Demographic and clinical features of neuromyelitis optica: A review.

The comparative clinical and demographic features of neuromyelitis optica (NMO) are not well known. In this review we analyzed peer-reviewed publications for incidence and prevalence, clinical phenotypes, and demographic features of NMO. Population-based studies from Europe, South East and Southern Asia, the Caribbean, and Cuba suggest that the incidence and prevalence of NMO ranges from 0.05-0.4 and 0.52-4.4 per 100,000, respectively. Mean age at onset (32.6-45.7) and median time to first relapse (8-12 months) was similar. Most studies reported an excess of disease in women and a relapsing course, particularly in anti-aquaporin 4 antibody (anti AQP4-IgG)-positive patients. Ethnicity may have a bearing on disease phenotype and clinical outcome. Despite limitations inherent to the review process, themes noted in clinical and demographic features of NMO among different populations promote a more global understanding of NMO and strategies to address it.

Pulmonary Hypertension and Hyperglycemia-Not a Sweet Combination.

Hyperglycemia and pulmonary hypertension (PH) share common pathological pathways that lead to vascular dysfunction and resultant cardiovascular complications. These shared pathologic pathways involve endothelial dysfunction, inflammation, oxidative stress, and hormonal imbalances. Individuals with hyperglycemia or pulmonary hypertension also possess shared clinical factors that contribute to increased morbidity from both diseases. This review aims to explore the relationship between PH and hyperglycemia, highlighting the mechanisms underlying their association and discussing the clinical implications. Understanding these common pathologic and clinical factors will enable early detection for those at-risk for complications from both diseases, paving the way for improved research and targeted therapeutics.

COVID-19 infection and vaccination against COVID-19: Impact on managing demyelinating CNS disorders in Southern India- experience from a demyelinating disease registry.

BACKGROUND AND OBJECTIVE: The impact of COVID-19 infection and the effect of COVID-19 vaccinations on patients with demyelinating central nervous system disease in low middle income countries (LMIC's) have not been reported in detail earlier. We sought to identify risk factors associated with COVID-19 infection and the role of vaccination in order to develop management guidelines relevant to our patients. METHODS: A total of 621 patients from our registry that included 297 MS and 324 non MS disorders (Aquaporin- 4 antibody positive [50], Myelin oligodendrocyte glycoprotein antibody positive [81], seronegative [162] and clinically isolated syndrome [31]) were contacted. COVID-19 infection and vaccination status were queried. Patients who self reported COVID-19 infection based on a positive RT PCR report were compared with non infected patients to identify factors associated with susceptibility for COVID-19 infection. Univariate and multivariate analysis of potential risk factors included demographic and clinical features, body mass index (BMI), presence of comorbidities, absolute lymphocyte count, treatment types and vaccination status. RESULTS: Sixty seven patients with MS and 27 with non MS disorders developed COVID-19 infection. Among them 81 patients had mild infection and remained quarantined at home. All 13 patients who needed hospitalization recovered. Vaccination status was known in 582 patients among whom 69.8% had completed or taken one dose of vaccine at the time of inquiry. Majority of treated patients (61.3%) were on nonspecific immunosuppressants. In univariate analysis, presence of ≥1 comorbidity was significantly associated with COVID-19 infection in both MS (p value 0.01, OR-2.28, 95%CI- 1.18-4.4) and non MS patients (p- 0.001, OR-4.4, 95% CI-1.88-10.24). In the latter, BMI ≥ 30 (p-0.04, OR-3.27, 95% CI- 0.98-10.87) and EDSS score ≥ 3 (p-0.02, OR- 2.59,95% CI- 1.08-6.23) were other significant associations. History of prior COVID-19 vaccination was associated with reduced frequency of COVID-19 infection among MS (p- 0.001,OR- 0.24,95% CI- 0.13-0.43) and non MS patients (p- 0.0001,OR-0.14, 95% CI- 0.058-0.35). In multivariate analysis presence of comorbidities significantly increased and prior vaccination significantly reduced frequency of COVID-19 infection for both MS and related disorders. Concurrent disease modifying treatments showed a trend for association with infection. In the unvaccinated group, patients on disease modifying treatment were significantly at risk of infection, 81.5% unvaccinated and treated versus 18.5% who were unvaccinated and untreated (p- 0.0001, OR-10.1, 95% CI-0.56-2.11). CONCLUSION: Frequency and severity of COVID-19 infection was low among our patient cohort. Higher rate of infection in the treated group was significantly seen among unvaccinated patients. Our preliminary results suggests that in LMIC's, where "off label therapies" with inexpensive immunosuppressives are the main disease modifying drugs, mRNA vaccinations appear safe and effective against severe COVID-19 infection.

