The photopic negative response of the Light-adapted 3.0 ERG in clinical settings.

PURPOSE: To analyze the effects of different methods of measurement on the photopic negative response (PhNR), recorded as part of a standard ISCEV Photopic 3.0 ERG responses from patients with a variety of clinical diagnoses. METHODS: ERGs were recorded from both eyes of 97 patients (187 eyes) as part of a standard clinical assessment. The average age was 56.4 ± 15.7 years, the gender balance was 35 M, 62F, and only recordable responses of acceptable quality were included. PhNR was measured at an identifiable trough before (PhNR1) and after the i-wave (PhNR2), and the amplitudes and peak times were compared with a-, b- and i-wave corresponding parameters. PhNR components were measured: from baseline and from b-wave peak. Correlation between PhNR troughs and with ERG parameters were tested for right eyes. The possibility to predict and substitute PhNR2 amplitude from PhNR1 amplitude was also tested. RESULTS: PhNR1 was recordable in 97.3% of eyes and PhNR2 in 85.6%. An identifiable PhNR2 peak was found to occur before 65 ms at ~ 50% of the records, while in ~ 38% of the cases was within 65-75 ms in ~ 12%-after 75 ms. The correlation between the PhNR1 and PhNR2 peaks was quite strong (with coefficients 0.81-0.98, depending on method of measurement, and slopes close to 1). The average difference between predicted and measured PhNR2 was reasonably small in absolute (< 2 µV) and relative (< 2%) terms. The correlations between PhNR amplitudes and other ERG component amplitudes showed different ranges of correlation coefficients depending on the method of measurement: for the a-wave amplitudes the range of coefficients was 0.48-0.73, while for the b-wave amplitudes it was 0.30-0.95 and 0.39-0.65 for i-wave. CONCLUSION: The strong correlation between the two PhNR troughs could allow using PhNR1 when PhNR2 is poorly defined due to artifacts. Different methods of PhNR measurement lead to different correlations with other ERG parameters, and this needs to be considered when analyzing and comparing PhNR data between studies.

Russell Body Esophagitis: A Possible Indication to Screen for Hematologic Malignancy.

This is a case of an elderly man with lymphoplasmacytic lymphoma on a direct oral anticoagulant for atrial fibrillation who presented with weakness. Esophagogastroduodenoscopy found herpes esophagitis and islands of salmon-colored mucosa suspicious for Barrett's esophagus. Biopsies showed no signs of Barrett's Esophagus but returned positive for Russell bodies. This is the only reported case of Russell body esophagitis in the absence of Barrett's esophagus. This case adds to the mounting evidence that Russell body esophagitis and potentially all gastrointestinal Russell bodies should prompt further work-up for hematologic malignancy.

Campylobacter jejuni: A Previously Unreported Cause of Toxic Shock Syndrome.

This is a case of a previously healthy middle-aged woman who presented with dyspnea after several days of an acute diarrheal illness. She developed acute respiratory distress syndrome (ARDS) requiring mechanical ventilation and met clinical and laboratory criteria for toxic shock syndrome (TSS). Stool studies were positive for Campylobacter jejuni. After a literature review, this was found to be the only reported case of C. jejuni gastroenteritis leading to TSS. This is the first documentation of TSS as a rare, life-threatening, complication of Campylobacter infection.

Therapies, Research Funding, and Racial Diversity in Essential Tremor: A Systematic Review of the Literature.

Background: Essential tremor (ET) is one of the most common tremor disorders in the world. Despite this, only one medication, propranolol, is approved by the Food and Drug Administration to treat it. Objectives: We analyzed controlled clinical trials in ET, spanning the last 50 years, to identify potential shortcomings in the therapeutic clinical pipeline. Methods: Outcomes reviewed included demographics (specifically gender and race), therapeutic modalities, funding information, location of research, and trends over time. Clinical trials published in English were identified in scientific databases (Pubmed, SCOPUS, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform from 1970 through December 2021. Included trials were prospective, either single- or double-blinded (including blinded video assessments for surgical trials), with change in limb, head, or voice tremor as the primary outcome measure. Results: One hundred and eighty-six controlled clinical trials were accepted for extraction, including 4207 patients. Of the 145 trials that included gender, males comprised 59% of the patient population. Only 6.4% of studies provided racial demographics; in these studies, 70.5% of patients were Caucasian. The most common therapeutic modality over the past 50 years was "pharmaceutical" (56%), and the most common pharmaceutical studied was propranolol (32%). 41% of clinical trials reported no specific funding. Conclusions: Future efforts should focus on increasing funding for clinical trial research in ET worldwide, and trials should be designed to be more inclusive of disadvantaged minorities.

Current and emerging treatment modalities for spinocerebellar ataxias.

