From the Editor
The tarantella is an ancient southern Italian dance form, characterized
by feverish, writhing, jerking movements of the limbs, ostensibly danced
to fend off the poisonous effects of a spider bite. It bears a striking
resemblance to the dyskinesia experienced by a Parkinson’s patient with
full-blown motor fluctuations associated with their medication regimen.
But when the same patient’s medication level drops transiently between
doses, the very opposite occurs. In his compelling book Awakenings, Dr.
Oliver Sacks vividly describes patients with a post-infectious parkinson-like syndrome, living in
the rigid prison of their own unresponsive frame, and the dramatic “awakening” of these patients
given Levo-dopa. The advent of Levo-dopa therapy was hailed as a medical miracle, and indeed
it is, freeing Parkinson’s patients from the rigidity, tremor, and difficulty initiating movement
that are the hallmarks of the disease very effectively. But as the disease progresses and medication
regimens escalate, the huge and often sudden swings from dyskinesia to rigidity and “freezing”
can make the uncertainty of daily living a huge functional problem. Smoothing out these motor
fluctuations is just one goal of movement disorders neurologists. This issue of the CNI REVIEW
takes a look at a few of the things these very special neurologists are doing to fight disorders of
movement and bring a modicum of functional ability and independence back into the lives of
Take a moment to look at the words we use to describe movement disorders. We
characterize these disorders using terms such as chorea, bradykinesia, dystonia, dyskinesia,
tremor, dysmetria, dysdiadochokinesis, nystagmus, oscillopsia. The common denominator is
kinesis—movement. These disorders change the way we move. Not only arms and legs, but fine
motor control, voice, swallowing, head control, and eye motion can be affected. Like a rock in a
pond, these disorders can interrupt more than just motor function in ever expanding circles.
Rigidity of muscle tone, inability to initiate movement, incoordination of movement, loss of
smoothness and fluidity, diminished speed of movement, loss of movement control, even violent
uncontrollable movement can occur. Beyond motor function, the epiphenomenon of the
underlying disease processes may induce cognitive deterioration and dementia, behavioral
changes, attentional disorders, and obsessive thoughts and behaviors. These present additional
challenges to our patients as they relentlessly and progressively steal independence and ability.
Our contributors to this issue span a wide breadth of expertise in the neurology of
movement. Pinky Agarwal, MD, and Lauren C. Seeberger, MD, describe Huntington’s disease
and the current treatment options available for this dramatically disabling disease. Michael J.
Frank, PhD and Randall C. O’Reilly, PhD summarize their research in computer modeling of
basal ganglia, arriving at surprising and novel predictions about how this impacts a Parkinson’s
patient’s cognition. Steven G. Ojemann, MD, updates us on the surgical management of
Parkinsons Disease and Essential Tremor, outlining the indications, contraindications,
complications and outcomes that can be expected with implantation of deep brain stimulators
for these disorders. Thomas Politzer, OD, FCOVD, FAAO, describes the sometimes subtle but
potentially disabling ocular effects of Parkinsons Disease, and what can be done to improve the
affected Parkinson’s patient’s visual function. Josette Pressler, LPN, presents the many
Fall 2005 1 www.thecni.org
community resources available to patients with movement disorders with an emphasis on
Parkinson’s disease. Lauren C. Seeberger, MD defines the characteristics of cerebellar tremor,
outlines the etiology of this disorder, and reports on the effectiveness of new interventions for
this disabling affliction.
I hope you will find this issue of the CNI REVIEW enlightening and interesting. I’m sure it
will give you useful information on the availability and effectiveness of new treatments for these
disorders, as well as the clinical, research and community resources available to your patients with
movement disorders through the CNI Movement Disorder Center and Thompson Center for
Restorative Neurosurgery at the Colorado Neurologic Institute. And if you have never had the
opportunity, I invite you to read Dr. Sack’s book, Awakenings, to get a vivid picture of the battle
our movement disorders neurologists are waging every day.
John H. McVicker, MD, FACS
President, Colorado Neurological Institute
CNI REVIEW 2
Cognitive Processes in Parkinson’s Disease:
From Dopamine to Behavior
Michael J. Frank, PhD and Randall C. O’Reilly, PhD
We present a summary of our ongoing research into the cognitive functions of the basal ganglia
and their implication in Parkinson’s disease (PD). Diverse cognitive functions are impaired in
PD, which are sometimes enhanced, but sometimes worsened, by dopaminergic medication.
Computer modeling of the basal ganglia dopamine system and its involvement in cognition has
been useful for understanding these effects and for making novel predictions regarding core
cognitive deficits in PD.
Introduction. Parkinson’s disease (PD) the general aspects of our model of this
is a progressive neurodegenerative disease system, and then describe how cognitive
that selectively damages dopaminergic cells impairments in PD are consistent with
that target the basal ganglia (BG). The most this model.
Michael Frank is a
obvious behavioral change associated with
postdoctoral fellow at the
PD is characterized by muscular rigidity, Relating Basal Ganglia Roles in Motor
University of Colorado.
slowness of movements, and tremor. Control and Cognitive Function. In the His research involved
Nevertheless, a number of cognitive changes context of motor control, various authors computational modeling
have been documented as well, which are the have suggested that the role of the BG is to of neural mechanisms
focus of this review. These cognitive selectively facilitate the execution of a single underlying implicit
impairments are often complex and motor command, while suppressing all learning, working
seemingly unrelated, ranging from deficits in others.1-3 Thus, the BG is thought to act as a memory, and attention.
reinforcement learning and decision making brake on competing motor actions that are He received a PhD in
(ie, choosing among multiple menu items at represented in motor cortex. Only the most neuroscience and
a restaurant and learning from the outcome appropriate motor command is able to psychology from CU and
of this decision) to working memory (holding release the brake and get executed at any his dissertation title was
and manipulating information in mind, as in point in time. Further, the BG does not
modulation in the basal
mental arithmetic) and attentional control come up with the motor responses itself, but
(directing attention to task-relevant versus instead modulates the execution of cortical
distracting information). In the present responses by signaling “Go” or “No-Go”.4
review we present our ongoing theoretical This functionality also helps to string simple computational studies.”
account of these phenomena. Rather than motor commands together to form a He has published more
proposing separate mechanisms for the complex motor sequence, by selecting the than 10 articles in peer-
various cognitive and motor impairments in most appropriate command at any given review scientific journals.
