Climate change, malaria and neglected tropical diseases: a scoping review.

To explore the effects of climate change on malaria and 20 neglected tropical diseases (NTDs), and potential effect amelioration through mitigation and adaptation, we searched for papers published from January 2010 to October 2023. We descriptively synthesised extracted data. We analysed numbers of papers meeting our inclusion criteria by country and national disease burden, healthcare access and quality index (HAQI), as well as by climate vulnerability score. From 42 693 retrieved records, 1543 full-text papers were assessed. Of 511 papers meeting the inclusion criteria, 185 studied malaria, 181 dengue and chikungunya and 53 leishmaniasis; other NTDs were relatively understudied. Mitigation was considered in 174 papers (34%) and adaption strategies in 24 (5%). Amplitude and direction of effects of climate change on malaria and NTDs are likely to vary by disease and location, be non-linear and evolve over time. Available analyses do not allow confident prediction of the overall global impact of climate change on these diseases. For dengue and chikungunya and the group of non-vector-borne NTDs, the literature privileged consideration of current low-burden countries with a high HAQI. No leishmaniasis papers considered outcomes in East Africa. Comprehensive, collaborative and standardised modelling efforts are needed to better understand how climate change will directly and indirectly affect malaria and NTDs.

Circulating cell-free DNA as a biomarker for molecular diagnosis of Neurocysticercosis.

Taenia solium is a widespread zoonotic tapeworm that predominantly affects regions of Latin America, South and South-East Asia, and Sub-Saharan Africa. Neurocysticercosis (NCC), the presence of T. solium cysts in the brain is associated with diverse clinical manifestations, such as epilepsy, seizures, and neurological deficits. It is a significant cause of preventable epilepsy globally, accounting for approximately 30% of cases in endemic regions. The diagnosis of neurocysticercosis relies on neuroimaging techniques, but these resources are often limited in low-income countries, resulting in an underestimation of the disease burden. The present study enrolled 141 patients who were clinically suspected and radiologically confirmed for NCC at the Neurology OPD of PGIMER, Chandigarh. Additionally, 98 control subjects attending the PGIMER OPD for investigation were also included. Plasma and urine samples were collected from all participants for further analysis. Cell-free DNA extraction was performed using specific kits, and the quality of the extracted DNA was assessed. The RT-LAMP assay targeted the cox1 gene. Real-time RT-LAMP results were evaluated using a fluorescence graph obtained with the Genei III fluorimeter. Among a group of patients diagnosed with NCC, the gene was identified in 74.4% of plasma samples and 67.3% of urine samples. In comparison, the T. solium cox1 gene was found in 6.1% of control subjects in plasma and urine samples using the LAMP assay. In conclusion, the study emphasises the need for improved diagnostic methods for NCC and presents promising alternatives, such as RT-LAMP and urine-based cell-free DNA analysis. These approaches offer advantages in terms of cost-effectiveness, simplicity, and diagnostic accuracy.

Establishing continuum in Transcranial Doppler characteristics of IIH, migraine and healthy controls- An exploratory study.

BACKGROUND: IIH is a severe form of headache that often has superimposed migraine and often it is very difficult to distinguish the two forms of headache. Intracranial hemodynamics is a relatively unexplored means of distinguishing between the two forms of headache. OBJECTIVES: We aimed to study intracranial flow dynamics using Transcranial Doppler in patients with IIH, migraine, and normal controls. MATERIALS AND METHODS: It was a hospital-based observational study that included 51 people with IIH, 87 people with migraine, and 101 healthy controls and all were subjected to TCD study after detailed clinical examination. RESULTS: Mean age of patients in three groups were similar with the mean age in IIH being 33.41 ± 10.75 (age in years ± SD). Vision loss was present in 66.67% of patients with IIH, and most common field defect was generalized constriction (27.5%). Neuroimaging was abnormal in 94.11% of patients of IIH with mean CSF pressure was 31.27±5.32 cm of water. Of all the TCD-measured velocities, mean flow velocity (MFV) showed a significant difference in all three groups with (p-value <0.001). The pulsatility index, both for middle cerebral arteries as well as ophthalmic arteries showed a significant difference in the three groups with the highest values in IIH patients (p-value<.001). The mean VMR in IIH (1.11±0.32) was lower than the mean VMR in migraine (1.34±0.43) as well as controls (1.49±0.46). CONCLUSION: TCD parameters like MFV and PI are useful parameters that show considerable variation and can be used to differentiate between IIH and migraine.

