Dystonia treatment

Response fluctuations occur with disease progression as the patient s dopamine reserves are depleted in the brain and as a complication of PD treatment. Motor fluctuations include delayed peak response, early wearing off, random unpredictable on-off, and freezing. Dyskinesias include chorea, dystonia, and diphasic dyskinesia. Wearing off can be visualized by imagining the therapeutic window of dopamine narrowing over time. The therapeutic window is defined as the minimum effective concentration of dopamine required to control PD symptoms (on without dyskinesia) and the maximum concentration before experiencing side effects from too much dopamine (on with dyskinesia). Early in the disease, a dose of... 

Dystonia due to identifiable structural or biochemical abnormalities ( secondary dystonia) often occurs weeks or months after strokes or other focal lesions, which commonly involve the basal ganglia, but may also involve the thalamus or cerebellum. Dystonia is also seen in children with cerebral palsy and in patients with abnormalities of dopaminergic transmission. For instance, dystonia may develop in the context of Parkinson s disease, either as an early parkinsonian sign, or in response to dopaminergic drugs. A particularly interesting inherited disease results in a combination of dystonia and parkinsonian features at a young age, which responds dramatically to treatment with low-dose levodopa ( dopamine-responsive dystonia ). 

Treatment. Treatment for dystonia is for the most part symptomatic, except in rare instances where known mechanisms are present and specific therapies are available. The available treatments include support and rehabilitation, pharmacotherapy and, in some cases, functional neurosurgery. Sensory retraining in humans with focal dystonias has resulted in a substantial recovery of function in some patients. 

Van Harten PN, Hoek HW, Kahn RS. Acute dystonia induced by drug treatment. BMJ 1999 319(7210) 623-626. 

Cervical dystonia (CD) (Botox only) For the treatment of CD in adults to decrease the severity of abnormal head position and neck pain associated with CD. Glabellar lines (Botox Cosmetic only) For the temporary improvement in the appearance of moderate to severe glabellar lines associated with corrugator or procerus muscle activity in adult patients 65 years of age or younger. 

Botulinum toxin is used clinically in the treatment of blepharospasm, writer s cramp, spasticities of various origins, and rigidity due to extrapyramidal disorders. It is also used to treat gustatory sweating and cosmetically to decrease facial wrinkles. Botulinum toxin A Botox, Oculinum) injected intramuscularly produces functional denervation that lasts about 3 months. Clinical benefit is seen within 1 to 3 days. Adverse effects range from diplopia and irritation with blepharospasm to muscle weakness with dystonias. 

Two extrapyramidal conditions, acute dystonia and akathisia, occur early during treatment, while parkinsonism tends to evolve gradually over days to weeks. All three reactions occur most commonly with the high-potency antipsychotics (Table 34.1) and are related to high Dz-receptor occupancy. Acute dystonia, which occurs in about 5% of patients on antipsychotic therapy, consists of uncontrollable movements and distortions of the face, head, and neck. It can be treated with centrally acting an-timuscarinic agents, such as benztropine, while antipsychotic therapy is temporarily discontinued. When this reaction subsides, the anticholinergic can be withdrawn. 

CS390 Fox, S. H., M. Kellett, A. P. Moore, A. R. Crossman, and J. M. Brotchie. Randomised, double-blind, placebo-controlled trial to assess the potential of cannabinoid receptor stimulation in the treatment of dystonia. Mov Disord 2002 17(1) 145-149. 

Lorazepam (2 mg i.m.) was found to be equivalent to haloperidol (5 mg i.m.) either alone or when added to ongoing antipsychotic treatment, and significantly reduced the likelihood of akathisia and dystonia (167). In the treatment of acute mania, lorazepam has also been reported useful as an adjunct to lithium, as well as antipsychotics (157, 163, 165, 168, 169). 