Treatment of MOG antibody associated disorders: results of an international survey.

INTRODUCTION: While monophasic and relapsing forms of myelin oligodendrocyte glycoprotein antibody associated disorders (MOGAD) are increasingly diagnosed world-wide, consensus on management is yet to be developed. OBJECTIVE: To survey the current global clinical practice of clinicians treating MOGAD. METHOD: Neurologists worldwide with expertise in treating MOGAD participated in an online survey (February-April 2019). RESULTS: Fifty-two responses were received (response rate 60.5%) from 86 invited experts, comprising adult (78.8%, 41/52) and paediatric (21.2%, 11/52) neurologists in 22 countries. All treat acute attacks with high dose corticosteroids. If recovery is incomplete, 71.2% (37/52) proceed next to plasma exchange (PE). 45.5% (5/11) of paediatric neurologists use IV immunoglobulin (IVIg) in preference to PE. Following an acute attack, 55.8% (29/52) of respondents typically continue corticosteroids for ≥ 3 months; though less commonly when treating children. After an index event, 60% (31/51) usually start steroid-sparing maintenance therapy (MT); after ≥ 2 attacks 92.3% (48/52) would start MT. Repeat MOG antibody status is used by 52.9% (27/51) to help decide on MT initiation. Commonly used first line MTs in adults are azathioprine (30.8%, 16/52), mycophenolate mofetil (25.0%, 13/52) and rituximab (17.3%, 9/52). In children, IVIg is the preferred first line MT (54.5%; 6/11). Treatment response is monitored by MRI (53.8%; 28/52), optical coherence tomography (23.1%; 12/52) and MOG antibody titres (36.5%; 19/52). Regardless of monitoring results, 25.0% (13/52) would not stop MT. CONCLUSION: Current treatment of MOGAD is highly variable, indicating a need for consensus-based treatment guidelines, while awaiting definitive clinical trials.

Acute thyrotoxic neuropathy--Basedow's paraplegia revisited.

A forty seven year old woman with previously undetected goitre, developed thyroid storm in the immediate postoperative period. Forty eight hours after undergoing nephrolithotomy for renal calculus, she was noted to have flaccid areflexic quadriparesis, most marked in the lower limbs. Electrophysiologic studies revealed evidence of an asymmetric, mixed axonal and demyelinating, motor-sensory peripheral neuropathy. Ultrastructure of the sural nerve showed predominant abnormalities in the mitochondria and cytoskeletal elements compatible with thyrotoxicosis. Treatment of thyrotoxicosis coincided with recovery of symptoms. We believe that thyrotoxicosis precipitated an acute polyneuropathy the ultrastructure of which is being described for the first time.

Epilepsy care in six Indian cities: a multicenter study on management and service.

BACKGROUND: Epilepsy care in developing countries is lagging behind than in the developed countries. Precise data on delivery of neurological services for epilepsy is essential to optimize the medical services for epilepsy care with limited resources. OBJECTIVE: This study was carried out in order to examine the management practices and utilization of various medical services for epilepsy in different parts of India. METHODOLOGY: University centers with epilepsy clinics, one each from six states of India, had participated in this study. Demographic data, clinical details, and data on epilepsy care were collected simultaneously on standard proforma. RESULTS: Data on 285 patients with epilepsy (generalized epilepsy: 49.1%, localization-related epilepsy: 49.9%, others: 1%) were included. Mean age of onset of epilepsy was 14.8+11.1 years. Mean delay in diagnosis was 1.5+/-4 years. Mean distance from place of residence to the consulting neurologist was 70+/-82 km. Medical consultations before referral to epilepsy center included general practitioners (54.1%) and specialists (43.3%). Very few patients received services from clinical psychologist or social worker. Investigations included, EEG (63.2%), CT Scan (36.2%). MRI brain (8.5%) and video EEG (2.1%) were limited to a few. Nearly 75.5% were on monotherapy. Newer Anti-Epileptic Drugs (AEDs) were used only in less than 5% patients. CONCLUSION: The services for epilepsy are urban-based and there is underutilization of services, general practitioners and specialists. Newer AEDs (although expensive) are gradually emerging in Indian market. Facilities for epilepsy surgery, therapeutic drug monitoring and services of clinical psychologist or medical social workers are limited.

