Pseudobulbar laughter as a levodopa off phenomenon exacerbated by subthalamic deep brain stimulation.

Pseudobulbar affect is a common symptom in neurodegenerative diseases and can also result from lesions in cortical, subcortical and brainstem regions. In Parkinson's disease (PD), pseudobulbar affect (PBA) can occur as a wearing off phenomenon, manifested usually as crying without emotionality. In addition, subthalamic (STN) deep brain stimulation (DBS) has been reported to induce PBA in PD patients with no prior history of such episodes. We present a case of inappropriate laughter lacking mirth as a levodopa OFF phenomenon in a patient with PD, whose laughter also worsened with STN-DBS in his non-medicated state. Levodopa ameliorated his PBA both with and without stimulation. The case demonstrates pseudobulbar laughter as a levodopa OFF phenomenon that is also exacerbated by STN-DBS.

A single-blind, open-label trial of sodium oxybate for myoclonus and essential tremor.

The authors performed an open-label, rater-blinded, add-on study of sodium oxybate in 20 patients with ethanol-responsive myoclonus or essential tremor. Blinded ratings of videotaped examinations showed improvements in myoclonus at rest, stimulus-sensitive myoclonus, action myoclonus, functional performance, and postural and kinetic tremor. Tolerability was acceptable, and more than half of the patients chose to continue treatment after the trial. Double-blind placebo-controlled studies in these disorders are warranted.

The natural history of embouchure dystonia.

Focal task-specific dystonias are unusual disorders of motor control, often affecting individuals who perform complex repetitive movements. Musicians are especially prone to develop these disorders because of their training regimens and intense practice schedules. Task-specific dystonia occurring in keyboard or string instrumentalists usually affects the hand. In contrast, there have been few descriptions of musicians with task-specific dystonia affecting the muscles of the face and jaw. We report detailed clinical observations of 26 professional brass and woodwind players afflicted with focal task-specific dystonia of the embouchure (the pattern of lip, jaw, and tongue muscles used to control the flow of air into a mouthpiece). This is the largest and most comprehensively studied series of such patients. Patients developed embouchure dystonia in the fourth decade, and initial symptoms were usually limited to one range of notes or style of playing. Once present, dystonia progressed without remission and responded poorly to oral medications and botulinum toxin injection. Patients with embouchure dystonia could be separated by the pattern of their abnormal movements into several groups, including embouchure tremor, involuntary lip movements, and jaw closure. Dystonia not infrequently spread to other oral tasks, often producing significant disability. Effective treatments are needed for this challenging and unusual disorder.

Transplantation of embryonic dopamine neurons for severe Parkinson's disease.

BACKGROUND: Transplantation of human embryonic dopamine neurons into the brains of patients with Parkinson's disease has proved beneficial in open clinical trials. However, whether this intervention would be more effective than sham surgery in a controlled trial is not known. METHODS: We randomly assigned 40 patients who were 34 to 75 years of age and had severe Parkinson's disease (mean duration, 14 years) to receive a transplant of nerve cells or sham surgery; all were to be followed in a double-blind manner for one year. In the transplant recipients, cultured mesencephalic tissue from four embryos was implanted into the putamen bilaterally. In the patients who received sham surgery, holes were drilled in the skull but the dura was not penetrated. The primary outcome was a subjective global rating of the change in the severity of disease, scored on a scale of -3.0 to 3.0 at one year, with negative scores indicating a worsening of symptoms and positive scores an improvement. RESULTS: The mean (+/-SD) scores on the global rating scale for improvement or deterioration at one year were 0.0+/-2.1 in the transplantation group and -0.4+/-1.7 in the sham-surgery group. Among younger patients (60 years old or younger), standardized tests of Parkinson's disease revealed significant improvement in the transplantation group as compared with the sham-surgery group when patients were tested in the morning before receiving medication (P=0.01 for scores on the Unified Parkinson's Disease Rating Scale; P=0.006 for the Schwab and England score). There was no significant improvement in older patients in the transplantation group. Fiber outgrowth from the transplanted neurons was detected in 17 of the 20 patients in the transplantation group, as indicated by an increase in 18F-fluorodopa uptake on positron-emission tomography or postmortem examination. After improvement in the first year, dystonia and dyskinesias recurred in 15 percent of the patients who received transplants, even after reduction or discontinuation of the dose of levodopa. CONCLUSIONS: Human embryonic dopamine-neuron transplants survive in patients with severe Parkinson's disease and result in some clinical benefit in younger but not in older patients.