PD, our approach unites the diverse pattern portion of the sequence and inhibiting the
of results by adopting a mechanistic other ones until the time is appropriate.1
approach that attempts to decipher the A simplified analysis of BG anatomy helps
underlying roles of the basal ganglia/ clarify the basis for this functional
dopamine system. We begin by describing characterization. In brief, 2 BG pathways are
Fall 2005 3 www.thecni.org
thought to independently facilitate or disease? As described above, it is generally
suppress cortical motor commands. More accepted that the BG acts as the motor
specifically, 2 main projection pathways controller by dynamically modulating
from the striatum go through different basal activity in frontal motor cortex. Similarly,
ganglia output structures on the way to various researchers now propose a key role of
thalamus and up to cortex (Figure 1). parallel circuits linking the BG, thalamus,
Activity in the direct pathway sends a “Go” and PFC that are essentially identical to
signal to facilitate the execution of a those involved in the motor circuit.9
response considered in cortex, whereas
activity in the indirect pathway sends a “No- Working Memory. Based on the
Go” signal to suppress competing responses. general suggestions of basal ganglia
Dopamine modulates the relative balance of involvement in prefrontal circuits made by
these pathways by exciting “Go” cells while Alexander and colleagues, we developed a
inhibiting “No-Go” cells. This effect is computational model that explicitly
dynamic, such that transient increases in DA formulated the role of the BG in working
leads to more “Go” and less “No-Go”, and memory.2 We suggested that just as the BG
vice versa for decreases. 3 Note that in PD, facilitates motor command execution in
Randall O’Reilly is an motor neurons themselves are not damaged, premotor cortex by disinhibiting or
associate professor in the and patients can in fact perform movements “releasing the brakes” it may also facilitate
Department of quite smoothly under some circumstances the updating of working memory in
Psychology at the (eg, externally driven motor commands). prefrontal cortex. For task-relevant stimuli
University of Colorado.
Instead, these patients may have difficulty that are suitable for working memory
He also holds appoint-
selecting among various competing motor maintenance, the BG direct pathway may
ments in the Institute of
actions and executing the most appropriate activate a “Go” signal to disinhibit the
Cognitive Science and
one. It is often suggested that depleted thalamus and gate the updating of PFC.
the Center for Neuro-
dopamine in PD leads to an imbalance of In contrast, due to “No-Go” BG output,
sciences. His research
interests include the direct and indirect pathways.5 task-irrelevant information would not be
specialization of function Specifically, PD is thought to be associated robustly maintained. For example, when
in and interactions with too much “No-Go” and not enough someone is telling you their telephone
between hippocampus, “Go”, leading to slowness of movements or number, you have learned to activate “Go”
prefrontal cortex, and bradykinesia. In essence, depleted DA in the signals to encode this into working memory,
posterior neocortex in BG may result in raising the threshold for while also being able to have “No-Go”
learning, memory, facilitating a motor program while signals to ring to distracting information (eg,
attention, and controlled continuing to suppress competing actions.1, 6 if your pesky friend later tries to distract you
processing. He received a The observation that treatment with DA with other numbers).
PhD in Psychology at
agonists and L-Dopa sometimes lead to
jerking movements, or dyskinesia 7 is Reinforcement Learning / Decision
consistent with this hypothesis by shifting Making. When faced with a decision, such
the balance the other way and making the as which menu item to order at a restaurant,
threshold for motor execution too low, people often use implicit, “gut-level”
rather than too high.8 How does the above strategies. They simply “know” they want to
depiction of BG involvement in motor choose the steak in favor of the salmon,
control relate to cognition in Parkinson’s often without being able to explicitly state
CNI REVIEW 4
Figure 1a and 1b Figure 1a
cortical loops, including the
direct (“Go”) and indirect
(“No-Go”) pathways of the
basal ganglia. The “Go” cells
disinhibit the thalamus via
GPi, thereby facilitating the
execution of an action
represented in cortex. The
“No-Go” cells have an
opposing effect by increasing
inhibition of the thalamus,
suppressing actions from
getting executed. Dopamine
from the SNc projects to the
dorsal striatum, causing
excitation of “Go” cells via
D1 receptors, and inhibition
of “No-Go” via D2
receptors. GPi: internal
segment of globus pallidus;
GPe: external segment of
globus pallidus; SNc:
substantia nigra pars
the basis of their decision. In fact, in such modifies synaptic plasticity, such that on compacta; SNr: substantia
situations, the implicit value of alternative subsequent trials the model is more likely to nigra pars reticulata.
decisions has been integrated over multiple respond “Go” to a decision that has been Figure 1b
The Frank (2005) neural
prior experiences—your intuition is really recently rewarded. Conversely, dopamine
network model of this
just the integration of your experience in a dips lead to “No-Go” learning to avoid non- circuit (squares represent
units, with height and color
very generalized way. reinforced incorrect decisions. See below for
reflecting neural activity;
Given that the BG are thought to a more detailed description of how this yellow = most active, red =
less active, grey = not active).
participate in selecting among various model functions, and its implications for
The Premotor Cortex selects
competing low-level motor responses, it is Parkinson’s disease. an Output response via
direct projections from the
natural to extend this functionality to
sensory Input, and is
include higher-level decisions. The question Cognitive Impairments in Parkinson’s modulated by the BG
projections from Thalamus.
is, how do the BG learn which decision has Disease. Next, we review the evidence for Go units are in the left half
the highest value? Insight comes from cognitive deficits in PD and how it can be of the Striatum layer; “No-
Go” in the right half, with
various experiments showing that when understood within the context of our model.
separate columns for the 2
monkeys are rewarded following a correct We divide the cognitive deficits in PD into responses R1 (left button),
R2 (right button). In the
choice, transient increases in BG dopamine 2 general classes and address them in turn.
case shown, striatum “Go” is
firing are observed.10 Conversely, choices The first class concerns “frontal-like” stronger than “No-Go” for
R1, inhibiting GPi,
that do not lead to reward are associated deficits, and the second is related to
disinhibiting Thalamus, and
with dopamine dips that drop below impairments in implicit reinforcement facilitating execution of the
response in cortex. A tonic
baseline. These changes in dopamine are learning.
level of dopamine is shown
adaptive, and are thought to lead to the in SNc; a burst or dip ensues
in a subsequent error
learning of rewarding behaviors. In our Frontal Deficits. Frontal-like cognitive feedback phase (not shown),
models, transient dopamine increases deficits have long been attributed to patients causing corresponding
changes in “Go”/“No-Go”
preferentially activate “Go” cells in the direct with PD. Anecdotally, patients report
unit activations, which drive
pathway via D1 receptors, while suppressing difficulty with manipulating information in learning.
