Anthony Davidson

Metoclopramide, an Increasingly Recognized Cause of Tardive Dyskinesia

T dyskinesia (TD), a hyperkinetic movement disorder causally related to dopamine receptorblocking drug (DRBD) exposure, is a well-recognized iatrogenic disorder in adults and less commonly seen in children and infants. Although the literature on TD mainly focuses on patients treated with DRBDs used as antipsychotics, DRBDs are also used to treat a wide array of medical, chiefly gastrointestinal, conditions. Although most of the drugs that cause TD are DRBDs that antagonize dopamine D2 receptors, other classes of drugs have the potential to cause TD, including antidepressants and calcium channel blockers. The reported lifetime prevalence of TD in patients treated with traditional DRBDs has varied greatly, with an average of about 25% of exposed adults. Risk factors associated with the development of TD include advanced age, female gender, and, more important, total cumulative drug exposure. We sought to determine which drugs most commonly cause TD in patients referred to our clinic.

Correlation between Kinesia system assessments and clinical tremor scores in patients with essential tremor.

The primary aim of this study was to determine whether scores on The Essential Tremor Rating Assessment Scale (TETRAS) correlate with quantitative assessments using the Kinesia™ (CleveMed) system in patients with essential tremor (ET). Patients sequentially evaluated and diagnosed with ET at the Parkinsons Disease Center and Movement Disorders Clinic, Baylor College of Medicine were enrolled in the study. The Kinesia portable device was attached to the wrist and subjects were instructed to hold their arms in an outstretched position and then touch their nose while data were wirelessly transmitted to a computer. Subjects were rated on the arm where the system was placed using specific TETRAS items. A linear regression model was constructed for each task using the logarithmic values of both clinical scores and objective motion data parameters to compute a Kinesia score. Twenty subjects underwent complete clinical TETRAS and Kinesia quantitative assessments. TETRAS clinical scores significantly correlated with predicted Kinesia quantitative variables for postural (r = 0.738; P < 0.001) and kinetic (r = 0.57; P = 0.009) tremor. We conclude that the Kinesia system may, therefore, have a utility in quantitative assessments of ET when combined with standard clinical assessment.

Deep Brain Stimulation Hardware Complications in Patients with Movement Disorders: Risk Factors and Clinical Correlations

Background: Deep brain stimulation (DBS) has proven to be an effective treatment for Parkinson’s disease (PD) and other movement disorders, but its usefulness is limited by complications related to the hardware. Methods: We reviewed the records of all our patients treated with DBS from January 1996 to August 2010 and analyzed those with hardware complications and reasons for surgical revision. Results: A total of 512 patients underwent 856 electrode implantations during the study period. A total of 297 (58%) patients had PD, 127 (24.8%) had essential tremor (ET), 40 (7.8%) had dystonia, and 48 (9.37%) had another movement disorder. The mean age at the first electrode implantation was 57.6 ± 14 years and patients were followed for a mean of 3.9 ± 2.8 years. A total of 44 patients (8.6%) had a hardware complication or system revision. Lead fracture was the most common complication and occurred in 13 (2.5%) patients, followed by infections (n = 10, 1.9%), electrode misplacement (n = 10, 1.9%), electrode migration (n = 9, 1.75%), and other complications (n = 2 , 0.39%). Patients with ET had a higher risk of hardware complications compared to those with PD, 13 vs. 7% (OR 2.03; p = 0.042). Conclusions: DBS is a safe intervention with a relatively low rate of hardware complications.

Placebo-controlled trial of lubiprostone for constipation associated with Parkinson disease

Objective: To evaluate the efficacy and tolerability of lubiprostone (Amitiza) for constipation in Parkinson disease (PD) in a double-blind, randomized, controlled study. Methods: Patients with PD and clinically meaningful constipation (constipation rating scale score > 10 [range: 0−28]) were recruited from 2 academic movement disorder centers to participate in the study. After enrollment, patients were initially followed for 2 weeks and then were randomly assigned 1:1 to lubiprostone, and the dose was titrated up to 48 μg/day. They returned 4 weeks later for a final assessment. Data included stool diaries and global impressions (coprimary endpoints), demographics, Unified Parkinsons Disease Rating Scale scores, constipation scale scores, visual analog scale (VAS) scores, a stool diary, and adverse events. Results: Fifty-four subjects (39 male, mean age 67.0 ± 10.1 years, and mean duration of PD 8.3 ± 5.4 years) were randomly assigned to lubiprostone or placebo. One patient in the drug group discontinued the study because of logistics, and one patient in the placebo group discontinued the study because of lack of efficacy. A marked or very marked clinical global improvement was reported by 16 of 25 (64.0%) subjects receiving drug vs 5 of 27 (18.5%) subjects receiving placebo (p = 0.001). The constipation rating scale (p < 0.05), VAS (p = 0.001), and stools per day in the diary (p < 0.001) all improved with drug compared with placebo. Adverse events with drug were mild, most commonly intermittent loose stools. Conclusion: In this randomized controlled trial, lubiprostone seemed to be well tolerated and effective for the short-term treatment of constipation in PD. Level of Evidence: This study provides Class I evidence that lubiprostone improves constipation in PD over 4 weeks.

