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Movement disorders associated with the use of gabapentin.

PURPOSE: We report two cases of unusual movement disorders associated with the use of gabapentin (GBP) in patients being treated for epilepsy who were otherwise neurologically intact. METHODS: We describe two cases of unusual movement disorders associated with the use of GBP. RESULTS: There were significant differences in the clinical findings between the two cases. In the first case, movements were very pronounced and the patient was in oculogyric crisis. Movements in the second case were quite subtle but nonetheless problematic for the patient. In each case, discontinuation of GBP led to rapid resolution of the movements, although a single dose of lorazepam was used in the first case. CONCLUSIONS: Although formal electrophysiologic studies have not been performed, the movements associated with GBP use appear to be dystonic or myoclonic. Discontinuation of GBP led to rapid resolution of the movements. In severe cases, as in patients with oculogyric crisis, small doses of a benzodiazepine (BZD) appear to be efficacious and safe.

Acetates↗

Rating scale for psychogenic movement disorders: scale development and clinimetric testing.

We developed and tested the clinimetric properties of a scale for psychogenic movement disorders (PMDs). PMDs are disabling but lack any generally accepted treatment strategies. To develop treatments, means of assessing disease severity must be provided. No scale to assess PMDs existed. The PMD scale developed here rates 10 phenomena (rest tremor, action tremor, dystonia, chorea, bradykinesia, myoclonus, tics, athetosis, ballism, cerebellar incoordination), 2 functions (gait, speech), and 14 body regions. To study interrater agreement, three movement disorder neurologists independently rated 88 videotapes of PMD patients. Data analysis was performed using a kappa coefficient of agreement, Kendall's coefficient of concordance, Spearman correlations, and intraclass correlation coefficients. Validity and scale responsiveness were tested as well. All phenomena and speech and gait dysfunction occurred in the patient sample. A wide range of affected body regions, severity, and incapacitation was captured. Ratings showed excellent interrater reliability for presence or absence of each phenomenon (kappa range, 0.63 to 0.86). Kendall's concordance coefficients for phenomenology, function, and total PMD scores were 0.92, 0.93, and 0.91. Spearman correlations between raters ranged from 0.86 to 0.90. The scale was responsive to changes that occurred as a result of a neuropsychiatric intervention. The PMD scale adequately captures the complex movements of PMDs and can be used to assess PMDs and test the efficacy of intervention strategies.

Adolescent↗

Postural control, gait, and dopamine functions in parkinsonian movement disorders.

Balance impairments and falls, which are common in patients who have parkinsonian movement disorders, are a serious threat to the health of these individuals. However, the underlying mechanisms cannot be fully explained by presynaptic dopaminergic denervation, because balance impairment is at least responsive to L-dopa therapy. This article reviews the latest clinically relevant literature relating postural control, gait, and dopamine in patients who have parkinsonian movement disorders.

Dopamine↗

The spasticity paradox: movement disorder or disorder of resting limbs?

BACKGROUND: Spasticity is defined/assessed in resting limbs, where increased stretch reflex activity and mechanical joint resistance are evident. Treatment with antispastic agents assumes that these features contribute to the movement disorder, although it is unclear whether they persist during voluntary contraction. OBJECTIVES: To compare reflex amplitude and joint resistance in spastic and normal limbs over an equivalent range of background contraction. METHODS: Thirteen normal and eight hemiparetic subjects with mild/moderate spasticity and without significant contracture were studied. Reflex and passive joint resistance were compared at rest and during six small increments of biceps voluntary contraction, up to 15% of normal maximum. A novel approach was used to match contraction levels between groups. RESULTS: Reflex amplitude and joint mechanical resistance were linearly related to contraction in both groups. The slopes of these relations were not above normal in the spastic subjects on linear regression. Thus, reflex amplitude and joint resistance were not different between groups over a comparable range of contraction levels. Spastic subjects exhibited a smaller range of reflex modulation than normals because of decreased maximal contraction levels (weakness) and significant increases of resting contraction levels. CONCLUSIONS: Spasticity was most evident at rest because subjects could not reduce background contraction to normal. When background contractions were matched to normal levels, no evidence of exaggerated reflex activity or mechanical resistance was found. Instead, reduced capacity to modulate reflex activity dynamically over the normal range may contribute to the movement disorder. This finding does not support the routine use of antispastic agents to treat the movement disorder.

