ORIGIN

(vv)CurrentMedicalSurgicalTreatmentDystonia2.m4v(tt)Lecture: Current Medical and Surgical Treatments for Dystonia: Professor E Moro

Broadly speaking, dystonia is related to disorganized sensorimotor integration, and abnormal modulation of cortical plasticity. Dystonic tremor (DT) arises in certain types of dystonia, and may be the most obvious manifestation of underlying dystonia

Although not universally true, the following is a nice schema of the development of dystonia:

• “Dystonic movements are frequently worsened during voluntary movement (action dystonia), and idiopathic dystonia commonly begins with a specific action i.e. action dystonia.
• In some cases, as the dystonic condition progresses, less specific action of the leg affected by dystonia may activate dystonia (e.g. when tapping the floor).
• With further evolution of underlying dystonia, action in other parts of the body can induce dystonic movements of the involved leg, a state referred to as overflow.
• With further deterioration, dystonia is present even at rest. Eventually the limb may go into sustained posturing”¹.

CLASSIFICATION

Tremor in dystonia may be related to carrying out a specific task, or be more generalized. Note that patients with segmental or multifocal dystonia are more likely to be tremulous than patients with focal dystonia.

When the trembling body part is not affected by dystonia, but dystonic posturing occurs in other body parts, this is referred to as “tremor associated with dystonia”.  See below (Tremor Characteristics).

Dystonia related task specific tremors include:

• Primary Writing Tremor (PWT). PWT can be exclusively task-induced or position-sensitive. The age of onset is variable with reported cases presenting even during childhood. The disorder typically begins slowly, progresses for many years and then stabilizes. Some patients report that at the onset they only had difficulties with specific letters but their condition then progressed in terms of severity, spread/topography (also involving the non-dominant side) or the nature of the tremor (e.g. becoming a resting/action tremor). PWT, however, is distinguished from focal task-specific dystonia (‘writer’s cramp’) by the lack of excessive overflow of EMG activity into adjacent muscles, although abnormal co-activation of antagonist muscles may be present, as might be anticipated for a dystonic process. No other neurological signs are evident except for slight postural and terminal kinetic tremor.
• Musician’s tremor and golfer’s tremor.
• Rarely, focal dystonic tremor may be a manifestation an underlying genetic illness, for example due to a mutation in the DYT-TOR1A gene².

CLINICAL FEATURES

Presentation of Dystonia with tremor:

Tremor may be a clinical feature of dystonia and patients with dystonia may present with tremor. Some patients display isolated or focal tremor in the absence of any signs of dystonia, which may not become apparent until many years later. Virtually every dystonic syndrome may present with tremor, with typical examples including head tremor in torticollis, hand tremor in writer’s cramp, and jaw tremor in orofacial dystonias.

Tremor characteristics

The tremor in dystonia is irregular in amplitude and periodicity with a broad range of tremor frequency. The tremor is characteristically asymmetrical and jerky (due to variability in axis and amplitude). There may be brief bursts or flurries of tremor, typically enhanced by a task such as rolling the arm back and forth.

• Rest tremor: this form of rest tremor is frequently unilateral and in those patients where the tremor is bilateral, it is often asymmetric. In a patient presenting with rest tremor, the presence of thumb extension is suggestive of dystonia (although this sign may likely be inaccurate³).  Rest tremor appears to be common in adult onset primary dystonia, affecting as many as 40% of patients, with the vast majority being unilateral.
• Action tremor: typically postural but also with a kinetic component, and often task related.
• Tremor associated with dystonia: is a more generalized form of tremor in body sites that are not affected by dystonia, but which is present elsewhere in the same subject. This is a relatively symmetric tremor, and is typically both postural and kinetic. The tremor usually shows higher frequencies than actual DT and is often seen in the upper limbs in patients with spasmodic torticollis. This tremor can resemble enhanced physiological tremor or essential tremor. VID

(vv)DystonicT.mp4(tt)

Patient with long-standing retrocollis, who developed severe postural tremor.

(vv)Albanese.mp4(tt)

This patient has unilateral right hand resting and postural tremor. During movement with the right fingers, a slight tremor occurs in the left hand (overflow). Reduced right arm swing during gait is associated with right hand tremor, abnormal posturing, and extension of the right wrist⁴.

  

(vv)six.mp4(tt)

69-year-old man with mild right torticollis. On posture, he has mild bilateral arm tremor that becomes slightly more severe during pronation and supination movements. He has writer’s cramp and severe action tremor in the right arm interfering with both writing and drawing. There is also action tremor in the left arm that is less pronounced compared with the right but still incapacitating.

