Hyperkinetic movement disorders

Parkinson s disease (PD) is a hypokinetic movement disorder 766 Huntington s disease is a hyperkinetic movement disorder 771 Wilson s disease is a disease of copper accumulation 773 Dystonia is characterized by sustained muscle contractions 775 Many drugs and toxins induce movement disorders 776... 

Kenney C et al Long-term tolerability of tetrabenazine in the treatment of hyperkinetic movement disorders. Mov Disord 2007 22 193.[PMID 17133512]... 

Hyperactivity of dopamine in the nigrostriatal pathway is thought to underlie various hyperkinetic movement disorders, such as chorea, dyskinesias, and tics. Chronic blockade of dopamine 2 receptors in this pathway may result in a hyper-... 

Worse yet, if these D2 receptors in the nigrostriatal DA pathway are blocked chronically (Fig. 11—5), they can produce a hyperkinetic movement disorder known as tardive dyskinesia. This movement disorder causes facial and tongue movements such as constant chewing, tongue protrusions, and facial grimacing, as well as limb movements, which can be quick, jerky or choreiform (dancing). Tardive dyskinesia is thus caused by long-term administration of conventional antipsychotics and is... 

FIGURE 11-5. Long-term blockade of dopamine 2 receptors by dopamine 2 antagonists in the nigrostriatal dopamine pathway may cause these receptors to up-regulate. A clinical consequence of this may be the hyperkinetic movement disorder known as tardive dyskinesia. This up regulation may be the consequence of the neuron s futile attempt to overcome drug-induced blockade of its dopamine receptors. 

Potentially irreversible, late onset, extrapyramidal hyperkinetic movement disorder often associated with the long-term administration of neuroleptics. Abnormal movements generally involve the mouth, lips and tongue. 

It appears, therefore, that D-1 blockade is not relevant to the antipsychotic effect or suppression of hyperkinetic movement disorders. 

Lindemann S, Lessenich A, Ebert U, Loscher W (2001) Spontaneous paroxysmal circling behavior in the ci2 rat mutant Epilepsy with rotational seizures or hyperkinetic movement disorder Exp Neurol 172 437-445. 

Since the gamut of the clinical pharmacology of tics is broad, it is often difficult to differentiate tics from other hyperkinetic movement disorders. Of 373 cases of Gilles de la Tourette syndrome, 18 had both tics and other abnormal movements 12 were secondary to neuroleptic drug treatment (167). Akathisia was the most common movement disorder. 

Kompoliti K, Goetz CG. Hyperkinetic movement disorders misdiagnosed as tics in Gilles de la Tourette syndrome. Mov Disord 1998 13(3) 477-80. 

Tardive tremor is a hyperkinetic movement disorder associated with chronic neuroleptic drug treatment. It was first described in 1991 as a symmetrical tremor, of low frequency, present at rest and during voluntary movements but most prominent during maintenance of posture, and often accompanied by tardive dyskinesia. Tetrabenazine is the current treatment. Sequential responsiveness to both tetrabenazine and clozapine has been reported (97). 

Trade names Nitoman (Lifehealth LTD) Xenazine Indications Hyperkinetic movement disorders Huntington s chorea, hemiballismus, senile chorea, Tourette syndrome, and tardive dyskinesia... 

Tourette s syndrome (TS) is a hyperkinetic movement disorder with symptoms of sudden, rapid and brief, recurrent, stereotyped motor movements or sounds (tics) and can range from mild to severe. TS is commonly treated with dopamine antagonists such as haloperidol, which may be effective but has significant adverse side effects and is ineffective in up to 30% of cases. While the etiology is not known it is proposed that, unlike PD, TS represents a disorder of excess dopamine transmission in the striatum (Shapiro et al., 1989 Wolf et al., 1996), either through dopamine excess or receptor hypersensitivity. 

Muscle spasms, particularly those associated with multiple sclerosis or dystonia, may improve significantly with cannabinoid therapy. However, while CBD has been found effective in combination with standard therapy (which was insufficient to adequately control dystonic motor symptoms without CBD), both A -THC and marijuana were found to have untoward side-effects at the doses required to reduce muscle tone. Additionally, CBD may prove beneficial for other hyperkinetic movement disorders such as drug-induced dystonia and possibly tardive dyskinesia. 

Susceptibility factors Age In a review of tetrabenazine therapy in 31 children with hyperkinetic movement disorders refractory to other medications, adverse effects were similar to those in adults however, the children had a lower incidence of drug-induced parkinsonism [7 ]. 