“No-Go” cells in the indirect pathway via memory, such as counting backwards from
D2 receptors.3 This change in activity 100. In the laboratory, PD patients are
Fall 2005 5 www.thecni.org
Example stimulus pairs
impaired at many of the same tasks as procedural learning” tasks, in which
(Hiragana characters) used observed in patients with damage to participants have to classify stimuli into
in the cognitive probabilistic
learning task, designed to
prefrontal cortex.11 The theoretical account different categories using trial-and-error.
minimize verbal encoding. for these observations consistently implicates Patients perform as well as controls in other
One pair is presented per
trial, and the participant
a damaged BG that is interconnected in a implicit learning tasks, such as those learned
makes a forced choice. The functional circuit with prefrontal cortex.12 by simple observation not involving error
frequency of positive
feedback for each choice is
Our framework holds that diminished DA feedback.15-16 In implicit categorization tasks,
shown. in the BG results in a higher threshold for successful integration of information
Figure 2b updating information in PFC, which leads depends on both error feedback and BG
Novel test pair performance
to working memory impairments and integrity.17 Perhaps the most well known
in Parkinson patients on
and off medication tested at rigidity, as is also observed in primates with cognitive impairment in PD is that of the
the Colorado Neurological
selective striatal DA depletion. Specifically, a “weather prediction” categorization task in
Institute (Frank, Seeberger
and O’Reilly, 2004). Note lack of BG DA in PD would lead to too which category members are determined
that choosing A depends on
little updating of relevant information into probabilistically and participants have to
having learned from positive
feedback, while avoiding B PFC, just as it leads to too little execution of figure out statistical regularities by trial-and-
depends on having learned
motor commands. Conversely, too much error.14 Healthy participants implicitly
from negative feedback.
DA in the BG would lead to excessive integrate information over multiple trials,
This pattern of results was updating of PFC, just as it leads to L-Dopa progressively improving, despite not being
predicted by the Frank induced motor tics and dyskinesia. Finally, a able to explicitly state the basis of their
(2005) model. The figure
shows “Go” - “No-Go” suboptimal level of DA in the PFC would choices. PD patients are reliably impaired in
associations for stimulus A, lead to insufficient maintenance of task- the early stages of the task. At first glance,
and “No-Go” - “Go”
associations for stimulus B, relevant information. Any of these DA implicit learning deficits might appear
recorded from the model’s dysfunctions would lead to “frontal-like” unrelated to the frontal impairments of PD
striatum after having been
trained on the same task cognitive deficits. patients described above. While frontal tasks
used with patients. Error demand manipulation of information in
bars reflect standard error
across 25 runs of the model Implicit/Reinforcement Learning conscious awareness, implicit learning tasks
with random initial weights. Deficits. In support of the “multiple specifically measure the ability of partici-
1. Mink J. The basal memory system” hypothesis, researchers pants to pick up on regularities that do not
ganglia: Focused have found that different patient reach conscious awareness. The current
selection and inhibition
of competing motor populations have different kinds of memory framework provides a unified account for
programs. Progress in impairments. Amnestics with medial both classes of deficits: diminished DA in
1996;50:381-425. temporal lobe damage have impaired the BG causes a lack of working memory
2. Frank MJ, Loughry B, episodic, but intact procedural memory— updating in PFC, but through interactions
that is, they cannot remember individual with premotor cortex it also reduces the
the frontal cortex and trials but nevertheless successfully integrate implicit learning of stimulus-response
basal ganglia in working
error feedback across multiple trials and relationships.3 Stimulus-response execution
computational model. perform normally in trial-and-error tasks.13 requires facilitating some responses while
Cognitive, Affective, and
PD patients show the opposite pattern of suppressing others, and the learning of these
2001;1:137-160. results: they can remember individual mappings depends on dynamic modulatory
experiences but have difficulty integrating properties of DA in the BG.
error feedback across multiple trials.14-15
These deficits are typically studied with A Model of Reinforcement Learning
probabilistic classification or “cognitive in PD. Computational modeling of the
CNI REVIEW 6
Figure 2 3. Frank M. Dynamic
in the basal ganglia: A
account of cognitive
deficits in medicated
of Cognitive Neuro-
4. Hikosaka O. Role of
basal ganglia in initia-
tion of voluntary
movements. In: Arbib
MA, Amari S, Eds.
interactions in neural
networks: Models and
data. 1989; 153-167.
dynamics of BG-cortical interactions result in positive feedback. Conversely, after 5. Albin R, Young A,
provided an explicit formulation for how the incorrect responses phasic dips in DA release Penney J. The func-
tional anatomy of basal
BG is involved in cognitive reinforcement the “No-Go” pathway from suppression, ganglia disorders.
learning, and how this is impaired in PD.3 increasing its activity and driving “No-Go” Trends in Neurosciences.
Specifically, the model (Figure 1b) learning. Over the course of training, this
6. Wichmann T, DeLong
addressed how phasic changes in DA during model learns how to respond in the weather M. Pathophysiology of
error feedback are critical for modulating prediction task, with performance levels
The MPTP primate
“Go/No-Go” representations in the BG that similar to that of healthy human participants. model of the human
disorder. Annals of the
facilitate or suppress the execution of motor When 75 percent of simulated dopamine
New York Academy of
commands. The main assumption is that neurons were removed (to model the Sciences. 2003;991:
during positive and negative feedback (eg, approximate amount of damage in PD
7. McAuley J. The
correct or incorrect), bursts and dips of DA patients), the model was impaired similarly physiological basis of
occur that drive learning for the response. to patients. clinical deficits in
This assumption was motivated by a large Progress in
amount of evidence for bursts and dips of Modeling Dopaminergic Medication Neurobiology.
DA during rewards or their absence in Effects on Cognitive Function in PD. The 8. Gerfen C. D1 dopa-
monkeys,10 which have also been inferred to same model was used to explain certain mine receptor
supersensitivity in the
occur in humans for positive and negative negative effects of dopaminergic medication dopamine-depleted
feedback.18 These phasic changes in DA on cognition in PD.3 While medication striatum animal model
of Parkinson’s disease.
modulate neuronal excitability, and may improves performance in task-switching, it Neuroscientist.
therefore act to reinforce the efficacy of actually tends to impair performance in 2003;9:455-462.
recently active synapses, leading to the probabilistic reversal.19 These authors noted 9. Alexander, GE,
DeLong MR, Strick
learning of rewarding behaviors. Thus in the that the task-dependent medication effects PL. Parallel organiza-
model, “correct” responses are followed by are likely related to the fact that different tion of functionally
transient increases in simulated DA that tasks recruit different parts of the striatum. linking basal ganglia
enhance synaptically driven activity in the Dopaminergic damage in early stage PD is and cortex. Annual
Review of Neuroscience.
direct/“Go” pathway, while concurrently restricted to the dorsal striatum, leaving the 1986;9:357-381.
suppressing the indirect/“No-Go” pathway. ventral striatum with normal levels of DA.20 10. Schultz W. Getting
formal with dopamine
This drives “Go” learning, and enables the This explains why DA medication alleviates and reward. Neuron.
model to facilitate responses that on average deficits in taskswitching, which relies on 2002;36: 241-263.
