For dystonia

Pathophysiology. Research into the pathophysiology of primary dystonia has demonstrated that this disorder is associated with widespread loss of inhibition and a loss of specificity in sensorimotor maps at the cortical level. The notion that dystonia may result from aberrant plasticity in susceptible individuals is also indirectly supported by the observation that the beneficial effect of neurosurgical interventions for dystonia, such as pallidotomy or DBS, is typically delayed for several weeks or months. 

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. 

Injection of BoNT is currently recognized as the best available treatment for dystonias and for certain types of strabismus, and new uses are continuously found (Bhidayasiri and Truong 2005 Montecucco and Molgo 2005). In addition, BoNT/A inhibit ACh release at autonomic nerve terminals which innervate the glands and smooth muscle, and it is currently used to treat diseases such as hypersalivation and hypersudoration (Brisinda et al. 2004 Naumann and Jost 2004). 

A 64-year-old woman started to take oral haloperidol 0.5 mg tds, and 3 days later was given intravenous benzatropine 2 mg for dystonia plus a second dose 1 hour later because she had not responded to the first dose. Her dystonia improved, but she started to develop abdominal distension and discomfort, and within the next 3-4 hours her whole abdomen had become significantly distended. Haloperidol and benzatropine were withdrawn and she was treated with hydration, nasogastric suction, a rectal tube, and frequent change of position. With this conservative therapy, her abdominal distension resolved completely in 24 hour. 

Bhatia KP, Munchau A, Thompson PD, Houser M, Chauhan VS, Hutchinson M, Shapira AH, Marsden CD. Generalised muscular weakness after botulinum toxin injections for dystonia a report of three cases. J Neurol Neurosurg Psychiatry 1999 67(l) 90-3. 

Karp BI, Goldstein SR, Chen R, Samii A, Bara-Jimenez W, Hallett M. An open trial of clozapine for dystonia. Mov Disord 1999 14(4) 652-7. 

Perry D, Birthi P, Salles S, McDowell S. Neuroleptic malignant syndrome associated with the use of cartridopa/levodopa for dystonia in persons with cerebral palsy. PM R 2012 4(5) 383-4. 

The answer is c. (Hardman, pp 414-4163) Unwanted pharmacologic side effects produced by phenothiazine antipsychotic drugs (e.g., perphenazine) include Parkinson-like syndrome, akathisia, dystonias, galactorrhea, amenorrhea, and infertility. These side effects are due to the ability of these agents to block dopamine receptors. The phenothiazines also block muscarinic and a-adrenergic receptors, which are responsible for other effects. 

Botulinum exotoxin impedes release of neurotransmitter vesicles from cholinergic terminals at neuromuscular junctions. Botulinum exotoxin is ingested with food or, in infants, synthesized in situ by anaerobic bacteria that colonize the gut. A characteristic feature of botulinum paralysis is that the maximal force of muscle contraction increases when motor nerve electrical stimulation is repeated at low frequency, a phenomenon attributable to the recruitment of additional cholinergic vesicles with repetitive depolarization of neuromuscular presynaptic terminals. Local administration of Clostridium botulinum exotoxin is now in vogue for its cosmetic effects and is used for relief of spasticity in dystonia and cerebral palsy [21]. 

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 ). 

Pharmacologic studies suggest that abnormalities in both the indirect and direct pathway contribute to dystonia. Thus, D2LR antagonists have a substantial potential for... 

Injectable dosage form can be given intramuscularly for relief of acute dystonia. 

In 1985, 1 finally took the county public health psychiatrist s recommendation to try Desipramine, an ostensibly mild tricyclic antidepressant. I took tiny dot doses, and for a month or so I felt encouraged except for intense muscle tension and clenching. The psychiatrist said it was not remotely possible that this response was related to the medication. I took a low dose for four more months before throwing them out. The side effects had escalated horribly, and become what I later learned are called tardive dyskinesia and tardive dystonia. Subsequently, chemical and electromagnetic field exposures, feeling compromised or ashamed, or stress can trigger uncontrollable movement, hyperactivity, rigid posture and then, frequently, paralysis. 

Side effects can also occur quickly after a single dose of a medication. For example, some antidepressants (e.g., selective serotonin reuptake inhibitors) can cause nausea, stomach upset, loose stools, and even diarrhea. Likewise, some anti-psychotics (e.g., haloperidol (Haldol)) can cause unpleasant or painful muscle spasms called dystonias. All of these side effects can occur within minutes or hours of taking a single dose of the medication. These side effects are also a result of the direct effects of the medication in the synapse. 

Acute dystonias occur immediately after neuroleptization and are manifested by motor impairments, particularly in the head, neck, and shoulder region. After several days to months, a parkinsonian syndrome (pseudoparkinsonism) or akathisia (motor restlessness) may develop. All these disturbances can be treated by administration of antiparkin-son drugs of the anticholinergic type, such as biperiden (i.e., in acute dystonia). As a rule, these disturbances disappear after withdrawal of neuroleptic medication. Tardive dyskinesia may become evident after chronic neuroleptization for several years, particularly when the drug is discontinued. It is due to hypersensitivity of the dopamine receptor system and can be exacerbated by administration of anticholinergics. 

Promethazine is not recommended in children younger than 2 years of age. Exercise caution when administering promethazine to children because of the potential for fatal respiratory depression. Limit antiemetics to prolonged vomiting of known etiology. Avoid use in children whose signs and symptoms may suggest Reye syndrome or other hepatic diseases. In children with dehydration, there is an increased susceptibility to dystonias with the use of promethazine. 

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. 

Strabismus and blepharospasm associated with dystonia (Botox only) For the... 

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