**3. Treatment options of dystonia**

### **3.1 Indications of treatment**

Treatment options of the management of dystonia include pharmacological therapies, injections, and surgical interventions. The main pharmacological therapies are anticholinergics (particularly trihexyphenidyl), baclofen, benzodiazepines (particularly clonazepam), and dopamine-related medications. However, medical therapy in dystonia is largely empiric and at times may seem anecdotal. Three main neurotransmitter systems are involved: cholinergic generally acting as antagonist at postsynaptic M1 receptor, GABAergic-like baclofen, and dopaminergic systems. Dopaminergic treatments can be divided into two: levodopa and dopamine reducing medications like presynaptic dopamine depleters such as tetrabenazine and postsynaptic dopamine-blocking agents, such as clozapine or neuroleptics. The therapeutic strategy, carried out by Fahn [71], is to "start low and go slow": medications should be started at a low dose and upped slowly to the lowest effective dose, in order to reduce symptoms without side effects. The rate of titration may depend on age: every 3–4 days in children, compared to every 1 week in adults. A combination approach is used when monotherapy achieves a "good" dose, but symptom control is incomplete. The question is which medications should be started first?

### **3.2 Cholinergic system agents**

In 1952, beneficial effects of trihexyphenidyl in writer's cramp and "dystonia musculorum deformans" were first reported [72, 73]. The first open-label study of high-dose anticholinergics in dystonia using trihexyphenidyl and ethopropazine was conducted by Fahn [71]. Various forms of dystonia, both "primary and secondary," can be treated with anticholinergics, except for tardive dystonia and Meige syndrome. Studies showed a good effect in 61% of the children and 38% of the adults, with mean trihexyphenidyl doses of 41 and 24 mg, respectively. More benefit was demonstrated in children, possibly due to better tolerability, and in patients who received treatment earlier, within 5 years of disease onset [74]. Several studies have demonstrated that anticholinergic drugs may be useful to treat various forms of dystonia including focal [75], cranial [76], and secondary dystonia including dystonia in cerebral palsy [74], after ischemic stroke [77], and in tardive dystonia [78]. Side effects can be divided into central ones, which include sedation, cognitive slowing, confusion, memory impairment, psychosis and chorea, and autonomic side effects, which include blurred vision, due to mydriasis, dry mouth, urinary retention, and constipation.

### **3.3 GABAergic system agents**

Baclofen was reported to be useful in tardive dystonia [79]. Just in 1988, Greene published a retrospective open-label study, showing that 20% of 108 patients had benefits from baclofen at a mean daily dose of 82 mg [80]. Later, Greene and Fahn also reported beneficial effects of baclofen in 7 of 16 patients with idiopathic childhood dystonia [81]. ITB was tried initially for spasticity and later in dystonia [82]. In 1991 Narayan and colleagues showed the efficacy of ITB in axial dystonia not responding to other drugs [83] and subsequently in dystonic cerebral palsy with lower extremity involvement [84]. Albright reported the use of intraventricular baclofen in two patients with dystonic cerebral palsy, one of whom previously failed ITB therapy and the other has a complex spinal anatomy precluding the intrathecal procedure [85]. Nevertheless, baclofen is generally considered as a second-line agent, due to its significant side effects like drowsiness, dizziness, fatigue, and nausea. Regarding benzodiazepines, diazepam therapy was described in "dystonia musculorum deformans progressiva" and spasmodic torticollis [86]. In 1988, the benefit of clonazepam was shown by Greene in 16% of 115 patients with dystonia, also including secondary dystonia [80]. Also in acquired hemidystonia, as shown in a report of 33 patients, clonazepam and diazepam were found to be the most effective drugs. Clonazepam and diazepam are the two most commonly used drugs, partly due to their relatively long half-lives. The side effects of benzodiazepines include sedation, depression, nocturnal drooling, and behavioural disinhibition. Benzodiazepines are considered a second- or third-line agent.

### **3.4 Dopaminergic system agents**

In 1976 Segawa firstly used levodopa as a treatment in dystonia, showing a dramatic response to low-dose levodopa in two patients affected by "hereditary progressive dystonia with marked diurnal fluctuations" [87], later named Segawa syndrome. In dystonia therapy, levodopa is used (1) as an aetiology-specific treatment in dopa responder dystonia and (2) as a symptomatic therapy in other forms of dystonia where the dramatic response to levodopa is unfortunately not replicated. Levodopa may also be used to treat dystonia symptoms which may complicate a parkinsonian syndrome [88]. In clinical practice, levodopa or dopamine agonists are rarely used to treat dystonia symptomatically. The side effects of levodopa include nausea, orthostatic hypotension, and psychosis. In 1972, Swash reported only a slight benefit of tetrabenazine in spasmodic torticollis [89]. In 1982, a double-blind crossover trial by Jankovic demonstrated an improvement in 11 of 12 patients [90].

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*Spasticity and Dystonia: A Brief Review DOI: http://dx.doi.org/10.5772/intechopen.91780*

individual needs of the patient.

**Conflict of interest**

**4. Conclusions**

Tetrabenazine has been used in various forms of dystonia; however, benefits are greater in tardive dystonia than that of the other forms [91]. Tetrabenazine is rarely

Spasticity and dystonia syndromes and their consequences negatively impact the quality of life of patients, so management of symptoms represents an important care issue. The best choice of antispastic treatments depends not only on the level of spasticity but also on the outcome achievable, according to a task-oriented rehabilitation programme. In this respect, it is important to underline the importance of the individualised rehabilitative project, which can be carried out only through a multidisciplinary approach, in which all available options must be targeted to the real needs of the patients, keeping into account that the final goal is the reduction of disability and improvement of the quality of life. With advances in diagnosis and treatment, therapeutic strategies for the management of spasticity and dystonia symptoms, including pharmacological treatments, have evolved. Progresses in other areas such as BTX, neuromodulation, and disease-specific treatment have changed the way patients are treated. Nevertheless, dystonia remains a challenging field in both diagnostic and therapeutic aspects. Further understanding of its pathophysiology may shed light on more specific therapies. In conclusion, the management of spasticity and dystonia may include a proper diagnosis and classification with an evaluation of the aetiology underlying the pathological features and a clinical assessment of the functional impairment. For both conditions, therapeutic approaches, usually limited to symptomatic therapy, must then be tailored to the

Vincenzo Cimino has received grants for congress participation from Biogen

Clara Grazia Chisari has received grants for congress participation from Almirall, Biogen Idec, Merck Serono, Novartis, Roche, Sanofi Genzyme, and TEVA. Francesco Patti has received honoraria for speaking activities by Almirall, Bayer

Schering, Biogen Idec, Merck Serono, Novartis, Roche, Sanofi Genzyme, and TEVA; he also served as an advisory board member of the following companies: Bayer Schering, Biogen Idec, Merck Serono, Novartis, Roche, Sanofi Genzyme, and TEVA; he was also funded by Pfizer and FISM for epidemiological studies; he received grants for congress participation from Almirall, Bayer Schering, Biogen

Idec, Merck Serono, Novartis, Roche, Sanofi Genzyme, and TEVA.

Idec, Merck Serono, Novartis, Roche, Sanofi Genzyme, and TEVA.

used as a first-line agent, except in tardive dystonia [92].

Tetrabenazine has been used in various forms of dystonia; however, benefits are greater in tardive dystonia than that of the other forms [91]. Tetrabenazine is rarely used as a first-line agent, except in tardive dystonia [92].