Fall 2005 7 www. thecni.org
11. Nieoullon A. (2002). “No-Go” learning, but impaired “Go”
Dopamine and the
dorsal striatal interactions with dorsolateral
regulation of cognition prefrontal cortex. However, the amount of learning (which depends on DA bursts). We
and attention. Progress in further predicted that dopaminergic medica-
medication necessary to replenish the dorsal
2002;67:53-83. striatum might “overdose” the ventral stria- tion should alleviate the “Go” learning
12. Middleton FA, Strick tum with DA, and is therefore detrimental deficit, but would block the effects of
PL. Basal ganglia output
and cognition: Evidence to tasks that recruit it. dopamine dips needed to support “No-Go”
from anatomical, In order to simulate medication learning, as was simulated to account for
behavioral, and clinical
studies. Brain and Cogni- effects, it was hypothesized that medication other medication-induced cognitive deficits
tion. 2000;42:183-200. increases the tonic level of DA, but that this in Parkinson’s disease.3 Results were consis-
13. Knowlton BJ, Squire tent with these predictions (Figure 2). In a
LR, Gluck MA. interferes with the natural biological system’s
Probabilistic category ability to dynamically regulate phasic DA probabilistic learning task, all patients and
learning in amnesia. aged-matched controls learned to make
Learning and Memory. changes. Specifically, phasic DA dips during
1994;1:1-15. negative feedback may be partially blocked choices that were more likely to result in
14. Knowlton BJ, Mangels
by DA agonists that continue to bind to positive rather than negative reinforcement.
JA, Squire LR. A
neostriatal habit learning receptors. When this was simulated in the The difference was in their strategy: patients
system in humans.
model, selective deficits were observed taking their regular dose of dopaminergic
during probabilistic reversal, despite medication implicitly learned more about the
15. Shohamy D, Myers C,
Grossman S, Sage J, equivalent performance in the acquisition positive outcomes of their decisions (ie, they
Gluck M, Poldrack R.
phase,3 mirroring the results found in were better at “Go” learning), whereas those
contributions to medicated patients. Because increased tonic who had abstained from taking medication
levels of DA suppressed the indirect/“No- implicitly learned to avoid negative outcomes
converging data from
neuroimaging and Go” pathway, networks were unable to learn (better “No-Go” learning). Age-matched
“No-Go” to override the prepotent response controls did not differ in their tendency to
16. Reber PJ, Squire LR. learned in the acquisition stage. This learn more from the positive/negative
(1999). Intact learning
account is consistent with similar reversal outcomes of their decisions.
of artificial grammars
and intact category deficits observed in healthy participants We have also tested predictions for a
learning by patients with
administered an acute dose of more a general role for BG/dopamine in
Behavioral Neuroscience. bromocriptine, a D2 agonist.21 cognitive function by administering low
1999;113:235. doses of dopamine agonists/antagonists to
17. Ashby F, Alfonso-Reese
L, Turken A, Waldron
Empirical Tests of the Model. young, healthy participants.23-24 The drugs
E. A neuropsychological Recently, we have tested various aspects of used (cabergoline and haloperidol) were
theory of multiple
systems In category
the hypothesized roles of the basal ganglia/ selective for D2 receptors, which are by far
learning. Psychological dopamine system across both reinforcement most prevalent in the BG. By acting on
learning and working memory processes. presynaptic D2 receptors, cabergoline
18. Holroyd CB, Coles First, we demonstrated striking support for a reduces, while haloperidol enhances, the
MGH. The neural basis central prediction of our model regarding amount of phasic dopamine that is released
of human error
processing: Reinforce- dopamine involvement in “Go” and “No- during dopaminergic cell bursting.25 Again,
ment learning, Go” cognitive reinforcement learning.3, 22 We results were consistent with our model.
dopamine, and the
error-related negativity. tested Parkinson’s patients on and off Increases in dopamine during learning
Psychological Review. medication, along with healthy senior caused participants to learn more about the
control participants matched for age, educa- positive outcomes of their decisions (as in
tion and a measure of verbal IQ. We medicated Parkinson’s patients), whereas
predicted that decreased levels of dopamine decreases in dopamine caused the same
in Parkinson’s disease would lead to spared participants to learn more about negative
CNI REVIEW 8
outcomes (as in non-medicated patients). Conclusions and Practical 19. Cools R, Barker R, Saha-
kian B, Robbins T. (2001).
Notably, these same effects were borne Implications. In summary, we have Enhanced or impaired
out in the context of a working memory and presented a mechanistic account of how cognitive function in
Parkinson’s disease as a
attentional task. Specifically, increases in dopamine in the basal ganglia may play a function of dopaminergic
dopamine by haloperidol enhanced selective functionally similar role across multiple medication and task
demands. Cerebral Cortex.
working memory updating of task-relevant cognitive processes. We have showed that 2001;11:1136-1143.
(ie, “positively-valenced”), but not distracting while dopaminergic medication used to treat 20. Kish S, Shannak K, Horn-
ykiewicz O. Uneven
(“negatively-valenced”) information. By our PD sometimes enhances cognitive function, pattern of dopamine loss in
model’s account, dopamine release evoked it can also worsen or even cause cognitive the striatum of patients
with idiopathic Parkinson’s
during the presentation of task-relevant deficits. At this stage it is far too preliminary disease. New England
information reinforces BG “Go” firing to to recommend changing medication Journal of Medecine.
update this information. Consistent with this prescriptions based on these results, especially
21. Mehta M, Swainson R,
analysis, increased dopamine release also considering their important benefits for Ogilvie A, Sahakian B,
caused difficulty not updating (ie, ignoring) treating the more profound and debilitating Robbins T. Improved
short-term spatial memory
this information when it subsequently motor impairments associated with the but impaired reversal
became distracting in the set-shift. Finally, disease. Nevertheless, we expect that this learning following the
dopamine D2 agonist
and perhaps most suggestive for a role of BG research will lead to a better understanding bromocriptine in human
dopamine in working memory, participants of the dopaminergic system, and ultimately volunteers. Psycho-
with low baseline working memory span better design of medications that can 2000;159:10-20.
were most subject to the effects of increases specifically target underlying neural dysfunc- 22. Frank M, Seeberger L,
O’Reilly R. By carrot or by
in dopamine by haloperidol, while those tion without causing unwanted side effects. stick: Cognitive reinforce-
with high span were most subject to Finally, because our approach is based on ment learning in
decreases in dopamine by cabergoline.23- 24 low-level neural mechanisms which are not 2004;306:1940-1943.
