Brain Disease Flashcards
General neurological assessment of patients will include…
Cognitive function Gait State of consciousness Mental state, attitude insight Co-ordination/fine movements Cranial nerves Motor system (wasting, tremor, power, tone, reflexes) Sensory system (touch, pain, vibration, 2 point discrimination)
General psychiatric assessment will include…
Appearance and general behaviour
Mood and affect
Speech, disorders of thought (stream, form, content)
Insight
Abnormal beliefs and perceptions
Cognitive state (concentration, confusion, memory)
Parkinson’s symptoms
Decrease in spontaneous movements Gait difficulty Postural instability Rigidity Tremor
Pathology of Parkinson’s
Degeneration of pigmented neurons in the substantia nigra of the brain
Decreased dopamine availability
Incidence of Parkinson’s
1-2%
Frequency increases exponentially after 60 years
Higher incidence in developed countries
Are men or women more affected by Parkinson’s
Both equally affected
Where is the most effective site for deep brain stimulation in Parkinson’s patients?
Subthalamic nucleus (STN)
What frequency of DBS alleviates Parkinson’s symptoms?
> 60 Hz
What frequency of DBS exacerbates Parkinson’s symptoms?
< 30 Hz
What is the hypothesis behind DBS for Parkinson’s patients?
Stimulation prevents low frequency rhythm generation and desynchronises the extrastriatal basal ganglia and cortex
Does Parkinson’s have a monogenetic basis?
<10% monozygotic twins show concordant expression of PD
Why do the substantia nigra dopamine neurons die in Parkinson’s disease?
Most cases are idiopathic
Aberrant proteostasis
Environmental factors which disrupt mitochondrial function e.g. pesticides
What are the genetic forms of Parkinson’s disease?
Associated with mutations in the a-synuclein, Parkin, PINK1, DJ-1, LRRK2, ATP13A2, PLA2G6
Identical mutations in family members can be associated with different onsets and severities
21st century treatments for Parkinson’s disease
Protection
Regeneration
Stimulation
Protection against Parkinson’s disease
Voltage-gated Ca2+ channel blockers, glial derived neurotrophic factor (Amgen)
Regeneration in Parkinson’s disease
Transplantation Stem cells (induced, embryonic)
Stimulation in Parkinson’s disease
Smart stimulators
Optogenetics
Who first described Parkinson’s disease?
Dr. James Parkinson
1817
Who first described Huntington’s disease?
George Huntington
1872
Symptoms of Huntington’s disease
Progressive hyper/dyskinesias followed by akinesia and dystonia and dementia/psychoses
Incidence of Huntington’s disease
Rare
0.04-0.1%
Pathology of Huntington’s disease
Autosomal dominant hereditary disease
Abnormal number of CAG
Animal models suggest that ____ _____ is the initial trigger in Huntington’s disease
Cortical dysfunction
Role of mutant huntingtin
- Important for synaptic vesicle dynamics and transmitter release
- Pathological changes due to widespread not specific expression of mutant huntingtin
- Pathology due to aberrant circuit activity
Treatments for Huntington’s disease
- Memantine
- Tetrabenazine
- Deep brain stimulation
- RNA interference
- Stem cell transplantation
Positive symptoms of schizophrenia
- Delusions
- Hallucinations
- Disordered thought and speech
Negative symptoms of schizophrenia
- Flat affect
- Alogia (inability to speak)
- Anhedonia (inability to feel pleasure)
- Asociality (lack of motivation to engage in social activity)
- Avolition (decrease in the motivation to initiate and perform self-directed purposeful activities)
Pathology of schizophrenia
Increased levels of dopamine in the mesolimbic pathway
Incidence of schizophrenia
0.6% of population worldwide
When does schizophrenia start?
