Avoid antipsychotics- can make Parkinsonism worse
- Treat with AChEs – most evidence is for rivastigmine.
16
Q
Frontotemporal dementia summary
A
- This is a progressive dementia, which typically affects the frontal and/or temporal lobes (atrophy)
- Probably 4th most common form of dementia (5%)
- One of the more common causes of dementia before the age of 65
- Features include: Loss of inhibition, Inappropriate social behaviour, Loss of motivation but without depression (apathy vs depression!!), Loss of empathy and sympathy, Change in preferences, Repetitive or compulsive behaviours, rituals, Loss of control over eating or drinking, Difficulties with planning, organisation or decision making.
- Memory and visuospatial skills usually preserved in early stages. Cognitive deficit less apparent than behavioural changes.
- Lack of insight.
- Loss of awareness of personal hygiene, and incontinence as the disease progresses.
- No pharmacological treatment available