These latter results are consistent with the specific to PD per se, we are hopeful that this 23. Frank M, O’Reilly R.
notion that individual differences in working basic science will lead to a better under-
differences in learning and
memory span are partially characterized by standing of, and ultimately better medica- attention: Opposing D2
underlying differences in dopamine levels,26 tions to treat, other pathological conditions
24. Frank M, and O’Reilly R.
but extend this hypothesis in a more involving the BG/DA system, including (submitted-b). A
mechanistic fashion consistent with our schizophrenia, obsessive compulsive disorder, mechanistic account of
striatal dopamine function
modeling. ADHD, and Huntington’s disease. in cognition: Psycho-
Taken together, these results provide with cabergoline and
strong support that BG signals, under haloperidol.
modulation by dopamine, are critical for the Address questions and comments to: 25. Wu Q, Reith M, Walker
Q, Kuhn C, Caroll F,
updating of PFC working memory repre- Michael J. Frank, PhD Garris P. Concurrent
sentations. Further, the model’s success in Randall C. O’Reilly, PhD autoreceptor-mediated
control of dopamine release
capturing subtle cognitive effects in both Department of Psychology and uptake during
Parkinson’s disease and controlled dopamine Center for Neuroscience neurotransmission: an in
vivo voltammetric study.
manipulation suggests that it can also be University of Colorado at Boulder Journal of Neuroscience.
applied to mechanistically understand cogni- 345 UCB 2002;22:6272-6281.
26. Kimberg DY, D’Esposito
tive deficits in those with more complex Boulder, CO 80309 M, and Farah MJ. Effects
disorders involving BG/dopamine dysfunc- of bromocriptine on
human subjects depend on
tion, such as attention deficit hyperactivity working memory capacity.
disorder (ADHD) and schizophrenia. Neuroreport. 1997;8:3581-
Fall 2005 9 www. thecni.org
Visual Disturbances in Parkinson’s Disease
Thomas Politzer, O.D, FCOVD, FAAO
Patients with Parkinson’s disease may complain of vision problems such as reading problems,
double vision, abnormal perception of motion (oscillopsia), and problems with eye tracking.
Signs of problems may include nystagmus, ataxic ocular pursuits, slow and inaccurate saccades,
reduced convergence and strabismus. Treatment options that include the use of partial selective
occlusion, prism and lenses are discussed.
Introduction. Parkinson’s disease (PD) function and difficulty with reading. Their
is a progressive degeneration of the neurons study found that visual symptoms suggesting
in the central nervous system that produce ocular surface irritation, altered tear film,
Dr. Politzer is an the neurotransmitter dopamine. Located in visual hallucinations, decreased blink rate,
optometrist specializing the substantia nigra, these neurons innervate and decrease convergence were more
in vision rehabilitation the Caudate Nucleus and Putamen. The common in Parkinson’s patients than in
for patients with double symptoms of PD are a direct result of control subjects. Newman2 writes that ocular
vision, visual field loss,
dopamine depletion. signs in Parkinson’s may mimic, but should
dizziness and imbalance,
Primary symptoms of PD include not be confused with progressive supra-
and binocular disorders.
tremor, rigidity, bradykinesia, difficulty in nuclear palsy. Clinical presentation includes
He graduated from
gait and ambulation, and difficulty in blepharospasm and eye movement
Pacific University in
1981. He consults at
balance. Secondary issues include respiratory abnormality. Verhagen and Schimsheimer3
Craig Rehabilitation problems, dysphagia, dysarthria, depression, note abnormalities of the electro-retinogram
Hospital, Swedish sleep disorders, speech disturbance, and and visual evoked potential in patients with
Hospital, and Spalding visual problems. Parkinson’s. Muchnick writes that
Rehabilitation Hospital. Patients with PD may complain of Parkinson’s “may cause a loss of upward gaze,
He has Fellowships in vision problems. Common complaints followed by downward gaze, and finally
the College of Optome- include reading problems, double vision, horizontal eye movements. Convergence
trists in Vision Develop- abnormal perception of motion (oscillopsia), may fail producing diplopia at near.”4
ment and the American and problems with eye tracking. Since vision
Academy of Optometry. is our dominant sense, these symptoms can Examination. A comprehensive
be quite troubling and interfere with many ophthalmic exam with careful evaluation of
activities of daily living. Appropriate vision ocular fixations, eye movements, and
intervention can often help compensate for binocular vision is indicated for patients
the problem and improve functional with PD. Signs of problems may include
outcomes. nystagmus, ataxic ocular pursuits, slow and
inaccurate saccades, reduced convergence,
Review of Literature. Biousse et al1 and strabismus.
noted that patients with Parkinson’s would Nystagmus connotes an instability, or
commonly complain of impaired visual ataxia of ocular fixation. There are many
CNI REVIEW 10
1. Biousse V, et al.
different types of nystagmus including, but Exotropia at near is the most common Ophthalmologic features
not limited to rhythmic, horizontal, vertical, finding in patients with PD. of Parkinson’s disease.
rotary, vestibular, congenital, and central. 180.
The name refers to a description of the Treatment. The goal of treatment 2. Newman N. Neuro-
disorder, or source of origin. If nystagmus is for vision problems is to find a functional Ophthalmology A
Practical Text. Appleton
acquired, such as in PD from a central solution to the patient’s symptoms & Lange. 1992:190,366.
dysfunction, the patient is generally not able (double vision, oscillopsia, reading 3. Verhagen W,
to suppress the image generated from the difficulty). Treatment should be relatively Current Neuro-
abnormal eye movements. This results in easy to employ, cost effective and Ophthalmology, Vol. 3.
Eds. Lessell and Van
oscillopsia, which is the abnormal functionally based. Dalen. Mosby
perception of movement. 1991:368-369.
