Therapeutic Applications of Botulinum Neurotoxin in Parkinson’s Disease

By Dr. Evan Friedman | July 25, 2022

Therapeutic Applications of Botulinum Neurotoxin in Parkinson’s Disease (PD), is the eighth article in a series, to address applications of Botulinum neurotoxin (BoNT).

The following article is presenting a short review of therapeutic applications of botulinum neurotoxin in Parkinson’s Disease, with a focus on the benefit of using the Myoguide™ EMG/ESTIM BoNT injection guidance system.

The article presents some background specifically aimed at the management of PD sequelae. The information within, is simply informative and not considered to be instructive, in any way. Please have a look at the article and the appropriate reference materials for more details.

PD hand

Parkinson disease (PD) is recognized as one of the most common neurologic disorders, affecting approximately 1% of individuals older than 60 years. PD cases progressive disability that can be slowed, but not halted, by treatment [1-5]

The 2 major neuropathologic findings in PD are:

  • Loss of pigmented dopaminergic neurons of the Substantia Nigra Pars Compacta
  • The presence of Lewy Bodies and Lewy Neurites [6]

Parkinson’s Disease Features

The cardinal features of PD are:

  • Resting tremor
  • Bradykinesia
  • Rigidity

Postural instability is commonly mentioned but does not generally occur until much later in the disease process, and is not usually included in most published diagnostic criteria for PD [2-4, 9-10]. 

The severity of motor symptoms appears to be an independent predictor of mortality in patients with PD.

Tremor

The rest tremor that occurs in PD, is typically described as “pill-rolling”.  This is characterized by occurring when the tremulous body part is supported by gravity and not engaged in purposeful activities.

Tremors in other conditions, such as essential tremor or multiple sclerosis, are typically “action tremors”.  Action tremors occur when the affected limb is being used.

Parkinsonian tremor is usually present within postural maneuvers or with action.  The tremor is generally much more severe at rest.

Parkinsonian tremor decreases with purposeful action.  As such, it is considered the least disabling of the cardinal manifestations.

However, when the tremor is severe, it can be difficult to distinguish a primary resting tremor from a primary action tremor.

Some patients with PD may have a “re-emergent tremor”.  This is a postural tremor that manifests after a latency of several seconds, and has a frequency typical of the rest tremor in PD [11,14].

This distinction is important, as patients with PD who have a re-emergent postural tremor may be misdiagnosed as having essential tremor.

The tremor of early PD is most often intermittent and may not be noticeable to others.

Approximately 50% of PD patients report a sensation of internal tremulousness in the limbs or body, that is unrelated to the presence of observable tremor.  However, as the disease progresses, these tremors become more evident [59-61].

Tremor in the limbs can be seen clinically, when the patient is relaxed with the hands resting quietly on the lap. Distracting the patient by asking them to perform mental calculations, or voluntary repetitive movements of the contralateral limb, often accentuates a mild tremor and may uncover a latent tremor. In fact, a resting hand tremor may be present only during the gait evaluation.

PD tremor frequency is between 3 and 7 Hz, and most often is between 4 and 5 Hz.  Tremor is the presenting symptom in approximately 70 to 80% of patients with PD.   The percentage of patients with tremor within the course of the disease, ranges from 79 to 100%.

Tremor usually starts unilaterally in the hand, and then spreads contralaterally several years after the onset of symptoms. The side that is initially affected tends to be the more affected side throughout the course of the disease.

The tremor of PD can also involve the legs, lips, jaw, and tongue, but rarely involves the head. Anxiety, emotional excitement, or stressful situations can exacerbate the tremor [11-29]

Bradykinesia

“Bradykinesia” is a generalized slowness of movement, or the decreased ability to initiate voluntary movement.  It is generally thought to be the major cause of disability in PD and is eventually seen in most patients [30]. Bradykinesia is present at onset of PD in approximately 80 percent of patients.  

