Dystonia

INDEX

 

Limb dystonias vary more widely in the pattern of dystonic movement and involved muscles than cervical dystonia or blepharospasm. There is considerable variation in the way which normal individuals carry out skilled hand movements.  Additionally,  the large number of muscles in the hand and forearm, and the presence of compensatory actions in patients with dystonia add to the complexity of choosing muscles for injection.

With respect to the current classification of dystonia, the features described under Axis I, as applied to focal limb dystonia are1:

AXIS 1

1. Age of onset
Early-late adulthood; the usual age of onset is in the 4th–5th decade.

2. Body distribution
Limb dystonia, is  described as being focal when restricted to a single limb or part of a single limb. However, the limbs are often involved in hemi-, segmental, multifocal, and generalized dystonias. Even in patients with writer’s cramp, the proximal arm muscles including the shoulder girdle may be involved and the dystonic process may be bilateral, affecting both hands.

3. Temporal pattern
Adult onset focal limb dystonia frequently evolves to its full expression over weeks to months. Once fully manifest, adult onset limb dystonia tends to be static but can progress, even years later. Spread tends to be towards proximal muscles and to the contralateral limb.

4. Associated features:
Tremor, similar in nature to essential tremor, is a not uncommon accompaniment to limb dystonia. Note that adult onset limb dystonia may be an early manifestation of Parkinson’s disease.

AXIS 2
Aetiology
The limbs are involved in many symptomatic dystonias including those associated with structural nervous system pathology. 
Although many focal limb dystonias, not associated with other neurologic signs, are currently considered sporadic. It is predicted that, as genes associated with dystonia continue to be identified, many of these presentations are likely to be reclassified as inherited. (Up to 25% of those with focal hand dystonia have a family history of dystonia).
Known gene disorders: in some patients with apparently focal limb dystonia, such as dopa-responsive dystonia, and others.

 

Task specific dystonia
Focal limb dystonia of the upper or lower extremity is often task-specific, present only during the performance of a particular activity. In task-specific dystonia, other activities, including those which use the same muscles, are performed normally. 
Writer’s cramp is the most common focal hand dystonia, and was initially reported in the 18th century2. Similar symptoms in other professions led to the term “occupational palsies”, affecting tailors, cobblers, musicians and others performing skilled, usually fine-motor, repetitive tasks. Estimates of the prevalence of focal hand dystonia range from 7–15/100,000 population. Musician’s dystonia affects up to 1% of professional musicians. Unlike most other adult onset focal dystonias that typically affect women, writer’s cramp affects men and women about equally, while musician’s dystonia is more prevalent in men. Over-practice or overuse likely contributes to the emergence of dystonic symptoms, which may be a manifestation of a genetic predisposition.

TREATMENT
Even before seeking medical attention, many patients with focal hand dystonia try to alter their performance of affected tasks, equipment or instruments. Those with writer’s cramp try altering their grip on the pen or try new, often thicker, pens. Musicians attempt to adjust their technique or instrument. These approaches rarely provide more than minimal to mild benefit. Oral medications are similarly ineffective. Given the lack of effective alternatives, botulinum toxin has become the treatment of choice for focal hand dystonia.
Although there are dosing guidelines for botulinum toxin for upper limb spasticity, there is little consensus information on dosing for focal hand dystonia, although the doses used for dystonia are typically lower than those used to treat spasticity in the same muscles. The mean starting dose in one retrospective series of botulinum toxin was 25 units of onabotulinumtoxinA (Botox). The optimal effective dose among patients continuing injections for at least 10 years was 50 units. 
A retrospective series of musicians had a mean starting dose of abobotulinumtoxinA (Dysport) of 127 units and final dose of 112 units3. In general, dosing starts at the low end of the potentially therapeutic range with titration over successive injection sessions until benefit is maximized and weakness or other adverse effects are minimized. The total dosing is, importantly, based at least in part on the particular muscles to be injected and the number of muscles to be included in a given session.

Muscle Selection for Upper Limb Botulinum Toxin Injection 
A key component of the key to success of botulinum toxin therapy for dystonia is appropriate selection of muscles for injection. Muscle selection in focal hand dystonia is not straightforward: the forearm alone has approximately twenty muscles, including some muscles where separate component fascicles mediate individual digit actions. In addition, one or more than one muscle may contribute to the same movement or action. Table 1 delineates major muscles contributing to different acting on elbow, wrist and finger joints.

