Oral ENT-01 Targets Enteric Neurons to Treat Constipation in Parkinson Disease : A Randomized Controlled Trial.

BACKGROUND: Parkinson disease (PD) is associated with α-synuclein (αS) aggregation within enteric neurons. ENT-01 inhibits the formation of αS aggregates and improved constipation in an open-label study in patients with PD. OBJECTIVE: To evaluate the safety and efficacy of oral ENT-01 for constipation and neurologic symptoms in patients with PD and constipation. DESIGN: Randomized, placebo-controlled phase 2b study. (ClinicalTrials.gov: NCT03781791). SETTING: Outpatient. PATIENTS: 150 patients with PD and constipation. INTERVENTION: ENT-01 or placebo daily for up to 25 days. After baseline assessment of constipation severity, daily dosing was escalated to the prokinetic dose, the maximum dose (250 mg), or the tolerability limit, followed by a washout period. MEASUREMENTS: The primary efficacy end point was the number of complete spontaneous bowel movements (CSBMs) per week. Neurologic end points included dementia (assessed using the Mini-Mental State Examination [MMSE]) and psychosis (assessed using the Scale for the Assessment of Positive Symptoms adapted for PD [SAPS-PD]). RESULTS: The weekly CSBM rate increased from 0.7 to 3.2 in the ENT-01 group versus 0.7 to 1.2 in the placebo group (P < 0.001). Improvement in secondary end points included SBMs (P = 0.002), stool consistency (P < 0.001), ease of passage (P = 0.006), and laxative use (P = 0.041). In patients with dementia, MMSE scores improved by 3.4 points 6 weeks after treatment in the ENT-01 group (n = 14) versus 2.0 points in the placebo group (n = 14). Among patients with psychosis, SAPS-PD scores improved from 6.5 to 1.7 six weeks after treatment in the ENT-01 group (n = 5) and from 6.3 to 4.4 in the placebo group (n = 6). ENT-01 was well tolerated, with no deaths or drug-related serious adverse events. Adverse events were predominantly gastrointestinal, including nausea (34.4% [ENT-01] vs. 5.3% [placebo]; P < 0.001) and diarrhea (19.4% [ENT-01] vs. 5.3% [placebo]; P = 0.016). LIMITATION: Longer treatment periods need to be investigated in future studies. CONCLUSION: ENT-01 was safe and significantly improved constipation. PRIMARY FUNDING SOURCE: Enterin, Inc.

Drug-induced movement disorders: emergencies and management.

Movement disorders uncommonly require emergent intervention; however, there are acute/subacute clinical settings in which the neurologist is consulted for recommendations about the diagnosis and management of a movement disorder. In these circumstances the neurologist must be comfortable with the diagnostic evaluation and be prepared to properly manage the patient. This article focuses on diagnosis and management of acute-onset movement disorders occurring secondary to prescription drug use, illicit drug abuse, and drug withdrawal syndromes. In addition, drug-induced emergencies occurring in patients with movement disorders are reviewed.

Exposure to high dosage trihexyphenidyl during pregnancy for treatment of generalized dystonia: case report and literature review.

INTRODUCTION: Trihexyphenidyl is 1 of the most effective agents for treatment of young-onset dystonia. As such, women of childbearing potential use trihexyphenidyl despite inadequate information about potential effects on pregnancy, labor, and fetal development. CASE REPORT: We report 2 uncomplicated pregnancies in 1 woman with early-onset, sporadic, primary generalized dystonia (DYT1 negative) treated with high dosage trihexyphenidyl and review the literature on antidystonic agents and pregnancy. CONCLUSION: Although there is limited data, our case demonstrates that high-dosage trihexyphenidyl treatment is not necessarily a contraindication to pregnancy.

Movement disorders emergencies Part 2: hyperkinetic disorders.

Although movement disorders do not usually present as neurologic emergencies, there are times when the abrupt onset of an unusual movement abnormality results in emergency department or intensive care unit consultations. Part 1 of this review discussed hypokinetic movement disorders emergencies. Part 2 provides a diagnostic approach to the recognition and treatment of hyperkinetic movement disorders emergencies by identifying phenomenology and reviewing common etiologies.

Movement disorders emergencies. Part 1: Hypokinetic disorders.