Acute dystonias are typically seen in the first few days to weeks of treatment and can occur with even limited exposure (e.g., children treated with a single dose of prochlorperazine for nausea). Although dystonias may disappear spontaneously, they should be treated aggressively, as they are often painful and upsetting to the patient. Rarely, laryngeal dystonias may seriously compromise respiration. Occasionally, an acute dystonic reaction is resistant to standard treatment but may respond to parenteral diazepam, caffeine sodium benzoate, or barbiturate-induced sleep. 

Gagrat D, Hamilton J, Belmaker RH. Intravenous diazepam in the treatment of neuroleptic-induced acute dystonia and akathisia. Am J Psychiatry 1978 135 1232-1233. 

Friedman J. Clozapine treatment of psychosis in patients with tardive dystonia. Movement Disord 1994 9 321-324. 

Adityanjee AM, Estrera AB. Successful treatment of tardive dystonia with clozapine. Bioi Psychiatry 1996 39 1064-1066. 

These alkaloids contain pyrrole or modified pyrrole, e.g. pyrrolidine, ring system. The simplest example of this class is nicotine. A pyrrolidine ring is the central structure of the amino acids proline and hydroxyproline. These alkaloids are also found in many drug preparations, e.g. procyclidine hydrochloride, which is an antichohnergic drug mainly used for the treatment of drug-induced Parkinsonism, akathisia and acute dystonia. 

The pharmacologic basis of these disorders is unknown, and there is no satisfactory medical treatment for them. A subset of patients respond well to levodopa medication (dopa-responsive dystonia), which is therefore worthy of trial. Occasional patients with dystonia may respond to diazepam, amantadine, antimuscarinic drugs (in high dosage), carbamazepine, baclofen, haloperidol, or phenothiazines. A trial of these pharmacologic approaches is worthwhile, though often not successful. Patients with focal dystonias such as blepharospasm or torticollis often benefit from injection of botulinum toxin into the overactive muscles. The role of deep brain stimulation for the treatment of these conditions is being explored. 

Bhidayasiri R, Tarsy D Treatment of dystonia. Expert Rev Neurother 2006 6 863. [PMID 16784410]... 

JankovicJ Treatment of dystonia. Lancet Neurol 2006 5 864. [PMID 16987733]... 

Substituted benzamides include metodopramide (discussed previously) and trimethobenzamide. Their primary mechanism of antiemetic action is believed to be dopamine-receptor blockade. Trimethobenzamide also has weak antihistaminic activity. For prevention and treatment of nausea and vomiting, metodopramide may be given in the relatively high dosage of 10-20 mg orally or intravenously every 6 hours. The usual dose of trimethobenzamide is 250 mg orally, 200 mg rectally, or 200 mg by intramuscular injection. The principal adverse effects of these central dopamine antagonists are extrapyramidal restlessness, dystonias, and parkinsonian symptoms. 

Botulinum toxin has been used for some time to control localized muscle dystonias, including conditions such as spasmodic torticollis, blepharospasm, laryngeal dystonia, strabismus, and several other types of focal dystonias.6 25,26,87 93 When used therapeutically, small amounts of this toxin are injected directly into the dystonic muscles, which begin to relax within a few days to 1 week. This technique appears to be fairly safe and effective in many patients, but relief may only be temporary. Symptoms often return within 3 months after each injection, necessitating additional treatments.40 Still, this technique represents a method for treating patients with severe, incapacitating conditions marked by focal dystonias and spasms. 

Balash Y, Giladi N. Efficacy of pharmacological treatment of dystonia evidence-based review including meta-analysis of the effect of botulinum toxin and other cure options. Eur J Neurol. 2004 11 361-370. 

Botulinum toxin is the treatment of choice for focal dystonias such as torticollis and writer s cramp and for hemifacial spasm, and may complement the management of spasticity. 

Despite the lack of controlled studies, there is evidence that cannabinoids are of therapeutic value in the treatment of tics in Tourette syndrome, the reduction of levodopa-induced dyskinesia in Parkinson s disease, and some forms of tremor and dystonia. 

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