Parkinsonism, dystonia, and hemiatrophy.

Hemiatrophy has been reported in association with a variety of neurologic conditions, including parkinsonism. Patients with the hemiparkinson-hemiatrophy syndrome (HP-HA) have asymmetric parkinsonism with limb atrophy on the more affected side. Several authors have suggested that asymmetric brain damage early in life results in both atrophy and parkinsonism. Dopa-responsive dystonia (DRD) is a disease in which a deficiency of tetrahydrobiopterin, or, less commonly, of tyrosine hydroxylase, results in levodopa-responsive dystonia with parkinson features in children. We have recently identified four patients with DRD who had asymmetric dystonia and limb atrophy on the more affected side. Based on these patients, we suggest that a deficiency of the nigrostriatal dopamine system may, by itself, be sufficient to cause body atrophy and may underlie the limb atrophy in both DRD and HP-HA.

Localization of a gene for myoclonus-dystonia to chromosome 7q21-q31.

Essential myoclonus-dystonia is a neurological condition characterized by myoclonic and dystonic muscle contractions and the absence of other neurological signs or laboratory abnormalities; it is often responsive to alcohol. The disorder may be familial with apparent autosomal dominant inheritance. We report a large kindred with essential familial myoclonus-dystonia and map a locus for the disorder to a 28-cM region of chromosome 7q21-q31.

Falling asleep at the wheel: motor vehicle mishaps in persons taking pramipexole and ropinirole.

The authors report a new side effect of the dopamine agonists pramipexole and ropinirole: sudden irresistible attacks of sleep. Eight PD patients taking pramipexole and one taking ropinirole fell asleep while driving, causing accidents. Five experienced no warning before falling asleep. The attacks ceased when the drugs were stopped. Neurologists who prescribe these drugs and patients who take them should be aware of this possible side effect.

Clinical presentation and pharmacological therapy in corticobasal degeneration.

BACKGROUND: To date, to our knowledge, there is no systematic presentation of treatment outcome in large series of patients clinically diagnosed as having corticobasal degeneration. OBJECTIVE: To evaluate the clinical presentation and treatment outcome of patients clinically diagnosed as having corticobasal degeneration. SUBJECTS: We gathered case patients seen in 8 major movement disorder clinics during the last 5 years who were diagnosed as having corticobasal ganglionic degeneration. METHODS: Using a chart review method, we recorded the clinical presentation, medications used, response to medications, and adverse effects. RESULTS: A total of 147 case patients were reviewed, 7 were autopsy proven. Parkinsonian features were present in all, other movement disorders in 89%, and higher cortical dysfunction in 93%. The most common parkinsonian sign was rigidity (92%), followed by bradykinesia (80%), gait disorder (80%), and tremor (55%). Other movement disorders were dystonia in 71% and myoclonus in 55%. Higher cortical dysfunction included dyspraxia (82%), alien limb (42%), cortical sensory loss (33%), and dementia (25%). Ninety-two percent of the case patients received dopaminergic drugs, which resulted in a beneficial effect for 24%. Parkinsonian signs were the elements improving the most and levodopa was the most effective drug. Benzodiazepines, primarily clonazepam, were administered to 47 case patients, which resulted in improvement of myoclonus in 23% and dystonia in 9%. The most frequent disabling adverse effects of drug trials in these case patients were somnolence (n = 24), gastrointestinal complaints (n = 23), confusion (n = 16), dizziness (n =12), hallucinations (n = 5), and dry mouth (n = 5). CONCLUSIONS: Pharmacological intervention was largely ineffective in the management of corticobasal degeneration, and new treatments are needed for ameliorating the symptoms of this syndrome.

Exteroceptive and interoceptive stimuli in dystonia.

Some patients with torsion dystonia experience a dramatic increase or decrease in symptoms when performing specific activities. The activities that influence dystonic symptoms vary from person to person. An activity or sensory stimulus that reduces symptoms has been called a "sensory trick" or, in cervical dystonia, a "geste antagoniste." When a single activity induces symptoms of dystonia, the dystonia is called "task specific." We have discovered that in some patients, thinking about a sensory trick or task affects the dystonia in the same way as actually performing the activity. We present three representative patients, and discuss the relevance of this observation to the understanding of dystonia.

