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.

Herpes simplex encephalitis with two false-negative cerebrospinal fluid PCR tests and review of negative PCR results in the clinical setting.

INTRODUCTION: Herpes simplex virus encephalitis (HSE) is an acute infection accompanied by significant morbidity and mortality with the diagnosis often made by cerebrospinal fluid (CSF) polymerase chain reaction (PCR) testing. CASE PRESENTATION: We report a case of a healthy 35-year-old woman presenting with altered mental status. Due to suspicion of herpes encephalitis, a CSF PCR for herpes virus was sent for examination and acyclovir was started. The patient had an immediate response to acyclovir; however, when the PCR returned negative she was discharged without therapy. The altered mental status returned and she was started on acyclovir therapy and a second CSF PCR sample was sent and was again negative. MRI performed at initial hospitalization was negative, but a repeat MRI demonstrated bilateral temporal lobe involvement suggestive of herpes encephalitis. The patient was successfully treated for 21 days with acyclovir. CONCLUSION: CSF PCR for herpes virus is highly sensitive and specific and remains the standard for diagnosing herpes encephalitis. Clinicians should be aware of the pitfalls of CSF PCR testing, specifically false-negative results. Although rare, these false negatives can result in premature termination of treatment.

Transpharyngeal Echocardiographic Diagnosis of Carotid Bulb and Left Internal Carotid Artery Stenosis.

We report a patient in whom we were able to make an accurate diagnosis of left carotid bulb and left internal carotid artery stenosis by carefully and slowly withdrawing the probe from the esophagus into the pharynx.