Sodium phenylbutyrate-taurursodiol access, adherence and adverse event in patients with amyotrophic lateral sclerosis: Experience at one center in the United States.

INTRODUCTION/AIMS: Sodium phenylbutyrate-taurursodiol (PB-TURSO) was recently approved for treating amyotrophic lateral sclerosis (ALS). Third-party payors' coverage policies are evolving, and adverse events are just being fully assessed. The goals of this study were to evaluate patients' experiences in obtaining and continuing PB-TURSO and assess adverse events and medication adherence. METHODS: Medical records of 109 ALS patients who were considered PB-TURSO candidates by the treating physician at a tertiary ALS clinic from October 2022 to May 2023 were reviewed. Data was recorded for demographics, clinical, and insurance information. A survey was e-mailed to patients asking about out-of-pocket expenses for PB-TURSO, financial assistance, medication start and (if applicable) stop dates, and reasons for discontinuation. RESULTS: Insurance information was available for 91 patients [57 males (62%); mean age 64.8 years (range 25.7-88)]. Of 79 who applied for insurance approval, 71 (90%) were approved; however, 19 required 1-3 appeals. Among 73 patients with available data about medication status, 54 started PB-TURSO and 19 did not, most commonly due to personal choice or out-of-pocket expenses. About 44% of patients (24/54) stopped taking PB-TURSO, primarily due to adverse events. Monthly out-of-pocket expenses varied from $0 to $3500 and 36 patients qualified for financial assistance. Administrative and nursing staff devoted 7.2 hours/week to the insurance authorization process. DISCUSSION: Most patients received insurance approval for PB-TURSO, but one-fourth required appeals. Some out-of-pocket costs were very high. Investment of staff time was substantial. These findings have implications for insurance coverage of, and adherence to, future ALS treatments.

Enhancing diagnostic accuracy using a side-to-side cross-sectional area ratio for the diagnosis of unilateral ulnar mononeuropathy at the elbow.

INTRODUCTION: Neuromuscular ultrasonography (NMUS) is a valuable adjunct to electrodiagnostic testing for the diagnosis of entrapment neuropathy. The aim of this study was to determine whether diagnostic accuracy of NMUS could be enhanced in patients with unilateral ulnar mononeuropathy at the elbow (UNE) by utilizing side-to-side ulnar nerve cross-sectional area (CSA) ratios. METHODS: Retrospective case-control analysis of unilateral UNE cases identified cutoff values for elbow segment ulnar nerve maximum CSA (MCSA) of the symptomatic/asymptomatic limb (M ratio), as well as side-to-side ratios comparing MCSA with ipsilateral CSA at the Guyon canal (E/G), middle forearm (E/F), and middle humerus (E/H). Diagnostic accuracy values were calculated. RESULTS: The optimal M-ratio cut-off was 1.22 (sensitivity, 92.9%; specificity, 97.8%; accuracy, 95.4%). Optimal cutoffs for inter-E/G, -E/F, and -E/H ratios were 1.07 (sensitivity, 98%; specificity, 78%; accuracy, 87.7%), 1.11 (sensitivity, 95%; specificity, 80%; accuracy, 87.2%), and 1.18 (sensitivity, 95%; specificity, 93%; accuracy, 94%), respectively. DISCUSSION: The M ratio and inter-E/H ratio exhibited high diagnostic accuracy for unilateral UNE. Prospective studies are needed to compare the accuracy of the new measures with a single MCSA measurement.

Ocular Syphilis and Syphilitic Meningitis as the Initial Symptoms of Neurosyphilis in an HIV-Negative Patient: A Case Report.