The Neuro-Ophthalmology of Tuberculosis.

Tuberculosis (TB) is a global health concern and central nervous system (CNS) TB leads to high mortality and morbidity. CNS TB can manifest as tubercular meningitis, tuberculoma, myelitis, and arachnoiditis. Neuro-ophthalmological involvement by TB can lead to permanent blindness, ocular nerve palsies and gaze restriction. Visual impairment is a dreaded complication of tubercular meningitis (TBM), which can result from visual pathway involvement at different levels with varying pathogenesis. Efferent pathway involvement includes cranial nerve palsies and disorders of gaze. The purpose of this review is to outline the various neuro-ophthalmological manifestations of TB along with a description of their unique pathogenesis and management. Optochiasmatic arachnoiditis and tuberculomas are the most common causes of vision loss followed by chronic papilloedema. Abducens nerve palsy is the most commonly seen ocular nerve palsy in TBM. Gaze palsies with deficits in saccades and pursuits can occur due to brainstem tuberculomas. Corticosteroids are the cornerstone in the management of paradoxical reactions, but other immunomodulators such as thalidomide and infliximab are being explored. Toxic optic neuropathy caused by ethambutol necessitates careful monitoring and immediate drug discontinuation. Cerebrospinal fluid diversion through ventriculo-peritoneal shunting may be required in patients with hydrocephalus in stage I and II of TBM to prevent visual impairment. Early diagnosis and prompt management are crucial to prevent permanent disability. Prevention strategies, public health initiatives, regular follow-up and timely intervention are essential in reducing the burden of CNS TB and its neuro-ophthalmological complications.

Pituitary Dysfunction in Idiopathic Intracranial Hypertension: An Analysis of 80 Patients.

BACKGROUND: Empty sella is a commonly described imaging entity in patients with idiopathic intracranial hypertension (IIH). Though menstrual and hormonal disturbances have been associated with IIH, available literature lacks systematic analysis of pituitary hormonal disturbances in IIH. More so, the contribution of empty sella in causing pituitary hormonal abnormalities in patients of IIH has not been described. We carried out this study to systematically assess the pituitary hormonal abnormalities in patients with IIH and its relation to empty sella. METHODS: Eighty treatment naïve patients of IIH were recruited as per a predefined criterion. Magnetic resonance imaging (MRI) brain with detailed sella imaging and pituitary hormonal profile were done in all patients. RESULTS: Partial empty sella was seen in 55 patients (68.8%). Hormonal abnormalities were detected in 30 patients (37.5%), reduced cortisol levels in 20%, raised prolactin levels in 13.8%, low thyroid-stimulating hormone (TSH) levels in 3.8%, hypogonadism in 1.25%, and elevated levels of gonadotropins were found in 6.25% of participants. Hormonal disturbances were independent and were not associated with the presence of empty sella (p = 0.493). CONCLUSION: Hormonal abnormalities were observed in 37.5% patients with IIH. These abnormalities did not correlate with the presence or absence of empty sella. Pituitary dysfunction appears to be subclinical in IIH and responds to intracranial pressure reduction, not requiring specific hormonal therapies.

A Neurological Complication in Rheumatoid Arthritis - A Scenario of Catastrophic Proportions.

Background: Rheumatoid Arthritis (RA) is a common systemic inflammatory disease that can present with a plethora of extraarticular manifestations. Many patients with RA from low- and middle-income countries do not get timely and adequate treatment with disease-modifying therapies. This results in the perpetuation of a chronic inflammatory state. Focus: Rheumatoid vasculitis (RV) is one of the most aggressive complications of RA resulting from a prolonged proinflammatory milieu. Usually, it has the involvement of multiple organ systems, with cutaneous manifestations being the most common. Neurological presentation is uncommon but severe when present. Highlight: We present a case of severe RV presenting with an unexpected neurological complication consisting of cranial and peripheral neuropathy with small vessel disease and intracerebral haemorrhage. We intend to highlight the morbidity and long-term consequences of inadequately treated RA, the most common inflammatory disease of the connective system especially in light of the neurological presentation.