 

Table 1. Important muscles of the upper limb

 

ELBOW

Flexion Biceps Extension Triceps
  Brachialis   Anconeus
  Brachioradialis    
  Pronator teres    
  ECR    
  FCR    
Pronation Pronator teres Supination Supinator
  Pronator quadratus   Biceps

WRIST

Flexion FCR Extension ECR
  FCU   ECU
  FDS   EDC
  FDP   EIP
  Palmaris longus   EDM
  FPL   EPL
Radial deviation FCR Ulnar deviation FCU
  FCU   ECU

FINGERS

MP flexion FDS MP extension EDC
  FDP   EDM
  Lumbricals   EIP
  Interossei   Lumbricals
      Interossei
PIP flexion FDS PIP extension EDC
  FDP   EIP
Abduction Dorsal interossei Adduction Palmar interossei
  EDC   FDS
  EIP   FDS
  ADM    

THUMB

Flexion proximal FPB Extension proximal EPB
  OP    
  APB    
  FDI    
Distal FPL Distal EPL
      APL
Abduction APL Adduction Add Pol
  APB   FDI
Opposition OP    
  APB    
  FPB    
  FPL    
  Add pol    

 

Limb dystonias vary more widely in the pattern of dystonic movement and involved muscles than cervical dystonia or blepharospasm. Hand movement is intricate and tightly coordinated, and there is considerable variation in the way which normal individuals carry out skilled hand movements.  Additionally,  the large number of muscles in the hand and forearm, and the presence of compensatory actions in patients with dystonia add to the complexity of choosing muscles for injection1
Thus, the muscle interactions underlying fine hand motor functions are complex; the distortion of muscle interaction in dystonia adds to that complexity. The identification of which muscles are involved in dystonic movements is further complicated by the presence of compensatory muscle activity, which is often subconscious. Many patients have difficulty identifying which of their muscles are actively dystonic and which are involuntarily trying to counteract the dystonia. 

Muscle discomfort is similarly not a straightforward indication of dystonia, as it can also arise both from excessive dystonic contraction and muscular compensation.

1. The first line of approach to muscle selection is a careful history.
The pattern of abnormal contraction at the onset of symptoms should be discussed and may be a clue to the primary dystonic involvement. The patient should be questioned about how and which activities are solely or disproportionately affected and to report where they feel muscle tension. They should be asked about their perception of which areas are involved and direction of movement distortion.

2. The next line of approach is physical examination.
A careful neurologic examination should be done to rule out non-dystonic conditions as a cause of the symptomatology, indicated by sensory loss, reflex changes or weakness would indicate a non-dystonic disorder. 
Throughout these evaluations, it is important to have an understanding of what the action looks like when performed by unaffected individuals. For example, a typical tripod pen grip has the fingers flexed at the metacarpal and interphalyngeal joints.
Note that in a right-handed individual, the wrist tends to be slightly flexed when starting a sentence on the left hand side of a piece of paper and that the wrist extends as the hand moves across the paper to the right. In left-handed writers, the wrist may be more flexed so that the writing is not smeared as the pen moves from left to right. In both left- and right-handers, the position of wrist and individual fingers is highly variable during writing.

Figure 1. Normal pen or pencil grip

From: Karp BI, Alter K. Muscle selection for focal limb dystonia. Toxins (Basel) 2018; 10: 1–14.

EXAMINATION

1. At rest
With severe focal dystonias, abnormal postures may be present at rest. There may be other dystonic features present, such as decreased arm swing or dystonic posturing on walking.
Activities provoking the dystonia:

2. Examination from a range of perspectives:
To fully visualize the posture of all fingers during writing when evaluating writer’s cramp, the writing hand should be observed from both dorsal and palmar aspects.
Additional observation from above the writing surface will enable better visualization of wrist flexion or extension. Inspection from the front allows identification of proximal arm and limb girdle position. It is important to check for forearm pronation and supination as well as wrist and finger deviation. In writer’s cramp, flexion dystonia is more common than extension.  Since a writing hand normally has flexed fingers, it can be difficult for an examiner to appreciate superimposed dystonic finger flexion. However, the patient may report a “death grip” on the pen.

3. Addition of pressure to reduce the dystonia
During examination, muscle selection can be aided by the examiner applying pressure that counters the apparent dystonic movement. For example, in a patient where there is concern that pronation is contributing to dystonic disability, the examiner can apply pressure in the antagonist direction of supination while the patient writes or performs the dystonic-eliciting activity. Improvement with counter-pressure indicates likely involvement of the agonist muscle. 

Examination of musicians’ dystonia
With musical instruments
Whenever possible, musicians should be evaluated playing their instrument using music selected to provoke the dystonia. Musicians and others with occupational hand dystonia should be asked about their usual or intended upper limb position when playing as approaches to the instrument and technique vary widely. 
In musicians, the intricacy demanded of the hand or fingers influences the dystonic pattern. In pianists, higher technical demand is usually on the right hand compared to the left, so dystonic flexion of the right 4th and 5th fingers is disproportionately seen. In violinists, the higher technical demand is on the fingers of the left hand, which is hence more frequently affected by dystonia. Close communication during examination is critical: in musicians especially, careful discussion of hand and finger involvement can avoid misunderstanding. The neurology literature and pianists often number the fingers 1 through 5, starting with the thumb. However, violinists do not use the thumb of the left hand on the strings and therefore number their fingers 1 through 4, starting with the index finger. Thus, the index finger would be called digit “2” by a pianist but would be digit “1” for a violinist. 
Examination should also include observation of the performance of other activities that might elicit dystonia without additional tasks (such as holding a pen or playing an instrument). A simple five-finger tapping exercise can bring out dystonic posturing in some patients with FHD (Figure 2). 