Syphilis is an infectious disease caused by the spirochete bacteria Treponema pallidum and is most commonly transmitted via contact of mucous membranes with infectious lesions during sexual intercourse. It is called the "great mimicker" due to its ability to infect a wide variety of organs and, as a result, produce a multitude of symptoms. Neurosyphilis, an infection of the central nervous system, can occur at any stage of infection. Cases of early neurosyphilis may not present with any prior history of syphilis infection or classical symptoms of primary or secondary infection. Homosexual men are disproportionately affected by the increasing rate of transmission.In this case, a 43-year-old man was diagnosed with neurosyphilis, initially presenting with bilateral papilledema concerning for idiopathic intracranial hypertension. A detailed social history revealed that the individual was sexually active with a male partner. Despite nonreactive results from the rapid plasma reagin and CSF Venereal Disease Research Laboratory tests, further serum workup yielded positive results for treponemal antibodies. Evidence of facial nerve involvement was also found on MRI. These findings were consistent with a diagnosis of ocular syphilis with syphilitic meningitis involving cranial nerve VII. This case demonstrates the importance of clinical suspicion for syphilis when indicated by social history, even when screening tests are negative, due to the potential for false negatives and highly variable clinical presentation.

Rapid Conversion to a Completely Virtual Multidisciplinary ALS Clinic in Response to the COVID-19 Pandemic: Implications for Future Care Delivery.

OBJECTIVES: The goals of this study were to assess the feasibility of maintaining multidisciplinary remote care, patient preferences, and outcomes of this transition because of COVID-19. METHODS: From March 18, 2020 to June 3, 2020, 127 patients with amyotrophic lateral sclerosis (ALS) who were scheduled to be seen in our ALS clinic were contacted and scheduled according their preference for a telemedicine visit, telephone visit, or postponement until the next available in-person visit. Age, time from disease onset, ALS Functional Rating Scale-Revised, patient choices, and outcomes were recorded. RESULTS: Patient visit preferences were 69% telemedicine, 21% telephone, and 10% postpone for a later in-clinic visit. Patients with higher ALS Functional Rating Scale-Revised were more likely to choose the next in-person opening (P = 0.04). Age and time from disease onset were not related to visit type preference. There were 118 virtual encounters, of which 91 (77%) began as telemedicine and 27 (23%) as telephone visits. Most telemedicine visits were conducted successfully, but 10 were converted to a telephone visit. The clinic maintained 88.6% of patient volume compared with the prior year, during which most visits were in-person. CONCLUSIONS: Telemedicine care using synchronous videoconferencing is preferable and feasible for most patients on short notice, with telephone as back-up. Clinic volumes can be maintained. These findings support the conversion of a multidisciplinary ALS clinic to 1 with exclusively virtual visits when future events again disrupt in-person care.

Assessment of outcome predictors after first attack of optic neuritis.

BACKGROUND: Optic Neuritis (ON) is one of the most common clinically isolated syndromes which develops into clinically diagnosed Multiple Sclerosis (CDMS) over time. OBJECTIVE: To assess the conversion rate of Iranian patients presenting with idiopathic ON to CDMS as well as monitoring potential demographic and clinical risk factors. METHODS: Atotal of 219 patients' medical records of idiopathic ON from March 2001 to May 2009 were reviewed. Demographic findings, ophthalmologic characteristics on admission and discharge, diagnostic approaches, type and dosage of therapy were retrospectively reviewed. A structured telephone interview was then conducted to identify patients who had subsequently been diagnosed with MS. Survival analysis was used to evaluate the cumulative probability of MS conversion and contributory risk factors. RESULTS: From the 219 ON patients, 109 [age 11-51, female: 81%] were followed up. Among the male gender the mean age of patients developing MS was significantly lower (P=0.01). In cox regression model, female sex (p=0.07), bilateral ON (p=0.003), MRI abnormalities (p <0.001) and high dose (5g) corticosteroid therapy (p<0.001) were identified as risk factors for the development of MS. The two and five year cumulative probability of developing MS were 27% and 45%, respectively. CONCLUSIONS: Idiopathic ON in Iranian patients carries higher risk of progression to MS compared to other Asian countries. MRI lesions are the strongest independent risk factor of developing CDMS. Bilateral ON, female gender and high dose corticosteroid therapy are also important factors in predicting CDMS development.

Is the Latency from Progressive Supranuclear Palsy Onset to Diagnosis Improving?