Adult↗

Antipsychotic drug-induced movement disorders.

Very early in the process of diagnosing abnormal involuntary movement (AIM) disorders, one can be rewarded by keeping a high index of suspicion for possible drug-induced causes, not only through a complete list of current medications, but also identification of the drugs the patient used to take and other possible offending medications that might be available from family members and other sources. Among drug-induced movement disorders, antipsychotic drugs and other dopamine receptor blocking agents occupy a central place. Their various acute and tardive motor complications provide the template of this short review. Movement disorders caused by antidepressants, lithium, antiemetics, antiparkinsonian agents, anticonvulsants, calcium channel blockers, sympathomimetics and others are only briefly covered in table form.

Akathisia, Drug-Induced↗

[Drug-induced movement disorders: tardive syndromes].

Persistent drug-induced movement disorders (tardive syndromes) remain an important clinical problem and consist of a variety of involuntary movements appearing in a patient exposed to a dopamine-blocking agent. The current state of knowledge on this topic is summarised in this article. Clinical aspects (tardive dyskinesia, tardive dystonia and other forms), prevalence, risk factors, prevention and management are discussed.

Akathisia, Drug-Induced↗

Estrogen and movement disorders.

Female sex hormones, and more specifically estrogen, can have biochemical and behavioral effects on the dopaminergic system. The effects of estrogen on the dopaminergic system can be classified as either neuroprotective or symptomatic. The neuroprotective effects refer to the ability of estrogen to prevent or modulate insults to the dopaminergic system and therefore to alter the natural history of disease processes affecting the dopaminergic circuitry in the brain. With regard to the symptomatic effects, support for suppressive and enhancing effects has been documented in humans and laboratory animals. The preclinical literature for neuroprotective and symptomatic effects of estrogen on the mesostriatal dopaminergic system forms the basis for studies on the influence of estrogen on the prevalence, disease progression, clinical signs, and medication effects of movement disorders, including Parkinson's disease, chorea, dystonia, tics, and myoclonus. Understanding the role of estrogen in modulating the dopaminergic system will allow clinicians to tailor therapies for women with movement disorders and optimize therapies for menstrually related symptom fluctuations. Such clarifications may also guide recommendations on the use of postmenopausal hormonal replacement therapy in women with movement disorders or those genetically at risk.

Animals↗

Brain sites of movement disorder: genetic and environmental agents in neurodevelopmental perturbations.

In assessing and assimilating the neurodevelopmental basis of the so-called movement disorders it is probably useful to establish certain concepts that will modulate both the variation and selection of affliction, mechanisms-processes and diversity of disease states. Both genetic, developmental and degenerative aberrations are to be encompassed within such an approach, as well as all deviations from the necessary components of behaviour that are generally understood to incorporate "normal" functioning. In the present treatise, both conditions of hyperactivity/hypoactivity, akinesia and bradykinesia together with a constellation of other symptoms and syndromes are considered in conjunction with the neuropharmacological and brain morphological alterations that may or may not accompany them, e.g. following neonatal denervation. As a case in point, the neuroanatomical and neurochemical points of interaction in Attention Deficit and Hyperactivity disorder (ADHD) are examined with reference to both the perinatal metallic and organic environment and genetic backgrounds. The role of apoptosis, as opposed to necrosis, in cell death during brain development necessitates careful considerations of the current explosion of evidence for brain nerve growth factors, neurotrophins and cytokines, and the processes regulating their appearance, release and fate. Some of these processes may possess putative inherited characteristics, like alpha-synuclein, others may to greater or lesser extents be endogenous or semi-endogenous (in food), like the tetrahydroisoquinolines, others exogenous until inhaled or injested through environmental accident, like heavy metals, e.g. mercury. Another central concept of neurodevelopment is cellular plasticity, thereby underlining the essential involvement of glutamate systems and N-methyl-D-aspartate receptor configurations. Finally, an essential assimilation of brain development in disease must delineate the relative merits of inherited as opposed to environmental risks not only for the commonly-regarded movement disorders, like Parkinson's disease, Huntington's disease and epilepsy, but also for afflictions bearing strong elements of psychosocial tragedy, like ADHD, autism and Savantism.