VENOUS OVERLOAD CHOROIDOPATHY ASSOCIATED WITH IDIOPATHIC INTRACRANIAL HYPERTENSION.

PURPOSE: To report a case of venous overload choroidopathy associated with idiopathic intracranial hypertension in a 41-year-old man. METHODS: History and clinical examination, fluorescein angiography, ultra-widefield indocyanine green angiography, swept-source optical coherence tomography, and contrast-enhanced magnetic resonance imaging. RESULTS: The patient was diagnosed as having idiopathic intracranial hypertension 2 years ago, was being managed on oral acetazolamide, and retained 20/20 visual acuity in both eyes until now when he presented with a complaint of visual loss in the right eye. Ophthalmoscopy revealed serous detachment in the fovea of the right eye. Swept-source optical coherence tomography showed the presence of subretinal fluid and detachments of the retinal pigment epithelium in both eyes. Fundus fluorescein angiography showed multiple dot leaks at the level of the retinal pigment epithelium in both eyes. Indocyanine green angiography revealed vortex vein anastomoses and choroidal vascular hyperpermeability in both eyes. Contrast-enhanced magnetic resonance imaging revealed dilated optic nerve sheath diameter and a partial empty sella and magnetic resonance venography showed bilateral stenosis of the transverse sinus. CONCLUSION: Transverse sinus stenosis is a common finding in "idiopathic" intracranial hypertension and contributes to the intracranial pressure through intracranial venous hypertension. Increased venous back pressure seemed to have overloaded the choroid resulting in choroidal vascular congestion and hyperpermeability, leaks from the level of the retinal pigment epithelium, and accumulation of subretinal fluid.

MPT51 and MPT64-based antigen detection assay for the diagnosis of extrapulmonary tuberculosis from urine samples.

In view of WHO's "End-TB" strategy, we developed a non-invasive, urine-based ELISA, targeting 2 Mycobacterium tuberculosis antigens namely MPT51 and MPT64 for extrapulmonary TB (EPTB) diagnosis. Suspected EPTB patients (n = 137) [Pleural TB, Abdominal TB and Tuberculous meningitis] were categorized in "Definite" EPTB (n = 10) [Xpert-MTB/RIF and/or culture-positive], "Probable" EPTB (n = 77) and "Non-EPTB" (n = 50) groups using defined composite reference standards. ROC-curves were generated using ELISA results of "Definite" EPTB and "Non-EPTB" groups for both antigens independently and cut-off values were selected to provide 86.3% (95%CI:73.3-94.2) specificity for MPT51 and 92% (95%CI:80.8-97.8) for MPT64. The sensitivity of MPT51-ELISA and MPT64-ELISA was 70% (95%CI:34.7-93.3) and 90% (95%CI:55.5-99.7) for "Definite" EPTB group and 32.5% (95%CI:22.2-44.1) and 30.8% (95%CI:20.8-42.2) for "Probable" EPTB group, respectively. Combining the results of both ELISAs showed a 100% (95%CI:69.1-100) sensitivity in "Definite" EPTB group and 41.6% (95%CI:30.4-53.4) in "Probable" EPTB group, with an 80% (95%CI:66.3-89.9) specificity. The results demonstrated the potential of urine-based ELISAs as screening tests for EPTB diagnosis.

Effectiveness of therapeutic plasma exchange in case of rare neurological disorder Isaacs syndrome.

Isaacs syndrome is a disease characterized by nerve hyperexcitability and pseudomyotonia and treated with immunomodulatory and symptomatic therapy approaches. Here, we report a case of anti-(leucine-rich glioma-inactivated 1) antibody-positive patient diagnosed as Isaacs syndrome and accomplished a nearly complete response to only four sessions of therapeutic plasma exchange (TPE). Our experience suggests that TPE along with other immunomodulatory agents may be beneficial and well-tolerated approach in patient with Isaacs syndrome.

Serum Calcitonin Gene-Related Peptide Is Elevated in Patients With Migraine and Ophthalmoplegia.