Development of systemic immunologic responses against hepatic metastases during gene therapy for peritoneal carcinomatosis with retroviral HS-tk and ganciclovir.

Gene therapy with retroviral mediated gene transfer of the herpes simplex thymidine kinase (HS-tk) gene into a tumor mass confers sensitivity of the tumor cells to ganciclovir (GCV). Tumor-specific immunologic responses may develop following treatment of the primary tumor with retroviral HS-tk and GCV. In the present study we assessed whether GCV treatment of HS-tk transduced colon cancer (TK+) implanted in the peritoneal cavity induced a systemic antitumor response that would inhibit growth of a second wild-type (TK-) tumor implanted in the liver. DHDK12 rat colon cancer cells were transduced in vitro with the retroviral HS-tk vector and established as a permanent cell line (TK+ cells). TK+ or TK- DHDK12 cells (6x10(6) cells) were injected intraperitoneally on day 0 into BD-IX rats. On day 10, TK- cells (3x10(6) cells) were injected into the liver in all the groups. The animals were then treated with GCV (150 mg/kg) for 13 days. TK+ peritoneal tumors underwent significant regression during therapy with GCV (0.05+/-0.004 g; n=7) compared to wild-type (TK-) tumors (2.2+/-0.7g; n=6) (P<0.05). The volume of TK- tumors in the liver was significantly lower in GCV-treated rats with TK+ peritoneal tumors (12.5+/-8.3 mm3) compared to rats with TK- peritoneal tumors (96.7+/-18.1 mm3) (P<0.05). Histology of the liver tumors in the TK+ groups showed a dense monocytic infiltrate with fibrosis and only occasional viable tumor cells. Gene therapy with retroviral HS-tk vectors may provide a novel approach to treatment of gastrointestinal cancer by both direct cytotoxicity and an indirect mechanism that may include enhanced immuno logic responses against disseminated disease.

Postmenopausal vaginal atrophy and atrophic vaginitis.

Menopause is associated with a marked reduction in endogenous estrogen production. Lower levels of circulating blood estrogen have various deleterious effects, including those on the lower urinary tract. The vaginal epithelium becomes atrophied and dry, which can cause vaginal discomfort, itching, and dyspareunia. The epithelium may become inflamed and contribute to urinary symptoms, including frequency, urgency, dysuria, and incontinence. Diminished estrogen effects on periurethral tissues can contribute to pelvic laxity and stress incontinence. Changes in vaginal pH and normal flora may predispose older women to urinary tract infection. Although estrogen replacement therapy can result in maturation of the vaginal epithelium, the optimal form of administration and the dosage regimen for improving symptoms and quality of life of the geriatric female population have not been well studied.

Computerised tomography in Tolosa-Hunt syndrome.

Twelve patients who satisfied the clinical criteria of Tolosa-Hunt syndrome (THS), underwent axial computerised tomography (CT) scan of the head. Two patients had abnormalities detected in the cavernous sinus on the affected side which supported the clinical diagnosis. This coupled with steroid responsiveness and long-term asymptomatic follow-up firmly established the diagnosis of THS. We discuss the computerised tomographic findings seen in THS and the relevance of using accurate imaging techniques as the first line of investigation in these cases.

Multiple sclerosis in coastal Karnataka.

Over the last 10 years from 1982-1992, we have diagnosed 29 cases of multiple sclerosis at our centre. In this hospital based retrospective study, 22 cases were definite (including 4 cases of Neuromyelitis optica) and the remaining 7 were probable cases of multiple sclerosis according to Poser's criteria (Poser et al 1983). There was no sex preponderence. Striking clinical presentations included high incidence of optic nerve, brain stem and spinal cord involvement. Sympathetic disturbance in the form of Horner's syndrome was seen in two patients. Major depressive psychosis was an associated disease in 2 cases. One patient developed multiple sclerosis after receiving anti rabies vaccine.

Multiphasic disseminated encephalomyelitis.

