Clustering of motor and nonmotor traits in leucine-rich repeat kinase 2 G2019S Parkinson's disease nonparkinsonian relatives: A multicenter family study.

OBJECTIVES: The objective of this study was to determine phenotypic features that differentiate nonparkinsonian first-degree relatives of PD leucine-rich repeat kinase 2 (LRRK2) G2019S multiplex families, regardless of carrier status, from healthy controls because nonparkinsonian individuals in multiplex families seem to share a propensity to present neurological features. METHODS: We included nonparkinsonian first-degree relatives of LRRK2 G2019S familial PD cases and unrelated healthy controls participating in established multiplex family LRRK2 cohorts. Study participants underwent neurologic assessment including cognitive screening, olfaction testing, and questionnaires for daytime sleepiness, depression, and anxiety. We used a multiple logistic regression model with backward variable selection, validated with bootstrap resampling, to establish the best combination of motor and nonmotor features that differentiates nonparkinsonian first-degree relatives of LRRK2 G2019S familial PD cases from unrelated healthy controls. RESULTS: We included 142 nonparkinsonian family members and 172 unrelated healthy controls. The combination of past or current symptoms of anxiety (adjusted odds ratio, 4.16; 95% confidence interval, 2.01-8.63), less daytime sleepiness (adjusted odds ratio [1 unit], 0.90; 95% confidence interval, 0.83-0.97], and worse motor UPDRS score (adjusted odds ratio [1 unit], 1.4; 95% confidence interval, 1.20-1.67) distinguished nonparkinsonian family members, regardless of LRRK2 G2019S mutation status, from unrelated healthy controls. The model accuracy was good (area under the curve = 79.3%). CONCLUSIONS: A set of motor and nonmotor features distinguishes first-degree relatives of LRRK2 G2019S probands, regardless of mutation status, from unrelated healthy controls. Environmental or non-LRRK2 genetic factors in LRRK2-associated PD may influence penetrance of the LRRK2 G2019S mutation. The relationship of these features to actual PD risk requires longitudinal observation of LRRK2 familial PD cohorts. © 2018 International Parkinson and Movement Disorder Society.

Adult-Onset Tics After Being Crushed by an Air Conditioner: A Case Report.

Tics are sudden, repetitive, non-rhythmic movements and/or vocalizations. Generally, tics begin during childhood as a part of Tourette syndrome (TS) and rarely have an onset during adulthood. We describe a 30-year-old male who presented with multiple motor and vocal tics two weeks following a closed head injury with alteration of consciousness as a result of being crushed against the wall by a 4,100-pound air-conditioning unit. He started having motor tics that developed in a rostrocaudal distribution, followed by simple and complex vocal tics. His tics increased in severity over several months following the injury until presentation. He was started on pimozide and received hyperbaric oxygen treatment which improved both motor and vocal tics.

Deep brain stimulation targeting the Globus pallidus internus for Parkinson's disease and Tourette syndrome.

We present a case with co-existing Parkinson's disease and Tourette syndrome. Patient takes aripiprazole for Tourette syndrome, which unfortunately worsens his parkinsonian symptoms. We placed deep brain stimulation targeting the Globus pallidus internus. Strikingly, his parkinsonian motor symptoms and his tics are both well controlled with deep brain stimulation.

A comparison of the mini mental state exam to the Montreal cognitive assessment in identifying cognitive deficits in Parkinson's disease.

Dementia is an important and increasingly recognized problem in Parkinson's disease (PD). The mini-mental state examination (MMSE) often fails to detect early cognitive decline. The Montreal cognitive assessment (MoCA) is a brief tool developed to detect mild cognitive impairment that assesses a broader range of domains frequently affected in PD. The scores on the MMSE and the MoCA were compared in 88 patients with PD. A pronounced ceiling effect was observed with the MMSE but not with the MoCA. The range and standard deviation of scores was larger with the MoCA(7-30, 4.26) than with the MMSE(16-30, 2.55). The percentage of subjects scoring below a cutoff of 26/30 (used by others to detect mild cognitive impairment) was higher on the MoCA (32%) than on the MMSE (11%) (P < 0.000002). Compared to the MMSE, the MoCA may be a more sensitive tool to identify early cognitive impairment in PD.

Successful deep brain stimulation for central post-stroke pain and dystonia in a single operation.

BACKGROUND: Central post-stroke pain is known to be refractory to medications and difficult to manage. We present a case of central post-stroke pain associated with dystonia. Both conditions were successfully treated with a single deep brain stimulation (DBS) operation. CASE DESCRIPTION: A 60-year-old female suffered a right posterior cerebral artery stroke following emergent clipping of a ruptured posterior cerebral artery aneurysm resulting in central post-stroke pain. This manifested as delayed left face and hemibody allodynia and hyperesthesia. The patient also developed marked left-sided dystonia. These progressive symptoms were disabling and refractory to conservative management. The patient underwent a single-stage DBS surgery with stereotactic targeting and implantation of two leads. One lead was placed in the right-sided ventral capsule/ventral striatum for treatment of pain and a second lead in the right-sided globus pallidus interna for treatment of dystonia. The surgical implantation proceeded without complication. The patient's dystonia markedly improved following surgery. While her pain improved, she required multiple, meticulous programing sessions to achieve significant pain relief and decrease in pain medication use. Overall, the patient was satisfied with the results of her intervention. She did, however, have occasional intermittent spells of severe pain on top of her residual discomfort throughout her treatment course. Unfortunately, she died from small cell lung carcinoma a year after her DBS surgery. CONCLUSIONS: Deep brain stimulation targeting multiple brain networks in one operation is feasible and safe. Deep brain stimulation may be considered in some refractory cases of central post-stroke pain; however, it requires meticulous programming.