BACKGROUND: There is ongoing debate about whether the oculomotor (III), trochlear (IV), or abducens (VI) nerve paresis in patients with migraine is directly attributable to migraine (ophthalmoplegic migraine [OM]) or is due to an inflammatory neuropathy (recurrent painful ophthalmoplegic neuropathy [RPON]). As migraine is associated with elevated serum calcitonin gene-related peptide (CGRP) levels, we studied serum CGRP levels among patients with OM/RPON to determine whether they are elevated during and between attacks. This is the first study assessing CGRP levels in the serum of patients with OM/RPON. METHODS: The aim of this case-control study was to assess serum CGRP levels in patients with ophthalmoplegia and a headache consistent with migraine according to ICHD-3 criteria. Serum CGRP levels were measured during the ictal and interictal phases in 15 patients with OM/RPON and compared with age-matched and sex-matched controls without migraine (12 patients). RESULTS: The median serum CGRP levels were significantly elevated ( P = 0.021) during the ictal phase (37.2 [36.4, 43.6] ng/L) compared with controls (32.5 [30.1, 37.3] ng/L). Serum CGRP levels during the attack correlated with the total duration of ophthalmoplegia. A CGRP level of 35.5 ng/L in the ictal phase of the attack had a sensitivity of 86.7% and specificity of 75.0% in diagnosing a patient with OM/RPON. CONCLUSIONS: Elevated serum CGRP levels during the ictal phase of OM/RPON favor migraine as the underlying cause of episodic headache with ophthalmoplegia.

Determinants of patients' delay with disability in the diagnosed leprosy cases in the three major states of India: A case-control study.

BACKGROUND: Skin lesions are the most common early symptoms of leprosy, often ignored by patients at an early stage and misdiagnosed as other dermatological diseases by healthcare personnel, leading to delay in diagnosis and treatment of leprosy precipitating permanent neurological deficit, deformities and serious disabilities. AIMS: The objective is to evaluate the duration of delay and factors responsible for the delay in reporting of patients, among the newly detected leprosy cases (Grade 1 and Grade 2 disability patients). METHODS: A case-control study was conducted during 2014-2016 in three major states of India (Delhi, Gujarat and West Bengal) in 140 randomly recruited newly registered adult leprosy patients (aged 18 years and above) with Grade 2/1 disabilities (cases) and 140 Grade 0 disability patients (controls) in each of these Indian states. RESULTS: It is established that the major contributors for the delay in the early diagnosis of leprosy have been patient-related factors. The median patient delay in the three states of Delhi, Gujarat and West Bengal were five months (0.7-1.8), 2.8 months (2-14) and 12 months (2-24), respectively. LIMITATIONS: The study design is case-control and has an inbuilt reporting bias due to the retrospective nature of data collection but the data collection was carried with caution to reduce the recall bias. As the study is carried out in three states, generalisation of interpretation was cautiously executed. The matching ratio of cases and controls was 1:1 in this study, but we could not increase the controls due to operational feasibility during the conduct of the study. CONCLUSION: Patient delay is a crucial factor responsible for the disability among new leprosy cases. A higher patient delay in these three states reflects that the community is not aware about the signs and symptoms of leprosy. Reducing patient delay is very important for reducing disabilities in the newly diagnosed cases.

A 12-YEAR-OLD ASIAN INDIAN BOY WITH BILATERAL RAPIDLY PROGRESSIVE NECROTIZING MACULAR RETINITIS.

PURPOSE: To describe clinical and imaging findings in a young boy presenting with bilateral rapidly progressive necrotizing macular retinitis. METHODS: A 12-year-old Asian Indian boy developed bilateral progressive macular retinitis. He had generalized tonic-clonic seizures for the past 3 months and gave a history of poor scholastic performance with dementia of recent onset. Multimodal imaging comprising and detailed systemic and laboratory work-up was performed. RESULTS: Both eyes showed rapidly progressive full-thickness retinitis lesions observed as disruption of retinal architecture in both eyes. Left eye optical coherence tomography shows full-thickness retinal involvement with sparing of the internal limiting membrane. Electroencephalogram and magnetic resonance imaging (brain) were suggestive of subacute sclerosing panencephalitis and the diagnosis was confirmed by elevated cerebrospinal fluid and serum IgG measles. The patient did not survive despite treatment with systemic interferon therapy. CONCLUSION: It is important to look for the measles virus as a probable cause of necrotizing retinitis and neurologic symptoms in immunocompetent unvaccinated young patients. Early referral to a neurologist may assist in the early diagnosis of subacute sclerosing panencephalitis and targeted therapy.