INTRODUCTION: Spinocerebellar ataxias (SCA) are a group of rare neurodegenerative diseases that dramatically affect the lives of affected individuals and their families. Despite having a clear understanding of SCA's etiology, there are no current symptomatic or neuroprotective treatments approved by the FDA. AREAS COVERED: Research efforts have greatly expanded the possibilities for potential treatments, including both pharmacological and non-pharmacological interventions. Great attention is also being given to novel therapeutics based in gene therapy, neurostimulation, and molecular targeting. This review article will address the current advances in the treatment of SCA and what potential interventions are on the horizon. EXPERT OPINION: SCA is a highly complex and multifaceted disease family with the majority of research emphasizing symptomatic pharmacologic therapies. As pre-clinical trials for SCA and clinical trials for other neurodegenerative conditions illuminate the efficacy of disease modifying therapies such as AAV-mediated gene therapy and ASOs, the potential for addressing SCA at the pre-symptomatic stage is increasingly promising.

Esophageal Cancer Complicated by a Distal Acquired Esophagopulmonary Fistula.

Description Esophageal respiratory fistulas, commonly found as a tracheoesophageal fistula (TEF), are abnormal connections between the esophagus and trachea. These can be congenital (infants) or acquired (malignancy). A more rare form of an esophageal respiratory fistula is an abnormal connection between the esophagus and the lung parenchyma-also known as an esophagopulmonary fistula. In our case, we present a middle-aged male with a history of esophageal cancer undergoing chemotherapy and radiation presenting into the intensive care unit for increasing shortness of breath and vomiting after eating found to have a rare form of a TEF causing his symptoms.

Case of Enterococcus cecorum Human Bacteremia, United States.

Description Enterococcus cecorum rarely serves as a human pathogen, and only 6 cases of this microbe inoculating humans have been documented. We present an elderly female with a marked vascular history presenting with epigastric pain and diarrhea, followed by shaking chills. Laboratory findings revealed leukocytosis, with imaging showing diffuse colonic thickening. She had a bout of bloody diarrhea, raising the likelihood of ischemic colitis with her vascular history. To our surprise, both sets of blood cultures drawn on admission grew Enterococcus cecorum. This case is unique as it is the first documented case of E. cecorum human infection in the United States.

Gastric Ischemia and Cecal Necrosis: A Simultaneous Presentation of Two Rare Entities.

A 65-year-old woman presented with right lower quadrant (RLQ) abdominal pain of three days duration. During her hospitalization, she underwent computed tomography (CT) of the abdomen, duplex ultrasound of the abdomen, esophagogastroduodenoscopy (EGD), and colonoscopy as part of a diagnostic workup. The workup identified high-grade obstructions of the celiac artery (CA), superior mesenteric artery (SMA), atypical appearing gastric ulcers, and a diffusely ulcerated cecum, which created a mass-like appearance. The patient developed cecal perforation despite mesenteric vessel stenting and ultimately required right hemicolectomy for definitive management. This case report represents a rare presentation of simultaneous gastric ischemia and cecal ischemia with necrosis in a patient with underlying peripheral vascular disease.

Endothelial and Astrocytic Support by Human Bone Marrow Stem Cell Grafts into Symptomatic ALS Mice towards Blood-Spinal Cord Barrier Repair.

Vascular pathology, including blood-CNS barrier (B-CNS-B) damage via endothelial cell (EC) degeneration, is a recently recognized hallmark of Amyotrophic Lateral Sclerosis (ALS) pathogenesis. B-CNS-B repair may be a new therapeutic approach for ALS. This study aimed to determine effects of transplanted unmodified human bone marrow CD34+ (hBM34+) cells into symptomatic G93A mice towards blood-spinal cord barrier (BSCB) repair. Thirteen weeks old G93A mice intravenously received one of three different doses of hBM34+ cells. Cell-treated, media-treated, and control mice were euthanized at 17 weeks of age. Immunohistochemical (anti-human vWF, CD45, GFAP, and Iba-1) and motor neuron histological analyses were performed in cervical and lumbar spinal cords. EB levels in spinal cord parenchyma determined capillary permeability. Transplanted hBM34+ cells improved behavioral disease outcomes and enhanced motor neuron survival, mainly in high-cell-dose mice. Transplanted cells differentiated into ECs and engrafted within numerous capillaries. Reduced astrogliosis, microgliosis, and enhanced perivascular end-feet astrocytes were also determined in spinal cords, mostly in high-cell-dose mice. These mice also showed significantly decreased parenchymal EB levels. EC differentiation, capillary engraftment, reduced capillary permeability, and re-established perivascular end-feet astrocytes in symptomatic ALS mice may represent BSCB repair processes, supporting hBM34+ cell transplantation as a future therapeutic strategy for ALS patients.

Emerging therapies in Friedreich's ataxia.