 

WRITING AND DRAWING

When drawing a spiral, patients with dystonic tremor are likely to generate multiple axes, whereas patients with ET are likely to have a single predominant axis).  In dystonia, the direction of the oscillations varies because dystonic tremor involves co-contraction of agonist and antagonist muscles affecting proximal (shoulder/elbow) as well as distal (wrist/digits) parts. The commonly observed exacerbation of dystonic tremor with certain postures and an overflow of muscle activity with voluntary actions are other contributing factors.

 

 

 

 

 

 

 

 

 

Spiral drawing of a patient with dystonic tremor; tremor is present but no single predominant axis stands out 5.

 

 

 

 

 

 

 

 

 

 

 

 

(A) Dystonia and spiral drawing: oscillations occur in all sections of the spirals, denoting a multidirectional axis. The amplitude and frequency also vary, giving a jerky appearance6.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

(B) There is evidence of forceful pen pressure consistent with dystonic posturing in the spiral drawings and handwriting samples. Many patients with dystonia have a tendency to draw more than three turns of the spiral. The left-handed spiral demonstrates a multidirectional tremor axis. Straight lines drawn at a steady rate, particularly the vertical one, show that the frequency is variable. On horizontal line and spiral drawings, the tremor amplitude is asymmetric, being larger on the right6.

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(C) The spiral and line drawings demonstrate a multidirectional tremor axis with a jerky pattern caused by variable amplitude and frequency—all features consistent with dystonic tremor. In this case, the handwriting is normal with very little tremor intrusion6.

 

 

 

 

 

Characteristics of tremor in writing and drawing tasks6 . From: Alty J, Cosgrove J, Thorpe D, Kempster P. How to use pen and paper tasks to aid tremor diagnosis in the clinic. Pract Neurol. 2017;17(6):456-463. doi:10.1136/practneurol-2017-001719

 

 

 

 

 

 

AGE OF ONSET

Dystonic tremor syndromes have a bimodal age of onset, with 90% of dystonia-associated tremor manifesting by 60 years of age and 90% by 70 years:

Distributions of ages of tremor onset for 95 patients with dystonic tremor syndromes (DTS).

DT: dystonic tremor; TAD: tremor associated with dystonia; DT & TAD: patients with both DT and TAD. From Bain⁷.

 

 

DISTRIBUTION

Like ET, dystonic tremor, and tremor associated with dystonia usually affects the head, voice or upper limbs.  Most studies report a higher incidence of head tremor than upper-limb tremor, and there is an even lower incidence of voice and leg tremor. Although less common, either isolated voice tremor or a presentation where voice tremor is more severe than hand tremor, is suggestive of dystonic tremor.

Distinguishing ET from Cervical Dystonia associated with tremor.

Although the table below contrasts ET and dystonia, note that head tremor may rarely also be described in PD (both no-no, and yes-yes types). 

• Cranial and other dystonic tremors are especially notable for the fact that the tremor may be reduced by adopting a particular posture of the neck to develop without resistance (“null point”).
• Equally, dystonic tremor can be exacerbated by an attempt to maintain certain postures.

(vv)dyt1.mp4(tt)

Dystonic head tremor. The patient has right torticollis with horizontal tremulous and jerky head movements.

(vv)mmc2.mp4(tt)

Dystonic head tremor. The patient has retrocollis with yes-yes type of dystonic tremor

DIAGNOSIS

Diagnosis is usually made by the presence of typical dystonic features, which may be obvious, but may also need to be carefully looked for.

It is consequently important to examine for features of dystonia by:

1. Careful inspection of the arms during posture holding and batwing positions. Dystonic features may be brought out by asking the patient to hold the arms extended in front of their body for 30–60 seconds. In this setting, dystonic thumb flexion and other dystonic postures may be seen.
2. The patient should slowly rotate the outstretched arms from pronation to supination, since this may show a position-specific tremor, indicating an underlying dystonic tremor⁸.
3. Ask the patient to perform repetitive hand tasks with each hand sequentially such as finger tapping, rapid opening and closing of the hand, and hand pronation–supination.

