bg Flashcards
Nigrostriatal pathway
control of movement
affected in parkinson’s disease
Substantia nigra pars compacta > striatum
Describe cortical input to the basal ganglia
Cortical inputs are excitatory (glutamate) for the medium spiny neurons in the striatum.
GPi, Substantia nigra pars reticulata are the same nucleus. The neurons are inhibitory (Gabaergic)
Describe the circuit from GPI to motor output
GPi is inhibitory, it will release GABA onto the VA/VL of the thalamus
The thalamus is excitatory onto the primary motor cortex
Motor output.
Subthalamus is activated, what does it do to the pathway?
Subthalamic nucleus excites GPi, causing inhibition of the cortex (and movement)
Lesions of the subthalamic nucleus produce too much movement (contralateral hemiballismus)
What is the “Direct Pathway”
Cortex excites Striatum
Striatum increases inhibition of Gpi.
Disinhibition: Gpi decreases inhibition on thalamus
Thalamus increases excitatory output to primary motor cortex
Increased output
What is the indirect pathway
Cortex releases excitatory input to striatum
Striatum is inhibitory for GPe! (inhibitory)
GPe decreases inhibition of subthalamic.
Subthalamic is more excitatory for GPi.
GPi increases inhibition of thalamus.
Thalamus decreases stimulation of motor cortex, decreases output.
How does SNpc influence the direct?
Dopamine activates DA1 receptors on the striatum.
Striatum increases inhibitory output to Gpi, thereby increasing motor output.
How does SNpc affect the indirect pathway
Dopamine activates DA2 receptors on the striatum.
This time it is inhibitory, so the striatum decreases inhibition of GPe.
GPe increases inhibition of the subthalamic
Subthalamic decreases stimulation of the Gpi
GPi decreases inhibition on the thalamus, increasing excitation of the cortex, increasing motor output.
What is the role of ACh in striatum?
It will increase striatal output for both pathways.
However it will preferentially increase striatal output into the indirect pathway, increase inhibition of GPe.
This is why anticholinergics are used for parkinsons disorder
Hemiballismus
Chorea
Athetosis
Hemiballismus:
• Spontaneous, involuntary movements
• Usually caused by lacunar infarcts in the subthalamic nucleus
Chorea:
• Nearly continuous rapid movements of face, tongue, or limbs.
• Most common in Huntington’s disease.
Athetosis:
• Slow, writhing movements, mostly in hands and fingers. Patients
cannot maintain a fixed position. Often in children with cerebral
hypoxia, affecting the basal ganglia.
(somewhere between chorea and posture instability)
Hypokinesia
Rigidity
Hypokinesia – decreased amplitude of movements
Rigidity - described as “waxy” or “lead-pipe.”
May be “cogwheeling,” with regular interruptions.
Unlike spasticity, rigidity will resist the whole range of movement, and maybe push back at you.
Dystonia
Dystonia \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_ Slower than chorea, sustained contractions in twisting postures -Triggered by voluntary movements -Writer’s cramp is most common
Most cases are familial A causes:
• Genetic
• Focal lesions of basal ganglia
• Disorders of dopamine metabolism
Treatment:
• Botulinum toxin
• DBStimulation of the GP
Tardive dyskinesia
abnormality or impairment of voluntary movement:
resulting from drugs that have dopaminergic actions
- antipsychotic drugs (traditional>atypical)
- anti-emetic drugs
- manganese
- these drugs decrease dopamine, this can lead to an upregulation of dopamine receptors and too much sensitivity to dopamine.
Can persist after discontinuation of drugs. Less of a problem with new anti-psychotics
Parkinsons tremor vs Essential tremor
Parkinsons tremor:
(4-6 Hz at rest)
Hands and arms are more common, legs and mouth can also be affected -Begins unilaterally -At rest -BG \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_
Essential tremor:
(6-8 Hz)
Hands, arms, head, face, legs, trunk Usually bilateral Increases with activity or posture -no other motor abnormalities. -Cerebellum
Huntington Chorea
Autosomal dominant neurodegenerative disorder with cell loss in caudate and putamen
Also affects the cortex (mainly frontal and temporal)
Enkephalin-containing GABAergic cells affected in HD
> more inhibition of STN and increased movement.
Onset 40s and 50s. Progressive and neurodegenerative. Eventually leads to akinetic/rigid form of the disease
Median survival is 15 yrs due to respiratory complications.
Treatment: drugs that decrease dopamine
Major symptoms:
- Chorea
- Dementia
Psychiatric manifestations
- anxiety
- mood changes
- OCD
- impulsiveness
- cognitive impairment
- memory loss
Parkinsons
Parkinsons
Clinical symptoms:
- Bradykinesia: slowed movements
- Resting tremor (pill rolling)
- Rigidity: lead pipe through range of motion, or cog wheeling with regular jerking
- Postural instability
(postural instability comes later in the disease)
Motor: masked facies (hypomimia) -loss of automaticity -stooped posture -decreased arm swing -difficulty rising from chair -freezing -*RETropulsion - take 2 steps back when pulled from behind (instead of 1 step)
Non-motor
- loss of olfaction (hyposmia), very early sign.
- sleep problems
- personality changes
- pain
- urinary disturbances
- depression: MOST common psychiatric problem in PD.
- Dementia - dysexecutive syndrome, later in disease, no memory loss, loss of attention, loss of language fluency
Histological marker of PD
Neurons in the SN of people with PD contain Lewy Bodies
Lewy Bodies are spherical masses within the cell body that contain abnormal aggregations of proteins: particularly alpha-synuclein, a cytosol protein found in many regions of the brain.
Alpha-synuclein is normally involved in vesicle transport.
DBS and PD
the most common surgical approach to PD, thought to suppress excessive activity. For advanced and drug resistant PD.
GPi or subthalamic nucleus for PD symptoms (bradykinesia, rigidity, tremor)
VL for tremor predominant
What are preclinical symptoms of parkinsons
- Olfactory loss
- Depression
- Sleep abnormalities
- Sympathetic denervation
- Constipation
- Genetic markers
What are parkinsonism plus syndromes
Primary neurodegenerative syndromes that share characteristics of PD
- Lack of resting tremor
- symmetrical symptoms
- early postural instability
- lack of response to dopamine
Progressive Supranuclear Palsy
- most common form of atypical parkinsonism
- neurodegenerative
- affects rostral midbrain
- symptoms begin after age 50
- differences from PD
- *decreased range of vertical eye movement (first sign)
- imbalance, falling, trunk rigidity (vs limbs in PD)
- swallowing changes
- Dementia progresses more rapidly
-some relief from dopaminergic therapies but not strong
What side of the lesion are hypokinetic, hyperkinetic and dyskinesias found on?
The contralateral side.
What is contralalteral hemiballismus?
Ballismus or ballism (called hemiballismus or hemiballism in its unilateral form) is a very rare movement disorder. It is a type of chorea caused in most cases by a decrease in activity of the subthalamic nucleus of the basal ganglia, resulting in the appearance of flailing, ballistic, undesired movements of the limbs.
How does the Snpc play roles in indirect and direct pathways?
Dopamine always works on the striatum but
DA1: excitatory > increases striatal inhibitory output on Gpi
DA2: inhibitory > decreases striatal inhibitory output on Gpe > increases inhibition on subthalamic nuclei
