What is Parkinson’s disease?

Idiopathic Parkinson's Disease (PD) is a complex disease of the nervous system, that is degenerative and progressive in nature. It is characterized by the loss of dopaminergic nerve cells of the substancia nigra (SNc) of the midbrain, which are the main producers of a chemical compound called dopamine in the brain. The baseline clinical signs of the disease are: resting tremor, rigidity, bradykinesia, and postural instability.

It is the second most frequently diagnosed neurodegenerative disease after Alzheimer's dementia, and it generally begins in mid to late stages of life, so age is the main risk factor.

Causes of Parkinson’s disease

As of today, the ultimate cause of Parkinson's disease is not known. However, it is thought to be due to a combination of environmental and genetic factors and factors related to the body's own aging.

There are three factors involved in the risk of developing the disease:

Age

Age has shown itself to be a clear risk factor, with the median age of diagnosis being between 55-60 years. The prevalence increases exponentially from the sixth decade of life onwards. When Parkinson's disease appears before age 50, it is called early-onset Parkinson's.

Genetic predisposition

90% of Parkinson's cases are sporadic forms, that is, they are not due to a specific genetic alteration. However, it does run in families and it is estimated that between 15% and 25% of people who develop Parkinsons have a relative who also has it.

Environmental factors

Some studies cite the continued consumption of well water over the years, or having been exposed to pesticides and herbicides as risk factors.

Symptoms

The clinical expression of the disease is noted in the gradual development of the following symptoms: 

  • Bradykinesia (slowed movement): defined as a loss of speed, slowness in the ability to begin and execute movements, and a gradual reduction of the range of movement.
  • Stiffness: muscles become stiffer and do not stretch or relax as they should
  • Tremor: Parkinsonian tremor is distinguished by an activity at rest in the frequency of 3-5 Hz, with distal predominance and which is usually asymmetric. 
  • Postural instability and gait disorder: difficulty walking, especially at the beginning or making turns, and a tendency to lean unnaturally forwards when walking.
  • Other clinical indications of the disease: symptoms include scarcity of automatic movements such as blinking or swinging arms when walking, lack of facial expressivity, speech disorders, depression or apathy, urgent urination and incontinence, constipation, dizziness when getting out of bed, sleep problems such as insomnia and nightmares, anosmia (loss of smell), alteration of the reflexes with frequent falls and others.

Diagnosis

To diagnose Parkinson's, the neurologist gathers a detailed medical history of the patient with data provided by the patient and the patient’s family, and performs a physical examination. 

When necessary, this information will be complemented with laboratory tests. A blood test, and an MRI of the brain or a PET with F-dopa, which can help increase diagnostic certainty by differentiating it from other processes that share clinical characteristics (atypical and secondary parkinsonisms, etc.).

The criteria for the diagnosis of idiopathic PD are based on the presence of at least two of the four symptoms or signs mentioned in the previous section, in addition to proof of a good response to L-Dopa.

Treatment of Parkinson’s disease

Conventional Parkinson's treatment is based on the use of drugs that try to compensate for the deficiency of nigrostriatal dopamine. However, nowadays we know that pharmacological treatment does not control the clinical manifestations of the disease indefinitely. In fact, at least 50% of conventionally treated patients experience major complications, such as fluctuations in mobility, dyskinesias, psychic disturbances, and autonomic control, which seriously disrupt therapeutic control and lead to functional disability. The clinical picture is aggravated by the deterioration in the pharmacological response: posture, language changes, impeded gait, freezing and falls.

LIMITED PHARMACOLOGICAL PERSPECTIVES

Because of the limited pharmacological perspectives for successful treatment or prevention of these complications in the mid-term, and thanks to advances such as better pathophysiological knowledge of the structures involved in the origin of Parkinsonian syndrome, the notable technological advances in neuroimaging techniques, the development of new surgical software, the possibility of intraoperative monitoring and the improvement in some surgical techniques, interest has been maintained in surgical treatment options for Parkinson's disease.

SURGERY

Surgery would be indicated when pharmacological treatment fails to control the patient's symptoms throughout the day, significantly reducing their quality of life. As Parkinson's disease currently has no cure, the benefits of surgery are truly important. Very significant improvements in movement can be achieved, as well as a decrease in rigidity and tremors. In addition, it makes it possible to reduce the medication, which is beneficial for reducing the side-effects associated with their long-term use.