Movement disorders usually do not require emergent intervention; nevertheless, there are acute/subacute clinical settings in which the neurologist is consulted. It is in these circumstances that the neurologist must be prepared to accurately diagnose and properly treat the patient. We have reviewed the literature regarding movement disorder emergencies and divided them into hypokinetic (part 1) and hyperkinetic (part 2) presentations. In part 1, drug-induced syndromes including neuroleptic malignant syndrome, parkinsonism hyperpyrexia syndrome, and serotonin syndrome will be discussed. Emergency complications related to the management of Parkinson disease, including falling, motor fluctuations, and psychiatric issues, will also be reviewed.

Early-onset primary dystonia.

"Dystonia" is the term used to describe abnormal movements consisting of sustained muscle contractions frequently causing twisting and repetitive movements or abnormal postures. Dystonia is classified partly by age at onset because this helps guide the diagnostic work-up and treatment decisions. This chapter focuses on early-onset (<26 years old) primary dystonia. The history, clinical features, genetics, pathophysiology, diagnosis, and treatment of early-onset primary dystonia are discussed. Special emphasis is placed on DYT1 dystonia, the most common, autosomal-dominant, early-onset, primary dystonia. A diagnostic algorithm is proposed for gene-negative early-onset dystonia, and treatment recommendations for generalized, early-onset dystonia are made.

Efficacy, safety, and patient preference of monoamine oxidase B inhibitors in the treatment of Parkinson's disease.

Parkinson's disease (PD) is the second most common neurodegenerative disease and the most treatable. Treatment of PD is symptomatic and generally focuses on the replacement or augmentation of levodopa. A number of options are available for treatment, both in monotherapy of early PD and to treat complications of advanced PD. This review focuses on rasagiline and selegiline, two medications that belong to a class of antiparkinsonian drugs called monoamine oxidase B (MAO-B) inhibitors. Topics covered in the review include mechanism of action, efficacy in early and advanced PD, effects on disability, the controversy regarding disease modification, safety, and patient preference for MAO-B inhibitors.

Multiple system atrophy.

Multiple system atrophy (MSA) is an adult-onset, progressive, neurodegenerative condition that has several different initial presentations. Ultimately affected patients develop parkinsonian features, autonomic dysfunction, cerebellar ataxia, and corticospinal deficits. Patients with MSA are often misdiagnosed as having Parkinson disease. This article discusses the epidemiology and pathophysiology of MSA, in addition to addressing clinical and diagnostic signs and symptoms, and the limited treatment options available to physicians.

Essential tremor.

Essential tremor (ET) is one of the most common movement disorders. Although often considered a monosymptomatic disorder (postural and kinetic tremor), ET has more recently been considered a more heterogeneous syndrome, with motor and nonmotor features. The diagnosis is clinical and pharmacologic and surgical therapies exist. ET is frequently misdiagnosed as Parkinson disease or dystonia. The traditional notion of ET as a benign disorder has been challenged by those who view ET as a slowly progressive neurodegenerative disorder.

Metoclopramide-induced encephalopathy in Parkinson disease.

A case of prolonged encephalopathy and worsened parkinsonism in a Parkinson disease patient exposed to a short course of metoclopramide is described. Parkinson disease (PD) is the second most common neurodegenerative disease in the United States. Because of the increased susceptibility to adverse drug effects, PD presents a special challenge to physicians. Anti-emetic drugs such as metoclopramide are widely used and may be particularly deleterious to PD patients due to blockade of dopamine receptors.

Dementia in Parkinson's disease.

Parkinson's disease is the second most common neurodegenerative illness diagnosed in the United States. Dementia is recognized as a common component of advanced Parkinson's disease (PD). In patients with early PD, cognitive changes occur and primarily reflect impairment in executive function. It is unknown if the early cognitive changes detected on neuropsychological testing in Parkinson's disease are predictive of the subsequent development of Parkinson's disease with dementia (PDD). Many patients with PD develop dementia characterized by a wide range of cognitive deficits distinct from those seen in Alzheimer's disease (AD). Neuropsychiatric problems frequently accompany PDD. This chapter reviews the epidemiology, clinical characteristics of early and late cognitive changes, pathology, neuroimaging, diagnosis, and treatment of PDD.

Pregnancy in Parkinson's disease: case report and discussion.

Pregnancy in Parkinson's disease (PD) is an uncommon occurrence. Available reports suggest that there may be a worsening of PD symptom severity related to pregnancy. In this special report, medical literature on pregnancy in PD will be reviewed with regard to disease progression and the safety of antiparkinsonian medications. A case report of pregnancy in a woman with PD will be described. It is speculated that the symptoms of PD may be affected by changing hormone levels.