Jain S, Greene PE, Frucht SJ. Tetrabenazine therapy of pediatric hyperkinetic movement disorders. Mov Disord 2006 21 (11) 1966-72. 

A patient experienced symptoms of delirium and hyperkinetic movement disorders shortly after initiating treatment with cyclobenzaprine and oxycodone [26 ]. 

The basal ganglia are a group of subcortical nuclei which are components of modular circuits involved in many cortical functions. They have received considerable attention from basic scientists and clinicians alike because of their prominent involvement in movement disorders, a spectrum of diseases including disorders which are characterized by poverty of movement (hypokinetic disorders), as well as disorders characterized by excess movement (hyperkinetic disorders). It has become clear in recent years that most basal ganglia disorders are not restricted to motor disturbances, but involve cognitive and emotional features as well. 

Considerable evidence indicates that shifts in the balance between the activity in the direct and indirect striatal output pathways and the resulting alterations in the output of the SNr and the GPi may account for the hypo- and hyperkinetic features of basal ganglia movement disorders. In summary, excessive inhibition of GPe within the indirect pathway leads to disinhibition of the STN, which in turn provides excessive excitatory drive to basal ganglia output nuclei (GPi/SNr), thus leading to excessive thalamic inhibition. This is reinforced by reduced inhibitory input to GPi/SNr through the direct pathway. Overall these effects are postulated to results in a reduction in the usual reinforcing influence of the motor circuit upon cortically initiated movements.123 (For more reviews and references see ref. 117, 124-126). 

Tardive dyskinesia (TD) is a hyperkinetic, repetitive, purposeless, persistent drug-induced movement disorder, mostly of the face, caused by long-use of antipsychotic drugs (APDs). 

Luborzewski A, Regen F, Schindler F, Anghelescu 1. Modafinil-induced reversible hyperkinetic nondystonic movement disorder in a patient with major depressive disorder. J Neuropsychiatry Clin Neurosci 2006 18 248-9. 

Nervous system Tetrabenazine inhibits vesicular monoamine transporter 2, leading to depletion of dopamine and other monoamines in the central nervous system. In a retrospective chart review, 448 patients who had used tetrabenazine between 1997 and 2004 (mean age at onset of the movement disorder, 43 years 42% men) were treated for a variety of hyperkinesias, including tardive dyskinesia (n = 149), dystonia (n = 132), chorea (n = 98), tics (n = 92), and myoclonus (n = 19) [68"]. They took treatment for a mean of 2.3 years and efficacy was sustained in most cases. Common adverse effects included drowsiness (25%), parkinsonism (15%), depression (7.6%), and akathisia (7.6%). Although it has repeatedly been observed that tetrabenazine alleviates hyperkinetic movements, it can worsen parkinsonism [69 ]. 

Patients who have received neuroleptics for long periods of time may develop a hyperkinetic disorder of the extrapyramidal system characterized by involuntary, purposeless movements affecting many parts of the body. This is known as tardive dyskinesia. Most commonly, these are manifested in a syndrome involving abnormal movements of the tongue, mouth and masticatory muscles. There are also choreoathetoid movements of the extremities. The mechanism by which these symptoms develop remains unknown. 

A major effect of Huntington s chorea is the loss of neostriatal neurons, accompanied by the loss of dopamine Dj receptors. A group of investigators has found that this loss of neurons also causes a 97.5% reduction of CBj receptors in the substantia nigra pars reticulata. On the basis of these data, the authors have suggested a role for cannabinoids in the control of movement in, and possibly in the therapeutics or symptomology of, hyperkinetic and dystonic disorders, such as Huntington s disease, as well is in the treatment of Parkinson s disease. 

Found at the other end of the spectrum are the hyperkinetic basal ganglia disorders, which are represented by HD and essential tremor. In these two condidons, excessive abnormal movements such as chorea or tremor are superimposed onto and interfere with normal voluntary movements. Although hyperkinedc basal ganglia disorders are probably as diverse as hypokinedc basal ganglia disorders, their specific disease markers such as gene mutadons, which exist for several of the hyperkinedc syndromes create more accurate, less problemadc, classificadons. 

Diseases of the basal ganglia are essentially characterized by abnormal motor activity. Based on the type of motor problem, diseases of the basal ganglia can be classified into hypokinetic or hyperkinetic groups. Hypokinetic basal ganglia disorders include PD, in which the amplitude and velocity of voluntary movements are diminished or, in extreme cases, non-existent. 

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