The relationship between movement disorders and substance abuse which we previously reviewed are updated. according to their main phenomenology as either hyperkinetic or hypokinetic. Hyperkinetic disorders are characterized by an excess MK-2206 2HCl of movement, including tremor, dystonia, chorea, myoclonus, tics and akathisia. In hypokinetic disorders there is absence or Rabbit Polyclonal to P2RY13. paucity of movement that is unrelated to weakness or paralysis, and this suggests parkinsonism. These terms are defined in the prior version of this review [1]. Although many movement disorders may develop either in isolation or as part of main neurologic disease, they may also emerge from your acute use or withdrawal of medications. As an example, beta agonists, lithium and the chronic use of some anticonvulsants may lead to the development of action and postural tremors [2C4], and dopamine-blocking neuroleptic and antiemetic medications may trigger acute dystonic reactions and tardive syndromes [5]. Similarly, acute alcohol withdrawal may precipitate action tremors involving the hands or other body parts, along with other neuropsychiatric and autonomic disturbances. The description of disorders associated with drugs of abuse, however, is more challenging. Toxicity data is derived primarily from individual case reports and small observational case series. In addition, adulterants in drugs of abuse added for the purpose of increasing bulk, enhancing or mimicking a pharmacological effect, or to facilitate drug delivery [6] may themselves cause movement disorders. For example, heroin has been found to be mixed with the synthetic potent opioid fentanyl hydrochloride; cocaine with diltiazem; and methylephedrine and ecstasy with pseudoephedrine, dextromethorphan and caffeine [7]. Caffeine [8] and pseudoephedrine [9] are known to cause postural and action tremors that closely resemble essential tremor. Finally, performing studies on patients struggling with substance abuse and dependency may be particularly challenging due to the frequent psychosocial issues that either precede or result from drug use. Indeed, even within the medical community the terms of MK-2206 2HCl drug dependency and dependence have historically experienced an implicit moralistic connotation that is fortunately transitioning to a less judgmental one as our understanding of the neurobiology of these conditions continues to expand [10]. We will review the impact of these and other drugs of abuse in the genesis of some movement disorders, and will also describe those substances of abuse that have treatment-like effects on particular movement disorders. Each section will be launched and illustrated with clinical vignettes, and will finalize with a brief conclusion. Cocaine
Clinical Vignette #1: A 34-year-old homeless man with a history of frequent crack cocaine use for the last seven years offered to the emergency room with agitation several hours after smoking crack cocaine. The neurology support was consulted after he developed dance-like movements of his head and extremities. The patient acknowledged to similar symptoms in the past that resolved spontaneously within days of abstinence from crack cocaine.
Cocaine use remains a significant problem in the United MK-2206 2HCl States since its peak in the 1980s, and it affects millions of people worldwide [11], [12]. Cocaine blocks the dopamine transporter (DAT), preventing the MK-2206 2HCl reuptake of dopamine and other catecholamines at the presynaptic terminal and hence increasing extracellular dopamine levels. It also exhibits local anesthetic properties, presumably via inhibition of fast sodium channels in peripheral nerve endings [13]. The dopaminergic system is linked to many processes controlling reward, movement control and cognition [14], [15] and the increased extracellular levels of dopamine are thought to be involved with the euphoric effects of cocaine as well as explain its motoric side effects. With chronic use, dopamine MK-2206 2HCl depletion may occur from overstimulated dopaminergic terminals and excessive metabolism of the neurotransmitter, as suggested by neuropathologic studies. Chronic cocaine abusers have been found to have decreased levels of dopamine in the caudate nucleus and frontal cortex that is not paralleled by an increase of dopamine D1 and D2 receptor gene expression; they also have marked reductions in the vesicular monoamine transporter-2 [16]. Dopamine depletion may explain the dysphoric aspects and parkinsonism seen during cocaine abstinence and cocaine urges[17], [18],.