A forty five year old patient developed a chronic relapsing and remitting disease after receiving fourteen injections of beta propionalactone inactivated sheep brain vaccine. We offer evidence to support the view that this case is an illustration ofmultiphasic disseminated encephalomyelitis rather than multiple sclerosis.

Thymomatous myasthenia gravis.

Ten cases of thymoma associated myasthenia were seen in the last 7 years. They constitute 17.2% of all cases of Myasthenia gravis seen during the same period. Five of these patients presented in the third decade, all of them presenting with acute generalised Myasthenia (Osserman stage-III). Two patients presented with tumour related symptoms of chest pain, cough and dyspnea both of them having large, invasive and partially resectable tumours. Five patients underwent complete thymectomy and 3 patients underwent partial resection of tumour. Two patients underwent radiotherapy subsequently. Histologically, mixed lymphoepithelial tumours were common (70%). Tumour recurrence was seen in one patient. Two patients died, one in the post operative period. The surviving 8 patients followed up over 1-8 years remained in partial remission, on maintenance dose of steroids. The special problems related to thymomatous MG and practical approach to management are highlighted.

Screening for cystic fibrosis-related diabetes: a systematic review.

BACKGROUND: Cystic fibrosis (CF) is an inherited disease that leads to damage to lungs, pancreas and other organs. Most people with CF die prematurely from lung disease, but survival has improved markedly over the decades and it is estimated that children born with CF now will live to an average age of 50 years. CF-related diabetes (CFRD) is due to damage to the pancreas, which, over time, loses its capacity to produce sufficient insulin. CFRD is becoming more common owing to the improved survival of people with CF. OBJECTIVES: The initial aim was to review the methods for screening for CFRD, which can be symptomless but still be causing harm. As the aim of screening and early detection is to allow earlier treatment, a second aim was to assess the effectiveness of treatments. However, during the review it became clear that there were problems with how CFRD is defined, uncertainty about when hyperglycaemia should be treated. DATA SOURCES: Details of relevant studies were obtained from the usual bibliometric databases - MEDLINE (1950-2008), EMBASE (1980-2008), The Cochrane Library (all sections), Web of Science (1970-2008). Websites of relevant bodies were searched for guidelines and reports. Conference abstracts were searched. Expert co-authors identified key papers. REVIEW METHODS: Systematic reviews of treatments and screening tests. Screening studies were data extracted if they provided sufficient data to construct 2 × 2 tables. Other screening studies were described in narrative manner. The background to CF and CFRD were described in a narrative manner, as was Chapter 2 on problems with defining CFRD. A model was constructed for cost-effectiveness analysis, but was not used because of lack of data. RESULTS: Diabetes is usually defined based on the level of blood glucose (BG) at which the risk of retinopathy occurs. For CFRD, it would be better to define it on the level at which the risk of lung disease (pulmonopathy) rises. There seems little place for treatments other than insulin, but the best insulin regimen remains to be confirmed. The best screening test may be by continuous glucose monitoring systems but further evidence is required. Screening may need to detect BG levels of > 8 mmol/l because that may be the level above which pulmonopathy starts in people with CF. LIMITATIONS: The evidence base for treatment is disappointing with few large randomised controlled trials. The key question is when treatment should start, perhaps at the post-prandial hyperglycaemia stage. Research is needed. Until that is done, we cannot be sure what we are screening for, and, therefore, which screening strategy should be used. CONCLUSIONS: The definition of CFRD should probably be based on pulmonopathy risk, rather than using the classical definition of diabetes. That implies that we should be screening for a wider range of hyperglycaemia than in other forms of diabetes, perhaps to detect BG excursions of > 8 mmol/l. Insulin treatment may need to start at lower levels than formerly accepted. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Glossopharyngeal schwannoma: diagnostic and therapeutic aspects.

Among posterior fossa tumours, schwannomas arising from glossopharyngeal nerves are extremely rare, and only 39 cases of glossopharyngeal schwannomas have been described. The clinical and imaging features of glossopharyngeal schwannomas closely resemble that of acoustic schwannomas. Despite its accuracy, magnetic resonance imaging is not diagnostic of a ninth nerve schwannoma. This is because the schwannoma may be primarily localised to the cerebellopontine angle and may not cause enlargement of the jugular foramen. The diagnosis is possible only at surgery, once attachment to the ninth cranial nerve is seen. Because of the different surgical implications and management, preoperative recognition will help in determining the operative approach. We review the relevant literature and discuss the clinical presentation, radiological features and surgical findings in a 52-year-old woman with glossopharyngeal schwannoma.