BACKGROUND: Progressive supranuclear palsy (PSP) is a neuropathologically defined disease with a broad clinical spectrum. It can initially be mistaken for other neurodegenerative diseases. Diagnosis of PSP earlier in the course may reduce its psychological and financial burden, permit earlier access to neuroprotective interventions, and avoid unnecessary diagnostic and therapeutic measures. Our impression is that physicians are more aware of PSP in the 2010s than in the 1990s. This study tests that hypothesis using the latency from symptom onset to PSP diagnosis as a surrogate outcome. METHODS: We reviewed records of 385 patients with "possible" or "probable" PSP from 1990 to 2016 at the Movement Disorders Center, Rutgers Robert Wood Johnson Medical School. The time from symptom onset to diagnosis was calculated for each patient and labeled as latency. We used the Pearson correlation coefficient, Student's t-test, and ANOVA as appropriate. RESULTS: Our data show that the mean latency (SD) from symptom onset to diagnosis PSP, in months, was 43.76 (25.60) in the 1990s, 40.76 (28.73) in the 2000s, and 29.15 (16.80) in the 2010s (P < .001). There was also an inverse relationship between age at onset and latency (Pearson's r = -0.23, P < .001). This relationship did not affect the statistical significance of our main observation. CONCLUSION: Our finding suggests that there is a progressive reduction in the latency over the past three decades. It may reflect increased awareness of PSP by physicians in our referral area.

Case of Anti-Single Recognition Particle-Mediated Necrotizing Myopathy After Influenza Vaccination.

Immune-mediated necrotizing myopathy is a very rare inflammatory disease affecting skeletal muscles. Immune-mediated necrotizing myopathy may be associated with myositis-specific autoantibodies including anti-single recognition particle and anti-3-hydroxy-3- methylglutaryl-coenzyme A reductase, infectious agents (HIV or hepatitis C), other connective tissue disorders (such as scleroderma), and malignancy. We reported a 28-year-old healthy woman presented with subacute onset ascending muscle weakness 2 weeks after an annual influenza vaccination. Cerebral Spinal Fluid study showed normal cell counts with elevated protein and nerve conduction study showed reduced diffuse compound muscle action potential amplitudes suggesting a diagnosis of Guillain-Barré syndrome. Despite treatment using intravenous immunoglobulin, her condition continued to get worse with new bulbar and respiratory muscle weakness. Eventually, the diagnosis of anti-single recognition particle-mediated necrotizing myopathy was made based on elevated creatine kinase, thigh magnetic resonance imaging, muscle biopsy, and positive antibody testing. Our patient responded to the combination of intravenous immunoglobulin, prednisone, and anti-CD20 monoclonal antibody, rituximab.

Prospective Acid Reflux Study of Iran (PARSI): methodology and study design.

BACKGROUND: Gastroesophageal reflux disease is a common and chronic disorder but long term, prospective studies of the fate of patients seeking medical advice are scarce. This is especially prominent when looking at non-erosive reflux disease (NERD) patients. METHODS: We designed a prospective cohort to assess the long term outcome of GERD patients referring to gastroenterologists. Consecutive consenting patients, 15 years of age and older, presenting with symptoms suggestive of GERD referring to our outpatient clinics undergo a 30 minute interview. Upper gastrointestinal endoscopy is performed for them with protocol biopsies and blood samples are drawn. Patients are then treated according to a set protocol and followed regularly either in person or by telephone for at least 10 years. DISCUSSION: Our data show that such a study is feasible and follow-ups, which are the main concern, can be done in a fairly reliable way to collect data. The results of this study will help to clarify the course of various subgroups of GERD patients after coming to medical attention and their response to treatment considering different variables. In addition, the basic symptoms and biological database will fuel further molecular epidemiologic studies.

Inter- and intra-observer variability of the Los Angeles classification: a reassessment.