Figure 2. Finger tapping exercise

 

From: Karp BI, Alter K. Muscle selection for focal limb dystonia. Toxins (Basel) 2018; 10: 1–14.

Mirror movements
Mirror movements, in which involuntary dystonic posturing of the affected limb is evoked by performance of tasks by the uninvolved contralateral limb, is present in about 50% of those with focal hand dystonia. When present, mirror movement can demonstrate involved muscles unmasked by the presence of compensatory movements, which can aid selection of muscles for injection (Figure 3). 

Figure 3. Mirror movements

 



 From: Karp BI, Alter K. Muscle selection for focal limb dystonia. Toxins (Basel) 2018; 10: 1–14.

Injection often proceeds based on the history and physical examination and understanding of which muscles contribute to particular action at upper extremity joints. While it is important to evaluate carefully and document the likely involved muscles, it is not necessary to inject all muscles contributing to the abnormal posture. Injection of the primary muscles involved in the dystonia may be adequate to achieve significant benefit. Muscle selection is then refined over the course of subsequent injection sessions based on patient response and satisfaction.
Accurate targeting of upper extremity muscles is also the key to successful injection. The position and depth of muscles varies greatly in individuals and may change over time and with repeated injection. One also needs to consider normal anatomic variants, such as the presence or absence of palmaris longus. Needle placement based on anatomic landmarks has been shown to be inaccurate, especially when targeted to specific finger fascicles of compound muscles such as flexor digitorum superficialis or profundus. A localization technique to assure that the injection is given accurately into the selected muscle, such as EMG or ultrasound, is recommended for upper extremity injections

  
Muscle Selection for Lower Limb Dystonia 
The lower limb is commonly involved in many generalized dystonias including DYT-TOR1A and  dopa-responsive dystonia as well as in dystonias secondary to other disorders, such as Parkinson’s Disease, stroke, or cerebral palsy. 

Focal leg dystonia is more common in women than men and typically of middle age onset. Similarly to upper limb dystonia, lower limb dystonia can be task-specific; for example, cases have been reported of leg dystonia only when walking down steps. The most common task-specific focal lower extremity dystonia is “runner’s” dystonia.
The task-specificity can be lost over time and other actions, including walking, can be affected. Dystonic postures in the leg frequently involve foot inversion, often with toe flexion or extension. There may also be knee and/or hip flexion or extension. Of note is that gait may improve or normalize on walking backwards. A major concern with new onset focal dystonia of the lower limbs is that it may herald the onset of a neurodegenerative disorders, such as PD.

Treatment of Lower Limb Dystonia 
Since the leg is commonly affected in DRD and since leg dystonia can be a presenting symptom of Parkinson’s Disease, patients should receive a trial of levodopa. Other medications, such as anticholinergics, often offer only minor benefit and may be associated with significant adverse effects at the doses required. For most, however, the treatment of choice is botulinum toxin

Muscle Selection for Lower Limb Botulinum Toxin Injection

As with injections for upper limb dystonia, appropriate selection of lower limb muscles for injection is mandatory for successful treatment.
History:
The medical history will provide information on possible preceding trauma. The patient should be asked to describe the movements and the actions that precipitate dystonic contraction. A history of diurnal fluctuation may suggest dopa-responsive dystonia. Physical examination can help to rule out Parkinsonian syndromes. 

Examination:
The patient should be examined walking, both with and without shoes.
The shoes can also be checked, as abnormal wear patterns of the sole and upper shoe may provide clues as to nature and direction of postural distortions.
Stress gaits, such as walking on the toes or heels, may bring out additional dystonic posturing. Patients should be asked to walk backwards; normalization of gait on walking backwards demonstrates the task specificity of the dystonia. Runners should be observed while running in addition to walking. If the patient has sensory tricks or gestes antagonists that help, they should be displayed. Walking is a stereotyped activity, with identifiable phases and established patterns of phasic coordination of muscle agonist and antagonist activation at each stage.

Formal gait analysis may be considered: this includes monitoring gait kinematics and muscle activity by surface EMG, often with video motion capture during performance of various set walking tasks. A formal gait analysis may be helpful in characterizing how the pattern of muscle contraction in a patient with dystonia differs from standard gait norms, including identification of muscles contracting during phases of gait when they should be silent and co-contraction of agonist/antagonist pairs. As well as part of muscle selection, motion analysis may be useful when repeated after treatment to assess gait response to injection.

 

References

1    Karp BI, Alter K. Muscle selection for focal limb dystonia. Toxins (Basel) 2018; 10: 1–14.
2    Karp BI. Botulinum toxin treatment of occupational and focal hand dystonia. Mov Disord 2004; 19: 116–9.
3    Schuele S, Jabusch H-CH-C, Lederman RJ, Altenmuller E, Altenmüller E. Botulinum toxin injections in the treatment of musician’s dystonia. Neurology 2005; 64: 341–3.