Can start at any age, peak onset early 20s
Causes of schizophrenia
- Genetic
- Environment
- Development
- Social factors
- Drug abuse
- Dopamine hypothesis
- Reduced NMDAR function
Treatment of schizophrenia
- Antipsychotics (+ve symptoms)
- Intense psychotherapy
Symptoms of depression
- Lowered mood
- Anhedonia (lack of pleasure in activities)
- Avolition (decrease in the motivation to initiate and perform self-directed purposeful activities)
- Altered appetite
- Hyposomnia/hypersomnia
- Worthlessness and guilt
- Reduced ability to concentrate
- Recurrent thoughts of death
- Reduced life span
- 3-7%
Pathology of depression
- Reduced hippocampal volume
- Vascular lesions
- Reduced BDNF (brain-derived neurotrophic factor)
Incidence of depression
- 3% Japan
- 18% USA
- 10% average
- Women 2x more than men
Causes of depression
- Genetic 5-HT transporter abnormalities
- Monoamine hypothesis
- Psychological (self, others, future)
- Social (poverty, stress, abuse)
Treatment of depression
- Light therapy
- Psychotherapy
- Tricyclic antidepressants
- SSRIs
- Exercise
- ECT
Types of clot
- Ischaemic
- Haemorrhagic
Ischaemic stroke
- Embolus (wandering clot)
- Thrombus (local clot)
- Systemic hypoperfusion
- Venous thrombosis
Haemorrhagic stroke
Entry of blood into CNS via rupture of a blood vessel/sinus or an aneurysm
Classification of haematoma affecting the brain
- Epidural
- Subdural
- Subarachnoid
- Intracerebral
Epidural haematoma
Traumatic damage to a meningeal artery or dural venous sinus (blow to the head)
Subdural haematoma
Is caused by rapid movement of head causing tearing of the cerebral vein as it enters a dural venous sinus
Subarachnoid haematoma
Is caused by damage to a cerebral artery or vein and subsequent bleeding into the subarachnoid space
Intracerebral haematoma
Cause by damage of a blood vessel within the brain
Incidence of stroke
- 10% of deaths worldwide
- 95% occur > 45 years
Top 3 causes of death worldwide
- Heart disease
- Stroke
- Cancer
Cause of stroke
Ischaemic cascade
- ATP production reduced
- Ion pumps fail
- Glutamate levels rise
- NMDA receptors activated
- Ca enters neurons
- ROS/free radicals produced
- Cell death
- Inflammatory response may further exacerbate damage
Risk factors of stroke
- High blood pressure
- High cholesterol
- Diet
- Physical inactivity
- Drugs of abuse (alcohol, cigarettes, cocaine, amphetamine)
Preventative treatments for stroke
- Preventative
- Anticoagulants
- Carotid angioplasty/endarterectomy
- Diet/lifestyle
Acute ischaemic treatments for stroke
- Thrombolysis - tissue plasminogen activators (within 3 hours)
- Thrombectomy
- Angioplasty/stenting
Acute haemorrhagic treatments for stroke
Surgery
Chronic post stroke treatments
- Control of hypertension
- Aspirin
- Physical and occupational therapy
Types of epilepsy
- Partial/focal
- Generalised
Incidence of epilepsy
- 0.5-1.0%
- 5% will experience a non febrile seizure
Childhood absence epilepsy
- 4 - 12 years of age
- Absence seizures (10-30 second episodes of unresponsivity, sometimes with eye rolling, lip smacking, hand shaking) several hundred per day
Characteristic wave in childhood absence epilepsy
3 Hz spike-wave discharge
Mutation in childhood absence epilepsy
Mutation in low threshold voltage-dependent Ca channels
How is childhood absence epilepsy resolved?
Without pathology in puberty
Temporal lobe epilepsy
- Late childhood and adolescence
- Most common type in adults
- Complex partial seizures often with aura
- May develop into secondary generalised tonic-clonic/grand mal seizures
Where is the epileptogenic focus in temporal lobe epilepsy?
In hippocampus and/or amygdala and/or parahippocampal gyrus (recurrent excitatory circuits)
Causes of epilepsy
- 2/3 idiopathic
- Reflex seizures precipitated by a trigger (light)
- Genetic - mutations in Na+ channels
- Cerebrovascular disease
- Tumours
- Alcohol/drugs
- Trauma/hypoxia
- Infection
- Metabolic disorder
- Development disorder
- Degenerative disorder
- Pathological synaptic plasticity (producing an imbalance in excitation and inhibition in the nervous system)
Acute treatments for epilepsy
- Generalised or complex partial seizures - recovery position
- Simple partial seizures - reassurance, maintain safe environment
- BZs
Chronic treatments for epilepsy
- Pharmacological - ethosuximide (blocks/modulates Ca and Na channels) carbamazepine (modulates Na+ channels potentiates GABA receptors)
- Surgical - removal of tumour, AVM (Brain Arteriovenous Malformations) or epileptogenic tissue (temporal lobe, hippocampus)
- Electrical - vagal, deep brain stimulation
- Avoidance of seizure triggers
Symptoms of Alzheimer’s disease
- Short-term memory loss
- Progressive apathy, confusion, irritability, mood swings, long term memory loss, withdrawal, loss of control of bodily functions
- Death within 7 years of diagnosis
Pathology of Alzheimer’s disease
- Profound loss of neurons
- Plaques (amyloid B)
- Neurofibrillary tangles (hyperphosphorylated tau)
Incidence of Alzheimer’s disease
1.5 - 2.0%
Causes of Alzheimer’s disease
- Age, 10% over 65, 50% >84
- Genetics predominately for early onset (ApoE4 gene variant)
- Trauma
- High blood pressure
- Hypercholesteremia
- Environmental factors
Treatment of Alzheimer’s disease
- Acetyl cholinesterase inhibitors
- NMDA receptor antagonists (memantine)
- NSAIDs and caffeine
- Intellectual stimulation
- Diet
- Exercise