BACKGROUND: Los Angeles classification is widely adopted for reporting endoscopic gastroesophageal reflux disease. We assessed the inter- and intra-observer variability of the Los Angeles classification. METHODS: Still images (n = 254) of the lower esophagus were presented to 9 gastroenterologists (6 experts and 3 trainees) and they were asked to report the images according to the Los Angeles classification. After 2 weeks the images were reordered and they were asked to report them again. Kappa statistic was calculated for intra- and inter-observer variability. RESULTS: The kappa for intra-observer agreement was 0.54 (attendings: 0.54; trainees; 0.55; P = not significant) and the inter-observer agreement was 0.22 (attendings: 0.20; trainees: 0.31; P = 0.027). The inter- and intra-observer kappa values in differentiating nonerosive from erosive cases were 0.22 (attendings: 0.21; trainees: 0.31, P = not significant) and 0.57 (attendings: 0.58; trainees: 0.55, P = not significant), respectively. CONCLUSION: According to our data, the Los Angeles classification has acceptable intra-observer variability, both for detecting presence or absence of erosions and for differentiating between different degrees of esophagitis, while its inter-observer performance seems to be less acceptable. It may be reasonable and timely to have another look at the Los Angeles classification to see whether its performance can be improved even further.

Perianal pain as a presentation of lumbosacral neurofibroma: a case report.

Rectal and perianal pain is a common problem. Most people have experienced it at least once in their lifetime. It usually manifests as mild discomfort, but sometimes the pain can be so severe that it is incapacitating. A 59-year-old woman admitted with a 2-year history of paroxysmal perianal pain underwent a full work-up including proctoscopy, sigmoidoscopy, full colonoscopy, and barium enema that were unremarkable. Lumbosacral magnetic resonance imaging with and without gadolinium showed an intradural-extramedullary lesion at the level of L5. The pathologic diagnosis was a neurofibroma. She underwent surgery, and after a few weeks she felt well and medication was no longer needed for her paroxysmal pain. Although one should consider the usual causes of colorectal pain such as hemorrhoids, anal fissure, proctalgia fugax, and chronic perianal pain syndrome, we should keep in mind that some referral pain may mimic local pathologies and should be evaluated properly.

Relation of helicobacter pylori infection and multiple sclerosis in Iranian patients.

Multiple sclerosis (MS) is the most prevalent central nervous system demyelinating disease. There are known risk factors for MS. However, there is uncertainty in its protective factors. Few studies have demonstrated that some chronic infections may have protective effects on this disease. We carried this study to investigate the relation between Helicobacter pylori (HP) infection and the prevalence and severity of MS. In this case-control study, 163 MS patients and 150 sex- and age- matched controls were included. Blood samples for IgG and IgM anti HP antibodies were collected from all individuals. Also, the Expanded Disability Status Scale (EDSS) was used to evaluate the MS patients. Suitable statistical analysis was applied. A Significant difference was observed in seropositivity between these two groups (P<0.001) but no significant difference was seen in seropositivity between conventional and opticospinal MS (P=0.522). No significant difference was observed in seropositivity among ages (P=0.075) and between genders (P=0.204). A significant difference was seen in EDSS value between seropositive and seronegative patients (P=0.017). We concluded that patients with HP infection had lower incidence of multiple sclerosis and MS patients with HP infection showed lower neurologic complications, which can demonstrate that HP infection may have a protective influence on MS pathogenesis.

Serum 25-hydroxyvitamin D3 concentration in Iranian patients with Parkinson's disease.

BACKGROUND: Vitamin D is an important factor responsible for many physiologic functions. Vitamin D deficiency is associated with increased risk of neurodegenerative disease. The level of vitamin D in Iranian patients with Parkinson's disease and its relationship with severity of symptoms and signs were evaluated in this study. METHODS: Eighty-three patients with Parkinson's disease (PD) were recruited using simple non-random sampling. 25-hydroxyvitamin D [25(OH)D3] was measured by Electrochemiluminescence immunoassay (ECLIA). Serum level of calcium and phosphorus was measured to exclude other endocrine disorders. RESULTS: The mean 25(OH)D3 concentration was lower in the PD population than in the normal group. Lower levels of 25(OH)D3 were associated with more severe postural instability and abnormal posture. There was no significant association between levels of 25(OH)D3 and severity of other symptoms of parkinsonism. CONCLUSION: This analysis showed that serum 25(OH)D levels are lower in PD patients in comparison with normal range. In addition, there was a significant association between the presences of freezing, postural instability and abnormal postures with lower levels of 25(OH)D.