Barriers to research utilization for oncology staff nurses and nurse managers/clinical nurse specialists.

PURPOSE/OBJECTIVES: To describe and compare barriers to research utilization faced by oncology staff nurses and nurse managers/clinical nurse specialists (CNSs) and to compare these to barriers identified by other nurses. DESIGN: Exploratory descriptive. SETTING: National. SAMPLE: Proportional random sample of 2,000 Oncology Nursing Society (ONS) staff nurses (n = 769) from seven practice settings. ONS participants recruited oncology staff nurses (n = 331) and nurse managers/CNSs involved in cancer care (n = 407). METHODS: Mailings, including a demographic questionnaire and Barriers Scale, were sent to ONS nurses, and reminder postcards were sent to increase the return rate. MAIN RESEARCH VARIABLES: Barrier categories: characteristics of the adopter (nurse), organization, innovation (research itself), and communication, individual item barriers. Nurse and worksite characteristics. FINDINGS: Differences existed in oncology nurses' perceptions of the extent to which the adopter, organization, and innovation characteristics served as obstacles to research utilization. Nurse managers/CNSs perceived that each of these acted as a greater barrier than did staff nurses. Both groups perceived communication characteristics as a moderate barrier. Oncology nurses, as a group, responded similarly to other nurse samples regarding research and communication characteristics. Perceptions of oncology nurse managers/CNSs were similar to those of administrators in other studies. Oncology staff nurses rated barriers lower than nurses, including clinicians, in other samples. CONCLUSIONS: For oncology nurses, organization, research, and communication barriers persist as impediments to research utilization. Nurse adopter characteristics may be diminishing as obstacles for staff nurses but not for nurse managers/CNSs. The decreased strength that oncology nurses attributed to barriers may reflect a benefit of practicing nursing in a specialty. IMPLICATIONS FOR NURSING PRACTICE: Decreasing known barriers would facilitate research-based practice in oncology. Nurse leaders can create environments conducive to research utilization by altering existing mechanisms, facilitating access to nursing research experts, supporting time for research utilization efforts, giving authority for practice changes, and offering continuing education related to research utilization processes. Nurse managers/CNSs need to increase their familiarity with research and research utilization, ensuring their awareness of pertinent clinical findings. Perceptual gaps between staff nurses and nurse managers/CNSs regarding research utilization require discussion and formal investigation. Researchers must communicate in clinician-friendly ways. All nurses need to demand and facilitate access to research findings.

Idiopathic torsion dystonia linked to chromosome 8 in two Mennonite families.

The DYT1 locus on chromosome 9q34 is responsible for most childhood limb-onset idiopathic torsion dystonia (ITD). Linkage to DYT1 has been excluded in families with adult-onset, and predominantly cranial-cervical, ITD. We mapped a locus (DYT6) associated with prominent cranial-cervical ITD in two large Mennonite families to chromosome 8. An identical haplotype spanning 40-cM segregates with ITD in these families, suggesting a shared mutation from the recent past.

Secondary dystonia and the DYTI gene.

Early-onset (< 28 years) primary dystonia in most Ashkenazi Jews is due to a single founder mutation in the DYT1 gene on chromosome 9q34, as determined by very strong linkage disequilibrium with a haplotype of 9q34 alleles at surrounding marker loci. The role of this mutation in individuals with secondary causes for dystonia has never been tested, although environmental insults, such as neuroleptic exposure or perinatal asphyxia, are proposed to precipitate dystonia in genetically predisposed individuals. We assessed 9q34 haplotypes in 40 Ashkenazi patients with secondary dystonia; 25 had early onset of symptoms, including 15 with exposure to neuroleptic medication or perinatal asphyxia. Of the 25 patients with early onset, 9 were considered phenocopies of DYT1 having normal examinations except for dystonia, normal radiographic and other laboratory studies, and onset in a limb or the neck. Only one individual whose dystonia developed in the setting of a measles infection carried the associated haplotype. Our findings indicate that clinical diagnostic criteria that include historical information to detect tardive dystonia and perinatal asphyxia discriminate primary dystonia due to the DYT1 founder mutation. We found no evidence that the DYT1 founder mutation contributes to secondary dystonia.

Exclusion of the DYT1 locus in familial torticollis.