While it is the most common feature in PD, it is also the most difficult symptom for patients to describe the decreased ability to initiate voluntary movement.  Common descriptors include:

  • Weakness
  • Incoordination
  • Tiredness

Bradykinesia typically starts distally in the arms with decreased manual dexterity of the fingers.

Patients often complain of difficulty performing simple tasks, such as:

  • Buttoning clothes
  • Tying shoelaces
  • Double clicking a computer mouse
  • Typing
  • Picking up coins

Common complaints related to bradykinesia when walking include:

  • Dragging the legs
  • Shorter (shuffling) steps
  • Feeling of unsteadiness.
  • Difficulty standing up from a chair or getting out of a car

As the disease progresses, gait freezing, and festination may develop. James Parkinson defined festination as “an irresistible impulse to take much quicker and shorter steps, and thereby to adopt unwillingly a running pace” [31,32].

 Clinical examination of bradykinesia includes:

  • Evaluation of limb movements on each side of the body
  • The speed, amplitude, and rhythm of finger tapping
  • Hand opening-closing
  • Pronation-supination hand movements
  • Heel or toe tapping should be carefully observed

These tasks usually show some slowing and decreased amplitude, in mild PD, however, as the disease progresses, movements become less coordinated, with frequent hesitations and/or arrests.

Rigidity

Rigidity is an increased resistance to passive movement about a joint.   Rigidity occurs in approximately 75 – 90% of patients with PD Rigidity.  It often begins unilaterally, and typically on the same side as the tremor, if one is present. Rigidity eventually progresses to the contralateral side and remains asymmetric throughout the disease [33].

  • Cogwheel rigidity presents as a ratchet pattern of resistance and relaxation as the examiner moves the limb through its full range of motion.   The process is thought to be a manifestation of tremor superimposed over increased tone. Not all patients with PD have cogwheel rigidity. 
  • Lead pipe rigidity is a tonic resistance that is smooth throughout the entire range of passive movement.

Rigidity can affect any part of the body and may contribute to complaints of stiffness and pain. Features include:

  • Striatal hand
  • Decreased arm swing with walking
  • Stooped posture

Rigidity can be tested by passively manipulating the limbs. It can be brought about by having the patient perform repetitive maneuvers using the contralateral limb, or by performing mental arithmetic.

Postural Instability

Postural instability is an impairment of centrally mediated postural reflexes.  This brings about a feeling of imbalance and a tendency to fall with a significant risk of injury.  Postural instability occurs later in the PD disease process.  Earlier signs may be due to other Parkinsonian syndromes [34].

Clinical testing involves using the “pull” test. This is where the examiner stands behind the patient and firmly pulls the patient by the shoulders.

  • Patients with normal postural reflexes should be able to maintain balance and retro pulse no more than one step.
  • Patients with PD and postural instability are likely to fall or take multiple steps backwards.

Initially, a positive pull test may be the only sign of a balance impairment. However, as postural instability progresses, the gait may show signs of festination.  

James Parkinson defined festination as “an irresistible impulse to take much quicker and shorter steps, and thereby to adopt unwillingly a running pace”.

Once postural reflexes are lost, patients are generally wheelchair-bound. Postural instability and gait difficulty are major contributors to disability in patients with PD.

There have been numerous studies documenting treatment of various dystonic symptoms in patients with Parkinson’s disease [5, 35-42].

PD Dystonia

We can address these dystonic symptoms whether they would possibly benefit from treatment with BoNT, and more specifically with injection guided BoNT injections:

