Beyond Tremors: Unpacking Dystonia and STN-DBS in Parkinson’s
Hey there! Let’s dive into something pretty interesting happening in the world of Parkinson’s disease (PD) and a treatment called Deep Brain Stimulation (DBS), specifically when it targets a spot in the brain called the Subthalamic Nucleus (STN). Now, STN-DBS is fantastic for many folks dealing with the ups and downs of long-term L-dopa therapy – you know, those tricky motor fluctuations where movements get wild (dyskinesias) or really slow (bradykinesia) depending on medication levels. It’s been a game-changer for decades, and its effectiveness is totally acknowledged worldwide.
But, like anything complex, sometimes STN-DBS can bring its own set of motor surprises. We’re talking about side effects that pop up because of the stimulation itself. Most of the time, these happen during the surgery and can be tweaked by adjusting the stimulation settings. Think things like muscle twitches or eye movements. Easy enough to handle, usually.
However, some chronic side effects can be a bit more stubborn. Dyskinesias are probably the most common, showing up as involuntary movements, often on the opposite side of the body from the stimulated brain area. These can happen soon after the electrodes are in or a few months later. Sometimes, reducing the stimulation voltage or shifting to a different contact on the electrode helps. But, occasionally, they can be really tough to manage, even needing different approaches.
The Dystonia Connection
Now, here’s where it gets particularly intriguing: dystonia. This is another movement disorder, and it’s actually quite closely related to PD. They even share some similar underlying mechanisms. It’s not uncommon for people with PD to also have dystonia – up to 30% of patients! Sometimes, dystonia can even show up *before* the classic Parkinson’s symptoms.
In our recent look at a group of 60 PD patients who had STN-DBS at our center, we saw something noteworthy. Some patients developed new dystonic symptoms *after* the surgery (we call this “de novo” dystonia). Others had dystonia *before* the surgery, and unfortunately, the stimulation didn’t seem to help them at all, despite trying different settings.
This got us thinking: could there be a common thread, a shared neural pathway or mechanism, that explains both why some people develop new dystonia after stimulation and why others with pre-existing dystonia don’t get better? That’s what we set out to investigate.
Putting the Study Together
We decided to look back at our patient data from 2014 to 2019. We split the 60 patients into four groups to compare them:
- De novo dystonia: 16 patients who developed dystonia after STN-DBS.
- Not-improved dystonia: 11 patients who had dystonia before surgery that didn’t get better with stimulation.
- Improved dystonia: 14 patients who had dystonia that *did* significantly improve after the stimulation was turned on.
- Controls: 19 patients who never experienced dystonia, either before or after surgery.
We compared lots of clinical stuff: age, how long they’d had PD, medication doses, and standard clinical scores. Crucially, we also looked at the exact location of the active contact on the DBS electrode relative to the STN. Think of the STN as the target; we wanted to see how far the “sweet spot” of stimulation was from the bullseye.
Then, we got a bit fancy with brain mapping. We identified “sour spots” – basically, the areas where stimulation seemed to be linked to the dystonic symptoms (the opposite of the “sweet spot” that gives improvement). Using a special database of brain connections from other PD patients, we mapped out the structural and functional connections linked to these sour spots. We wanted to see which brain areas were talking to these “dystonia-linked” stimulation sites.
What We Found: The Clinical Clues
Turns out, there were some pretty significant differences between the groups, particularly for the de novo and not-improved dystonia patients compared to the others. These two groups:
- Had a statistically significant longer duration of Parkinson’s disease before they had the DBS surgery.
- Had a statistically significant greater distance between the active stimulation contact and the border of the STN.
So, it seems that if you’ve had PD for a longer time, and if the stimulation isn’t hitting the very center of the STN target but is a bit off, you might be more likely to either develop new dystonia or have existing dystonia that doesn’t respond well.
Interestingly, other things like age, sex, which side of the body was first affected by PD, or changes in medication dose after surgery didn’t show significant differences between the groups. We also looked at the characteristics of the dystonia itself (like if it was focal, generalized, or happened during ON/OFF states), and those didn’t differ significantly between the three dystonia groups either.
We did notice that for many patients with dystonia (both pre-existing and de novo), their dystonia tended to get worse at the peak effect of their levodopa medication, which is something that’s been seen before (“peak dose dystonia”). For the de novo dystonia patients, about half saw their dystonia improve when we adjusted the stimulation parameters, often by reducing the intensity or activating a contact slightly higher up on the electrode. But for others, lowering the stimulation to help the dystonia meant their tremor or slowness got worse, requiring more complex programming.