There are different types of surgical treatment. Here we will describe the techniques that are currently most frequently used. 

Surgical ablation

This type of surgery consists of producing an ablation or controlled injury in a selected small part of the brain. This treatment modality can be carried out interchangeably by three different methods and each of them constitutes a treatment technique in itself: radiofrequency thermal ablation, ionizing radiation injury (radiosurgery), and thermal ablation when administering a high dose of Ultrasonic energy using magnetic resonance-guided focal ultrasound.  

Deep brain stimulation (DBS)

This is the most widely used treatment modality worldwide today. It consists of high frequency stimulation in a small part of the brain. Through electrical impulses, the part of the brain that is abnormally overactive is inhibited or modulated – the part responsible for the symptoms of the disease. To do this requires implanting brain electrodes and a small neurostimulator similar to a cardiac pacemaker in the body. Once implanted, your doctor can adjust device settings and stimulation levels using an external programming device.

Three nuclear structures have been defined as surgical targets of choice for these modalities: 

  • The motor thalamus, at the level of the nucleus ventralis intemedialis (Vim)
  • The posteroventral region of the internal globus pallidus (GPi)
  • The sensory motor region of the subthalamic nucleus (STN)

In recent years, the continuously growing knowledge about the function of the basal ganglia and the pathophysiology of the motor disorders of Parkinson's disease have led physicians to focus on the subthalamic nucleus, considering its role as a nodal modulating structure of efferent nerve activity, the motor of the basal ganglia. It has been widely used since its introduction, and is considered the preferred target in the treatment of the motor signs of this disease.

This surgery is carried out following the methodology that we describe here. A stereotactic guide or crown is first placed on the patient's head. The radiological location of the surgical target is determined with neuroimaging fusion (CT/MRI), combining anatomical images and diffusion tensors (DTI tractography). Once this is done, the intracerebral trajectories are simulated by the computer with the support of very powerful surgical programs or software. 

The patient receives local anesthesia/sedation, and the highly accurate image-guided surgical technique is performed using the help of various neural electrical records and micro-stimulation to identify the electrophysiological location of the surgical target. The electrodes are immediately implanted in the selected structure. A small, rechargeable neurostimulator is also implanted in another part of the body (infraclavicular region or abdomen), which is connected to the electrodes to stimulate these brain structures. This system implanted in the patient is controlled by the doctor in each hospital visit in a non-invasive way, through a programming device that uses 3D graphics to allow the stimulation parameters to be easily adjusted, including the directional stimulation that helps increase the efficiency and safety.

Who are the doctors who treat idiopathtic Parkinson’s disease at Instituto Clavel?

