What Is the Main Idea?

People with Parkinson’s disease often have movement-related symptoms such as tremors. In the open-access research article “Long-Term Follow-Up of Unilateral Deep Brain Stimulation Targeting the Caudal Zona Incerta in 13 Patients with Parkinsonian Tremor”, published in the journal Stereotactic and Functional Neurosurgery, the authors investigate whether using deep brain stimulation that targets a region of the brain called the posterior subthalamic area to treat patients with Parkinson’s disease who have severe tremor still reduces their symptoms at least 3 years after surgery.

What Else Can You Learn?

The symptoms and causes of Parkinson’s disease are discussed. The roles of different areas of the brain in regulating movement and of the neurotransmitter dopamine are also described.

Take-Home Message

The results suggest that treating patients with Parkinson’s disease who have severe tremor with deep brain stimulation that targets the PSA is effective and safe, and significantly improves their tremor symptoms, while slowness of movement is slightly improved. Future studies directly comparing the effects of targeting the VIN or PSA in deep brain stimulation will provide researchers with more information that can be used to refine the techniques and improve the quality of life of people with Parkinson’s disease.

What Is Parkinson’s Disease?

Parkinson’s disease is an age-related neurodegenerative disorder that develops when nerve cells in the nervous system or brain stop functioning and eventually die, causing more severe symptoms over time. It is the most common movement-related brain disease and is slightly more common in men than in women. Although it can develop in adults as young as 20 years old this is extremely rare. It is inherited in around 10% of cases, but in most cases is not linked to gene changes inherited from a parent. The average age at which Parkinson’s disease develops is 60 years and it is estimated to affect more than 1% of people aged over 60 years worldwide.

What Are the Symptoms of Parkinson’s Disease?

Parkinson’s disease is characterized by a range of symptoms that can be broadly divided into two groups: those that are movement-related and those that are not. The two best known movement-related symptoms are bradykinesia and tremor:

  1. The term bradykinesia means that movement is slow and that a person’s continuous movements may be hesitant or halt midway. This is caused by problems with muscle control rather than a loss of strength.
  2. Tremor is a rhythmic shaking of the muscles, even when a person is resting and not using them.

Other movement-related symptoms include a hunched or stooped posture, rigidity or stiffness of the joints, changes in the way a person walks (often resulting in them taking shorter, shuffling steps and needing to take more steps when turning), difficulty swallowing, and blinking less often than usual.

Symptoms that are not related to movement and muscle control include a loss of sense of smell, problems with focusing and with sleep, depression, problems relating to the stomach and intestines (gastrointestinal problems), urinary incontinence, and low blood pressure when standing up. Some of these symptoms are now thought to be warning signs that Parkinson’s disease is developing, which begin years before movement-related symptoms start to be noticeable.

What Causes Parkinson’s Disease?

The brain is made up of several regions with different roles. The outside surface of the brain is made up of a thin layer of cells called the cerebral cortex. This area of the brain is responsible for language and social skills, memory, reasoning, and decision-making. Below it is the sub-cortex, which contains four regions that are important for emotion, thinking, and movement.

One of these is the brainstem, a stalk-like structure that connects the brain to the spinal cord. It is in an area of the brainstem that the neurotransmitter dopamine is produced (neurotransmitters carry chemical signals between neurons, a type of cell that transmits messages from one part of the brain and nervous system to another, and trigger an action or change in the target cell).

Dopamine has a wide range of roles including:

  • motivation and pleasurable reward,
  • attention,
  • behavior,
  • cognition (an umbrella term that describes a combination of processes that take place in the brain, such as the ability to learn, remember, and make judgements based on experience, thinking, and information from the senses), and
  • movement.

The basal ganglia is another important region in the sub-cortex.

How Is the Basal Ganglia Linked to Parkinson’s Disease?

The basal ganglia is a group of structures near the center of the brain that is about 10 cubic centimeters in size. The structures within it are responsible for important connections between different areas of the brain that enable them to work together and send signals back and forth, a bit like a circuit board in an electronic device. The basal ganglia plays a key role in our ability to move by managing the signals that the brain sends to help you move your muscles.

The structures within it can filter out signals that are unnecessary or wrong, and approve or reject movement signals so that you can control particular muscles without using other ones in the same area of your body. They also process sensory information, which helps you to further refine your movements, and are involved in emotions, motivation, and habits.

Parkinson’s disease develops when the basal ganglia begins to deteriorate and causes a major change in the chemistry inside the brain that results in there not being enough dopamine. Because the basal ganglia’s fine-tuning of your movements involves cells that require dopamine to function properly, this reduction in the amount of dopamine results in people having the slowed movement and tremors that are characteristic of the disease.

How Is Parkinson’s Disease Treated?

Although there is currently no cure for Parkinson’s disease, the symptoms of the condition can be treated with medication and/or surgery. Although many people with Parkinson’s disease can have their symptoms reduced by taking medication, which often works by increasing the levels of dopamine in the brain, it can become less effective and side effects (these are positive or negative unintended effects of a medication) can become more severe as the condition progresses.

Tremors can be particularly difficult to treat with medications that affect dopamine levels, and some researchers have reported evidence that as well as dopamine, levels of other neurotransmitters are involved in causing tremors in Parkinson’s disease.

Patients who do not experience significant improvements in their symptoms as a result of taking medication may be offered a type of surgical therapy called deep brain stimulation. This approach involves the reversible implantation of a device that works in a similar way to how a pacemaker regulates the heart. A device called a pulse generator is implanted under the skin in the stomach or chest area that is connected to one or two fine wires. These are inserted into specific areas of the brain and deliver a mild electrical current that changes some of the signals in the brain that cause the movement-related symptoms of Parkinson’s disease.

What Did This Study Investigate?

The thalamus, which is located close to the basal ganglia, acts as the main relay station of signals that come into the brain and passes them on to other areas for interpretation and response. An area of the thalamus called the ventral intermediate nucleus (VIN) is usually the location of choice for the implantation of wires when a patient with a tremor disorder like Parkinson’s disease is treated with deep brain stimulation.

However, over the last decade, targeting an area below the thalamus called the posterior subthalamic area (PSA) has been shown to be at least as effective as targeting the VIN in reducing tremors in patients. It has also been reported to reduce other Parkinson’s disease symptoms, such as rigidity and the loss of the ability to move muscles voluntarily, which is not seen when the VIN is targeted. To assess whether this approach is effective in reducing symptoms of tremor in the long term, the authors of this research study investigated whether deep brain stimulation targeting the PSA remained effective in reducing tremors more than 3 years after patients with Parkinson’s disease underwent surgery.

Thirteen patients were included in the study and 12–24 months after surgery their tremor symptoms had improved by an average of 88% and slowness of movement by an average of 40%. When they were assessed on average 62 months after surgery, the improvement in tremors was still seen and slowness of movement symptoms remained an average of 20% better than when they were assessed before surgery.

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