Neuroscience/Objectives/Lecture 46
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Objectives: 27 - 28 - 29 - 30 - 31 - 32 - 33 - 34 - 35 - 36 - 37 - 38 - 39 - 40 - 41-42 - 43 - 44-45 - 46 - 47 - 48 - 49 - 50 - 51 - 52 - 53 - 54
Objectives: 27 - 28 - 29 - 30 - 31 - 32 - 33 - 34 - 35 - 36 - 37 - 38 - 39 - 40 - 41-42 - 43 - 44-45 - 46 - 47 - 48 - 49 - 50 - 51 - 52 - 53 - 54
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Motor systems disease and deep brain stimulation
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Learn to identify and localize lesions associated with Parkinson's disease, essential tremor, ataxia, and dystonia.
- Essential tremor
- The most common movement disorder, essential tremor (ET) is characterized by involuntary, rhythmic tremor of a body part (usually hands and arms). Classical essential tremor is kinetic and postural and is slightly asymmetrical. Nonclassical tremor includes intention tremor and isolated rest tremor.
- Parkinson's disease
- The diagnostic signs of Parkinson's disease (PD) are bradykinesia (always present), resting tremor, and rigidity (only one of the latter must be present to make a clinical diagnosis). Postural instability is among the cardinal signs of PD; other signs include masked facies. It begins unilaterally, and progresses bilaterally. The etiology of PD is a biochemical abnormality, resulting in marked depletion of dopaminergic input to the striatum (DA input comes from the substantia nigra pars compacta). The severity of DA loss best correlates with bradykinesia in PD. The result is that the direct pathway is downregulated and the indirect pathway is upregulated, decreasing the amount of inhibition that reaches the GPi/SNr. As a result, the GPi/SNr complex is more active and it exerts more inhibition on the VA/VL thalamus, causing Parkinsonian symptoms.
- Ataxia
- Not discussed in lecture.
- Dystonia
- Characterized by the co-contraction of agonists and agonists, dystonia results in abnormal movements, postural difficulty, and possibly tremor.
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Discuss treatments for motor dysfunction.
- Parkinson's disease therapy
- Therapy includes surgical (eg, thalamotomy, DBS) and nonsurgical (eg, DA agonists) treatments. Surgical interventions include thalamotomy, pallidotomy, and transplantation of DA cells. DBS is discussed below. Pharmacological treatments include levodopa, COMT inhibitors, MAO-B inhibitors, anticholinesterases, and amantidine (to increase DA release).
- Essential tremor therapy
- Potentiation of GABA signaling (eg, with benzodiazepines and gabapentin) are among the pharmacological interventions for essential tremor. Surgical interventions include thalamotomy and DBS of the VIM.
- Dystonia therapy
- Includes stimulation of the GPi.
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Discuss applications of deep brain stimulation in motor system dysfunction.
| Disorder | DBS target | Rationale |
|---|---|---|
| Essential tremor | VIM of thalamus | Decrease excitatory input to cortex |
| Parkinson's disease | STN | Decrease inhibitory output of GPi/SNr complex |
| GPi | Decrease inhibitory output of GPi/SNr complex | |
| VIM | ??? | |
| Dystonia | GPi | Decrease inhibitory output of GPi/SNr complex |
| OCD | Internal capsule anterior limb | ??? |
| Depression (future) | Cingulate | ??? |
| Seizures (future) | Anterior thalamic nucleus | Anterior nucleus is a common focus of ictal activity |
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Review functional neurosurgery.
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List the advantages and disadvantages of deep brain stimulation.
Advantages:
- Reversible
- Does not destroy normal brain tissue
- Bilateral
- Adjustable
- Voltage
- Pulse width
- Frequency (100-130 Hz for ET, 185 Hz for PD)
- Polarity
- Lead location (4 leads)
- Bipolar mode → elliptical, concentrated stimulation → good for avoiding DBS side effects
Disadvantages (complications other than surgical ones apply primarily to DBS of the STN):
- Confusion and hallucinations
- Increased dyskinesia before medication adjustments
- Eyelid opening apraxia
- Weight gain
- Surgical complications