Dr. Salazar

Sources

  • Lozano AM, Lipsman N, Bergman H, Brown P, Chabardes S, Chang JW, Matthews K, McIntyre CC, Schlaepfer TE, Schulder M, Temel Y, Volkmann J, Krauss JK. Deep brain stimulation: current challenges and future directions. Nat Rev Neurol. 2019 Mar;15(3): 148-160.
  • Fox SH, Katzenschlager R, Lim SY, Barton B, de Bie RMA, Seppi K, Coelho M, Sampaio C; Movement Disorder Society Evidence-Based Medicine Committee. International Parkinson and movement disorder society evidence-based medicine review: Update on treatments for the motor symptoms of Parkinson's disease. Mov Disord. 2018 Aug;33(8):1248-1266.
  • Wolf ME, Klockziem M, Majewski O, Schulte DM, Krauss JK, Blahak C. Implementation of New Technology in Patients with Chronic Deep Brain Stimulation: Switching from Non-Rechargeable Constant Voltage to Rechargeable Constant Current Stimulation. Stereotact Funct Neurosurg. 2019;97(5-6):362-368.
  • Hartmann CJ, Fliegen S, Groiss SJ, Wojtecki L, Schnitzler A. An update on best practice of deep brain stimulation in Parkinson's disease. Ther Adv Neurol Disord. 2019 Mar 28;12:1756286419838096.
  • Limousin P, Foltynie T. Long-term outcomes of deep brain stimulation in Parkinson disease. Nat Rev Neurol. 2019 Apr;15(4):234-242.
  • Hitti FL, Ramayya AG, McShane BJ, Yang AI, Vaughan KA, Baltuch GH. Long-term outcomes following deep brain stimulation for Parkinson's disease. J Neurosurg. 2019 Jan 18:1-6. doi: 10.3171/2018.
  • Büttner C, Maack M, Janitzky K, Witt K. The Evolution of Quality of Life After Subthalamic Stimulation for Parkinson's Disease: A Meta-Analysis. Mov  Disord Clin Pract. 2019 Aug 16;6(7):521-530.
  • Lahtinen MJ, Haapaniemi TH, Kauppinen MT, Salokorpi N, Heikkinen ER, Katisko JP. A comparison of indirect and direct targeted STN DBS in the treatment of Parkinson's disease-surgical method and clinical outcome over 15-year timespan. Acta Neurochir (Wien). 2020 May;162(5):1067-1076.
  • Hacker ML, Turchan M, Heusinkveld LE, Currie AD, Millan SH, Molinari AL, Konrad PE, Davis TL, Phibbs FT, Hedera P, Cannard KR, Wang L, Charles D. Deep Brain Stimulation in Early-Stage Parkinson's Disease: Five Year Outcomes. Neurology. 2020 29:10.1212.
  • Steigerwald F, Matthies C, Volkmann J. Directional Deep Brain Stimulation. Neurotherapeutics. 2019 Jan;16(1):100-104.
  • Sabourin S, Khazen O, DiMarzio M, Staudt MD, Williams L, Gillogly M, Durphy J, Hanspal EK, Adam OR, Pilitsis JG. Effect of Directional Deep Brain Stimulation on Sensory Thresholds in Parkinson's Disease. Front Hum Neurosci. 2020 Jun 9;14:217.
  • Bezchlibnyk YB, Sharma VD, Naik KB, Isbaine F, Gale JT, Cheng J, Triche SD, Miocinovic S, Buetefisch CM, Willie JT, Boulis NM, Factor SA, Wichmann T, DeLong MR, Gross RE. Clinical outcomes of globus pallidus deep brain stimulation for Parkinson disease: a comparison of intraoperative MRI- and MER-guided lead placement. J Neurosurg. 2020 Mar 6:1-11.
  • Nguyen TAK, Nowacki A, Debove I, Petermann K, Tinkhauser G, Wiest R, Schüpbach M, Krack P, Pollo C. Directional stimulation of subthalamic nucleus sweet spot predicts clinical efficacy: Proof of concept. Brain Stimul. 2019 Sep- Oct;12(5):1127-1134.
  • Macerollo A, Zrinzo L, Akram H, Foltynie T, Limousin P. Subthalamic nucleus deep brain stimulation for Parkinson's disease: current trends and future directions. Expert Rev Med Devices. 2020 Apr 6:1-12.
  • Limousin P, Foltynie T. Long-term outcomes of deep brain stimulation in Parkinson disease. Nat Rev Neurol. 2019 Apr;15(4):234-242.
  • Kochanski RB, Bus S, Brahimaj B, Borghei A, Kraimer KL, Keppetipola KM, Beehler B, Pal G, Metman LV, Sani S. The Impact of Microelectrode Recording on Lead Location in Deep Brain Stimulation for the Treatment of Movement Disorders. World Neurosurg. 2019 Dec;132:e487-e495.
  • Contarino MF, Bour LJ, Verhagen R, Lourens MA, de Bie RM, van den Munckhof P, Schuurman PR. Directional steering: A novel approach to deep brain stimulation. Neurology. 2014 Sep 23;83(13):1163-9.
  • Brahimaj B, Kochanski RB, Sani S. Microelectrode accuracy in deep brain stimulation surgery. J Clin Neurosci. 2018 Apr;50:58-61.
  • Falconer R, Shah T, Rogers S, Green A, Shenai M. Utilizing the Flexibility of Directional Deep Brain Stimulation Intraoperatively (if Needed) to Minimize Microelectrode Lead Repositioning. Cureus. 2019 Jul 30;11(7):e5276.

Want to know more?
Tell us about your case!

Contact us so that we can give you a personalized assessment.

Contact
Share on: