Valproate-Associated Hyperammonemic Encephalopathy: Clinical Correlates and Management Strategies in a Tertiary Care Center.

BACKGROUND: Common adverse effects of valproate include sedation, tremor, gastrointestinal effects, and weight gain. Valproate-associated hyperammonemic encephalopathy (VHE) is an uncommon adverse effect of valproate therapy, which includes symptoms such as tremors, ataxia, seizures, confusion, sedation and coma. We report clinical features and management of 10 cases of VHE in a tertiary care center. METHODS: In a retrospective chart review of case records from January 2018 to June 2021, 10 patients with VHE were identified and included in this case series. The data collected include demographic information, psychiatric diagnosis, comorbidities, liver function tests, serum ammonia and serum valproate levels, dosages and duration of valproate, management of hyperammonemia including dosage variations, discontinuation, adjuvant drugs used, and whether rechallenge was done. RESULTS: The most common indication of starting valproate was bipolar disorder (n = 5). All the patients had more than one physical comorbidity and risk factors for developing hyperammonemia. Seven patients received valproate at a dose higher than 20 mg/kg. The duration of valproate use varied from 1 week to 19 years before developing VHE. Dose reduction or discontinuation and lactulose were the most common management strategies used. All 10 patients improved. Among the 7 patients in whom valproate was discontinued, for 2 patients valproate was reinitiated in inpatient care with careful monitoring and was found to be well tolerated. CONCLUSIONS: This case series highlights the need for a high index of suspicion for VHE as it is frequently associated with a delayed diagnosis and recovery in psychiatric settings. Screening for risk factors and serial monitoring may allow earlier diagnosis and management.

Electroconvulsive Therapy in Patients With Cardiac Implantable Electronic Devices: A Case Report and Systematic Review of Published Cases.

OBJECTIVE: The aims of the study were to report the case of a 54-year-old man with recurrent depressive disorder with multiple medical comorbidities having a dual-chamber pacemaker, treated successfully with 11 sessions of electroconvulsive therapy, and to conduct a systematic review of published cases documenting the use of electroconvulsive therapy (ECT) in patients with cardiac implantable electronic devices (CIEDs) for treating major psychiatric disorders. METHODS: We searched electronic databases (MEDLINE, PubMed, Google Scholar, Embase, Cochrane Library, PsycINFO, and Crossref) and included studies reporting on the use of electroconvulsive therapy in patients with CIEDs. RESULTS: Thirty-five publications across 53 years (1967-2021) reported on 76 patients (including current report) who received a pooled total of 979 modified ECT sessions. The most common adverse events were premature ventricular contraction and hypertension. There have been no reports of serious adverse effects that necessitated the cessation of ECT. CONCLUSIONS: Electroconvulsive therapy is a safe and efficacious treatment for major psychiatric disorders, and the presence of CIEDs should not delay or deter the use of ECT in these patients.

Glibenclamide attenuates brain edema associated with microglia activation after intracerebral hemorrhage.

OBJECTIVE: Glibenclamide, Sulfonylurea receptor 1 antagonist, reduces brain edema after cerebral hemorrhage. However, the effects of glibenclamide on microglial activation and inflammatory cell infiltration after cerebral hemorrhage are unclear. The present study investigated the effect of glibenclamide on microglial activation and inflammatory cell infiltration in a rat cerebral hemorrhage model. METHODS: A collagenase intracerebral injection model was used to cause cerebral hemorrhage in rats. After injury, glibenclamide was continuously administered at 1.0µL/h for 24hours. We evaluated hematoma volume, brain edema, expression of ABCC8, galectin-3 and CD11b, and anti-Iba-1 antibody staining. RESULTS: Glibenclamide significantly reduced water content. Meanwhile, glibenclamide significantly reduced expression of galectin-3 and CD11b in the cerebral cortex and putamen on the bleeding side. Immunohistochemical staining confirmed that glibenclamide attenuated activation of microglia around the hematoma. CONCLUSIONS: Glibenclamide reduced microglial activation and infiltration of inflammatory cells, resulting in amelioration of cerebral edema.

Scaling-up filariasis lymphoedema management into the primary health care system in Kerala State, Southern India: a case study in healthcare equity.