Homocysteine, vitamin B12 and folate levels in Iranian patients with Multiple Sclerosis: a case control study.

BACKGROUND: Recently, homocysteine (Hcy), folate, and vitamin B12 have been proposed to have several roles on MS pathogenesis. OBJECTIVE: We performed this study to determine the role of serum levels of Hcy, vitamin B12, and folate in patients with relapsing remitting MS (RRMS) and compared them with healthy controls. METHODS: We recruited 75 RRMS patients and 75 subjects as controls with the same age and sex. Homocysteine was measured using fluorimetric high-performance liquid chromatography. Plasma folate and vitamin B12 levels were measured through ion-capture method. RESULTS: Mean plasma levels of vitamin B12, folate, and Hcy in cases were 342.64 ± 210.66 pg/ml, 9.74 ± 4.77 ng/ml, and 22.73 ± 11.63 µM/L, respectively, which showed significant difference in comparison with the controls. In addition, there were significant correlations between mean serum Hcy levels and duration of disease (r=0.2, p=0.05) and treatment with interferon (r=0.21, p=0.01). In cases, Hcy level was higher among those on ß interferon (24.56 ± 11.87 vs. 19.71 ± 10.75, p=0.01). CONCLUSIONS: We concluded that serum levels of vitamin B12 and folate decreased in RRMS patients, but Hcy levels increased significantly. It seems necessary to conduct prospective trials to determine whether the treatment with supplements and correct biomarker levels in the early stage of the disease can change the course of the disease. We recommend regular checking of the serum level of Hcy in patients who use disease-modifying drugs.

Hypothyroidism, the main thyroid dysfunction in Iranian patients with myasthenia gravis: A case serie.

BACKGROUND: Several concomitant disorders especially thyroid abnormalities have been reported in patients with myasthenia gravis (MG). We aimed to estimate the frequency and pattern of thyroid disorders in Iranian patients with MG. METHODS: All consecutive patients with MG referred to neurology clinic of Rasool-e-Akram Hospital during 2006-2007 were enrolled. All patients underwent clinical assessment of thyroid gland as well as thyroid function test. AChR Ab titer was measured as well. Nerve conduction study (NCS), Electromyography (EMG), and Repetitive Nerve Stimulation (RNS) was done by a same neurologist. The diagnosis of MG was made on the basis of clinical examinations, an edrophonium chloride test and electrophysiological studies. The diagnosis of thyroid disorders were based on clinical presentation as well as thyroid function tests. RESULTS: FIFTY EIGHT PATIENTS (MEAN AGE [SD]: 37.1 [16.9], range: 10-80; female: 65.5%) were enrolled in this 12-month study. Four patients (6.9%) had abnormal thyroid function tests (Hypothyroidism: 3 [5.2%]; 4 females; 3 with hypothyroidism and 1 with hyperthyroidism). The mean age (SD) in men and women were 41.4 (21.3) and 34.9 (13.8) years (P: N.S.), respectively. In addition, once the MG patients are younger than 50, female gender is dominant while they are more than fifty, male is the dominant gender. CONCLUSION: Our results show that Iranian patients with MG tend to be female and young. Before sixth decade of life, women are the most presenting patients thereafter, men are the predominant gender. About 7 percent of them may suffer from concomitant thyroid problem especially hypothyroidism.

A comparison of cerebral vasomotor reactivity in diabetic and nondiabetic Iranian patients.