Ocular motor dysfunction (OMD) Double Vision. Double vision is a 4. Muchnick B. Ocular
can manifest as ataxia of ocular pursuit, or serious and intolerable condition that is Neurologic Disease. Ed.
slow and inaccurate saccades. When OMD caused by strabismus, ophthalmoplegia, gaze Blaustein. Mosby
is acquired such as in patients with PD, it is palsy, and decompensated binocular skills.
from a central cause. Associated symptoms Prism, visual rehabilitation therapy, and
include impairment of fine motor surgery are options to help the patient
coordination and reading problems such as recover binocular vision and alleviate the
loss of place when reading and words diplopia. Some patients may adapt to their
appearing to move and jump when reading. strabismus by suppressing the vision of one
Convergence describes the ability of eye, but this is rare in adult acquired onset.
the eyes to accurately align on, and track an As a general rule, vision rehabilitation and
object as it moves closer to and away from surgery are not as helpful as prism for
the person viewing it. In convergence patients with PD because of the variable
insufficiency the eyes lag behind the viewed nature and central cause of motor
object and are not able to track it as it dysfunction in PD.
approaches to closer than approximately 8 Prism is an ophthalmic device that
inches from the person. In mild cases this bends light. It is effective in compensating
may cause only blurring and eye strain. As it for diplopia in patients with PD because it
becomes more pronounced there will likely can be prescribed to offset the amount of eye
be double vision at near. deviation. If the diplopia is only with near
Strabismus is a misalignment of the vision, then reading lenses with prism are
eyes. It can manifest intermittently, or indicated. This authors’ experience is that an
constant, at distance and/or near, inward amount of prism between one half and two
(eso), outward (exo), vertical (hyper, or thirds of the measured ocular deviation is
hypo), or rotary (cyclo). It is commonly usually a sufficient and appropriate amount
found with a Cranial Nerve III, IV, or VI to prescribe. Using more than is necessary is
ophthalmoparesis, or ophthalmoplegia and counterproductive and may perpetuate the
also with progressive external ophthlmo- diplopia. If the double vision is only with far
plegia. When acquired, such as in patients vision, then distance lenses with prism are
with PD, there will typically be double prescribed. If there is double vision both
vision because of the inability to suppress distance and near, then either two separate
central vision from the deviating eye. prescriptions can be fabricated, or a Ben
Fall 2005 11 www. thecni.org
Franklin bifocal can be used. This is a lens peripheral vision.
that is manufactured from two separate
lenses with different prism and lens prescrip- Oscillopsia. Oscillopsia is the
tions. One is made for far vision and the symptom of abnormal perception of
other for near vision. They are then cut in movement, usually related to nystagmus, or
half and glued together to make a single abnormal pursuits without retinal
bifocal lens. suppression. Patients may acquire a varied
If prisms and/or therapy are not head position and direction of gaze to help
successful and the patient does not suppress, compensate by finding a null point where
intractable diplopia may occur. In these the nystagmus is decreased. Partial selective
cases, and before current treatment occlusion with bi-nasal, and/or bi-temporal
strategies, complete patching of one eye has patching can help dampen the perception of
been used. While effective in eliminating oscillopsia by enhancing a stable frame of
diplopia, patching renders the patient reference. Rigid contact lenses can be used
monocular. in a type of biofeedback mechanism to
Monocular as opposed to binocular sometimes reduce nystagmus.
vision will affect the individual primarily in
2 ways; absence of stereoscopic depth Reading Difficulties. Reading
perception and a roughly 25 percent problems are one of the main causes for
reduction of the peripheral field of vision. people seeking vision care. There are many
These in turn cause problems in eye hand causes and types of reading problems, and
coordination, depth judgments, orientation, the specific treatment depends on an
balance, mobility, and many activities of accurate diagnosis.
daily living such as playing sports, driving, Convergence insufficiency may also
climbing stairs, crossing the street, threading impair reading ability. It can cause double
a needle, etc. vision, eyestrain, fatigue, or the appearance
A new method of treating diplopia of words seeming to move and swim on the
that does not have these limitations has been page when reading. For patients with PD
successfully developed by this author. It is effective treatment options include lenses
called the “spot patch” and is a method used and prism.
to eliminate intractable diplopia without Accommodative deficiency may also
compromising peripheral vision. It is a cause reading problems. It can cause
small, usually round or oval, patch made of symptoms of blur, eyestrain, fatigue, or the
Transpore tape, 3-M blurring film, or any appearance of words seeming to pulse and
other such translucent tape. It is placed on float on the page when reading. Lenses to
the lens of glasses directly in the line of sight assist accommodation are a good
of the deviating eye. The diameter is intervention.
generally about 1 centimeter, but will vary Double vision will impair reading and
on the individual angular subtense required should be treated as noted above.
for the particular strabismus, or gaze palsy. Saccadic (scanning) movements are
The spot patch works by blurring central required for efficient reading. When slow
vision, where diplopia is perceived, to a and/or inaccurate they will impair reading.
point where it is eliminated while preserving This can cause loss of place, skipping lines,
CNI REVIEW 12
type of mask measuring about 10 centimeters
long by 5 centimeters wide, and is made
from heavy card stock paper. It has a slit cut
in it approximately 8 centimeters long and 1
centimeter wide. It is placed over reading
material to isolate the line being read.
Conclusion. Parkinson’s disease mainly
affects vision through motor dysfunction.
Patients frequently complain of vision
problems including difficulty with reading,
double vision and the abnormal perception
of movement. Examination may reveal the
diagnoses of nystagmus, ocular motor
dysfunction, convergence insufficiency
and/or strabismus. Treatment options
including lenses, prism and partial selective
occlusion are effective and affordable means
to treat these conditions.
Address questions and comments to:
Thomas Politzer, O.D.
333 S. Allison Parkway, #120
Lakewood, CO 80120
Fall 2005 13 www.thecni.org
Surgical Treatment of Movement Disorders
Steven G. Ojemann, M.D.
The surgical treatment of movement disorders has evolved considerably over the last decade in
terms of the scope of the indications for surgery, and in terms of technique. Deep Brain
Stimulation (DBS) has an established role in the treatment of Parkinson’s disease and essential
tremor. As a surgical procedure, it offers inherent advantages over ablative therapies, as the
therapeutic and side effects of stimulation can be modulated by adjustment of multiple
stimulation parameters. DBS is finding increasing application for the treatment of dystonias, and
for tremor disorders other than essential tremor. These conditions, many of which are notoriously
difficult to treat medically, are reviewed in this article. The objective is to focus on the conditions
for which surgical treatments may be beneficial, the indications and contraindications to these
procedures, and on the surgical techniques and outcomes.