Features of dystonia should be actively sought, including the following:

• Presence of a geste (sensory trick) Patients with dystonic tremor can reduce tremor amplitude by using a sensory trick.
• Action dystonia when initiating a movement.
• Presence of directionality  Usually, dystonic tremor increases in amplitude when moving away from the usual direction of the dystonic contractions, and tends to show much greater right–left asymmetry than ET ^9,10. In patients with dystonic tremor of the head, the head tends to be pulled in one direction and released back in the other direction, rather than for the head to rotate symmetrically around a central vertical axis. As the patient moves their head from right to left, there may be clear asymmetry of tremor.
• Position specific tremor The patient should slowly rotate their outstretched arms from the prone to the supine position, which may reveal a position-specific tremor, an indication of dystonic tremor.
• Presence of a null point  This is a specific position in which the tremor almost fully abates. Limbs may be passively positioned by the examiner in search for a “null point” as well. Common positions include extreme pronation, supination, flexion and extension of the wrists.
• Presence of overflow. Overflow refers to unintentional muscle contraction which accompanies, but is separate to the primary dystonic movement, and commonly occurs at the peak of dystonic movements. Overflow may be on the same side as the focal dystonia. Overflow may also be contralateral, with involuntary movement or dystonic posturing in the normal, contralateral limb during movements of the hand primarily affected by focal dystonia. Overflow tends to be more marked when dystonia is severe.
• Listen for breaks in the voice when the patient is asked to sustain “ahh” or “eee” for 10 to 15 seconds, as evidence of vocal cord dystonia.  Patients with dystonic vocal tremors cannot change pitch during vocalization, and performing this manoeuvre can aide in the bedside diagnosis.
• Ask the patient to write When evaluating the writing task, make sure shirt sleeves are pulled up. Ideally, the feet are exposed as well. Ask the patient to write a sentence repetitively. In an affected limb, look for tight grip of the pen, unusual posturing of the hand that may progress as the patient continues to write, dystonic mirroring/overflow in another limb, and involvement of more proximal muscles. Ask the patient if (s)he feels tightness in the limb. Look for involuntary toe flexion, extension or foot inversion that would suggest dystonic overflow.
• Look for dystonic neck tremor by asking the patient to sustain “ahh” or “eee” for 10 to 15 seconds. The sustained phonation can induce or amplify neck tremor during the task or immediately afterwards. Ask the patient if (s)he feels tightness in the limb. Look for involuntary toe flexion, extension or foot inversion that would suggest dystonic overflow.

Mirror dystonia represents the expression of motor overflow in dystonia. Mirroring is defined as a unilateral posture or movement that is the same or similar in character to a dystonic feature that can be elicited, usually in the more severely affected side, when contralateral movements or actions are performed. In the case of focal hand dystonia, an example would that a specific task such as writing with the normal hand brings about a dystonic movement or posture in the affected, dystonic side. Mirror movements are also detected in normal individuals, without dystonia or dystonic tremor.

Mirror dystonia (A) Patient starts writing with the non-affected (left) hand and (B) within a few seconds develops mirror dystonia, manifested by extension of the 2nd and 3rd digits in the right hand ¹¹.

 (vv)MirrorWritingTremorDystonicClues.mp4(tt)

Mirror tremor in a dystonic patient.  A 34‐year‐old right‐handed male  presented with a 3‐year history of a gradually progressive shaking in his right hand that only became evident when writing.  Irregular, low‐amplitude, high‐frequency, jerky tremor became apparent in the right hand upon writing. In addition, this tremor was also evident when he was assuming a writing or similar position (see Video 1, Segment 1) during performance of other tasks, but stopped immediately upon slight positional changes of the wrist (see Video 1, Segment 3). During writing with the right hand, slight dystonic posturing of the wrist became apparent. In addition, when writing with the left hand, the same arrhythmic, jerky tremor started in the right hand, representing a task‐specific mirror tremor (see Video 1, Segment 2) ¹².  

 

DIFFERENTIAL DIAGNOSIS

Potentially broad, and includes:

1. Parkingon's Disease
2. Essential Tremor

1. Parkinson's Disease:

In patients with arm tremor, including a resting tremor, and reduced arm swing on the affected side, it can be difficult to differentiate between PD and dystonia at an early stage. 

Signs that may be noted in patients with dystonic tremor and  which might suggest PD include:

• Reduced arm swing (due to upper limb dystonia)
• Asymmetric jerky rest and postural tremor
• Hypomimia
• Increased limb tone
• Slow repetitive finger movements which may be mistaken for bradykinesia (known as dystonic slowness)¹³.

Clinical features suggesting dystonic, rather than parkinsonian, tremor include:

• Thumb extension tremor
• ‘‘flurries’’ or task/position-specific tremor
• Head tremor
• Dystonic voice

The diagnosis may also be made in patients believed to have tremor typical of PD, but whose PET or SPECT imaging rules out a nigrostriatal deficit, that is patients with a ‘‘Scan Without Evidence of Dopaminergic Deficit’’. 

However, it should be noted that patients with dystonic tremor may have:

reduced arm swing, asymmetric jerky rest and postural tremor, hypomimia, increased limb tone, and slow repetitive finger movements which may be mistaken for bradykinesia¹³.