Mapping the “Sour Spots” and Connections
When we mapped out the “sour spots” – those stimulation locations associated with dystonia – for the de novo and not-improved groups, they looked quite similar. Both extended upwards from the STN. The sour spot for the de novo group also spread a bit outwards and forwards, towards fibers that have been linked to poorer outcomes in GPi-DBS (a different type of DBS) for dystonia. Both sour spots were also close to a neighboring area called the rostral Zona Incerta (rZI).
The rZI is an interesting neighbor. While another part of the Zona Incerta (cZI) seems involved in helping with dyskinesias and tremor, stimulating the rZI might affect different brain networks, perhaps linked to neuropsychiatric stuff. Given that the rZI talks to areas like the cerebellum and upper brainstem (which our sour spots also connected to), it’s plausible it plays a role in dystonia.
Speaking of connections, the structural and functional connectivity maps from our sour spots were pretty telling. They showed strong links to areas we already know are important for movement, like the motor cortex and thalamus. But they also connected to wider brain regions, including:
- Infratentorial structures: The cerebellum and parts of the midbrain.
- Supratentorial areas: Somatosensory and posterior parietal cortices, and parts of the temporal cortex.
Why are these connections significant? Well, the cerebellum is increasingly recognized as playing a role in dystonia. Studies in animals and humans have shown altered cerebellar activity in dystonia, and stimulating the cerebellum has even shown promise in treating it. The upper brainstem also has structures (like the interstitial nucleus of Cajal) that, when affected, can cause movements resembling dystonia.
On the cortical side, the brain’s outer layer, particularly the somatosensory and parietal areas, seems to have altered “plasticity” or wiring in dystonia – a loss of normal inhibition. The frontal and temporal cortices also show abnormal activity. It’s fascinating that the same parietal and frontal areas connected to our sour spots have been negatively correlated with clinical outcomes in other dystonia studies. This really reinforces the idea that the cortex is a key player in dystonia.
Our “Two-Hit” Hypothesis
Based on all this, we’ve come up with a hypothesis – a “two-hit” model – to explain why dystonia might show up or persist after STN-DBS. Think of it like this:
- The First Hit: This is something inherent to the Parkinson’s disease itself, especially when it’s been present for a long time. We speculate that longer disease duration might cause changes in brain wiring (altered plasticity) at both cortical and subcortical levels. This creates a predisposition, making the brain more vulnerable to developing dystonic symptoms.
- The Second Hit: This is the STN-DBS stimulation itself. If the stimulation spreads or is delivered in areas connected to those “dystonia-related” brain regions (like parts of the cerebellum, brainstem, or specific cortical areas), it acts as the second hit, triggering or perpetuating the dystonic symptoms in a brain that’s already predisposed.
So, in this model, someone with long-standing PD (Hit 1) might develop new dystonia if the stimulation hits these vulnerable areas (Hit 2). Or, someone who already has dystonia (perhaps also due to Hit 1 factors) doesn’t get better because the stimulation in these areas keeps the dystonia circuits active, or maybe the stimulation isn’t hitting the *most* effective part of the STN to counteract it.
This whole picture really supports the idea that dystonia isn’t just one simple problem but a “circuitopathy” – a disorder caused by dysfunction or poor communication within a network of brain areas, including the basal ganglia, cerebellum, thalamus, midbrain, and cortex. Understanding these connections is key to figuring out better ways to treat this challenging symptom.
Looking Ahead
Of course, our study has its limits. It’s based on looking back at patient data, which can sometimes introduce biases. Also, the dystonia itself varied among patients. While our findings about disease duration and contact location are strong, we need bigger, prospective studies to confirm these ideas and maybe find other “first hit” factors we didn’t spot.
Mapping the “sour spots” is helpful, but it’s based on models and averages, not perfect for every single patient. Still, even with these limitations, our work adds a piece to the puzzle, suggesting that the connectivity of the stimulated area to a wider network of brain regions is super important for understanding why dystonia happens after STN-DBS.
We’re hopeful that this kind of “connectomic” view – focusing on how brain areas are connected and communicate – will ultimately help us better understand and treat dystonia, making life better for people living with Parkinson’s.
Source: Springer