Factors associated with dopaminergic drug-related pathological gambling in Parkinson disease.

OBJECTIVE: To evaluate factors associated with pathological gambling (PG) in Parkinson disease (PD). DESIGN: Case-control study. SETTING: Outpatient tertiary clinic. Patients Twenty-one patients with idiopathic PD with PG after the patients began receiving medications compared with a consecutive sample of 42 patients with idiopathic PD without compulsive behaviors. MAIN OUTCOME MEASURES: Clinical features, comorbid psychiatric and substance use disorders, personality traits, and impulsivity scores. RESULTS: Patients with PG had a younger age at PD onset (P = .006), higher novelty seeking (P<.001), medication-induced hypomania or mania (P = .001), impaired planning (P = .002), or a personal or immediate family history of alcohol use disorders (P = .002). Novelty seeking, a personal or immediate family history of alcohol use disorders, and younger age at PD onset accurately predicted PG at 83.7% in a logistic regression model, with the model accounting for 62% of the variance. CONCLUSIONS: Patients with PD having a younger age at PD onset, higher novelty seeking traits, and a personal or family history of alcohol use disorders may have a greater risk for PG with dopamine agonists.

Epidural Spinal Cord Stimulation: A Novel Therapy in the Treatment of Restless Legs Syndrome.

BACKGROUND: We report a unique finding of a patient whose restless legs syndrome (RLS) symptoms abated after the placement of a spinal cord stimulator for chronic neuropathic pain. RLS is a common disorder, with many patients unable to find sufficient relief from their symptoms. CASE DESCRIPTION: A patient diagnosed with neuropathic pain who also suffered from RLS symptoms despite medication therapy underwent implantation of a spinal cord stimulator after a successful trial. This patient was interviewed formally about his RLS symptoms immediately before his procedure and at 6 weeks, 6 months, and 2.5 years after the procedure. The patient also completed the International Restless Legs Syndrome Scale questionnaire to objectively quantify the severity of his symptoms. Finally, the patient kept a 5-day journal detailing when the stimulator was in use. The patient reported subjective symptomatic improvement in his RLS symptoms with improved sleep quality and quantity, in addition to improvement in his back pain. The patient's score on the International Restless Legs Syndrome Scale improved after implantation from 33 to 0 on a 40-point scale. Moreover, when asked to keep a journal record of his stimulator use, the patient noted that he only used the stimulator before going to bed to help his RLS symptoms and no longer required any medication for his previous RLS symptoms. CONCLUSIONS: Epidural stimulation may be an additional, alternative, or novel therapy in the treatment of RLS.

Lateralized effect of pallidal stimulation on self-mutilation in Lesch-Nyhan disease.

Lesch-Nyhan disease (LND) is an X-linked hereditary disorder caused by a deficiency of hypoxanthine-guanine phosphoribosyltransferase. This syndrome is characterized by hyperuricemia, self-mutilation, cognitive impairment, and movement disorders such as spasticity and dystonia. The authors describe the case of a 15-year-old boy who underwent bilateral placement of globus pallidus internus (GPi) deep brain stimulation (DBS) electrodes for the treatment of generalized dystonia. His self-mutilating behavior gradually disappeared several weeks after the start of GPi stimulation. The dystonia and self-mutilating behavior returned on the left side only after a right lead fracture. This case is the first reported instance of LND treated with DBS in which the stimulation was interrupted and the self-mutilation returned in a lateralized fashion. The findings indicate that the neurobehavioral aspect of LND is lateralized and that contralateral GPi stimulation is responsible for lateralized improvement in self-injurious behavior.

Phase I/II randomized trial of aerobic exercise in Parkinson disease in a community setting.