BACKGROUND: Cerebral microangiopathy is one of the most important complications in diabetes. It may interfere with cerebral vasomotor reactivity (VMR) which may lead to disability, stroke or even death. The aim of the present study was to determine and compare VMR changes in diabetic and non- diabetic patients. METHODS: Fifty three diabetic and 51 non- diabetic patients (with no other vascular abnormality) were recruited. Vasomotor reactivity was evaluated with Trans- Cranial Doppler (TCD) before and after CO2 inhalation. RESULTS: There were 69 (66.30%) males. The mean age was 41.53 ± 17.80 years. The general average of VMR was 5.79 ± 3.00%, the figures in diabetic and nondiabetic patients were 5.31 ± 2.60% and 6.62 ± 2.00%, respectively (p = 0.02). The average of flow velocity (FV) change was 42.47± 29.00 in diabetics and 53.34 ±16.70 in non- diabetic patients (p = 0.04). CONCLUSIONS: It is recommended that such non- invasive method is necessary for evaluation of cerebral vasculature in diabetic patients for better prevention.

Homocysteine, vitamin B12 and folate levels in Iranian patients with ischemic stroke.

OBJECTIVES: Homocysteine, folate, and some group B vitamins have been proposed as a cause of Cerebro-Vascular Accidents (CVA). We conducted a case-control study to compare the plasma levels of folate, vitamin B12 and homocysteine in Iranian subjects with and without cerebro-vascular accident. METHODS: We recruited 82 patients with ischemic stroke as cases and 60 subjects as controls (using simple nonrandom sampling). Homocysteine was measured by fluorimetric high-performance liquid chromatography. Plasma folate and vitamin B12 levels were measured by an ion-capture method. RESULTS: Mean plasma level of vitamin B12 in cases and controls were 358.4 ± 290.3 Pg/ml and 369.8 ± 110.4 Pg/ml, respectively which did not show any significant difference. Mean plasma level of folate in cases was significantly lower than the controls (6.8 ± 4.5 ng/ml vs. 12.2 ± 3.0 ng/ml, p = 0.001). It was also shown that mean plasma level of total homocysteine in cases was significantly higher than the controls (21.1 ± 9.8 µM/L vs. 13.5 ± 3.2 µM/L, P=0.001). Homocysteine and folate but not plasma B12 had linear relation with age. Male cases had significantly lower Folate and B12 in contrast to women. In addition, male cases had significantly higher Homocysteine level in contrast to women. CONCLUSIONS: Our data shows that the level of homocysteine was higher and the level of folate was significantly lower in patients with ischemic stroke in contrast to controls. Effectiveness of supplementary folate and B 12 in such patients needs further well-structured prospective placebo controlled studies.

Liver histology and HBV DNA levels in chronically HBV infected patients with persistently normal alanine aminotransferase.

BACKGROUND: Data on histological activity and HBV DNA levels in patients with chronic HBV infection and persistently normal alanine aminotransferase levels are sparse. We aimed to investigate the histological activity and HBV DNA levels in these patients. METHODS: There were 132 patients with HBeAg negative chronic HBV infection and persistently normal alanine aminotransferase levels that were included prospectively. Data were dichotomized according to the median levels. Associations of histology with HBV DNA and other variables were assessed. RESULTS: A total of 80 patients were male. The median age was 36 years. The median baseline HBV DNA was 2.9Log10 IU/mL. There were 50 cases (38%) with a total score > or = 5, 53 cases (40.2%) had grade > or = 4 and 40 cases (30.3%) had stage > or = 2. A baseline HBV DNA <2000 IU/mL was seen in 24 cases (48%) of those with total score > or = 5, 28 cases (53%) of those with grade > or = 4 and 9 cases (22.5%) with stage > or = 2. Multivariate analysis of baseline HBV DNA above the median level significantly predicted the total score, grade and stage with an adjusted odds ratio of 5.43, 3.47, and 4.23, respectively when compared to below median values. A second liver biopsy was performed in 61 patients. The median time interval between the two biopsies was 40 months. Total scores of 23 cases (38%) progressed by > or = 2 scores and the HBV DNA of 18 cases (22.5%) increased by > or = 1 Log10 IU when compared to baseline values. CONCLUSION: HBeAg negative chronic HBV infection with persistently normal alanine aminotransferase is not a silent disease. Active liver disease may be seen in such patients with viral loads less than 2000 IU/mL.