Steven G. Ojemann is Overview of Surgical Procedures. segment of the Globus Pallidus (GPi), the
an Assistant Professor of Surgical techniques can be roughly divided subthalamic nucleus (STN), and the
Neurosurgery at the into ablative procedures, neurostimulation Ventralis intermedius nucleus of the
University of Colorado, procedures, and procedures aimed at the thalamus (Vim). The modern targets for
and Director of Stereo-
enhancement of drug delivery. Added to this surgical treatment of movement disorders
tactic and Functional
scheme more recently are the trials of were discovered somewhat serendipitously,
augmentative and restorative therapies, such with the observation over 50 years ago that
completed his neuro-
as transplantation of fetal mesencephalic an iatrogenic infarct in the basal ganglia
surgical training at the
University of California,
tissue into the striatum of patients with produced effective tremor control in a
San Francisco in 2002. Parkinson’s disease. The different surgical Parkinsonian patient. Further exploration of
His clinical interests strategies are summarized in Table I. the effects of lesions in multiple sites within
include the surgical Currently, Deep Brain Stimulation (DBS) the basal ganglia gave rise to the stereotactic
treatment of movement represents the most commonly employed thalamotomy and pallidotomy. Lesions of
disorders, epilepsy, brain procedure, with an extensive literature that the subthalamic region were complicated by
tumors, and chronic supports efficacy for the treatment of hemiballismus, and bilateral lesions of the
pain disorders. Parkinson’s disease and essential tremor. It thalamus or pallidum were frequently
possesses an inherent advantage over ablative accompanied by fixed corticobulbar or
procedures, because of the ability to corticospinal deficits. The ability to
modulate both therapeutic and adverse modulate the majority of therapeutic and
effects of stimulation—effects are typically side effects with adjustable stimulation has
fixed following lesioning. Several restorative overcome these serious limitations of lesion
therapies have been subjected to controlled surgery. Deep Brain Stimulation has
studies to date; none have demonstrated generally supplanted ablative techniques,
efficacy similar to that seen with DBS. because DBS makes possible bilateral
Targets of surgical treatments consist surgery, and surgery employing the
largely of the structures of the basal ganglia subthalamic nucleus as a target. While the
and thalamus, specifically the internal risks specific to the creation of a lesion (ie,
CNI REVIEW 14
Table 1. Summary of Neurosurgical Procedures Used for the Treatment of Movement Disorders 1. Binder DK, Rau G,
Starr PA. Hemorrhagic
PROCEDURE CURRENT STATUS
deep brain stimulation.
Lesioning and Ablative Procedures
Thalamotomy Proven benefit for tremor only, not recommended for use on both sides Neurosurg. 2003; 80
of the brain. (1-4): 28-31.
Pallidotomy Proven benefit up to 5 years for tremor, rigidity, bradykinesia, and 2. Lyons KE, Pahwa R.
Deep brain stimulation
levodopa induced dyskinesias. Not recommended for use on both sides
and essential tremor. J
of the brain. Clin Neurophysiol.
Denervation Procedures Examples include partial denervation of the accessory nerve for cervical 2004:21(1); 2-5.
dystonia, selective dorsal rhizotomy for spasticity. As with lesioning 3. Pahwa R, et al. Bilateral
thalamic stimulation for
procedures, denervation does not afford the opportunity to modulate
the treatment of
either the therapeutic or adverse effects. essential tremor.
Deep Brain Stimulation 1999;53(7):1447-1450.
Chronic thalamic stimulation (Vim DBS) Reduces tremor but not the other signs of PD; approved by U.S. Food 4. Deep-brain stimulation
and Drug Administration in 1997 for unilateral use in the treatment of of the subthalamic
tremor. Commonly used off-label for the treatment of bilateral essential nucleus or the pars
interna of the globus
tremor. Growing literature on the use of thalamic stimulation for the pallidus in Parkinson’s
treatment of non essential tremor, such as tremor from MS, and disease. N Engl J Med.
Holmes’ tremor. 2001; 345(13):956-963.
Chronic pallidal stimulation (GPi DBS) Reduces tremor, rigidity, bradykinesia, and gait disorder; approved by 5. Pinter MM, et al.
Apomorphine test: a
FDA in 2002 for use in Parkinson’s disease. FDA granted Humanitarian predictor for motor
Device Exemption in 2003 for use in the treatment of dystonia. responsiveness to deep
Chronic stimulation of subthalamic Reduces tremor, rigidity, bradykinesia, and gait disorder; approved by brain stimulation of the
subthalamic nucleus. J
nucleus (STN DBS) FDA in 2002 for use in Parkinson’s disease. FDA granted Humanitarian
Device Exemption in 2003 for use in the treatment of dystonia. 1999;246(10):907-913.
6. Tarsy D, et al. Adverse
“Restorative” Therapies & Drug Delivery Strategies
effects of subthalamic
Human fetal cell transplantation Experimental; human trials have not shown overall efficacy. One recent nucleus DBS in a
trial showed only modest benefit in a subgroup of younger patients, and patient with multiple
production of uncontrollable dyskinesias was an adverse effect in some
Stem cell transplantation Studied in laboratory animals only; not yet applicable in humans 7. Chou KL, et al.
Intracerebral injection of growth factors Experimental; Most recent trial of intracerebral administration of Glial Subthalamic nucleus
deep brain stimulation
cell. Derived Neurotrophic Factor (GDNF) halted by manufacturer due to
in a patient with
safety concerns. levodopa-responsive
Gene therapy by intracerebral injection Studied in laboratory animals, initial human studies (Phase I) are being multiple system atrophy.
of genetically modified viral vectors conducted. Case report. J Neurosurg.
8. Vidailhet M, et al.
stimulation of the
dysarthria, ataxia) are clearly lower with general, less than half of these are globus pallidus in
DBS, there remains with this surgery a risk symptomatic.1 primary generalized
dystonia. N Engl J Med.
of hemorrhagic complications, and of 2005;352(5):
hardware-related complications, including Essential Tremor. Thalamic DBS for 459-467.
infection. The risk of intracranial hemorr- the treatment of medically refractory
hage with DBS surgery is typically cited at essential tremor (ET) is extremely effective
around 3 percent in large series, though in in the treatment of upper extremity tremor,
Fall 2005 15 www.thecni.org
9. Starr PA, et al.
often with secondary improvement in head levodopa, dopaminergic agonists, and other
implantation of deep tremor, and sometimes in voice tremor. medications can often address these motor
brain stimulators into
the globus pallidus
Surgical treatment is reasonable to consider fluctuations and complications of levodopa
internus for dystonia: in patients with a clear diagnosis of ET, who therapy for a period of time. Continued
have substantial disability and impairment difficulties with fluctuations in motor
outcomes. Neurosurg in quality of life despite therapy with beta- symptoms and/or levodopa-induced
blockers and primidone. Additional medical dyskinesas are the primary indications for
10. Wishart HA, et al.
Chronic deep brain therapy including topirimate, baclofen, or surgical treatment. Table 2, adapted from the
stimulation for the clonazepam may be attempted prior to University of California, San Francisco,
treatment of tremor in
multiple sclerosis: considering surgery, though some estimates summarizes the selection criteria employed
review and case have as many as 50 percent of patients with for DBS surgery at the University of
reports. J Neurol
Neurosurg Psychiatry. persistence of disabling symptoms despite Colorado, along with the rationale for
2003;74(10): maximal medical therapy.2 While the FDA each criterion.