OBJECTIVES: To (1) investigate effects of aerobic walking on motor function, cognition, and quality of life in Parkinson disease (PD), and (2) compare safety, tolerability, and fitness benefits of different forms of exercise intervention: continuous/moderate intensity vs interval/alternating between low and vigorous intensity, and individual/neighborhood vs group/facility setting. METHODS: Initial design was a 6-month, 2 × 2 randomized trial of different exercise regimens in independently ambulatory patients with PD. All arms were required to exercise 3 times per week, 45 minutes per session. RESULTS: Randomization to group/facility setting was not feasible because of logistical factors. Over the first 2 years, we randomized 43 participants to continuous or interval training. Because preliminary analyses suggested higher musculoskeletal adverse events in the interval group and lack of difference between training methods in improving fitness, the next 17 participants were allocated only to continuous training. Eighty-one percent of 60 participants completed the study with a mean attendance of 83.3% (95% confidence interval: 77.5%-89.0%), exercising at 46.8% (44.0%-49.7%) of their heart rate reserve. There were no serious adverse events. Across all completers, we observed improvements in maximum oxygen consumption, gait speed, Unified Parkinson's Disease Rating Scale sections I and III scores (particularly axial functions and rigidity), fatigue, depression, quality of life (e.g., psychological outlook), and flanker task scores (p < 0.05 to p < 0.001). Increase in maximum oxygen consumption correlated with improvements on the flanker task and quality of life (p < 0.05). CONCLUSIONS: Our preliminary study suggests that aerobic walking in a community setting is safe, well tolerated, and improves aerobic fitness, motor function, fatigue, mood, executive control, and quality of life in mild to moderate PD. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that in patients with PD, an aerobic exercise program improves aerobic fitness, motor function, fatigue, mood, and cognition.

Diagnosis and treatment of impulse control disorders in patients with movement disorders.

Impulse control disorders are a psychiatric condition characterized by the failure to resist an impulsive act or behavior that may be harmful to self or others. In movement disorders, impulse control disorders are associated with dopaminergic treatment, notably dopamine agonists (DAs). Impulse control disorders have been studied extensively in Parkinson's disease, but are also recognized in restless leg syndrome and atypical Parkinsonian syndromes. Epidemiological studies suggest younger age, male sex, greater novelty seeking, impulsivity, depression and premorbid impulse control disorders as the most consistent risk factors. Such patients may warrant special monitoring after starting treatment with a DA. Various individual screening tools are available for people without Parkinson's disease. The Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease has been developed specifically for Parkinson's disease. The best treatment for impulse control disorders is prevention. However, after the development of impulse control disorders, the mainstay intervention is to reduce or discontinue the offending anti-Parkinsonian medication. In refractory cases, other pharmacological interventions are available, including neuroleptics, antiepileptics, amantadine, antiandrogens, lithium and opioid antagonists. Unfortunately, their use is only supported by case reports, small case series or open-label clinical studies. Prospective, controlled studies are warranted. Ongoing investigations include naltrexone and nicotine.

Juvenile parkinsonism: epidemiology, diagnosis and treatment.

Juvenile parkinsonism, with onset prior to age 21 years, is a relatively rare syndrome. It is caused by a group of heterogeneous entities that can present with a clinical picture similar to idiopathic Parkinson's disease or manifest parkinsonism as part of a spectrum of other signs. Diagnostic testing is guided by the presenting symptoms and aimed at uncovering potentially reversible and/or treatable causes. If an underlying condition is found, treatment is tailored accordingly. Otherwise, treatment is symptomatic and relies on medications commonly employed to treat idiopathic Parkinson's disease. Juvenile parkinsonism patients tend to be plagued by treatment-induced complications, so caution must be employed.

Medication-related impulse control and repetitive behaviors in Parkinson's disease.

PURPOSE OF REVIEW: A range of impulse control and repetitive behaviors presumed to be related to dopaminergic medications has been recognized in Parkinson's disease. These behaviors are linked by their incentive or reward-based and repetitive natures and overlap with addictions. The behaviors include pathological gambling, hypersexuality, compulsive shopping, and compulsive eating and are related to punding and compulsive medication use. In patients on dopamine agonists, these behaviors as a group are relatively common, can have potentially devastating psychosocial consequences and are commonly hidden. RECENT FINDINGS: Recent studies have investigated prevalence rates and associated factors. The literature on these behaviors in Parkinson's disease, including definitions, epidemiology, pathophysiology and management, is reviewed. The relationship to medications, Parkinson's disease and individual susceptibility is examined. SUMMARY: These behaviors can affect up to 14% of Parkinson's disease patients on dopamine agonists. Clinicians should warn patients prior to initiating dopamine agonists and enquire about these behaviors during follow up.

Ipratropium bromide spray as treatment for sialorrhea in Parkinson's disease.

Sialorrhea is a significant problem in advanced Parkinson's disease (PD). Current treatment options include systemic anticholinergics which frequently cause side effects. We hypothesized that sublingual application of ipratropium bromide spray, an anticholinergic agent that does not cross the blood brain barrier, may reduce drooling without systemic side effects. We performed a randomized, double blind, placebo-controlled, crossover study in 17 subjects with PD and bothersome drooling. Patients were randomized to receive ipratropium bromide or placebo (one to two sprays, maximum of four times per day) for 2 weeks followed by a 1 week washout and crossover for further 2 weeks of treatment. The primary outcome was an objective measure of weight of saliva production. Secondary outcomes were subjective rating of severity and frequency of sialorrhoea using home diaries, United Parkinson's Disease Rating Scale (UPDRS) part II salivation subscore, parkinsonian disability using UPDRS, and adverse events. Ipratropium bromide spray had no significant effect on weight of saliva produced. There was a mild effect of treatment on subjective measures of sialorrhea. There were no significant adverse events. Ipratropium bromide spray was well tolerated in subjects with PD. Although it did not affect objective measures of saliva production, further studies in parkinsonism may be warranted.