Ataxia↗

Movement disorders during sleep in cats and dogs.

Spontaneous sleep movement disorders in 5 cats and 3 dogs were studied. Objective abnormalities during sleep were confirmed by electrographic or behavioral monitoring techniques in all animals. The cause of the disorder was CNS disease in 3 animals. A cause was not discovered in the other 5 animals, although at necropsy, 2 were found to have thyroid tumors. Many pharmacologic treatments were ineffectual, but trials with the benzodiazepine tranquilizer, clonazepam, suggested it will prove useful in controlling violent movements during rapid-eye-movement sleep.

Animals↗

Characteristics of stereotypic movement disorder and self-injurious behavior assessed with the Diagnostic Assessment for the Severely Handicapped (DASH-II).

The first experiment involved 143 individuals with severe and profound mental retardation. Individuals with Stereotypic Movement Disorder, Self-Injurious Behavior (SIB), and Stereotypic movement disorder with self-injurious behavior as assessed by the Diagnostic Assessment for the Severely Handicapped-II DASH-II were validated against Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV; American Psychiatric Association, 1994) criteria. In a second study DASH-II scores for 1480 individuals with severe and profound mental retardation were compared on demographic variables, core and associated features of each disorder. Characteristics of persons in each group were reviewed. Persons with profound mental retardation were more likely to evince stereotypies or self-injury compared to their severely impaired counterparts. Also, those with stereotypies were more likely to present with Pervasive Developmental Disorder (PDD)/autism, organicity, and eating disorders, while persons with SIB were more likely to evince sleep, sexual, and eating disorders.

Adult↗

The emerging role of clozapine in the treatment of movement disorders.

Clozapine, the only commercially available atypical neuroleptic, is approved for the treatment of schizophrenic patients who are unresponsive to or intolerant of typical neuroleptics. It has an unusual pharmacologic profile compared with standard neuroleptics, and it follows that clinical response to this drug is also different. It has shattered the notion that a drug must be capable of inducing or worsening parkinsonism to be a potent antipsychotic. Based on these findings, it is being used increasingly by neurologists for psychiatric and nonpsychiatric problems in patients with movement disorders. The most common use for clozapine among neurologists is in the management of drug-induced psychosis in Parkinson's disease (PD). This problem has been a source of increased morbidity and mortality in PD because of a lack of adequate therapeutic intervention. At this time, because of success in numerous open trials, with improvement of > 80% of patients, clozapine therapy for psychosis in PD is becoming the standard of care. It also appears to be of value in the management of some motor features of PD, including tremors and dyskinesia and possibly even sensory symptoms such as akathisia and pain. The literature also suggests that clozapine may be of potential benefit in hyperkinetic movement disorders including essential tremor, Huntington's disease, and tardive dyskinesia. We review the current data concerning the use of clozapine in patients with these movement disorders and others.

Antiparkinson Agents↗

In vivo and in vitro studies of the dopaminergic system in movement disorders.

Over the past 20 years, tritiated radioligand receptor binding has been used to study the relationship between dopamine receptor binding and various movement disorders, in particular Parkinson disease. More recently, in vivo imaging techniques like positron emission tomography and single photon emission computed tomography have been used to study the dopaminergic system in these disorders. This review describes the data that have been obtained using in vivo and in vitro measurements of the dopaminergic system in movement disorders, and examines the relationship between them. The contribution of these techniques to clinical management is described.

