Parkinson disease is a progressive neurodegenerative disorder characterized by rigidity, tremor, bradykinesia, and postural instability, ultimately leading to disability.^1,2 Because medications have adverse effects and reduced effectiveness over time,³ disease-modifying nonpharmacologic interventions are needed. One intervention, endurance exercise, promotes neurogenesis and neuroprotection in animals^4-8 and has had symptom-modifying and health-related benefits in patients with Parkinson disease.^9-13 Retrospective studies^14,15 have found that moderate to vigorous exercise in midlife can protect against Parkinson disease. Studies^9,16 in humans suggest that high-intensity endurance exercise improves motor symptoms, but current evidence is insufficient to determine whether exercise intensity influences symptom modification or disease progression. To date, no study has been conducted at 80% to 85% maximum heart rate, and typically most studies were powered on fitness or functional measures but not disease severity.^9-11,17,18 This study (Study in Parkinson Disease of Exercise [SPARX]) was a phase 2 randomized clinical trial to investigate the dose response of treadmill exercise performed at 2 different intensities (high and moderate). To remove the potential confounder of medication, this study included patients with de novo Parkinson disease.¹⁹ The study examined whether patients with de novo Parkinson disease can consistently and safely exercise on a treadmill at high intensity (80%-85% maximum heart rate) or moderate intensity (60%-65% maximum heart rate) at least 3 days per week and whether high- or moderate-intensity treadmill exercise warrants further investigation for treatment of motor symptoms.

Neuroleptic malignant syndrome (NMS) is a life-threatening idiosyncratic reaction to antipsychotic drugs characterized by fever, altered mental status, muscle rigidity, and autonomic dysfunction. It has been associated with virtually all neuroleptics, including newer atypical antipsychotics, as well as a variety of other medications that affect central dopaminergic neurotransmission. Although uncommon, NMS remains a critical consideration in the differential diagnosis of patients presenting with fever and mental status changes because it requires prompt recognition to prevent significant morbidity and death. Treatment includes immediately stopping the offending agent and implementing supportive measures, as well as pharmacological interventions in more severe cases. Maintaining vigilant awareness of the clinical features of NMS to diagnose and treat the disorder early, however, remains the most important strategy by which physicians can keep mortality rates low and improve patient outcomes.

Objective: To investigate the safety and efficacy of intermittent theta-burst stimulation (iTBS) in the treatment of motor symptoms in Parkinson disease (PD). Background: Progression of PD is characterized by the emergence of motor deficits, which eventually respond less to dopaminergic therapy and pose a therapeutic challenge. Repetitive transcranial magnetic stimulation (rTMS) has shown promising results in improving gait, a major cause of disability, and may provide a therapeutic alternative. iTBS is a novel type of rTMS that may be more efficacious than conventional rTMS. Methods: In this randomized, double-blind, sham-controlled study, we investigated safety and efficacy of iTBS of the motor and dorsolateral prefrontal cortices in 8 sessions over 2 weeks (evidence Class I). Assessment of safety and clinical efficacy over a 1-month period included timed tests of gait and bradykinesia, Unified Parkinson9s Disease Rating Scale (UPDRS), and additional clinical, neuropsychological, and neurophysiologic measures. Results: We investigated 26 patients with mild to moderate PD: 13 received iTBS and 13 sham stimulation. We found beneficial effects of iTBS on mood, but no improvement of gait, bradykinesia, UPDRS, and other measures. EEG/EMG monitoring recorded no pathologic increase of cortical excitability or epileptic activity. Few reported discomfort or pain and one experienced tinnitus during real stimulation. Conclusion: iTBS of the motor and prefrontal cortices appears safe and improves mood, but failed to improve motor performance and functional status in PD. Classification of evidence: This study provides Class I evidence that iTBS was not effective for gait, upper extremity bradykinesia, or other motor symptoms in PD.

Background: Deep brain stimulation (DBS) of the globus pallidus internus (GPi) is an effective and well-tolerated treatment for idiopathic generalized dystonia. More recently, it has been applied as a treatment for focal and segmental dystonias. This patient population offers an opportunity to study the effects of alteration of pallidal outflow on previously normal limb function. Methods: We sought to retrospectively characterize the extent of novel GPi DBS-induced adverse motor effects in patients with adult-onset cervical and cranial-cervical dystonia using a questionnaire, and compared the findings to dystonia improvement as measured by standard scales. Results: Despite significant improvement in dystonia (65% in mean Burke-Fahn-MarsdenDystonia Rating Scale motor score, p < 0.005, and 59% in mean Toronto Western Spasmodic Torticollis Rating Scale score, p < 0.008), slowing and difficulty with normal motor function was reported in previously nondystonic extremities in 10 of 11 patients. Symptoms were common in both upper and lower extremities and included new difficulties with handwriting (82%), getting up from a chair or in/out of a car (73%), and walking (45%), and were not associated with aberrant lead placement near the internal capsule. Conclusion: Although GPi DBS was shown to be effective in these patients, the influence of GPi DBS on nondystonic body regions deserves further investigation.