Friedreich's ataxia (FRDA) is an inherited, progressive neurodegenerative disease that typically affects teenagers and young adults. Therapeutic strategies and disease insight have expanded rapidly over recent years, leading to hope for the FRDA population. There is currently no US FDA-approved treatment for FRDA, but advances in research of its pathogenesis have led to clinical trials of potential treatments. This article reviews emerging therapies and discusses future perspectives, including the need for more precise measures for detecting changes in neurologic symptoms as well as a disease-modifying agent.

Critical appraisal of rotigotine transdermal system in management of Parkinson's disease and restless legs syndrome - patient considerations.

Rotigotine (RTG) is a dopamine agonist that is used as mono and adjunct therapy to treat Parkinson's disease, and as therapy for moderate-to-severe restless legs syndrome. RTG is the only dopamine agonist currently available as a 24-hour/day transdermal system, providing once-a-day dosing. As a transdermal patch, RTG bypasses the gastrointestinal tract, making it a treatment option for patients with dysphagia. The use of RTG also avoids the need to schedule administration of medication around meals. This review provides a critical appraisal of RTG as treatment of Parkinson's disease and RLS.

Unusual wrist tremor: unilateral isometric tremor?

BACKGROUND: Tremors may be difficult to classify. CASE REPORT: An 83-year-old male presented with an unusual left wrist tremor. The tremor could be reproducibly elicited by making a fist or carrying a weighted object (e.g., a shopping bag, bottle of water) of approximately 1 lb or more, and it intensified with heavier weights. The tremor was difficult to classify, although it shared features with isometric tremor. DISCUSSION: This specific presentation of tremor has not been reported previously. We hope that the detailed description we provide will aid other neurologists who encounter this or similar tremors in their clinics.

Update on treatment of essential tremor.

OPINION STATEMENT: Essential tremor is one of the most common movement disorders in the world. Although millions of people worldwide are affected by ET, only one medication, propranolol, is approved by the United States Food and Drug Administration to treat it. None of the medications currently used as ET therapy were developed specifically for this purpose, and select antihypertensive and antiepileptic medications remain at the forefront of ET therapy. Propranolol and primidone are considered "effective" agents that treat ET; topiramate, atenolol, and alprazolam are "probably effective", and nimodipine, nadolol, and clonazepam are "possibly effective". Medications that probably do not adequately treat ET include levetiracetam and pregabalin. Gabapentin appears to improve ET when used as monotherapy, but not when used as adjunct therapy. Sotalol has been found to be "probably effective" in treating ET in previous reviews, but it may be associated with arrhythmias and should not be routinely recommended. Botulinum toxin A may reduce limb tremor, but may cause dose dependent weakness. Deep brain stimulation (DBS) of the VIM is used as an alternative to pharmacological therapy of ET in patients who fail to adequately respond to medical therapy. The magnitude of effect from DBS is greater than from medical management, but more severe side effects are possible with surgery. Future treatment options for ET will depend on valid animal models, and a better understanding of its pathophysiology.

A double-blind placebo-controlled trial of zonisamide (zonegran) in the treatment of essential tremor.

Medical therapy for essential tremor (ET), a common movement disorder, is often inadequate. We performed a double-blind placebo-controlled randomized trial to evaluate the efficacy and tolerability of zonisamide (ZNS), an antiepileptic agent, in treating ET. Twenty patients (mean age, 60 +/- 15 years) with ET were randomized to receive ZNS or placebo. ZNS was initiated at a dosage of 100 mg/day and escalated to 200 mg/day at day 14. Patients were evaluated by accelerometry and the Fahn-Tolosa-Marin (FTM) rating scale at baseline and days 14 and 28, as well as the Clinical Global Impression (CGI-C) scale at day 28. At endpoint, subjects assigned to ZNS were taking a mean dosage of 160 +/- 50 mg/day. There were no significant improvements in the FTM total score or its subsections. Tremor amplitude as assessed by accelerometry significantly improved in the ZNS group compared to the placebo group at endpoint relative to baseline (-0.50 +/- 0.72 vs. 0.30 +/- 0.79 m/s(2); P = 0.03). On the CGI-C, 60% (n = 6) of patients in the ZNS group felt that their tremor was unchanged, while the remaining patients felt that their tremor was "minimally improved." Thirty percent (n = 3) of patients taking ZNS discontinued the study due to side effects (fatigue, headache, paresthesias) while taking 100 mg per day. ZNS did not provide significant improvements in clinical rating scales at study endpoint compared to placebo and was only modestly well tolerated. ZNS was effective in reducing tremor amplitude as measured by accelerometry.

Tegaserod (Zelnorm) for the treatment of constipation in Parkinson's disease.

We performed a double-blind randomized placebo-controlled pilot study to determine the efficacy of tegaserod (Zelnorm) in treating constipation in 15 patients with Parkinson's disease (PD). There was a trend for improvement in the Subject's Global Assessment (SGA) of satisfaction with bowel habits (NS) and the total SGA (including abdominal discomfort, bothersome constipation, and satisfaction; NS).