BACKGROUND: Lymphatic filariasis (LF) remains one of the world's most debilitating parasitic infections and is a major contributor to poor health in many endemic countries. The provision of continuing care for all those affected by LF and its consequences is an important component of the United Nations' Sustainable Development Goals. The aim of this study is to integrate lymphedema care into the primary health care system of the State by developing lymphedema clinics at each district, through training of health personnel to fulfill WHO recommendation for morbidity management and disability prevention. METHODS: Selected health care providers from all the districts in Kerala State of India participated in intensive training sessions endorsed by the State's health administration. The six training sessions (from 5 June 2017 to 25 May 2018) included appropriate self-care information and development of individual plans for each participating institution to provide instruction and care for their lymphoedema patients. The learning achieved by attendees was assessed by pre- and post-training tests. The number of lymphoedema patients receiving care and instruction from the post-training activities of each participating institution was assessed from local records, 6 months after the conclusion of the training sessions. RESULTS: One hundred and eighty-four medical personnel (91 doctors and 93 nurses) from 82 medical institutions were trained which quickly led to the establishment of active lymphoedema clinics providing the essential package of care (EPC) for lymphoedema patients at all the participating institutions. Six months after the training sessions the number of previously unidentified lymphoedema patients registered and receiving care at these clinics ranged from 296 to almost 400 per clinic, with a total of 3,477 new patients receiving training in EPC. CONCLUSIONS: Generalist health personnel, when appropriately trained, can provide quality lymphoedema care in public health settings and patients when provided services close to their home, are willing to access them. This is a feasible strategy for integrating long term care for LF patients into the national health system, and is a clear example of moving towards equity in health care for the medically underserved, and thus successfully addresses a major goal of the global program to eliminate lymphatic filariasis.

Valproate-associated hair abnormalities: Pathophysiology and management strategies.

OBJECTIVE: To review the literature on valproate-associated hair abnormalities and the available treatment options. METHODS: We searched PubMed and Google Scholar with keywords including "valproate", "valproic acid", "hair", "alopecia", and "effluvium," supplemented with hand search from cross-references. We included all types of studies including case reports in this review. RESULTS: The pathophysiology of hair loss includes telogen effluvium, biotin, mineral deficiency, and possibly hyperandrogenism. Diagnosis is based on history of hair loss or abnormalities following valproate treatment, and is confirmed by use of simple clinical tests such as pull test and modified wash test. Treatment involves reassurance and advice on hair care, and if possible drug discontinuation or dose reduction. Medications such as biotin and other vitamins with minerals supplementation is effective for most individuals with hair loss. Other treatment options are agomelatine, topical valproate or minoxidil, though these lack evidence. CONCLUSION: Hair abnormalities with valproate are common, benign adverse effects, and management includes general measures and specific treatment options.

High-dose thiamine strategy in Wernicke-Korsakoff syndrome and related thiamine deficiency conditions associated with alcohol use disorder.

Thiamine is essential for the activity of several enzymes associated with energy metabolism in humans. Chronic alcohol use is associated with deficiency of thiamine along with other vitamins through several mechanisms. Several neuropsychiatric syndromes have been associated with thiamine deficiency in the context of alcohol use disorder including Wernicke-Korsakoff syndrome, alcoholic cerebellar syndrome, alcoholic peripheral neuropathy, and possibly, Marchiafava-Bignami syndrome. High-dose thiamine replacement is suggested for these neuropsychiatric syndromes.

Ethical dilemmas in mental health resources for college students: A reflective case study.

Poised to have the highest number of young people in the world, India will have the onus of providing adequate mental health resources to a demographic considered among the most vulnerable with regard to mental well-being. While the Mental Healthcare Act 2017 pushed for greater accountability and care in supporting individuals with mental illness, these directions were specific to services provided by the state and did not address the care required in non-hospital settings. Since many manifestations and repercussions of mental health issues in young people occur in educational institutions, it becomes vital to address ways in which we can formulate ethical mental health services at those sites. This article is a reflective case study of the ethical dilemmas and challenges around issues of confidentiality and quality of care in relation to demand, contributing to a larger mental health ecology involved in providing mental health resources at the Student Support Centre, Manipal, that caters exclusively to students in an Indian campus town.

A Case of Urachal Yolk Sac Tumor With Spontaneous Rupture in a Child.

Tumors arising from urachus in children are exceedingly rare and sporadically reported in literature. Being a midline structure, the urachus may harbor neoplastic germ cell elements and can occasionally present as a case of acute abdomen. A 20-month-old toddler presented with spontaneous rupture of an urachal yolk sac tumor causing hemoperitoneum. He underwent resection, received platinum-based chemotherapy and presently remains well on follow-up. Despite its rarity, urachal germ cell tumors must be considered in a child with acute abdomen and tumor markers must be measured preemptively in such cases.

Assessment of Image Distortion from Head Rotation in Lateral Cephalometry.

BACKGROUND: The patient's head can be slightly rotated sagitally vertically or transversely within the head holding device. Because of such improper positions due to the head rotation, an error can occur in cephalometric measurements. The purpose of this study was to identify the potential projection errors of lateral cephalometric radiograph due to head rotation toward X-ray film in the vertical Z-axis. MATERIALS AND METHODS: Totally, 10 human dry skulls with permanent dentition were collected from the Department of Anatomy, J.J.M.C. Medical College, Davanagere. Each dry skull was rotated from 0° to -20° at 5° intervals. A vertical axis, the Z-axis, was used as a rotational axis to have 100 lateral cephalometric radiographs exposed. Four linear (S-N, Go-Me, N-Me, S-Go) and six angular measurements (SNA, SNB, N-S-Ar, S-Ar-Go, Ar-Go-Me, AB-Mandibular plane angle) were calculated manually. RESULTS: The findings were that: (1) Angular measurements have fewer projection errors than linear measurements; (2) the greater the number of landmarks on the midsagittal plane that are included in angular measurements, the fewer the projection errors occurring; (3) the horizontal linear measurements have more projection errors than vertical linear measurements according to head rotation. CONCLUSION: In summary the angular measurements of lateral cephalometric radiographs are more useful than linear measurements in minimizing the projection errors associated with head rotation on a vertical axis.

Antifilarial drugs, in the doses employed in mass drug administrations by the Global Programme to Eliminate Lymphatic Filariasis, reverse lymphatic pathology in children with Brugia malayi infection.

Lymphatic filariasis is increasingly viewed as the result of an infection that is often acquired in childhood. The lymphatic pathology that occurs in the disease is generally believed to be irreversible. In a recent study in India, Doppler ultrasonography and lymphoscintigraphy were used to explore subclinical pathology in 100 children from an area endemic for Brugia malayi infection. All the children investigated showed some evidence of current or previous filarial infection. Some were microfilaraemic but asymptomatic, some were amicrofilaraemic but had filarial disease or a past history of microfilaraemia and/or filarial disease, and the rest, though amicrofilaraemic, asymptomatic and without any history of microfilaraemia or filarial disease, were seropositive for antifilarial IgG(4) antibodies. All the children were treated every 6 months, with a single combined dose of diethylcarbamazine (6 mg/kg) and albendazole (400 mg), and followed up for 24 months. By the end of this period all but one of the children were amicrofilaraemic and the 'filarial dance sign' could not be detected in any of the 14 children who had initially been found positive for this sign. Although lymphoscintigraphy revealed lymph-node and lymph-vessel damage in 82% of the children at enrolment, in about 67% of the children this pathology was markedly reduced by the 24-month follow-up. These results indicate that the drug regimens used in the mass drug administrations run by the Global Programme to Eliminate Lymphatic Filariasis are capable of reversing subclinical lymphatic damage and can provide benefits other than interruption of transmission in endemic areas. The implications of these findings are presented and discussed.

Relevance of anti-BmR1 IgG4 antibodies in children from an area endemic for Brugia malayi infection in Kerala, India.

Brugian filariasis prevalent mostly in South-East Asian countries including India contributes to a small but significant proportion of the socioeconomic burden due to lymphatic filariasis. Along with bancroftian filariasis, brugian filariasis has been targeted for elimination globally. The lack of a reliable daytime diagnostic test has been seen as an important barrier to the successful implementation and monitoring of elimination programmes in brugia endemic areas. We evaluated an anti-BmRI-IgG4 antibody test namely, 'Brugia Rapid' in a large study meant to understand the clinical and pathological manifestations of brugian filariasis in children. We found the test superior to traditional night blood screening for microfilaraemia. Although an antibody detection test, we found it to be a reliable indicator of brugian infection. Among the 100 children studied extensively, 94% of the microfilaraemics, 86% of those showing filarial dance sign indicating presence of, live adult worms and 78% having abnormal lymphatics on lymphoscintigraphy were IgG4 positive. Coupled with its advantages like ease of use any time of the day, high sensitivity and specificity, this test may be the ideal tool to assist programme managers in their efforts to eliminate lymphatic filariasis where brugian infections are found.

Lymphoscintigraphic evidence of lymph vessel dilation in the limbs of children with Brugia malayi infection.

Lymphatic filariasis (LF) is targeted for global elimination by the year 2020. It was earlier believed that LF is mostly a disease of adults. Recent studies indicate that in endemic countries filarial infection starts mostly in childhood even though the disease manifestations occur much later in life. The initial damage to the lymph vessels where the adult worms are lodged is dilation, thought to be irreversible even with treatment. Most of these studies relate to bancroftian filariasis. Studies that address this early pathology in brugian filariasis in humans are scarce. We report here for the first time, the lymphatic abnormalities seen on lymphoscintigraphy (LSG) in children with Brugia malayi filariasis. LSG was performed in 100 children aged between 3-15 years, who were enrolled in the study either because they were microfilaremic; had present or past filarial disease or were positive for antifilarial IgG4 antibodies. Inguinal and axillary lymph nodes were imaged in most children. Dilated lymph vessels were visualized in 80 children and this pathology was evenly distributed in all the three study groups. Lymph vessels dilation was seen even in three year old children. The implications of these findings for management of LF and control programmes are discussed.

Preliminary findings from a cross-sectional study on lymphatic filariasis in children, in an area of India endemic for Brugia malayi infection.

As the more obvious clinical manifestations of the disease are very uncommon in children, lymphatic filariasis has been considered to be primarily a disease of adults. In many recent reports, however, there is evidence indicating not only that filarial infection is commonly acquired in childhood but also that many infected children already have irreversible damage to their lymphatics. The preliminary results of a cross-sectional study on the patterns of Brugia-attributable pathology in 7934 children (aged 3-15 years) who live in an area of India with endemic B. malayi infection confirm these trends. The children were screened for microfilaraemia, evidence of filarial disease, and the presence of antifilarial IgG(4) antibodies. One hundred children who were microfilaraemic but asymptomatic (32), with filarial disease or an history of such disease or microfilaraemia (29) or amicrofilaraemic and asymptomatic but seropositive for antifilarial IgG(4) (39) were investigated further. They were given detailed clinical examinations, their levels of microfilaraemia were evaluated (by counting microfilariae filtered out of blood samples), their lymphatics were explored by Doppler sonography, and their limbs were checked by lymphoscintigraphy. The 'filarial dance sign', which indicates the presence of live adult worms, was detected by sonography in 14 children (apparently the first time this sign has been observed in brugian filariasis). Lymphoscintigraphy revealed dilated lymphatic channels in the limbs of 80 of the children. At the end of the study, each of the 100 hospitalized children was treated with a single combined dose of diethylcarbamazine and albendazole; the aim is to follow-up the treated children every 6 months for 3 years. Even these preliminary results have important implications for filariasis-control programmes and emphasise the need for disability-alleviation efforts among children as well as adults.

Doppler ultrasonography reveals adult-worm nests in the lymph vessels of children with brugian filariasis.

Although ultrasonography has allowed 'nests' of live adult worms and dilated lymphatics to be detected in the early stages of infection with Wuchereria bancrofti, previous attempts to locate such adult-worm nests in brugian filariasis have been unsuccessful. In this study, the successful location of live adult Brugia malayi parasites, in the lymphatics of the axilla, thigh, epitrochlear region and/or popliteal fossa of children aged 3-15 years, is described for the first time. The 'filarial dance sign' (FDS), which indicates the presence of live adult worms, was observed in six children with microfilaraemia and in eight children who, though amicrofilaraemic, either had experienced an episode of lymphoedema (one) or were only positive for antifilarial IgG4 antibodies (seven). In bancroftian infection, the adult-worm nests have mostly been seen in asymptomatic but microfilaraemic subjects. The suspected worm nests, 18 in the 14 children, were all confirmed using colour-power and pulse-wave Doppler examinations. The worm nests were distinctly smaller and the wriggling movements were less rapid and less conspicuous than those seen in bancroftian filariasis. The importance of these findings in the management and control of lymphatic filariasis is discussed.