(vv)TORIASWEDD.mp4(tt)

Patient with normal I 123 -FP-CIT SPECT, and shown to test positive for the DYT-1 mutation. She shows rest and postural tremor in her arms (more so on the right) and had mild dystonic posturing of the right distal arm. There was no decrement in repetitive movements, and she had no facial hypomimia. While walking, there was a reduced bilateral arm swing, and she had a dystonic posturing of both legs

2. Essential Tremor:

Dystonic tremor is frequently misdiagnosed as ET, since patients with dystonia may have classic essential tremor phenomenology. It is not uncommon that patients with isolated upper limb postural/kinetic tremor are misclassified as having classic essential tremor if upper limb tremor is the presenting sign and the patients are observed before they develop any other signs of dystonia¹⁵.

Isolated focal, position-specific, and task-specific tremors are not likely to be ET and are often associated with subtle dystonia. Isolated neck tremor is suggestive of dystonia, not ET.

Isolated voice tremor is most suggestive of laryngeal dystonia.

DIAGNOSTIC TESTS

Consider F-dopa PET to distinguish PD from dystonic tremor.

TREATMENT

See reference: Pandey S, Sarma N. Tremor in dystonia. Parkinsonism Relat Disord ¹⁶.

Effects of thalamic (VIM) DBS were modest and transient¹⁷.

REFERENCES

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2. Edwards M, Wood N, Bhatia K. Unusual phenotypes in DYT1 dystonia: A report of five cases and a review of the literature. Mov Disord. 2003;18(6):706-711. doi:10.1002/mds.10411
3. Bajaj NPS, Gontu V, Birchall J, Patterson J, Grosset DG, Lees AJ. Accuracy of clinical diagnosis in tremulous parkinsonian patients: A blinded video study. J Neurol Neurosurg Psychiatry. 2010;81(11):1223-1228. doi:10.1136/jnnp.2009.193391
4. Albanese A, Lalli S. Is this dystonia? Mov Disord. 2009;24(12):1725-1731. doi:10.1002/mds.22597
5. Michalec M, Hernandez N, Clark LN, Louis ED. The spiral axis as a clinical tool to distinguish essential tremor from dystonia cases. Park Relat Disord. 2014;20(5):541-544. doi:10.1016/j.parkreldis.2014.01.021
6. Alty J, Cosgrove J, Thorpe D, Kempster P. How to use pen and paper tasks to aid tremor diagnosis in the clinic. Pract Neurol. 2017;17(6):456-463. doi:10.1136/practneurol-2017-001719
7. Bain PG. Essential tremor and senile varieties of action tremor an evolving ART. Mov Disord. 2015;30(10):1301-1303. doi:10.1002/mds.26342
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9. Buijink  a WG, Contarino MF, Koelman JHTM, Speelman JD, van Rootselaar  a F. How to tackle tremor - systematic review of the literature and diagnostic work-up. Front Neurol. 2012;3(October):146. doi:10.3389/fneur.2012.00146
10. LeDoux MS. 3.1.2 Dystonia: Phenomenology. Parkinsonism Relat Disord. 2011;18:S161. doi:10.1016/s1353-8020(11)70696-4
11. Sitburana O, Chen Wu LJ, Sheffield JK, Davidson A, Jankovic J. Motor overflow and mirror dystonia. Park Relat Disord. 2009;15(10):758-761. doi:10.1016/j.parkreldis.2009.05.003
12. Schreglmann SR, Baumann CR, Waldvogel D. Mirror Writing Tremor: Dystonic Clues…. Mov Disord Clin Pract. 2015;2(3):316-317. doi:10.1002/mdc3.12182
13. Bain PG. Dystonic tremor presenting as parkinsonism: long-term follow-up of SWEDDs. Neurology. 2009;72(16):1443-1445. doi:10.1212/WNL.0b013e3181a18809
14. Cáceres-Redondo MT, Carrillo F, Palomar FJ, Mir P. DYT-1 gene dystonic tremor presenting as a “scan without evidence of dopaminergic deficit” . Mov Disord. 2012;27(11):1469-1469. doi:10.1002/mds.25171
15. Albanese A, Di Giovanni M, Lalli S. Dystonia: diagnosis and management. Eur J Neurol. 2019;26(1):5-17. doi:10.1111/ene.13762
16. Pandey S, Sarma N. Tremor in dystonia. Parkinsonism Relat Disord. 2016;29(13):3-9. doi:10.1016/j.parkreldis.2016.03.024
17. Cury RG, Fraix V, Castrioto A, et al. Thalamic deep brain stimulation for tremor in Parkinson disease, essential tremor, and dystonia. Neurology. 2017;89(13):1416-1423.