Shoulder pain: a presenting symptom of Parkinson disease.

To the Editor: As noted in recent reports in the Journal of Clinical Rheumatology and elsewhere, note that painful deformities and symptoms in Parkinson disease (PD) may clinically be confused with that of rheumatoid arthritis (RA) or Parkinson disease coexists with RA. 4 Shoulder pain is often an underrecognized, misdiagnosed, or improperly treated symptom of PD. Failure to recognize this pain as a presenting symptom of PD may delay correct diagnosis and treatment, leading to unnecessary invasive procedures. A retrospective analysis of 309 consecutive patients diagnosed with PD in our clinic revealed that 35 (11%) complained of shoulder pain, in some cases preceding the onset of motor symptoms by several years. Side of shoulder pain significantly correlated with side of maximum severity of parkinsonian features (Pearson’s r 0.725, P 0.001), and in 7 (20%), shoulder pain was the presenting complaint (Table 1). The diagnoses offered as an explanation for the shoulder pain in the 7 cases included osteoarthritis, cervical radiculopathy, postpolio syndrome, rotator cuff injury, injury related to minor fall, cervical disc, and cause unknown. The mechanism of shoulder pain in PD is not clear, although rigidity and bradykinesia, leading to immobility and subsequent shoulder dysfunction and discomfort, is a possible explanation. Levodopa-related motor fluctuations and wearing off sensory symptoms are found in the majority of patients within 5 years after onset of PD. As the disease progresses painful levodopa-related dyskinesia, wearing off dystonia, “striatal” hand and foot deformities, abnormal spine postures such as scoliosis and marked cervical and trunk flexion (camptocormia), and end-stage contractures all contribute to PD-related pain. In addition, shoulder or other peripheral injury, including falls, may cause joint pain and, as a result of central reorganization, may lead to “peripherally induced” tremors and parkinsonism. Some chronic pain syndromes are associated with low basal ganglia dopamine levels, and improvement of PD-related shoulder pain with dopaminergic therapy is often accompanied by amelioration of rigidity and bradykinesia, suggesting that the pain may be associated with dopamine deficiency. Additionally, PD patients off levodopa have significantly lower pain thresholds than controls, and tend to normalize after a dose of levodopa. In conclusion, 20% of our PD patients with shoulder pain reported this complaint preceded the onset of motor symptoms of PD, a strong temporal association suggesting shoulder pain is a relatively frequent presenting symptom of PD. Although reported in only 11% of our patients with PD, this is probably an underestimate as shoulder pain was not specifically sought during the examination and often was included in a case history only if volunteered. Despite these limitations of a retrospective study, we believe that shoulder pain is a frequently misdiagnosed symptom of early PD. Recognition and better understanding of this PD-related symptom should lead to early diagnosis, prevention of unnecessary interventions, and may provide insights into the prodromal period of PD.

Tourette's Syndrome in Adults

Tourettes syndrome (TS) is defined as motor and phonic tics starting before age 18 years, and therefore most studies have focused on childhood TS, whereas the disorder in adults has not been well characterized. We reviewed medical records of all new TS patients referred to our Movement Disorders Clinic over the past 5 years, 19 years or older on initial evaluation and compared them with 100 TS patients 18 years or younger. The mean age at initial visit of 43 adult TS patients was 58.8 ± 6.7 years, whereas the mean age at initial visit of children with TS was 12.9 ± 2.0 years. Of the adult TS patients, 35 (81.4%) had a history of tics with onset before the age of 18 years (mean age at onset: 8.5 ± 3.4 years), with 8 (18.6%) reporting first occurrence of tics after the age of 18 years (mean age at onset: 37.8 ± 13.2 years). Only two (4.7%) patients reported tic onset after the age of 50 years. Adult patients with TS had significantly more facial and truncal tics, and a greater prevalence of substance abuse and mood disorders, but fewer phonic tics, and lower rates of attention‐deficit hyperactivity disorder and oppositional behavior than children with TS. Adult TS largely represents reemergence or exacerbation of childhood‐onset TS. During the course of TS, phonic and complex motor tics, self‐injurious behaviors, and attention‐deficit hyperactivity disorder tend to improve, but facial, neck, and trunk tics dominate the adult TS phenotype. In addition, adults with TS are more likely to exhibit substance abuse and mood disorders compared with children with TS.