Animals↗

Family history of primary movement disorders as a predictor for neuroleptic-induced extrapyramidal symptoms.

BACKGROUND: A genetic susceptibility to extrapyramidal symptoms caused by treatment with neuroleptic medication has been suggested. AIMS: To identify predictor variables for neuroleptic-induced extrapyramidal symptoms, particularly considering family history of primary movement disorders. METHOD: We investigated 100 in-patients receiving a stable neuroleptic medication with regard to occurrence of extrapyramidal symptoms, drug history and detailed family history of primary movement disorders. RESULTS: Step-wise logistic regression analysis revealed that a positive family history was a significant predictor for lifetime prevalence of extrapyramidal symptoms, including reported and currently observed symptoms. The duration of exposure to neuroleptic medication and age were further predictors. CONCLUSIONS: Our findings underline the notion of genetic susceptibility for secondary extrapyramidal symptoms and suggest possible shared genetic factors in primary and secondary movement disorders as well as psychotic disorders.

Adolescent↗

[Functional neuroimaging in movement disorders].

Positron Emission Tomography (PET) and Single Photon Emission. Computed Tomography (SPECT) highly contribute to the management of patients with movement disorders by measuring regional cerebral metabolism/blood flow and dopamine receptors. Imaging of the dopaminergic system is a powerful tool for distinguishing patients with neurodegenerative disorders, such as Parkinson's disease. Parkinsonism is most of the time caused by idiopathic Parkinson's disease. Considering the differences in therapeutic response and prognosis, differentiation between Parkinson's disease and "parkinsonism-plus syndromes" is important. Visualisation of pre- and post-synaptic D2 dopamine receptors by using receptor ligands helps to discriminate between Parkinson's disease and "parkinsonism-plus syndromes" as Parkinson's disease is a presynaptic disease. Early disease detection in subjects suspected at risk for developing Parkinson's disease has become possible using ligands for the dopamine transporter. Functional imaging modalities are useful in the management of patients with movement disorders, are able to monitor in an objective way the efficacy of new pharmacological therapies, can document the effect of neuronal grafting for Parkinson's disease, and delineate the progression of these diseases.

Brain↗

Inherited movement disorders.

A high proportion of neurological diseases characterized by movement disorders are caused by single genes; in others, such as Parkinson's disease, there appears to be a genetic component. Gene mapping studies have made substantial progress in unravelling the aetiology of dystonias and Huntington's disease, and are underway in other disorders such as essential tremor and Gilles de la Tourette syndrome. These advances are already applicable to clinical practice, particularly in Huntington's disease where identification of the disease mutation has led to the possibility of improved diagnosis and more widespread availability of predictive testing for asymptomatic family members.

Acanthocytes↗

Transcultural comparison of psychogenic movement disorders.

Prompted by the lack of cross-cultural comparative data, and because a better understanding in the different clinical presentations of psychogenic movement disorders (PMDs) is relevant to neurological assessment and interventions, we compared the phenomenology, anatomical distribution, and functional impairment of PMDs in the United States and Spain. Consecutive patients diagnosed with PMD by a movement disorder specialist from one US site and from eight Spanish university centers were included in the study. The two groups were similar in their movement types, anatomical distribution, and functional impairment. PMDs were more prevalent in women than in men and were most common in upper and lower extremities. Gait and speech dysfunctions were distributed similarly in both countries. We found action tremor to be the most frequent PMD in both countries.

Adult↗

Ablative surgery for movement disorders. Anatomic localization techniques.

The increased use of ablative movement disorder surgery, pallidotomy, and thalamotomy must be followed by our better understanding of regional neuroanatomy, use of imaging and physiologic techniques for targeting, and methods of lesion creation. The safety of these techniques has been established; efficacy will require additional studies. Selection of appropriate patients and our understanding of outcomes will assist the surgeon in choosing between ablative surgeries and other forms of management.

Globus Pallidus↗