Recurrent myelitis.

Three patients presented with acute complete transverse myelopathy which relapsed several times at the same site. These patients, two women and one man, had two to five attacks spanning three to seven years. All patients underwent detailed investigations including a complete myelogram and serial evoked potential studies. Oligoclonal bands were present in the CSF in one patient. Brain MRI was normal in two patients; MRI of the spinal cord was abnormal and showed cord oedema with multiple areas of hyperintense signals on T2 and proton density weighted scans and hypointense signals on T1 weighted images in areas corresponding to the clinical level, suggesting an inflammatory/demyelinating disorder. These patients may represent a relapsing demyelinating disorder restricted to the spinal cord, distinct from multiple sclerosis.

Gene therapy of metastatic pancreas cancer with intraperitoneal injections of concentrated retroviral herpes simplex thymidine kinase vector supernatant and ganciclovir.

OBJECTIVE: The objective of this study was to determine the efficacy of intraperitoneal (IP) injections of a new concentrated herpes simplex thymidine kinase (HS-tk) retroviral vector and ganciclovir (GCV) for peritoneal metastases from pancreas cancer. SUMMARY BACKGROUND DATA: Metastatic pancreas cancer is fatal. Gene therapy may provide a novel approach for this disease. Gene therapy with adeno- or retroviral-mediated transfer of the HS-tk gene into tumor cells renders the cells susceptible to GCV. Intratumoral or intracavity injections of retroviral vectors have been ineffective in previous studies. METHODS: Pancreatic cancer B x PC3 cells (3 x 10(7)) were injected into the tail of pancreas in nude mice. Mice received IP injections of a concentrated HS-tk vector (5 x 10(7)) cfu/mliters) or a control vector (G1Na) without the tk gene for 10 days and GCV (100 mg/kg) for 14 days. To determine whether the vector would survive in the milieu of the peritoneal cavity, the authors examined the effects of ascitic fluid on the vector. Pancreas cancer cells were transduced in vitro with HS-tk vector in presence of media or ascitic fluid and treated with GCV. RESULTS: Highly significant reductions in the mass of metastatic peritoneal tumor deposits were found in HS-tk-treated group (124 +/- 27 mg; n = 11) compared with G1Na vector controls (910 +/- 168 mg; n = 8; p < 0.0001). Results of polymerase chain reaction analysis demonstrated integration of the vector in the tumors, and on immunohistochemistry, expression of the TK protein was seen in the number of surviving colonies (representing nontransduced cells) were similar in both groups, suggesting that the vector effectively transduced tumor cells bathed in the ascitic fluid. CONCLUSIONS: Results demonstrate that IP administration of concentrated retroviral HS-tk vectors is effective treatment for pancreas cancer metastatic to the peritoneal cavity; furthermore, the vector is active in the presence of ascitic fluid. Intraperitoneal retroviral HS-tk may provide a novel approach to treatment of metastatic pancreas cancer.

Economic burden of epilepsy in India.

PURPOSE: The economic burden due to epilepsy is not adequately examined in developing countries. Cost estimates are very important in health care planning and delivery of services. We have estimated the direct and some of the indirect costs of epilepsy in India. METHODS: Epilepsy centers attached to University hospitals in six states of India participated in this study. Data on clinical characteristics, utilization of medical services, and costs were collected in a standardized format. RESULTS: There were 285 patients (mean age, 22.6 + 12.5 years) drawn from six centers in this study. The annual cost of epilepsy per patient was INR 13,755 (USD, 344). The direct cost was INR 3,725 (USD, 93), and the indirect cost was INR 10,031 (USD, 251). Direct cost included medical consultations (INR 329), laboratory services (INR 271), hospitalization charges (INR 316), and cost of travel to clinics (INR 659). The indirect cost included the cost of lost productivity due to seizures, its complications, or attendance to clinics. There are approximately 5 million people with epilepsy in India. The economic burden due to epilepsy to the nation is to the tune of INR 68.75 billion (USD, 1.7 billion). CONCLUSIONS: The annual economic burden of epilepsy in India is 88.2% of GNP per capita and 0.5% of the GNP.