Convergence spasm in conversion disorders: prevalence in psychogenic and other movement disorders compared with controls

Background Convergence spasm refers to transient ocular convergence, miosis and accommodation associated with disconjugate gaze mimicking abducens palsy. While it may be a manifestation of brainstem pathology, this sign is often associated with conversion (somatisation) disorders and, if unrecognised as a sign of a psychogenic disorder, it may lead to unnecessary and occasionally invasive evaluation. Methods To better characterise this neuro-ophthalmologic sign, 36 subjects were studied, 13 with psychogenic movement disorders, 11 with organic movement disorders and 12 normal controls. Patients were recorded during a manoeuvre to elicit convergence spasm and the videotapes were rated by two blinded raters on a scale of 0=normal, 1=mild convergence spasm and 2=marked convergence spasm. Results Convergence spasm was present in 9/13 (69%) psychogenic movement disorders cases, 4/11 (36%) non-psychogenic movement disorders cases and 4/12 (33%) controls (p=0.049 when psychogenic vs non-psychogenic disorders or controls were compared). Inter-rater reliability analysis of the presence (rating 1 or 2) versus absence (rating 0) showed good agreement (27/36 or 75%; kappa 0.491, SE 0.141, p=0.002). Analysis for the presence of marked convergence spasm (rating 2) yielded agreement in 32/36 (88.9%) examinations (kappa 0.652, SE 0.154, p<0.001) with a specificity of 87% (sensitivity 15%). Conclusion Convergence spasm may provide benefit in the clinical examination of psychogenic movement disorders patients.

Applause sign in parkinsonian disorders and Huntington's disease

The applause sign has been previously reported to be indicative of neurodegenerative disorders, such as progressive supranuclear palsy (PSP). In order to determine the sensitivity, specificity, and positive predictive value, we tested it in patients with PSP, Parkinsons disease (PD), multiple system atrophy (MSA), corticobasal degeneration (CBD), and Huntingtons disease (HD). Subjects were asked to clap three times after demonstration by the examiner. The performance was scored as follows: 3 = claps only three times; 2 = claps four times; 1 = claps 5 to 10 times; 0 = claps >10 times. The clap test was videotaped and rated. Patients with CBD, MSA, and PSP showed significant differences in clap scores compared with normal controls. The test differentiated patients with CBD from those with PD (P < 0.005) and HD (P < 0.005), but failed to discriminate patients with PSP from other parkinsonian groups. The specificity of the applause sign is 100% in distinguishing parkinsonian patients from normal subjects with the highest sensitivity in CBD patients. We concluded that the applause sign is highly specific for parkinsonian disorders but it is not a specific sign for PSP; it appears to be most sensitive for CBD.

Efficacy and tolerability of pregabalin in essential tremor: A randomized, double-blind, placebo-controlled, crossover trial

We performed a double-blind, crossover-design study to assess the tolerability and efficacy of pregabalin (PGB) in patients with essential tremor (ET). Twenty patients (11 women; mean age of 62.2+/-12.7 years, mean ET duration of 25.5+/-14.9 years) with ET were randomized for treatment with PGB (150-600 mg/day) or placebo, titrated over 6 weeks. Identical assessments of the Fahn-Tolosa-Marin Tremor Rating Scale (TRS) (primary endpoint), Clinical Global Impression of Change (CGI-C), Quality of Life in Essential Tremor Questionnaire (QUEST), Hamilton Anxiety Scale (HAM-A), and a sleep hygiene questionnaire (HD-16) were made at the baseline, at the end of treatment periods for both drug and placebo, and following the 2-week washout period preceding crossover. We found no improvement in any of the TRS measures and a statistically significant worsening of QUEST scores while patients were taking PGB. Adverse events were similar in frequency to previously published studies of PGB, the most common being drowsiness and dizziness.

Impact of STN-DBS on life and health satisfaction in patients with Parkinson's disease

Objective Advanced Parkinsons disease (PD) is associated with various motor and non-motor symptoms which adversely impact health-related quality of life (HRQoL). Subthalamic nucleus (STN) deep brain stimulation (DBS) has been reported to improve some dimensions of HRQoL in appropriately selected candidates. Prior studies of HRQoL following DBS have used instruments comprising a predetermined list of questions which assess issues that are generally relevant in PD, but that may not be of equal or consistent importance to all individuals. In this study, we evaluate the effect of STN DBS on quality of life using the QLSM, a modular questionnaire in which satisfaction scores for each item are weighted in light of patient-rated importance. Methods We prospectively analysed QLSM scores in 21 patients with PD (11 men, mean age 61.5±8.6 years) before STN DBS surgery and at a mean 7.4±1.5, and again at a mean 16.6±6.8 months postoperatively. Results Following STN DBS, patients experienced an improvement in HRQoL as measured by various items of the movement disorder and health modules of the QLSM. Specifically, QLSM items pertaining to energy level/enjoyment of life, independence from help, controllability/fluidity of movement and steadiness when standing and walking showed significant improvements, although items concerning general life issues (eg, occupational function, interpersonal relationships, leisure activities) did not improve. Conclusion Following STN DBS, symptomatic and functional improvements translate into higher HRQoL, with high satisfaction in domains related to movement disorders and general health.