Condition Description BoNT injection
BSP/lid Apraxia [107-113] Injection into the pretarsal and lateral canthus region of the orbicularis oculi of the affected eyelid. Counters an inability to initiate voluntary opening of the eyelid following a period of eyelid closure Typically, a non-guided injection
Bruxism
[97-106]		 Injection into Masseter muscle, which is responsible for chewing. It may also be injected into the Frontalis and Temporalis muscles Benefits from EMG Guidance
Limb Dystonia
[91-96]		 A neurological movement disorder characterised by continuous, or intermittent, muscle contractions which cause abnormal, often painful, repetitive movements with the leg, foot or toes. Benefits from EMG Guidance
Cervical Dystonia [59-90] also called spasmodic torticollis, is a painful condition in which neck muscles contract involuntarily, causing the head to twist or turn to one side Benefits from EMG Guidance
Camptocormia
[43-46]		 Characterized by an abnormal flexion of the trunk appearing in standing position, increasing while walking and abating in the supine position (“bent spine syndrome”): Rectus abdominis (RA) muscle Typically, a non-guided injection
Levodopa-induced Dyskinesia
[36]		 A form of dyskinesia associated with levodopa, used to treat PD.  It often involves hyperkinetic movements, including chorea, dystonia, and athetosis. This is often the result of long-term dopamine therapy. Benefits from EMG Guidance
Jaw Tremors
[40]  		 A neurological condition and movement disorder that causes involuntary shaking or trembling of the jaw.  Primarily Masseter M. (“anti-gravity muscle”), (Lateral Pterygoid M., Digastric M.) Benefits from EMG Guidance
Freezing of Gait [41-42] Freezing of gait (FOG) is thought to be due to activation of both agonist and antagonist muscle in the legs; Gastrocnemius-Soleus muscle complex/ Benefits from EMG Guidance  
PD Symptoms That Benefit from BoNT Therapy

The Value of EMG Guidance in The Therapeutic Application of Botulinum Neurotoxin in the Management of PD

Myoguide™ can play an essential role supporting EMG guided BoNT injection procedures, providing both EMG audio and visual feedback.

Many of the referenced studies recommend EMG guidance as the best way to approach BoNT injections for the management of Parkinson’s Disease sequelae.  Studies have shown that we all do better finding the optimal spots to locate the hypodermic needles, when using EMG guidance, regardless of whether the muscle is located easily on the surface or deeper.

It is the confirmation that you are indeed in the muscle you have identified requiring treatment, that is the point of the matter.  This will lead to improved results and a lower incidence of iatrogenic effects.

There are many compelling reasons to use EMG guidance. The first is that EMG ensures that the needle is located in a muscle. The second is confirmation that the needle is in a muscle that is actively contracting in association with the disorder.   

Speelman and Brans showed that even the most experienced “blind” injectors were frequently inaccurate in identifying needle placement in muscles of the neck [115].

Comella and colleagues illustrated that BoNT injection for spasmodic torticollis increased magnitude of benefit with electromyographic assistance. The article involved comparing experienced investigators using EMG versus palpation and showed that EMG was superior in terms of reducing side effects and obtaining clinical benefit 114].

Recent studies showed that both expert and novice needle placements improve with guidance when compared without, even in large easily accessible muscles [116].

A recent review article by Grigoriu et al, showed strong evidence that instrumented guided injections (Ultrasound, EMG, STIM) were more effective than manual needle placement for the treatment of Spasmodic Torticollis, and both upper and lower limb spasticity [117].

Studies clearly illustrate that we all do better finding the optimal spots to locate hypodermic needle electrodes when using EMG guidance, regardless of whether the muscle is located easily on the surface, deeper, or whether the needle insertions are being carried out by novice or expert injectors [114-117].  

Myoguide™ is equipped with what is essentially a single channel EMG machine with a full featured, built in stimulator.

Myoguide™ EMG/ESTIM BoNT injection guidance system is designed to amplify EMG signals from muscle and provide audio and visual feedback to assist clinicians in locating areas of muscle activity.

The other useful feature is Myoguide’s ability to mute the audio.  This is a design feature for times when it is better to operate in silence and rely upon the visual signal display.  This is pertinent in cases where patients are easily startled, or are likely to have issues with hearing EMG audio.

Myoguide on a table

Myoguide also has an integrated and well featured stimulator, capable of stimulation in either 1.0 mA or 0.1 mA steps, for muscle, nerve, and motor endplate location procedures.

Myoguide supports injection of neuromodulators and both chemodenervation and neurolytic procedures, as well as, peripheral nerve stimulation. Learn more about how to use Myoguide

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