11. Kim MC, et al. Vim has approved the device for unilateral The selection criteria are largely
thalamotomy for implantation for the treatment of disabling derived from the observed benefits of DBS
secondary to midbrain tremor, it is not unusual that patients with surgery. Stimulation of both the
tumour. J Neurol bilateral symptoms require bilateral Subthalamic nucleus (STN) and the internal
2002;73(4):453-455. stimulator placement for effective treatment. segment of the Globus Pallidus (GPi)
12. Nikkhah G. et al. The risks of irreversible dysarthria and gait produce significant improvement in the off-
disorder, which proved to be serious medication severity of all of the cardinal
stimulation of the
nucleus ventralis limitation to bilateral thalamotomy are symptoms of Parkinson’s disease (widely
much less seriuos with bilateral DBS surgery, accepted criteria for selecting between the
tremor and associated as such side effects are largely subject to GPi and STN targets do not exist as yet).
dystonia caused by
modulation with changes in stimulation The degree of benefit is rarely greater than
lesions. Report of two parameters. 3 that afforded by medication, but the same
cases. J Neurosurg.
level of benefit achieved by medications can
1079-1083. Parkinson’s Disease. Parkinson’s often be achieved surgically. Thus, benefits
13. Samadani U, et al. disease is characterized by the cardinal of stimulation can be maintained with a
Thalamic deep brain
stimulation for symptoms of tremor, rigidity, bradykinesia, substantial reduction or even elimination of
disabling tremor after and postural instability. For patients with medications, which in turn contributes to a
excision of a midbrain
cavernous angioma. early Parkinson’s disease, levodopa and other reduction of levodopa-induced dyskinesias.
Case report. antiparkinsonian medications are usually As well, the benefit achieved with surgery is
2003;98(4):888-890. effective for maintaining a good quality of typically sustained over the course of the
14. Goto S, Yamada K. life. As the disorder progresses, however, day, and thus addresses the problems related
thalamic Vim stimula-
most patients develop a fluctuating response to frequent “on-off ” fluctuations in motor
tion and GPi pallido- to levodopa, often vacillating between “on” symptoms experienced by most patients as
and “off ” states many times a day. Addition- the course of their disease progresses.4
tremor. J Neurol ally, levodopa-induced dyskinesias, Other selection criteria are also derived
consisting of involuntary, often choreo- from outcomes data. The few reports of DBS
1204. athetotic movements, can occur with the as a treatment for “atypical” parkinsonism,
peak dose or with the onset and wearing-off such as multiple systems atrophy, suggest
of the dose (diphasic dyskinesias). Dosing little or no benefit of surgery for these
changes, sustained-release preparations of patients.5-7 Thus, the certainty of the diag-
CNI REVIEW 16
15. Romanelli P, et al.
nosis of idiopathic Parkinson’s disease is side effects. If the most disabling dystonic Possible necessity for
important. Observations of the potential for symptoms are quite focal, then intramuscular deep brain stimulation
of both the ventralis
negative neuropsychological sequelae of injections of botulinum toxin can be an intermedius and
surgery have highlighted the importance of effective treatment. Care should be taken subthalamic nuclei to
resolve Holmes tremor.
identifying cognitive impairment in surgical when labeling symptoms refractory to Case report. J Neurosurg.
candidates, and counseling those with signi- botulinum toxin, as reasons for lack of 2003;99(3):566-571.
ficant impairment against the procedure. efficacy can include technical factors, and the
procedure is ideally performed with electro-
Dystonia. Dystonia is a heterogeneous myographic recording. Another reason for
disorder, classified roughly according to etio- lack of efficacy may be the development of
logy, insofar as this is known. It consists of neutralizing antibodies to specific serotypes
primary dystonias, secondary dystonias, of the toxin, and the use of alternative
heredodegenerative dystonias, and “dystonia- serotypes can sometimes restore benefit.
plus” syndromes. It can also be described as Consideration of surgery should be
focal, segmental, or generalized. As a symp- offered to patients with disabling dystonic
tom, it consists of simultaneous, sustained symptoms that are not effectively treated
contraction of agonist and antagonist with the above measures. DBS of the GPi
muscles, resulting in a fixed, abnormal, and target has been employed for a variety of
often painful postures. Surgical experience dystonias, and this has shown dramatic
with DBS for many different forms of dys- results in the treatment of primary
tonia has grown significantly over the last 5 generalized dystonias, especially when the
years, and the Food and Drug Administration patient harbors the DYT-1 genetic
(FDA) granted DBS therapy a “Humani- mutation.8 The results of GPi DBS in the
tarian Device Exemption” status in 2003 for case of secondary dystonias, including adult-
implantation of the Globus Pallidus Interna onset cervical dystonias, are more mixed,
or Subthalamic Nucleus for the whole spec- though some patients do make impressive
trum of disorders characterized as dystonia. gains with this surgery.9 Selective denervation
This designation has led to improvement in or rhizotomy of the spinal accessory nerve is
third party payer reimbursement for the another procedure sometimes employed in
procedure, making it an increasingly the treatment of cervical dystonias. The
accessible option for patients. As this surgical irreversible nature of any resultant weakness,
experience grows, recommendations are likely the tendency of symptoms to progress
to evolve regarding patient selection criteria, through this treatment, and the frequency of
ideal surgical target, and efficacy. bilateral involvement of the disorder make
As with all other surgical therapies, denervation a less attractive option than DBS
medical therapies and alternatives should be in many cases.
thoroughly explored before undertaking the
potentially irreversible risks of surgery. For Surgery for Non-Essential Tremor.
dystonia, the anticholinergic drug trihey- Increasingly, DBS is being applied to the
phenidyl and oral or intrathecal baclofen are treatment of tremor disorders other than
typically employed prior to consideration of Parkinson’s disease and ET. The tremor
surgery. Medical therapy may be deemed associated with multiple sclerosis (MS) can
ineffective due to lack of efficacy, or due to produce severe disability, and can be difficult
Fall 2005 17 www. thecni.org