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Definition

Idiopathic Parkinson’s disease (PD) is a diffuse neurodegenerative brain disease affecting olfactory, autonomic, limbic, and somato-motor components of the central nervous system.

Deep Brain Stimulation (DBS) is a neurosurgical procedure involving the implantation of electrodes within the brain. Through electrical stimulation of specific deep-located targets (brain nuclei) DBS attempts to restore and modulate pathological electrical brain networks in many movement and neuropsychiatric disorders.

 

Epidemiology

PD affects 6 million people globally. Age-standardised prevalence rate for subjects 65 years or older is 1-2%. Male are more often affected than female (ratio 3:2). PD must be differentiated from other similar conditions, the so-called secondary Parkinsonisms.

Secondary Parkinsonisms

Atypical/Secondary Parkinsonism and Parkinson’s Plus are all terms used to describe syndromes that can clinically resemble Idiopathic Parkinson’s disease, but show some atypical features:

  • Symptoms present on both sides of the body at onset
  • Early cognitive problems
  • Early problems with balance, falls and/or freezing of gait
  • Early problems with autonomic function such as orthostatic hypotension (light-headedness when standing from low blood pressure)
  • Earlier speech and swallowing problems
  • Faster progression
  • Limited improvement with medications
  • Significant visual problems such as double vision, trouble focusing while reading

 

Etiology

PD primary symptoms result from the loss of dopamine secreting cells in the SNpc (pars compacta of the substantia nigra) due to the abnormal accumulation of alpha-synuclein protein. SNpc is one of the main modulator of the basal ganglia network and its pathological activity leads to an imbalance between excitatory/inhibitory signals within basal ganglia and between basal ganglia and cortical structures.

 

Diagnosis and pharmacological treatment

Diagnosis is mainly based on clinical information and neurological examination (tremor, bradykinesia, rigidity and postural instability). Other common symptoms may be hyposmia, constipation, depression and REM sleep behaviour disorders. Once the diagnosis is established, pharmacological therapies include dopamine agonists, monoamine oxidase B (MAO-B) inhibitors, and the mainstay of treatment, carbidopa/levodopa

 

Surgical Treatment (DBS/Ablation)

Surgical treatment is reserved for those patients whose symptoms cannot be adequately controlled with medications, or whose medications have severe side effects. Surgery for PD can be divided in two main groups: ablative and Deep Brain Stimulation. Nowadays the latter is preferred due to its reversibility and low risk of complications. 

 

DBS surgical technique

Procedure: Stereotactic positioning of stimulating microelectrodes
Rationale: modulation of neuronal activity obtained by modifying the release of neuromediators
Features: High Frequency (130Hz) and Low Voltage (DC) Voltage (1-3.5V).

The patient must be awake and all dopaminergic medications must be withheld at least 12 hours before the procedure. Surgery may be performed in two different modalities: frame-based (application of a stereotactic head frame such as Leksell or CRW frame) or frameless (application of cranial fiducials and use of image-guided neuronavigation systems). Frame-based technique is still considered the gold standard due to its superior accuracy. The stereotactic frame is applied under local anestetic. 

DBS for PD: indications

  • Patients refractory to medical therapy with severe on-off fluctuations or levodopa-induced dyskinesias
  • Patients with good response to L-Dopa challenge test
  • Idiopathic PD

DBS for PD: contraindications

  • Dementia or severe cognitive impairment
  • Patients with severe risk of intracerebral haemorrhage 
  • Age>75 years
  • Patients with secondary Parkinsonism
  • Finding of lesions or anatomical variants on MRI
 

Description of the Surgical Procedure

A stereotactical CT scan is performed and then fused with the volumetric MRI (T2, T1 with gadolinium and IR sequences) obtained the day before surgery. Targeting of the nucleus may be performed both in a indirect (stereotactic atlas) and direct way (direct visualisation of the nucleus on radiological images). Electrophysiological and stimulation test will confirm the correct placement of the electrode during surgery. The main nuclei in DBS surgery for PD are the subthalamic nucleus and the internal globus pallidus. 

DBS surgical/hardware complications

DBS adverse effects are low (5-10%) and are related to surgical, hardware and stimulation complications. 

  • Intracerebral haemorrhage
  • Hardware infection
  • Electrode displacement
  • Seizure 

 

Results

After DBS for PD motor scores show on average an improvement up to 69%, a dyskinesia reduction of 20-90%, and levodopa equivalent reduction up to 71%.

  

References

Textbook of Stereotactic and Functional Neurosurgery. Lozano Andres M., Gildenberg Philip L., Tasker Ronald R. Springer 2009

Neuromodulation. Elliot Krames P., Hunter Peckham, Ali Rezai. Elsevier 2009

 

Authors

 

Vincenzo Levi, MD

Neurosurgeon Resident
University of Milan
Neurological Institute "C. Besta", Milan (Italy)
Scientific Team - UpSurgeOn