Clinical-genetic studies of idiopathic torsion dystonia (ITD) indicate that the DYT1 gene on chromosome 9q34 is responsible for most childhood limb-onset disease. The genetic basis of adult-onset ITD is less well studied. In most multiplex adult-onset ITD families, dystonia is limited to the cervical, cranial, or brachial muscles; in a few rare families, dystonia also involves the legs and trunk. Previous linkage studies have excluded the DYT1 locus in these atypical families. We studied two large non-Jewish families with adult-onset ITD limited to the cervical and brachial muscles and excluded the DYT1-containing region. This study further restricts the role of DYT1 to childhood limb-onset ITD and suggests that other genes are responsible for focal adult-onset ITD.

Response to botulinum toxin F in seronegative botulinum toxin A--resistant patients.

Botulinum toxin type A (btx A) injections are the most effective treatment for most patients with focal dystonia. Some patients who improve after btx A injections and later lose response have serologic evidence of antibodies to btx A with the mouse neutralization assay (seropositive patients). Another group of patients who lose response to btx A do not have detectable antibodies (seronegative patients). Seropositive patients may improve after injections of botulinum toxin type F (btx F), an alternative serotype of botulinum toxin. We treated nine seronegative resistant patients with btx F. None of these patients had muscle atrophy after injection with btx A. Five of the nine had improvement after btx F injection that was sustained for at least three consecutive btx F injections. This observation is consistent with the hypothesis that btx resistance in seronegative patients is caused by undetected antibodies to btx A. If this be the case, then there may be techniques for preventing or reversing btx resistance, as in the case of resistance of factor VIII in the treatment of hemophilia A.

Dystonia in Ashkenazi Jews: clinical characterization of a founder mutation.

A gene (DYT1) for idiopathic torsion dystonia maps to chromosome 9q34 in Ashkenazi Jewish families with early onset of symptoms. Further, there is linkage disequilibrium between DYT1 and a particular haplotype of alleles at 9q34 loci in this population. This implies that a large proportion of early-onset idiopathic torsion dystonia in Ashkenazi Jews is due to a founder mutation in DYT1. To characterize the phenotypic range of this mutation, we studied 174 Ashkenazi Jewish individuals affected with idiopathic torsion dystonia. We used GT(n) markers on chromosome 9q34 (D9S62, D9S63, and ASS) and classified individuals as having ("carriers"), not having ("noncarriers"), or being ambiguous with respect to a DYT1-associated haplotype. We assessed clinical features and found marked clinical differences between haplotype carriers and noncarriers. There were 90 carriers, 70 noncarriers, and 14 ambiguous individuals. The mean age at onset of symptoms was significantly lower in carriers than in noncarriers (12.5 +/- 8.2 vs 36.5 +/- 16.4 years). In 94% of carriers, symptoms began in a limb (arm or leg equally); rarely the disorder started in the neck (3.3%) or larynx (2.2%). In contrast, the neck, larynx, and other cranial muscles were the sites of onset in 79% of noncarriers; onset in the arms occurred in 21% and onset in the legs never occurred. Limb onset, leg involvement in the course of disease, and age at onset distinguished haplotype carriers from noncarriers with 90% accuracy. In conclusion, there are clinical differences between Ashkenazi Jewish individuals with idiopathic torsion dystonia who do or do not have a unique DYT1 mutation, as determined by a DYT1-associated haplotype of 9q34 alleles.(ABSTRACT TRUNCATED AT 250 WORDS)

A comparison of oral health status and need for dental care between abused/neglected children and nonabused/non-neglected children.

This paper compares oral health status and presence of untreated, decayed permanent teeth in abused/neglected children with nonabused/non-neglected controls. The sample comprised 903 children between 5 and 13 years old; 30 were confirmed cases of child abuse and 873 served as controls. Their oral health status was assessed by two calibrated dentists using the DMFS index. Presence of untreated, decayed teeth was determined from the decayed and unfilled component of the DMFS score. The data were analyzed using logistic regression so that the influence of other explanatory variables (sociodemographic characteristics) on oral health status and presence of untreated, decayed teeth could be controlled while the influence of abuse status was evaluated. Results show that abuse status is an important explanatory variable for both oral health status and presence of untreated, decayed teeth. While the impact of abuse status on oral health status is obscured by interactions with other explanatory variables, its impact on the presence of untreated, decayed teeth is clear. Abused children are eight times more likely to have untreated, decayed permanent teeth than nonabused children. Accordingly, it is recommended that confirmed cases of child abuse/neglect should be referred routinely for dental screening as part of their overall rehabilitation.